Clinical Handbook

of Insomnia
 CURRENT CLINICAL NEUROLOGY
Daniel Tarsy, MD, SERIES EDITOR

Clinical Handbook of Insomnia, edited by Hrayr P. Attarian, 2004

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Alzheimer’s Disease: A Physician’s Guide to Practical Management, edited
by Ralph W. Richter and Brigitte Zoeller Richter, 2004
Field of Vision: A Manual and Atlas of Perimetry, edited by Jason J. S.
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Surgical Treatment of Parkinson’s Disease and Other Movement
Disorders, edited by Daniel Tarsy, Jerrold L. Vitek, and Andres M.
Lozano, 2003
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 Clinical Handbook
of Insomnia

Edited by

Hrayr P. Attarian, MD
Sleep Program in Neurology
and Sleep Laboratory of the Clinical Neurophysiology Laboratories,
University of Vermont College of Medicine, Burlington, VT

Foreword by

Mark W. Mahowald, MD
Minnesota Regional Sleep Disorders Center, Hennepin County Medical Center
and University of Minnesota Medical School, Minneapolis, MN

Humana Press
Totowa, New Jersey
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Clinical handbook of insomnia / edited by Hrayr P. Attarian.
p. ; cm.-- (Current clinical neurology)
Includes bibliographical references and index.
ISBN 1-58829-272-X (alk. paper)
1. Insomnia--Handbooks, manuals, etc. I. Attarian, Hrayr P. II. Series. [
DNLM: 1. Sleep Initiation and Maintenance Disorders. WM 188 C6416 2004]
RC548.C56 2004
616.8'498--dc21 2003049988
To my wife Diana with unending love
 Series Editor’s Introduction

The areas of sleep research as a scientific discipline and sleep medicine as a

medical specialty are relatively new but rapidly growing areas of interest. Early
investigations in sleep emphasized disorders of excessive daytime sleepiness. How-
ever, among the sleep disorders, insomnia may be the most common and yet, at the
same time, the least well-managed sleep disorder. To many patients and physi-
cians, insomnia is presumed to be the result of underlying anxiety, recognized or
unrecognized. Perhaps for this reason, large numbers of affected individuals do not
seek medical attention but self-treat with alcohol or relatively ineffective over-the-
counter medications.
As stated in the Clinical Handbook of Insomnia, contrary to popular belief, psy-
chological factors are not the most common causes of insomnia and, very appropri-
ately, clues to possible physiologic causes of insomnia are given important
attention. On the other hand, the authors in this volume emphasize that untreated
insomnia may be an important risk factor for secondary psychiatric morbidity. Sur-
prisingly, it is currently unclear whether insomnia should be considered a disorder
of sleep or a disorder of arousal. Insomnia is a symptom, not a disease, but appar-
ently can occur as a primary or secondary disorder. Clinical Handbook of Insomnia
carefully defines insomnia, emphasizes the broad scope of the problem worldwide,
discusses its differential diagnosis, differentiates the primary and secondary
insomnias, and reports critically on the available modes of behavioral and pharma-
cologic treatment.
This collection within a single volume of very practical information concerning
a common, but often neglected, disorder will be a useful addition to the armamen-
tarium of the generalist or specialist who wishes to deal with insomnia in an intelli-
gent and responsible manner.
Daniel Tarsy, MD
Movement Disorders Center,
Beth Israel Deaconess Medical Center,
Harvard Medical School, Boston, MA

vii
 Foreword

It is a pleasure and honor for me to introduce this most important Clinical Hand-
book of Insomnia, edited by Hrayr Attarian, MD. For too long, the complaint of
insomnia has been ignored, trivialized, or summarily (often erroneously) attributed
to underlying or pre-existing psychiatric or psychological problems (themselves
often ignored or trivialized). This book clearly underscores the fact that insomnia
extracts a huge toll—in the form of personal misery, societal financial burden, lost
productivity, and strained interpersonal relationships.
One reason the complaint of insomnia is often not pursued by physicians is that
the evaluation and management may be time consuming and therefore difficult to
execute in the current medical climate. Another is that physicians tend not to want
to deal with conditions that are perceived as difficult or discouraging to manage.
Many physicians have not had positive reinforcement from predictable success in
treating insomnia—their past experience does not anticipate a favorable outcome.
Clinical Handbook of Insomnia provides a systematic approach to the diagnosis
and management of insomnia, which will result in more gratifying doctor–patient
encounters—with the patient improving, and the physician being positively rein-
forced.
As with other constitutional symptoms, such as pain, fever, or weight loss, in-
somnia is a manifestation of myriad underlying conditions that, appropriately iden-
tified, is effectively treatable. The algorithm in Chapter 4 is particularly helpful in
this regard.
One important emphasis of Clinical Handbook of Insomnia is the growing sci-
entific evidence that much insomnia has biological underpinnings, with many indi-
viduals having a genetic or constitutional predisposition to develop insomnia—
triggered by environmental events or situations. Once this insomnia has developed,
it may become persistent, despite resolution of the initial instigators, and will not
spontaneously improve until behavioral and/or pharmacologic treatment is under-
taken. This is reason enough for aggressive treatment of acute, situational insom-
nia—to prevent the development of persistent psychophysiologic, learned, or
conditioned insomnia.
Furthermore, it is now clear that insomnia, initially not associated with depres-
sion, is a major risk factor for the development of depression—another reason for
prompt diagnosis and aggressive treatment.
The encouragement of pharmacologic treatment of insomnia is welcome, inas-
much as there are now many very effective sedative/hypnotic agents available. The
tendency has existed to prescribe ineffective or potentially more toxic agents ow-
ing to exaggerated and unfounded fears associated with prescribing those agents
that are truly effective. Just as physicians are comfortable prescribing long-term
stimulants for hypersomnolent conditions such as narcolepsy or idiopathic central
ix
x Foreword

nervous system hypersomnia, they should be comfortable prescribing long-term

sedative/hypnotics in hyposomnolent conditions. There has been a failure to distin-
guish between drug-seeking behavior and therapy-seeking behavior. This fear of
drug abuse results in patient abuse.
This is certainly the most extensive insomnia textbook available. Dr. Attarian
should be commended for compiling this group of distinguished and experienced
authors who provided such thoughtful and excellent contributions. The benefactors
will be both patients and treating physicians.
Mark W. Mahowald, MD
Director, Minnesota Regional Sleep Disorders Center
Hennepin County Medical Center
Professor, Department of Neurology,
University of Minnesota Medical School
Minneapolis, MN
 Preface

Insomnia is the second most common complaint, after pain, in the primary care
setting. Persistent insomnia affects roughly more than one-third of the population
and is a risk factor for significant psychiatric morbidity.
Insomnia also leads to over-utilization of health care services, decreased pro-
ductivity in the workplace, more accidents, and more absenteeism from work. All
this costs about $100 billion annually. Hence, persistent insomnia is both a public
health and an economic problem. Insomnia is not, however, one distinct illness.
There are many causes and each naturally requires a different method of evaluation
and treatment. Patients with insomnia frequently self-treat with alcohol or over-
the-counter medications. There is no scientific evidence for the efficacy of these
medications in insomnia. Additionally, those taking these medications may suffer
impaired daytime functioning caused by lingering feelings of sedation.
Most medical school curricula suffer a dearth of material on sleep medicine as
well as insomnia. Primary care text and reference books often do not include chap-
ters that address the evaluation and treatment of insomnia. The Clinical Handbook
of Insomnia represents the first clinically oriented, easily readable textbook dedi-
cated to the evaluation and treatment of insomnia in the primary care setting. Our
goal is to provide practitioners in general and primary care providers specifically
with an easily accessible handbook to serve as a reference for the evaluation and
treatment of this important yet poorly recognized medical problem.
The Clinical Handbook of Insomnia is divided into four sections. The first dis-
cusses definitions, differential diagnosis of insomnia in adults and children, the
epidemiology, and the pathophysiology of insomnia. The second section focuses
on the primary insomnias. Part III discusses the secondary insomnias or insomnias
arising from other medical problems. Part IV reviews the pharmacological and
nonpharmacological treatments of insomnia. Most of the chapters are illustrated by
case studies, algorithms, and charts and graphs to better elucidate the points con-
veyed.
We hope the Clinical Handbook of Insomnia will fill an important niche in the
medical literature by providing the first comprehensive publication that addresses
insomnia in its multiple forms, summarizes the findings published in different medi-
cal journals, and presents the findings to the practicing health care provider in an
easily readable format.
Hrayr P. Attarian, MD

xi
 Contents

Series Editor’s Introduction .................................................................................. vii

Foreword ................................................................................................................. ix

Preface ..................................................................................................................... xi

Contributors ........................................................................................................... xv

Part I: Overview
1 Defining Insomnia ...........................................................................................3
Hrayr P. Attarian, Pallavi Nishith-Davis, Carla R. Jungquist,
and Michael L. Perlis
2 Epidemiology of Insomnia .......................................................................... 11
Hrayr P. Attarian
3 Physiological Basis of Insomnia ................................................................. 23
Michael H. Bonnet and Donna L. Arand
4 Differential Diagnosis of Insomnia ............................................................. 39
Hrayr P. Attarian

Part II: The Primary Insomnias

5 Insomnia in Children and Adolescents ....................................................... 53
John Garcia
6 Psychophysiological Insomnia .................................................................... 67
Hrayr P. Attarian
7 Idiopathic Insomnia ..................................................................................... 81
Hrayr P. Attarian
8 Sleep State Misperception ........................................................................... 89
Stephen Duntley
9 Sleep Hygiene .............................................................................................. 99
Hrayr P. Attarian

Part III: The Secondary Insomnias

10 Insomnia Caused by Medical and Neurological
Disorders ................................................................................................ 109
Kenneth E. Plotkin
11 Insomnia in Psychiatric Disorders ............................................................. 127
Samy S. Karaz

xiii
xiv Contents

12 Insomnia in Primary Sleep Disorders ....................................................... 141

Stephen Duntley

Part IV: Treatment of Insomnia

13 Cognitive-Behavioral Therapy for Insomnia ............................................ 155
Michael L. Perlis, Michael T. Smith, Carla R. Jungquist,
Sara Nowakowski, Henry Orff, and James Soeffing
14 Pharmacological Treatment of Insomnia .................................................. 173
Hrayr P. Attarian

Index .................................................................................................................... 187

 Contributors

HRAYR P. ATTARIAN, MD • Sleep Program in Neurology and Sleep Laboratory of the

Clinical Neurophysiology Laboratories,
University of Vermont College of Medicine, Burlington, VT
DONNA L. ARAND, PhD • Dayton Department of Veterans Affairs Medical Center,
Wright State University, and Kettering Medical Center,
Dayton, OH
MICHAEL H. BONNET, PhD • Dayton Department of Veterans Affairs Medical Center,
Wright State University, and Kettering Medical Center, Dayton, OH
STEPHEN DUNTLEY, MD • Multidisciplinary Sleep Medicine Center, Department of
Neurology, Washington University St Louis, St Louis, MO
JOHN GARCIA, MD • Minnesota Regional Sleep Disorders Center, Hennepin County
Medical Center, University of Minnesota, Minneapolis MN
CARLA R. JUNGQUIST, MSN • UR Sleep Research Laboratory, University
of Rochester Medical Center, Rochester, NY and Pain Treatment Clinic,
Canandaigua VA, Canandaigua, NY
SAMY S. KARAZ, MD • Merit Care Sleep Medicine Center, University of North
Dakota, and North Dakota Psychiatric Association, Fargo, ND
MARK W. MAHOWALD, MD • Minnesota Regional Sleep Disorders Center,
Department of Neurology, Hennepin County Medical Center, University
of Minnesota Medical School, Minneapolis, MN
PALLAVI NISHITH-DAVIS, PhD • Center for Trauma Recovery, Department of
Psychology, University of Missouri-St Louis, St Louis, MO
SARA NOWAKOWSKI • UR Sleep Research Laboratory, University of Rochester,
Rochester, NY
HENRY ORFF • UR Sleep Research Laboratory, University of Rochester, Rochester,
NY
MICHAEL L. PERLIS, PhD • Psychiatry and Psychology, UR Sleep Research Laboratory,
and Departments of Psychiatry and Clinical and Social Psychology, University
of Rochester Medical Center, Rochester, NY
KENNETH E. PLOTKIN, MD • Department of Neurology, University of Rochester
Medical Center, Rochester NY
MICHAEL T. SMITH, PhD • Department of Psychiatry, Johns Hopkins University,
Baltimore, MD
JAMES SOEFFING • UR Sleep Research Laboratory, University of Rochester, Rochester,
NY
DANIEL TARSY, MD • Movement Disorders Center, Beth Israel Deaconess Medical
Center, Harvard Medical School, Boston, MA

xv
Defining Insomnia 1

I Overview
2 Attarian et al.
Defining Insomnia 3

1
Defining Insomnia

Hrayr P. Attarian, Pallavi Nishith-Davis,

Carla R. Jungquist, and Michael L. Perlis

Tired Nature’s sweet restorer, balmy sleep!

He, like the world, his ready visit pays
Where fortune smiles; the wretched he forsakes

—Edward Young (1683–1765) “Night Thoughts”

INTRODUCTION
In the early 1980s, as the sleep medicine movement was just gathering steam,
there was perhaps no rallying cry as popular as “insomnia is a symptom, not a
disorder.” Presumably, this position was taken in part for medico-political reasons,
but also because it was genuinely believed that the polysomnographic study of sleep
was destined to reveal all the underlying pathologies that give rise to the “symp-
toms” of insomnia—fatigue and sleepiness. After two decades or more of sleep
research and sleep medicine, it is interesting to find that “all things old are new
again”: insomnia is once again considered a distinct nosological entity. Perhaps
what is different in the modern era is that the distinction between primary and sec-
ondary insomnia allows for difficulty initiating and maintaining sleep to be both a
disorder in its own right and a symptom of other disorders.

HISTORICAL PERSPECTIVES
The first references in the Western culture to insomnia, the inability to initiate
and or maintain sleep, date back to the ancient Greeks. The earliest mention of
insomnia is in the pre-Hippocratic Epidaurian tablets that list 70 cases, one of which
is of a patient with insomnia. The first scientific approach is found in the writings
of Aristotle from circa 350 BC, and the first records of treatment of insomnia come
from the first century BC Greek physician Heraclides of Taras, who lived in Alexan-
dria and recommended opium as the treatment of choice. Although there were sig-
nificant amounts of research and interest in insomnia in the 20th century, it was not
From: Current Clinical Neurology: Clinical Handbook of Insomnia
Edited by: H. P. Attarian © Humana Press Inc., Totowa, NJ

3
4 Attarian et al.

until the 1970s that distinct diagnostic criteria were created to describe different
forms of the disorder.
Over the years, insomnia has been featured in the writings of several prominent
literary figures, including William Shakespeare, who alluded to it in several of his
plays, to the pop culture icons the Beatles who referred to it in their song “I’m So
Tired.” Prominent historical figures who reportedly suffered from insomnia include
Winston Churchill, Charles Dickens, Napoleon Bonaparte, Marcel Proust,
Alexander Dumas, and Benjamin Franklin.

DEFINITIONS OF INSOMNIA
Insomnia is the most common sleep-related complaint and the second most com-
mon overall complaint (after pain) reported in primary care settings (1). It affects
35% of the general population, according to the 1984 report of the National Insti-
tutes of Mental Health (2), and is a cause of significant morbidity (1). It costs the
American public about $100 billion annually in medical expenses, ramifications of
accidents, and reduced productivity due to absenteeism and decreased work effi-
ciency (3).
Insomnia is not defined by total sleep time (TST) but by the inability to obtain
sleep of sufficient length or quality to produce refreshment the following morning
(4). For example, a person who needs only 4 hours of sleep does not have insomnia
if he or she is refreshed in the morning after having 4 hours of sleep, whereas some-
one who needs 10 hours of sleep may have insomnia if he or she does not feel
refreshed even after 8 hours of sleep. Contrary to popular lore, psychiatric or psy-
chological factors are not often causes of insomnia (1). In fact, long-standing in-
somnia can be a significant risk factor for development of depression and anxiety
disorders (5,6).

Classifications
There are three major classification systems used by professionals: The Interna-
tional Classification of Diseases (ICD) by the World Health Organization (WHO),
the American Psychiatric Association’s (APA) Diagnostic and Statistical Manual
on Mental Disorders, fourth edition (DSM-IV), and The International Classifica-
tion of Sleep Disorders-Revised (ICSD-R) by the American Academy of Sleep
Medicine (AASM).
WHO: ICD
The WHO defines insomnia as a problem initiating and/or maintaining sleep or
the complaint of nonrestorative sleep that occurs on at least 3 nights a week and is
associated with daytime distress or impairment (7).
APA: DSM-IV
The APA defines two types of insomnia, primary and secondary.
The term primary insomnia, which is adopted by the APA’s diagnostic nomen-
clature, DSM-IV (8), is used to distinguish insomnia that is considered to be a dis-
Defining Insomnia 5

Table 1
Diagnostic Criteria for Primary Insomnia
A. Difficulty initiating or maintaining sleep for at least 1 month.
B. The disrupted sleep and the associated daytime fatigue causes clinically significant
distress and impaired functioning.
C. The sleep disturbance cannot be attributed to any other sleep disorder.
D. The sleep disturbance cannot be attributed to any other psychiatric disorder.
E. The sleep disturbance cannot be attributed to any other medical disorder or substance
abuse.
Adapted from ref. 8.

tinct diagnostic entity from insomnia that is a secondary symptom of an underlying

medical and/or psychiatric condition. The APA specifies a duration criteria of 1 month
and stipulates that the diagnosis be made when the predominant complaint is diffi-
culty initiating or maintaining sleep or nonrestorative sleep. In either case, the com-
plaint must be associated with significant distress and daytime impairment, and not
due to other medical, psychiatric, or sleep disorders. Table 1 lists the diagnostic
criteria for primary insomnia.
AASM: ICSD-R
AASM’s nosology, the ICSD-R, does not have a distinct category of primary
insomnia but instead discusses three free-standing insomnia disorders: psycho-
physiological insomnia, idiopathic insomnia, and sleep state misperception (9).
PSYCHOPHYSIOLOGICAL INSOMNIA
The ICSD-R definition of psychophysiological insomnia is directly tied to the
etiologic underpinnings of the disorder. Psychophysiological insomnia is described
as “a disorder of somatized tension and learned sleep-preventing associations that
results in a complaint of insomnia and associated decreased functioning during
wakefulness” (9). “Somatized tension” refers to either the patient’s subjective sense
of, or objective measures of, somatic hyperarousal while attempting to sleep.
Somatic arousal is characterized by peripheral nervous system activity that is com-
monly marked by increased muscle tension, rapid heart rate, sweating, and so on.
“Learned sleep-preventing associations” refers to the pattern of pre-sleep arousal
that appears to be classically conditioned to the bedroom environment, where intru-
sive pre-sleep cognitions, racing thoughts, and rumination are often taken as indi-
cators of pre-sleep arousal. Table 2 presents the diagnostic criteria for
psychophysiological insomnia.
IDIOPATHIC, OR CHILDHOOD-ONSET, INSOMNIA
This condition presents as a chronic, serious inability to initiate and maintain
sleep, which can often be traced back to the first few weeks of life (10). Sleep
latency (i.e., the time it takes to fall asleep after going to bed) may be very long, and
sleep is riddled with awakenings. Daytime features typically include decreased
6 Attarian et al.

Table 2
Diagnostic Criteria for Psychophysiological Insomnia
A. Complaint of insomnia together with a complaint of decreased functioning during
wakefulness.
B. Learned sleep-preventing associations that include the following:
1. Trying too hard to sleep
2. Conditioned arousal to bedroom or sleep-related activities
C. Evidence for somatized tension.
D. On polysomnography there is
1. Increased sleep latency
2. Reduced sleep efficiency
3. An increased number and duration of awakenings,
E. The sleep disturbance cannot be attributed to any other medical disorder.
F. Other sleep disorders can co-exist.
Minimal Criteria: A plus B.
Adapted from ref. 9.

Table 3
Diagnostic Criteria for Idiopathic Insomnia
A. Complaint of insomnia together with a complaint of decreased functioning during
wakefulness.
B. The insomnia is long standing with onset in childhood and sometimes even at birth.
C. Relentless insomnia invariant through periods of both good and bad emotional
adaptation.
D. On polysomnography there is
1. Increased sleep latency
2. Reduced sleep efficiency
3. An increased number and duration of awakenings
E. The sleep disturbance cannot be attributed to any other medical disorder.
F. Other sleep disorders can co-exist.
Minimal Criteria: A plus B plus E.
Adapted from ref. 9.

attention and vigilance, low levels of energy and concentration, and deterioration
of mood that is usually described as grim and subdued rather than obviously
depressed or anxious.
The presumed underlying neurological abnormality may vary from mild to
severe, so the range of insomnia encountered also may vary from mild (essentially,
the patient is a light sleeper) to severe and incapacitating. In mild or moderate idio-
pathic insomnia, psychological functioning is remarkably intact. In severe cases,
daytime functioning may be severely disrupted, and the affected patient may be
unable to hold a job. During childhood and adolescence, idiopathic insomnia is
often associated with such neurological signs as dyslexia and hyperactivity. In many
cases, diffuse, nonspecific abnormalities are seen on an electroencephalogram
(EEG) (9). Table 3 lists the diagnostic criteria for idiopathic insomnia.
Defining Insomnia 7

Table 4
Diagnostic Criteria for Sleep State Misperception
A. Complaint of insomnia
B. Normal sleep quality and duration
C. Normal polysomnography
D. The sleep disturbance cannot be attributed to any other medical disorder.
E. Other sleep disorders can co-exist.
Minimal Criteria: A plus B.
Adapted from ref. 9.

SLEEP STATE MISPERCEPTION INSOMNIA

In this fascinating disorder, complaints of insomnia occur without any objective
evidence of sleep disturbance. Patients may report that they have not slept at all in
weeks, months, or years. However, on objective sleep studies, they sleep several
hours per night (4,11). When results of sleep evaluation are presented, patients with
sleep state misperception (SSM) may vehemently insist that the studies are in error
because they are convinced that they sleep very little, if at all. Table 4 lists the
diagnostic criteria for SSM.
Interestingly, none of the nosologies formally embrace the older descriptive
clinical characterizations of insomnia in terms of initial, middle, and terminal (late)
insomnia. Trouble falling asleep is often referred to as “initial,” early, or sleep-
onset insomnia. Trouble with frequent or prolonged awakenings is often labeled
“middle” or sleep maintenance insomnia. Waking up earlier than desired and being
unable to fall back asleep is referred to as “late,” “terminal,” or early morning awak-
ening insomnia. Waking up feeling unrefreshed is commonly referred to as
“nonrestorative” sleep. Patients often report some combination of these descrip-
tions, which is generally referred to as “mixed” insomnia. For the purpose of this
chapter, although we consider the ICD’s system to provide a more precise defini-
tion of the disorder, we use the term primary insomnia because it is the most widely
embraced in clinical practice in the United States. We adopt the more descriptive
terminology when a more specific characterization of the presenting complaint is
required.

Classification Based on Duration and Severity

Apart from presenting a specific definition of the disorder/disease entity, there
is the need to qualify the duration and severity of the defined illness. Typically,
duration is framed dichotomously in terms of acute and chronic stages. Severity
can be construed in one of two ways. In one case, standards are set for what consti-
tutes significant deviance from population norms with respect to frequency and
intensity of presenting symptoms. In the other case, standards are set by “setting
the bar” for “pathologic” at a level that is modal for patients who are help-seeking.
8 Attarian et al.

Duration of Illness
Insomnia lasting less than 1 month is generally considered “acute,” and is often
associated with clearly defined precipitants such as stress, acute pain, or substance
abuse. Insomnia is characterized as being chronic when symptoms persist unabated
for a duration of at least 1 month, and more typically for durations of time that are
6 months or greater. These cutoffs are relatively arbitrary and correspond to tradi-
tional medical definitions of what constitutes short and long periods of time. At this
time, there are no studies that use risk models to evaluate the natural course of insom-
nia. Thus, there is no way of definitively defining “chronicity” in terms that are related
to when the disorder becomes severe, persistent, and (for want of a better expression)
“self-perpetuating.” One clinical cue for differentiating between acute and chronic
insomnia resides in the way patients characterize their complaints. When patients
stop causally linking their insomnia to its precipitant and instead indicate that their
sleep problems seem “to have a life of their own,” this change in presentation may
serve to define the “cut point” between the acute and chronic phases of the disorder
and suggest when cognitive-behavioral therapy should be indicated.
Severity of Illness
INTENSITY
Although there are no formal diagnostic criteria, most investigators consider 30
or more minutes to fall asleep and/or 30 or more minutes of wakefulness after sleep
onset to represent the threshold between normal and abnormal sleep. Recent work
by Lichstein and colleagues suggests that this criteria should be set at “more than
30 minutes,” as this definition is better related to the occurrence of complaint in
population studies (12). With respect to “how much sleep,” many investigators are
reluctant to fix a value for this parameter. Of the investigators who are inclined to
set minimums, most specify that the amount of sleep obtained on a regular basis be
equal to or less than either 6 or 6.5 hours per night. The reluctance to establish TST
parameters is due, in part, to the difficulty in establishing precisely what one con-
siders to be abnormal. Representing what is pathological with a single number is
too confounded by factors like age, prior sleep, and the individual’s basal level of
sleep need. The lack of an established TST cutoff is also related to the possibility
that profound sleep initiation or maintenance problems may occur in the absence of
sleep loss. This is an important distinction because it is often assumed that insom-
nia is synonymous with sleep deprivation. Although it is certainly the case that the
daytime symptoms associated with insomnia might be explained, in part, by partial
chronic sleep loss, daytime symptoms need not be ascribable only to lack of sleep.
For example, it has been shown that patients with insomnia reliably exhibit sleep
micro-architectural disturbances such as enhanced high-frequency activity during
non-rapid eye movement (NREM) sleep (13–17). This type of activity, which
appears to be independent from sleep continuity and architecture parameters, has
been shown to be correlated with patient perceptions about sleep quality and quan-
tity (13,18,19).
Defining Insomnia 9

FREQUENCY
There is also no fixed benchmark for “frequency” of symptoms. Most clinical
researchers, in this case, require that subjects experience problems on at least 3
nights per week, but this may have more to do with increasing the odds of studying
the occurrence of the disorder in laboratory than an inherent belief that less than 3
nights per week is “normal.”

Commonalities and Problems with Current Definitions

All of the definitions just given show a degree of consistency, both in terms of
what “is” and “is not” delineated. Common to all is that (1) insomnia is defined as
a subjective complaint, (2) patients must report compromised daytime functioning,
(3) there are no specific criteria for how much wakefulness is considered patho-
logic (prior to desired sleep onset or during the night), and (4) there are no criteria
for how little total sleep must be obtained to fall outside the normal range. The
latter two of these issues have already been explicated (lack of quantitative criteria
for sleep latency, waking after sleep onset, and TST). The former two require fur-
ther discussion.

Insomnia as a Subjective Complaint

Defining insomnia as a subjective complaint without requiring objective verifi-
cation of signs and symptoms has advantages and disadvantages. The advantage of
having subjective criteria is that it recognizes the primacy of the patient’s experi-
ence of distress or disease. That is, ultimately patients seek, comply with, and dis-
continue treatment based on their perception of wellness. The disadvantage is that
such measures, when used alone, do not allow for a complete characterization of
either the patient’s condition or the disorder in general.

Insomnia and Daytime Impairment

The reason that daytime complaints are required for diagnosis is that in the
absence of such complaints, it is possible that the phenomena of “short sleep” may
be misidentified as insomnia. Frequent complaints associated with insomnia include
fatigue, irritability, problems with attention and concentration, and distress directly
related to the inability to initiate and/or maintain sleep.

SUMMARY
We are fortunate to have several nosologies that recognize insomnia as a pri-
mary disorder. The various classification systems provide the wherewithal to dif-
ferentiate types of insomnia both by presenting complaints as well as by the factors
that are thought to precipitate or perpetuate the illness. Perhaps what remains to be
accomplished in the present decade, from a definitional point of view, is for schol-
ars and scientists to complete the characterization of this important disorder by
providing for the formulation of the ultimate definition, one that formally lays out
the research diagnostic criteria and does so based on the force of empirical research.
10 Attarian et al.

REFERENCES
1. Mahowald, M. W., Kader, G., and Schenck, C. H. (1997) Clinical categories of sleep disorders I.
Continuum 3(4), 35–65.
2. NIH Consensus Development Conference Summary. Drugs and insomnia: the use of medication
to promote sleep. (1984) JAMA 251(18), 2410–2414.
3. Stoller, M. K. (1994) Economic effects of insomnia. Clin. Ther. 16(5), 873–897.
4. Hauri, P. J. (1998) Insomnia. Clin. Chest Med. 19(1), 157–168.
5. Gillin, J. C. (1998) Are sleep disturbances risk factors for anxiety, depressive and addictive disor-
ders? Acta Psychiatr. Scand. Suppl. 393, 39–43.
6. Chang, P. P., Ford, D. E., Mead, L. A., et al. (1997) Insomnia in young men and subsequent
depression: the Johns Hopkins Precursors Study. Am. J. Epidemiol. 146(2), 105–114.
7. World Health Organization. (1992) The ICD-10 Classification of Mental and Behavioural Disor-
ders: Clinical descriptions and diagnostic guidelines. Geneva, World Health Organization.
8. American Psychiatric Association. (1994) Diagnostic and Statistical manual of Mental Disor-
ders (4th ed.). APA, Washington, DC.
9. American Sleep Disorders Association. (1997) The International Classification of Sleep Disor-
ders: Diagnostic and Coding Manual-Revised. American Sleep Disorders Association, Roches-
ter, MN.
10. Sano, H. and Itoh, H. (1998) Idiopathic insomnia. Nippon Rinsho 56(2), 361–364.
11. Bonnet, M. H. and Arand, D. L. (1997) Physiological activation in patients with sleep state
misperception. Psychosom. Med. 59(5), 533–540.
12. Lichstein, K. L., Durrence, H. H., Riedel, B. W., Taylor, D. J., and Bush, A. J. (2002) Epidemiol-
ogy of sleep: Age, gender, and ethnicity. Erlbaum, Mahwah, NJ.
13. Perlis, M. L., Smith, M. T., Orff, H. J., Andrews, P. J., and Giles, D. E. (2001) Beta/Gamma EEG
activity in patients with primary and secondary insomnia and good sleeper controls. Sleep 24,
110–117.
14. Merica, H., Blois, R., and Gaillard, J. M. (1998) Spectral characteristics of sleep EEG in chronic
insomnia. Euro. J. Neurosci. 10, 1826–1830.
15. Merica, H. and Gaillard, J. M. (1992) The EEG of the sleep onset period in insomnia: a discrimi-
nant analysis. Physiol. Behav. 52, 199–204.
16. Freedman, R. (1986) EEG power in sleep onset insomnia. Electroencephalogr. Clin.
Neurophysiol. 63, 408–413.
17. Lamarche, C. H. and Ogilvie, R. D. (1997) Electrophysiological changes during the sleep onset
period of psychophysiological insomniacs, psychiatric insomniacs, and normal sleepers. Sleep
20, 724–733.
18. Hall, M., Buysse, D. J., Nowell, P. D., et al. (2000) Symptoms of stress and depression as corre-
lates of sleep in primary insomnia. Psychosom. Med. 62, 227–230.
19. Perlis, M. L., Giles, D. E., Mendelson, W. B., Bootzin, R. R., and Wyatt, J. K. (1997) Subjective–
objective discrepancies in psychophysiologic insomnia: a neurocognitive perspective. J. Sleep.
Res. 6, 179–188.
Epidemiology of Insomnia 11

2
Epidemiology of Insomnia

Hrayr P. Attarian

Insomnia is the most common sleep-related complaint and the second most com-
mon overall complaint (after pain) reported in primary care settings (1).
In 1979, in the United States, a survey conducted in a nationally representative
sample of 3161 people ages 18–79, found that insomnia affected 35% of the gen-
eral adult population in 1 year (2). About 50% of these people experienced the
problem as severe (2). Only 15% were treated with any sort of hypnotic medica-
tions (2). In 1996, another study by Ohayon in Montreal, looked at the prevalence
of insomnia in a representative sample (n = 5622) of the French population in sub-
jects of 15 years of age or older. Of the people who participated in the survey,
20.1% said that they were unsatisfied with their sleep or were taking medication to
alleviate sleep difficulties (3). The prevalence of frequent insomnia was 29% in a
representative sample of the French population that included 12,778 individuals
(4). Of the English-Canadian population age 15 or older, 24% reported insomnia as
well, according to a 2001 study by Sutton et al. (5). In a representative selection of
German citizens older than 13 years of age, 1997 were asked about their sleep com-
plaints. Of this group, 25% reported suffering at least sometimes from difficulties
in falling and/or staying asleep, which was not due to external factors, and 7%
frequently or always had problems (6). A similar survey in Japan, conducted in a
group of 6277 new outpatients from 11 hospitals, revealed a prevalence of 20.3%
with insomnia, with 11.7% of the people suffering from it for more than 1 month.
Only 37% were treated with hypnotics (7). A second study done in a representative
sample (n = 3030) of the general population reported almost identical results: 21.4%
during the month preceding the survey (8). A representative adult sample (18 years
and older) of the Norwegian population, comprising 2001 subjects, participated in
telephone interviews, focusing on the 1-month point prevalence of insomnia and
use of prescribed hypnotics. Employment of Diagnostic and Statistical Manual of
Mental Disorders-Fourth Edition (DSM-IV) inclusion criteria of insomnia yielded
a prevalence rate of 11.7% (9). A prior study had queried 14,667 subjects and
reported 41.7% of the women and 29.9% of the men complaining of occasional
insomnia (10).
From: Current Clinical Neurology: Clinical Handbook of Insomnia
Edited by: H. P. Attarian © Humana Press Inc., Totowa, NJ

11
12 Attarian

Another study in Austria, in a sample of 1000 individuals, revealed a prevalence

of 26% with 21% of insomnia symptoms being severe and chronic with a duration
of 1 year or more (11). In a representative sample of the South Korean general
population composed of 3719 noninstitutionalized individuals aged 15 years or
older, the prevalence of insomnia symptoms occurring at least 3 nights per week
was reported to be 17% (12). In Mexico, the prevalence of insomnia in a group of
1000 subjects ages 18–84, was found to be 36%, with 16% reporting severe insom-
nia (13). A host of other studies have shown similar prevalence in various groups of
adult subjects: in Finland, an early study reported a severe insomnia (daily of sev-
eral times a week) prevalence of 5–14%, depending on age group, in subjects be-
tween ages 15 and 64. In Singapore, the prevalence of persistent insomnia for more
than 1 year was 15.3% in subjects between ages 15 and 55 (14). Hyyppa and
Kronholm reported a prevalence of 9.6–12.8% (male/female) of frequent or nightly
insomnia and 57.6–62.7% of occasional insomnia in a group of 1099 subjects rep-
resentative of the Finnish population (15).
There are fewer studies in the pediatric population, but they show a similar preva-
lence. One of the earliest studies in preadolescent children showed that 14% of an
outpatient pediatric population between the ages of 6 and 12 had insomnia with a
mean duration of 5 years (16). Archbold et al. at Ann Arbor, surveyed parents of
1038 unselected children (554 boys) aged 2 to 13.9 years. Of these children, 40%
had at least one symptom of insomnia and 18% had two or more symptoms (17).
The prevalence of frequent insomnia in 1413 school children aged 6.2–10.9 years,
in Sweden, was reported to be 13% (18). In adolescent groups, insomnia preva-
lence is similar to that of younger children and slightly lower than in adults. In a
Chinese study, 1365 adolescents between the ages of 12 and 18 years were sur-
veyed and 16.9% reported insomnia (19). A representative sample of 1125 adoles-
cents aged 15–18 years, from four countries—France, Great Britain, Germany, and
Italy—revealed insomnia symptoms in approximately 25% and DSM-IV insomnia
disorder in approximately 4% (20). This confirms previously reported prevalence
rates of 4–5% of persistent insomnia in a group of 574 (ages 7–17) (21), 10.8–
33.2% of frequent insomnia (at least twice a week) in a group of 40,202 children
aged 11–16 (22), and several others that reported rates of 11–12.6% frequent
insomnia (23–25), occasional insomnia of 23–38%, and persistent insomnia of 1–
2% (26).
In summary, various studies from different countries all show a similar preva-
lence of insomnia. This confirms that the complaint of insomnia is prevalent uni-
versally and constitutes a major health issue.

RISK FACTORS
In a landmark study, Klink et al. identified major risk factors in developing
insomnia. They surveyed a large general adult population from 1984 to 1985. They
evaluated the relationship among current complaints of initiating and maintaining
sleep and obesity, snoring, concomitant health problems, socioeconomic status
Epidemiology of Insomnia 13

(SES), and documented complaints of difficulty with insomnia 10 to 12 years pre-

viously. The strongest risk factor for complaints of initiating and maintaining sleep
was previous complaints of insomnia (odds ratio [OR], 3.5). Additionally, female
gender (OR, 1.5), advancing age (OR, 1.3), snoring (OR, 1.3), and multiple types
of concomitant health problems (OR, 1.1–1.7) were all risk factors associated with
an increased rate of complaints of initiating and maintaining sleep. They concluded
that the complaints of insomnia tend to be a persistent or recurrent problem over
long periods of time. Female gender, advancing age, and concomitant health prob-
lems also are important risk factors (27). These results have been confirmed by
other investigators. Individual risk factors are discussed here.

Gender Predilection
All of the epidemiological studies in the medical literature that compare the
prevalence of insomnia between the genders report a higher prevalence in women
(3). The female to male ratio is roughly 1.5:1 (27). This is especially true when
comparing peri- or postmenopausal women to age-matched men. One of the most
common peri-menopausal symptoms in women ranging in age from 35 to 55 is
insomnia (28,29).
There are, however, other studies that report increased prevalence in younger
women and even in adolescent girls when compared to age-matched male counter-
parts. When studying a group of children and adolescents between the ages of 3 and
14 (n = 452), Camhi et al. found that the complaints of insomnia were much higher
in adolescent girls (ages 11–14) than in the rest of the group (30.4 to 16.8%) (30).
This suggests that the increased prevalence of insomnia seen in adult women may
begin in early adolescence. The increased prevalence of insomnia in adult women
of all ages when compared to men seems to be a universal phenomenon. Studies
from Hong Kong (31,32), Germany (33), Canada (3,5), the United States (2,34),
Norway (10), Scotland (35), and other countries (36,37) have all reported increased
prevalence in adult women when compared to age-matched male counterparts.

Ethnocultural Differences in Sleep Complaints

There are only a few studies that look at ethnocultural variables in terms of their
effect on insomnia. Most of these studies have shown that, especially in the elderly,
Euro-Americans had more complaints of insomnia than African Americans (38,39).
In one of the most recent studies, volunteers (n =1118) from a group of older Euro-
Americans and African Americans residing in Brooklyn, New York were inter-
viewed. Worse sleep and greater reliance on sleep medicine were observed among
the Euro-Americans. Caribbean Americans reported less sleep complaints than did
US-born African Americans, and immigrant Euro-Americans reported greater com-
plaints than did US-born Euro-Americans (39). When comparing Euro-American
elderly men with Japanese Americans of the same age group, geographic location,
and SES, there was no significant difference in reported prevalence of about 30%
(40). The impact of ethnicity on the prevalence of insomnia in younger people is
14 Attarian

even less well studied. One survey reported the following results among adoles-
cents. Compared with Euro-American youths, Chinese American youths were at
significantly lower risk for insomnia, whereas Mexican American youths had an
elevated risk, adjusting for the effects of age, gender, and SES (41).

Age and Its Impact on the Prevalence of Insomnia

Advancing age is thought to be a risk factor for developing insomnia. The odds
ratio is 1.3 (27). The prevalence of insomnia does increase with age and although
several studies from different countries have reported this increased prevalence
(8,9), there are in the medical literature a number of studies, especially ones target-
ing the elderly population exclusively, that have failed to show this effect of aging
on the prevalence of insomnia (36,42,43). In 2001, Ohayon et al. surveyed 13,057
subjects age 15 and older from three different countries (United Kingdom, Ger-
many, and Italy). Insomnia symptoms were reported by more than one-third of the
population age 65 and older. Multivariate models showed that age was not a predic-
tive factor of insomnia symptoms when controlling for activity status and social
life satisfaction. Ohayon et al. concluded that the aging process per se is not respon-
sible for the increase of insomnia often reported in older people. Instead, inactivity,
dissatisfaction with social life, and the presence of organic diseases and mental
disorders were the best predictors of insomnia, age being insignificant. Healthy
older people had a prevalence of insomnia symptoms similar to that observed in
younger people (44).

Other Factors Impacting Insomnia

Seasonal differences have been reported in patients with chronic insomnia. In
Norway, a survey done among a representative sample of 14,667 adults living in
the municipality of Tromso, north of the Arctic Circle, revealed increased inci-
dence of complaints of insomnia during the dark period of the year than during any
other time (10). Occupation, SES, marital status, and mental and physical health
also impact the prevalence of insomnia.
In Finland, in 1984, complaints of insomnia were inquired about in a question-
naire survey of 6268 persons (2801 men; 3467 women, mean age 50.5 years, range
45–57 years) in 40 different occupational groups. Sleep-onset insomnia was highest
among bus drivers (18.9%) followed by female cleaners (18.8%) and male teachers
(18%). Disturbed nocturnal sleep was highest among male laborers (28.1% waking
up at least three times a night), female cleaners (26.6%), and female hospital aides
(26.4%). Early morning awakenings were most common among female laborers
(13.2% often or always), male construction workers (9.1%), and female cleaners
(8.4%) (45). Another survey conducted among Japanese male factory workers re-
vealed that different types of work-related psychosocial stressors were associated
with different types of insomnia (sleep onset, sleep maintenance, or terminal in-
somnia) (46). There was a definite correlation between over involvement at the job
and reports of insomnia (47). In a group of US female construction workers, per-
Epidemiology of Insomnia 15

ceptions of having to overcompensate at work and job uncertainty were positively

associated with self-reports of insomnia (48). Shift work can naturally lead to com-
plaints of insomnia and several studies have demonstrated that people working on
rotating daytime shifts report sleep-onset insomnia more frequently than the fixed
daytime schedule workers (20.1% vs 12%) (49). The more shifts one works, the
higher the incidence of insomnia complaints. Insomnia and other sleep complaints
are significantly more common in three-shift workers than in two-shift workers. By
the same token, two-shift workers complain more of insomnia than do straight day-
shift workers (50). Also, working the night or third shift, when engaged in for a
significant amount of time, may not only acutely cause insomnia but may have
persistent deleterious effect on sleep quality even after the individual has reverted
to the working day or evening shift (51).
A few studies have reported a direct correlation between being unemployed
(3,8,32,52) or having a lower SES (27,32) or a lower education level (32) and
increased prevalence of insomnia. Higher prevalence of complaints of insomnia
has also been reported among single, widowed, or divorced adults as compared to
ones who were in a marital relationship (3,7,43,52). Noisy environments are asso-
ciated with increased reports of poor sleep particularly in women (32,53). Psycho-
social stressors appear to be a risk factor for insomnia as well (19). Poor physical
health is also associated with a higher prevalence of insomnia (7,19,27,31,37,42,43)
as is poor mental health (7,37,42,43). Medical problems associated with insomnia
include depressive disorders (42,54), anxiety disorders (54,55), substance abuse
(55), schizophrenia (54), congestive heart failure, obstructive airway disease and
other respiratory illnesses (56), back and hip problems, and prostate problems (57).

MORBIDITY AND MORTALITY OF INSOMNIA

In 1989, Ford and Kamerow questioned 7954 subjects at baseline and 1 year
later using standardized questionnaires. Of this community, 10.2% had insomnia at
baseline. The risk of developing new major depression was much higher in those
who had insomnia at both interviews compared with those without insomnia. The
risk of developing new major depression was much less for those who had insom-
nia that had resolved by the second visit (58).
In 1997, Chang et al. published a landmark paper on the subject of insomnia and
its relation to the development of depression. A total of 1053 men provided infor-
mation on sleep habits during medical school at The Johns Hopkins University
(classes of 1948–1964) and were followed after graduation. During a median
followup period of 34 years (range 1–45), 101 men developed clinical depression
(12.2%). Of those, 13 committed suicide. In Cox proportional hazards analysis
adjusted for age at graduation, class year, parental history of clinical depression,
coffee drinking, and measures of temperament, the relative risk of clinical depres-
sion was greater in those who reported insomnia in medical school (59).
In the same year, Weissman et al. published a paper that reported data from an
epidemiologic community survey of more than 10,000 adults living in three US
16 Attarian

communities. A structured diagnostic assessment of psychiatric disorders as well

as assessment of the presence of insomnia not due to medical conditions, medica-
tion, drug, or alcohol abuse, and a 1-year followup were completed. The results
revealed that 8% of subjects with primary insomnia had sought psychiatric help at
the end of that year for different psychiatric problems vs 2.5% of the normal con-
trols. Uncomplicated or primary insomnia was also associated with an increase in
risk for first onset of major depression, panic disorder, and alcohol abuse over the
following year (54). Other studies have confirmed these findings that insomnia is a
risk factor for the development of major depression (60).
Other disorders associated with untreated insomnia include alcohol abuse and
relapse into alcoholism (61,62), panic disorder (54), and possible coronary artery
disease (in men) (63).
Insomnia per se, however, is not a cause of increased mortality (60,64). Kripke
et al. surveyed and followed 1.1 million subjects for 6 years. Insomnia alone was
not associated with increased mortality. There was a suggestion that 8 or more
hours of sleep and sleeping pill use is associated with a slight increase in mortality
but no causality was determined (65). There is new evidence, however, that there is
an association between difficulties falling asleep and mortality due to coronary
artery disease in men (63).
There are a number of studies that have demonstrated decreased quality of life as
a direct result of the insomnia. Chevalier and colleagues, using SF-36 scores dem-
onstrated the degree of impairment in quality of life was directly related to the
severity of insomnia. They also demonstrated that individuals with severe insomnia
showed a higher level of health care consumption (36). Hajak and the Study of
Insomnia in Europe group in Germany and Leger and colleagues in France reported
very similar results regarding quality of life and health care consumption (33,66).
Zammit et al. and Hatoum et al., independently, reported similar results in the
United States (67,68). Cognitive deficits identified on objective testing have been
associated with chronic persistent insomnia as well (69,70).

EPIDEMIOLOGY OF HYPNOTIC USE

The use of hypnotics has been generally low among people reporting insomnia.
In the landmark study in the United States in 1979, Mellinger reported the use of
any kind of hypnotic medication to be only 15% and only 2.6% of insomniacs used
prescribed hypnotics (2). In 1998, Johnson et al. reported similar numbers; 18%
were using hypnotic medication, suggesting that there has not been a significant
change in the use of hypnotics over a period of 11 years (71). Other countries report
similar statistics in the use of hypnotics. Lopez et al. reported that only 10.5% of
insomniacs in Mexico used hypnotic medication (13). Sweden (72), Finland (15),
Great Britain (73), Australia (74), and France (3,75) reported similar numbers. Use
of hypnotics increases with age, particularly among middle-aged and elderly women
(75,76). Sleeping pill use varies with the person’s occupation also. According to
one study, male gardeners, female social office workers, and male construction
Epidemiology of Insomnia 17

workers tended to be frequent or habitual users of hypnotic medications more than

other surveyed occupations (45). Alcohol, unfortunately, is the most commonly
used hypnotic among insomniacs (roughly 15% have reported using alcohol in an
attempt to self-medicate) (55,71). The underutilization of proper hypnotic medica-
tion is also seen among health care providers treating patients with insomnia. From
1987 to 1996, there was a dramatic shift in the United States toward the use of
antidepressants in lieu of hypnotics for the symptomatic treatment of insomnia
despite a paucity of data regarding their efficacy and the potential for serious side
effects (77). Antidepressants and over-the-counter sleep aids remain the most com-
monly recommended and prescribed treatments for insomnia complaints (77).
Statistics available from Scandinavia (Finland, Norway, and Sweden) suggest
that benzodiazepines and nonbenzodiazepine hypnotics (zopiclone, zolpidem, and
zaleplon), particularly zopiclone, are the hypnotics of choice in those countries (78).

ECONOMIC IMPACT OF INSOMNIA

Insomnia costs the US public $92.5 to $107.5 billion annually, in both direct and
indirect expenses including medical expenses, ramifications of accidents, and
reduced productivity due to absenteeism and decreased work efficiency (79). In
France, it has a similar financial impact. According to a recent study, its direct
annual cost (i.e., medical expenses including medications and health care), in 1995,
was FF 10,232,992,500 ($2,067,271,100 US) (80). In the same year, Walsh and
Engelhardt reported a total direct cost of $13.9 billion in the United States (81).

CONCLUSION
Insomnia is a prevalent complaint in the health care field. It is costly and can
cause significant morbidity if not addressed appropriately. Women and the elderly
tend to suffer from insomnia more than other groups of the population. Other risk
factors include psychosocial stressors, psychiatric and medical problems, low
income, unemployment, excessive environmental noise, not having a life partner,
job-related stressors, and so on.
Patients with insomnia are undertreated and hypnotics are significantly
underutilized. Alcohol, unfortunately, remains the most commonly preferred
method of self-treatment for insomnia.

REFERENCES
1. Mahowald, M. W., Kader, G., and Schenck, C. H. (1997) Clinical categories of sleep disorders I.
Continuum 3(4), 35–65.
2. Mellinger, G. D., Balter, M. B., and Uhlenhuth, E. H. (1985) Insomnia and its treatment. Preva-
lence and correlates. Arch. Gen. Psychiatry 42(3), 225–232.
3. Ohayon, M. (1996) Epidemiological study on insomnia in the general population. Sleep 19(3
Suppl), S7–S15.
4. Leger, D., Guilleminault, C., Dreyfus, J. P., Delahaye, C., and Paillard, M. (2000) Prevalence of
insomnia in a survey of 12,778 adults in France. J. Sleep Res. 9(1), 35–42.
18 Attarian

5. Sutton, D. A., Moldofsky, H., and Badley, E. M. (2001) Insomnia and health problems in Canadi-
ans. Sleep 24(6), 665–670.
6. Simen, S., Hajak, G., Schlaf, G., et al. (1995) [Chronification of sleep disorders. Results of a
representative survey in West Germany]. Nervenarzt 66(9), 686–695.
7. Ishigooka, J., Suzuki, M., Isawa, S., Muraoka, H., Murasaki, M., and Okawa, M. (1999) Epide-
miological study on sleep habits and insomnia of new outpatients visiting general hospitals in
Japan. Psychiatry Clin. Neurosci. 53(4), 515–522.
8. Kim, K., Uchiyama, M., Okawa, M., Liu, X., and Ogihara, R. (2000) An epidemiological study of
insomnia among the Japanese general population. Sleep 23(1), 41–47.
9. Pallesen, S., Nordhus, I.H., Nielsen, G. H., et al. (2001) Prevalence of insomnia in the adult
Norwegian population. Sleep 24(7), 771–779.
10. Husby, R. and Lingjaerde, O. (1990) Prevalence of reported sleeplessness in northern Norway in
relation to sex, age and season. Acta Psychiatr. Scand. 81(6), 542–547.
11. Zeitlhofer, J., Rieder, A., Kopfhammer, G., et al.(1994) [Epidemiology of sleep disorders in Aus-
tria]. Wien Klin Wochenschr. 106(3), 86–88.
12. Ohayon, M. M. and Hong, S. C. (2002) Prevalence of insomnia and associated factors in South
Korea. J. Psychosom. Res. 53(1), 593–600.
13. Lopez, A. T., Sanchez, E. G., and Torres, F.G. (1995) Habitos y trastornos del dormir en residentes
del area metropolitana de Monterrey. Salud Mental 18, 14–22.
14. Yeo, B. K., Perera, I. S., Kok, L. P., and Tsui, W. F. (1996) Insomnia in the community. Singapore
Med. J. 37(3), 282–284.
15. Hyyppa, M. and Kronholm, E. (1987) How does Finland sleep? Sleeping habits of the Finnish adult
population and the rehabilitiation of sleep disturbances. Publ. Soc. Ins. Inst. ML(68), 1–110.
16. Dixon, K. N., Monroe, L. J., and Jakim, S. (1981) Insomniac children. Sleep 4(3), 313–318.
17. Archbold, K. H., Pituch, K. J., Panahi, P., and Chervin, R. D. (2002) Symptoms of sleep distur-
bances among children at two general pediatric clinics. J. Pediatr. 140(1), 97–102.
18. Neveus, T., Cnattinguis, S., Olsson, U., and Hetta, J. (2001) Sleep habits and sleep problems
among a community sample of schoolchildren. Acta Paediatr. 90(12), 1450–1455.
19. Liu, X., Sun, Z., Uchiyama, M., Shibui, K., Kim, K., and Okawa, M. (2000) Prevalence and
correlates of self-reported sleep problems among Chinese adolescents. Sleep 23(1), 27–34.
20. Ohayon, M. M., Roberts, R. E., Zulley, J., Smirne, S., and Priest, R. G. (2000) Prevalence and
patterns of problematic sleep among older adolescents. J. Am. Acad. Child Adolesc. Psychiatry
39(12), 1549–1556.
21. Saarenpaa-Heikkila, O. A., Rintanaka, P. J., Laippala, P. J., and Koivikko, M. J. (1995) Sleep
habits and disorders in Finnish schoolchildren. J. Sleep Res. 4(3), 173–182.
22. Tynjala, J., Kannas, L.,and Valimaa, R. (1993) How young Europeans sleep. Health Educ. Res.
8(1), 69–80.
23. Levy, D., Gray-Donald, K., Leech, J., Ziagulis, I., and Pless, I. B. (1986) Sleep patterns and
problems in adolescents. J. Adolesc. Health Care 7(6), 386–389.
24. Price, V. A., Coates, T. J., Thoreson, C. E., and Grinstead, O. A. (1978) Prevalence and correlates
of poor sleep among adolescents. Am. J. Dis. Child 132(6), 583–586.
25. Kirmil-Gray, K., Eagleston, J., and Gibson, E. (1984) Sleep disturbance in adolescents: sleep qual-
ity, sleep habits, beliefs about sleep, and daytime functioning. J. Youth Adolesc. 13, 375–384.
26. Rimpela, A. and Ahlstrom, S. (1983) Health habits among Finnish youth. National Board of
Health 71–83.
27. Klink, M. E., Quan, S. F., Kaltenbom, W. T., and Lebowitz, M. D. (1992) Risk factors associated
with complaints of insomnia in a general adult population. Influence of previous complaints of
insomnia. Arch. Intern. Med. 152(8), 1634–1637.
28. Mitchell, E. S. and Woods, N. F. (1996) Symptom experiences of midlife women: observations
from the Seattle Midlife Women’s Health Study. Maturitas 25(1), 1–10.
29. Owens, J. F. and Matthews, K. A. (1998) Sleep disturbance in healthy middle-aged women.
Maturitas 30(1), 41–50.
Epidemiology of Insomnia 19

30. Camhi, S. L., Morgan, W. J., Pernisco, N., and Quan, S. F. (2000) Factors affecting sleep distur-
bances in children and adolescents. Sleep Med. 1(2), 117–123.
31. Chiu, H. F., Leung, T., Lam, L. C., et al. (1999) Sleep problems in Chinese elderly in Hong Kong.
Sleep 22(6), 717–726.
32. Li, R. H., Wing, Y. K., Ho, S. C., and Fong, S. Y. (2002) Gender differences in insomnia-a study
in the Hong Kong Chinese population. J. Psychosom. Res. 53(1), 601–609.
33. Hajak, G. (2001) Epidemiology of severe insomnia and its consequences in Germany. Eur. Arch.
Psychiatry Clin. Neurosci. 251(2), 49–56.
34. Foley, D. J., Monjan, A. A., Izmirlian, G., Hays, J. C., and Blazer, D. G. (1999) Incidence and
remission of insomnia among elderly adults in a biracial cohort. Sleep 22(Suppl 2), S373–S378.
35. McGhie, A. and Russell, S. (1962) The subjective assessment of normal sleep patterns. J. Ment.
Sci. 108, 642–654.
36. Chevalier, H., Los, F., Boichut, D., et al. (1999) Evaluation of severe insomnia in the general popu-
lation: results of a European multinational survey. J. Psychopharmacol. 13(4 Suppl 1), S21–S24.
37. Janson, C., Lindberg, E., Gislason, T., Elmasry, A., and Boman, G. (2001) Insomnia in men-a 10-
year prospective population based study. Sleep 24(4), 425–430.
38. Blazer, D. G., Hays, J. C., and Foley, D. J. (1995) Sleep complaints in older adults: a racial
comparison. J. Gerontol. A. Biol. Sci. Med. Sci. 50(5), M280–M284.
39. Jean-Louis, G., Magai, C. M., Cohen, C. I., et al. (2001) Ethnic differences in self-reported sleep
problems in older adults. Sleep 24(8), 926–933.
40. Barbar, S. I., Enright, P. L., Boyle, P., et al.(2002) Sleep disturbances and their correlates in
elderly Japanese American men residing in Hawaii. J. Gerontol. A. Biol. Sci. Med. Sci. 55(7),
M406–M411.
41. Roberts, R. E., Roberts, C. R., and Chen, I. G. (2000) Ethnocultural differences in sleep com-
plaints among adolescents. J. Nerv. Ment. Dis. 188(4), 222–229.
42. Morgan, K. and Clarke, D. (1997) Risk factors for late-life insomnia in a representative general
practice sample. Br. J. Gen. Pract. 47(416), 166–169.
43. Foley, D. J., Monjan, A., Simonsick, E. M., Wallace, R. B., and Blazer, D. G. (1999) Incidence
and remission of insomnia among elderly adults: an epidemiologic study of 6,800 persons over
three years. Sleep 22(Suppl 2), S366–S372.
44. Ohayon, M. M., Zulley, J., Guilleminault, C., Smirne, S., and Priest, R. G. (2001) How age and
daytime activities are related to insomnia in the general population: consequences for older
people. J. Am. Geriatr. Soc. 49(4), 360–366.
45. Partinen, M., Eskelinen, L., and Tuomi, K. (1984) Complaints of insomnia in different occupa-
tions. Scand. J. Work Environ. Health 10(6 Spec No), 467–469.
46. Tachibana, H., Izumi, T., Honda, S., and Takemoto, T. I. (1998) The prevalence and pattern of
insomnia in Japanese industrial workers: relationship between psychosocial stress and type of
insomnia. Psychiatry Clin. Neurosci. 52(4), 397–402.
47. Tachibana, H., Izumi, T., Honda, S., Horiguchi, I., Manabe, E., and Takemoto, T. (1996) A study
of the impact of occupational and domestic factors on insomnia among industrial workers of a
manufacturing company in Japan. Occup. Med. (Lond.) 46(3), 221–227.
48. Goldenhar, L. M., Swanson, N. G., Hurrell, J. J. Jr., Ruder, A., and Deddens, J. (1988) Stressors
and adverse outcomes for female construction workers. J. Occup. Health Psychol. 3(1), 19–32.
49. Ohayon, M. M., Lemoine, P., Arnaud-Briant, V., and Dreyfus, M. (2002) Prevalence and conse-
quences of sleep disorders in a shift worker population. J. Psychosom. Res. 53(1), 577–583.
50. Harma, M., Tenkanen, L., Sjoblom, T., Alikoshi, T., and Heinsalmi, P. (1998) Combined effects
of shift work and life-style on the prevalence of insomnia, sleep deprivation and daytime sleepi-
ness. Scand. J. Work Environ. Health 24(4), 300–307.
51. Dumont, M., Montplaisir, J., and Infante-Rivard, C. (1997) Sleep quality of former night-shift
workers. Int. J. Occup. Environ. Health 3(Suppl 2), S10–S14.
52. Doi, Y., Minowa, M., Okawa, M., and Uchiyama, M. (2000) Prevalence of sleep disturbance and
hypnotic medication use in relation to sociodemographic factors in the general Japanese adult
population. J. Epidemiol. 10(2), 79–86.
20 Attarian

53. Kageyama, T., Kabuto, M., Nitta, H., et al. (1997) A population study on risk factors for insomnia
among adult Japanese women: a possible effect of road traffic volume. Sleep 20(11), 963–971.
54. Weissman, M. M., Greenwald, S., Nino-Murcia, G., and Demont, W. C. (1997) The morbidity of
insomnia uncomplicated by psychiatric disorders. Gen. Hosp. Psychiatry 19(4), 245–250.
55. Costa e Silva, J. A., Chase, M., Sartorius, N., and Roth, T. (1996) Special report from a sympo-
sium held by the World Health Organization and the World Federation of Sleep Research Societ-
ies: an overview of insomnias and related disorders—recognition, epidemiology, and rational
management. Sleep 19(5), 412–416.
56. Dodge, R., Cline, M. G., and Quan, S. F. (1995)The natural history of insomnia and its relation-
ship to respiratory symptoms. Arch. Intern. Med. 155(16), 1797–1800.
57. Katz, D. A. and McHorney, C. A. (1998) Clinical correlates of insomnia in patients with chronic
illness. Arch. Intern. Med. 158(10), 1099–1107.
58. Ford, D. E. and Kamerow, D. B. (1989) Epidemiologic study of sleep disturbances and psychiat-
ric disorders. An opportunity for prevention? JAMA 262(11), 1479–1484.
59. Chang, P. P., Ford, D. E., Mead, L. A., Cooper-Patrick, L., and Klag, M. J. (1997) Insomnia in
young men and subsequent depression. The Johns Hopkins Precursors Study. Am. J. Epidemiol.
146(2), 105–114.
60. Mallon, L., Broman, J. E. and Hetta, J. (2000) Relationship between insomnia, depression, and mortal-
ity: a 12-year follow-up of older adults in the community. Int. Psychogeriatr. 12(3), 295–306.
61. Shinba, T., Murashima, Y. L., and Yamamoto, K. (1994) Alcohol consumption and insomnia in a
sample of Japanese alcoholics. Addiction 89(5), 587–591.
62. Brower, K. J., Aldrich, M. S., Robinson, E. A., Zucker, R. A., and Greden, J. F. (2001) Insomnia,
self-medication, and relapse to alcoholism. Am. J. Psychiatry 158(3), 399–404.
63. Mallon, L., Broman, J. E., and Hetta, J. (2002) Sleep complaints predict coronary artery disease
mortality in males: a 12-year follow-up study of a middle-aged Swedish population. J. Intern.
Med. 251(3), 207–216.
64. Althuis, M. D., Fredman, L., Langenberg, P. W., and Mogaziner, J. (1998) The relationship
between insomnia and mortality among community-dwelling older women. J. Am. Geriatr. Soc.
46(10), 1270–1273.
65. Kripke, D. F., Garfinkel, L., Wingard, D. L., Klauber, M. R., and Marler, M. R. (2002) Mortality
associated with sleep duration and insomnia. Arch. Gen. Psychiatry 59(2), 131–136.
66. Leger, D., Scheuermaier, K., Philip, P., Paillard, M., and Guilleminault, C. (2001) SF-36: evalu-
ation of quality of life in severe and mild insomniacs compared with good sleepers. Psychosom.
Med. 63(1), 49–55.
67. Hatoum, H. T., Kong, S. X., Kania, C. M., Wong, J. M., and Mandelson, W. E. (1998) Insomnia,
health-related quality of life and healthcare resource consumption. A study of managed-care
organisation enrollees. Pharmacoeconomics 14(6), 629–637.
68. Zammit, G. K., Weiner, J., Damato, N., Sillup, G. P., and McMIllan, C.A. (1999) Quality of life
in people with insomnia. Sleep 22(Suppl 2), S379–S385.
69. Hauri, P. J. (1997) Cognitive deficits in insomnia patients. Acta Neurol. Belg. 97(2), 113–117.
70. Espie, C. A., Inglis, S. J., harvey, L., and Tessier, S. (2000) Insomniacs’ attributions. psychomet-
ric properties of the Dysfunctional Beliefs and Attitudes about Sleep Scale and the Sleep Distur-
bance Questionnaire. J. Psychosom. Res. 48(2), 141–148.
71. Johnson, E. O., Roehrs, T., Roth, T., and Breslan, N. (1998) Epidemiology of alcohol and medi-
cation as aids to sleep in early adulthood. Sleep 21(2), 178–186.
72. Asplund, R. (1995) Sleep and hypnotics among the elderly in relation to body weight and somatic
disease. J. Intern. Med. 238(1), 65–70.
73. Morgan, K. (1988) Hypnotic drug use for the elderly. Br. Med. J. (Clin. Res. Ed.) 296(6626), 930.
74. Henderson, S., Jorm, A. F., Scott, L. R., Mackinnon, A. J., Christensen, H., and Koretn, A. E.
(1995) Insomnia in the elderly: its prevalence and correlates in the general population. Med. J.
Aust. 162(1), 22–24.
Epidemiology of Insomnia 21

75. Quera-Salva, M. A., Orluc, A., Goldenbert, F., and Guilleminault, C. (1991) Insomnia and use of
hypnotics: study of a French population. Sleep 14(5), 386–391.
76. Asplund, R. (2000) Sleep and hypnotic use in relation to perceived somatic and mental health
among the elderly. Arch. Gerontol. Geriatr. 31(3), 199–205.
77. Walsh, J. K. and Schweitzer, P. K. (1999) Ten-year trends in the pharmacological treatment of
insomnia. Sleep 22(3), 371–375.
78. Partinen, M. and Hublin, C. (2000) Epidemiology of sleep disorders. In: Principles and Practice of
Sleep Medicine (Kryger, M., Roth, T., and Dement, W., eds.), Saunders, Philadelphia, pp. 558–579.
79. Stoller, M. K. (1994) Economic effects of insomnia. Clin. Ther. 16(5), 873–897; discussion 854.
80. Leger, D., Levy, E., and Paillard, M. (1999) The direct costs of insomnia in France. Sleep
22(Suppl 2), S394–S401.
81. Walsh, J. K. and Engelhardt, C. L. The direct economic costs of insomnia in the United States for
1995. Sleep 22(Suppl 2), S386–S393.
22 Attarian
Physiological Basis of Insomnia 23

3
Physiological Basis of Insomnia

Michael H. Bonnet and Donna L. Arand

INTRODUCTION
Patients with insomnia often have symptoms that include tension, anxiety,
depression, fatigue, and irritability (1–4). Frequently, insomnia begins in conjunc-
tion with significant stress (5). As a result, many investigators hypothesized that
insomnia is the result of internalization of emotions producing emotional arousal.
More recently, it has been hypothesized that insomnia can develop entirely from
physiological activation, as in phase-shift insomnia or in individuals predisposed to
physiological activation.
Several studies have found significantly increased physiological activation in
patients with insomnia. Table 1 summarizes the psychological changes in insomnia
patients. For example, Monroe (6) reported increased rectal temperature, heart rate,
basal skin resistance, and phasic vasoconstrictions 30 minutes prior to and during
sleep in patients with insomnia as compared to normal sleepers.
Other studies have shown that patients with sleep-onset insomnia had increased
frontalis (7) and mentalis electromyogram (EMG) (8,9), increased heart rate
(10,11), increased finger temperature, and more β and less α frequencies in the
electroencephalogram (EEG) (8,9). However, significantly elevated body tempera-
ture has not been reported in all studies of poor sleepers (12,13). Poor sleepers have
increased secretion of corticosteroids and adrenaline (12,14) compared with good
sleepers in most, but not all, studies (15).
The inconsistent results in some of these physiological activation studies may
indicate that physiological activation is not a major factor in all patients (16) or that
wide variability and small sample sizes may make it difficult to show clear physi-
ological differences. It might be that lack of control of daytime activity in the stud-
ies obscured differences. It is also possible that the involved physiological system(s)
differs from patient to patient and that more global measures, such as whole body
oxygen use or heart rate variability, would more consistently show differences.

From: Current Clinical Neurology: Clinical Handbook of Insomnia

Edited by: H. P. Attarian © Humana Press Inc., Totowa, NJ

23
24 Bonnet and Arand

Table 1
Reported Physiological Changes in Insomnia Patients
Physiological variable Studies (ref. no.)
Increased body temperature 6
Increased heart rate 6,10,11,26
Increased sympathetic nervous system activity 11
Decreased parasympathetic nervous system activity 11
Increased EMG 7–9
Increased EEG β 8,9
Decreased EEG α 8,9
Increased corticosteroids 12,14
Increased adrenaline 14
·
Increased V O2 24,25
Increased skin resistance 6
Increased phasic vasoconstrictions 6
Increased daytime sleep latency 20, 21, 24
EMG, electromyogram; EEG, electroencephalogram.

Other research has examined daytime function in patients with insomnia to verify
subjectively reported deficits in performance, mood, and alertness. The cumulative
partial sleep deprivation that should arise from chronic insomnia should produce
daytime sleepiness or increased susceptibility to acute sleep loss in patients with in-
somnia, but studies have consistently found that these patients are not sleepier than
normal controls on the Multiple Sleep Latency Test (MSLT) (13,17,18) or after sleep
loss (19). These individuals may actually have longer MSLT latencies (20,21).
Studies have found that patients with insomnia made more errors on a line-trac-
ing task (22), produced fewer responses in a word category test (13), and performed
worse on the Romberg (balance) test (23). However, such deficits may have reflected
that elevated arousal reduces steadiness or blocks higher order associates. Studies
that compared daytime performance of insomnia patients to performance of normal
controls have generally not found differences on tests that are sensitive to sleep loss
(18,23). Based on these results and on patient reports that they are fatigued or
“washed out” during the day, it has been hypothesized that standard sleep and sleep-
loss tests are confounded in that they “simultaneously measure sleep need and
hyperarousal, which is interfering with sleep onset” (p. 59) (20). This concept is
supported by studies (18,20,22) that reported significant negative correlations be-
tween total sleep at night and MSLT values the next day.
With this background in mind, we planned a series of experiments to define
more general measures of physiological activity in patients with psychophysiologi-
cal insomnia and to differentiate causal factors in the production of both poor noc-
turnal sleep and compromised daytime function. This chapter reviews our work to
define metabolic and cardiac changes in patients with insomnia and the relationship
of such physiological changes to poor sleep and the report of insomnia.
Physiological Basis of Insomnia 25

EXPERIMENTAL
Metabolic and Cardiac Change in Insomnia
Patients Compared with Normal Controls
Several similar studies were initially performed to compare sleep and physi-
ological measures of patients with psychophysiological insomnia and sleep state
misperception (SSM) with matched normal sleepers. It was hypothesized that
patients with both psychophysiological insomnia and SSM insomnia would differ
from controls by having increased physiological activation independent of their
sleep-stage parameters. The same general screening criteria were used for all stud-
ies. Subjects were required to be healthy, 18- to 50-year-old males and females.
Patients with Insomnia
Individuals we considered indicated that they had a sleep problem, that it took
them no less than 45 minutes to fall asleep at least 4 nights each week, or that they
were awake no less than 60 minutes each night after falling asleep for at least 4
nights each week for at least 1 year. Patients with insomnia were also required to
have EEG sleep latencies (SLs) greater than 30 minutes on 2 consecutive lab nights
or to have a sleep efficiency of less than 85% on both nights.
Patients with SSM
Patients with a complaint of insomnia who demonstrated normal sleep (SL < 30
minutes and sleep efficiency > 90%) despite their claim of insomnia, overestimated
their SL by at least 100% on both sleep laboratory nights, and had SL estimates of
20 minutes or longer on both nights were considered.
Normal Sleepers
Subjects with reported normal sleep were selected to match a qualified insomnia
patient by gender, age (within 5 years), weight (within 25 pounds), and general
time in bed (TIB) characteristics. Subjects were also required to have EEG SLs less
than 30 minutes on 2 consecutive laboratory nights and to have a sleep efficiency
greater than 90% on both nights.
Exclusions
Potential subjects who indicated excessive caffeine consumption (more than 250 mg
of caffeine per day), who were using psychoactive medication or drugs, or who had
completed a drug or alcohol abuse program within the previous year were excluded.
Individuals with a history of depression or psychiatric hospitalization were
excluded. Potential subjects who had histories strongly suggestive of circadian
desynchrony (e.g., shift workers), sleep apnea, or periodic leg movements (PLMs)
were excluded. Subjects with an apnea/hypopnea index or a PLM arousal index
greater than 10 were disqualified.
Design
Subjects spent 2 nights and the intervening day in the laboratory. On both nights,
a standard clinical polysomnogram was performed. On the second night, metabolic
·
measures, including V O2 were recorded.
26 Bonnet and Arand

On the day spent at the laboratory, subjects had a 20-minute metabolic observa-
tion after awakening, performed computer tests, took an MSLT followed by 20-
minute resting metabolic observations, and completed a Minnesota Multiphasic
Personality Inventory (MMPI) test and a sleep history. They were fed the same daily
menu of food prepared at the laboratory. Caffeinated beverages were not available.

Metabolic Rate in Psychophysiological Insomnia and SSM

Groups of 10 patients with psychophysiological insomnia and matched normal
sleepers who did not differ in age, weight, or time usually spent in bed per night
were identified (24). As expected by selection criteria, patients with insomnia had
significantly longer objective SLs (20.5 vs 12.5 minutes) and shorter total sleep
time (TST) per night (342 vs 442 minutes) compared to the matched controls.
·
The initial analysis was based on mean VO2 data for each minute across the
night. Each subject was compared to a matched control minute-by-minute by t-test.
The t values from each of the 10 subject pairs were in the same direction, and 9 of
10 were statistically significant (p < 0.01). The average t value was 13.10 with 475
·
degrees of freedom (df) (p < 0.0001). The respective means for V O2 for insomnia
patients and normal subjects were 296 and 266 mL/min.
In a second set of 10 t-tests with awakenings, movements, and arousals elimi-
nated from the data set, 9 t values were in the predicted direction, and 8 of 10 were
statistically significant (p < 0.02). The average t value was 13.38 with an average of
140 df (p < 0.0001). The overall mean sleep metabolic rates for the insomnia and
normal groups, respectively, were 280 and 256 mL/min.
When only slow-wave sleep (SWS) was examined, it was found that two sub-
jects (one insomniac and one normal subject) had no stage 3 or 4 sleep. Because the
two subjects were in different pairs, those pairs were eliminated, and the SWS
analysis proceeded on the eight pairs of subjects who all had SWS. In the set of
eight t-tests comparing metabolic values from SWS observations between matched
insomnia patients and normal subjects, seven t values were in the predicted direc-
tion, and five of eight were statistically significant. The average t value was 5.57
with an average of 51 df (p < 0.0001). The overall mean sleep metabolic rates for
the insomnia and normal groups, respectively, were 266 and 250 mL/min.

SSM
Groups of nine patients with SSM insomnia and matched normal sleepers who
did not differ in age, weight, or TIB per night were identified (25). As expected by
subjective historical report of sleep, patients with SSM insomnia reported signifi-
cantly longer SLs (98 vs 18 minutes) and shorter TST per night (5.3 vs 7.4 hours).
In the sleep laboratory, the patients with SSM estimated that their SL was sig-
nificantly longer than the normals (52 vs 24 minutes), that their TST during the
night was significantly shorter than the normal subjects (6.8 vs 7.5 hours), and that
their sleep quality was significantly worse than the normal subjects. However, the
Physiological Basis of Insomnia 27

patients with SSM did not differ significantly from the normal subjects on any EEG
sleep variable. In fact, TST was nonsignificantly longer in the patients as compared
to the normal sleepers.
·
The mean VO2 for each of the eight waking metabolic measurements and the
·
mean VO2 for each hour during the sleep period were entered into a repeated mea-
sures analysis of variance (ANOVA) with terms for the matched subjects (1 df) and
time (15 df). The time by group interaction was not significant, but both of the main
·
effects were significant. VO2 overall was elevated in the patients with SSM as com-
pared to their matched controls (F1,143 = 45.22, p < 0.001). The means for the groups
were 304 mL/min (SD 26) and 286 mL/min (SD 34).

Heart Rate and Heart Rate Variability

Groups of 12 patients with psychophysiological insomnia and matched normal
sleepers who did not differ in age, weight, or usual TIB per night were identified
(11). As expected by selection criteria, patients with insomnia had significantly
longer SLs (16.4 vs 6.6 minutes) and shorter TST per night (382 vs 445 minutes)
compared to normal sleepers.
Nocturnal heart data were examined for both groups by dividing each night into
5-minute blocks based on sleep stage. No significant interaction was found between
group and sleep stage. There was a significant main effect for Group for both beat-
to-beat interval (F1,44 = 44.67, p < 0.001) and the interval standard deviation (F1,44
= 56.16, p < 0.001). The intervals were significantly longer (i.e., heart rate was
lower) and the variability was greater in the normal subjects as compared to the
patients with insomnia. Heart rate during wake, stage 2, and rapid eye movement
(REM) sleep were, respectively 61, 58, and 59 beats per minute (BPM) for normal
subjects and 68, 64, and 68 BPM for the patients with insomnia. Several previous
studies showed increased heart rate in patients with insomnia as compared to nor-
mal sleepers during the night. Monroe (6) reported a nonsignificant 3.9 BPM
increase for patients with insomnia, Stepanski et al. (26) reported a significant 4.4
BPM increase for patients with insomnia, and Haynes and co-workers (10) reported
a significant 4.6 BPM increase for patients with insomnia compared to normal
sleepers. These reported differences agree well with the data from the present
groups, for which the overall mean difference in heart period translated to a heart
rate difference of 6.9 BPM.
The same 5-minute blocks of digitized heart data were analyzed by spectral
analysis to provide estimates of low frequency and high frequency spectral power.
ANOVA indicated that the interaction F value for group by stage was not signifi-
cant for either low-frequency power (LFP) or high-frequency power (HFP) ratios
(F3,33 = 1.407, NS and F3,33 = 1.766, respectively). There was a significant main
effect for group for both LFP (F1,32 = 12.93, p < 0.001) and HFP (F1,44 = 12.21, p <
0.001). These results indicated that LFP was increased and HFP was decreased in
patients with insomnia compared to normal sleepers across all sleep stages.
28 Bonnet and Arand

SUMMARY
These metabolic and heart rate data replicated previous studies that indicated
elevated levels of physiological arousal in patients with insomnia. The finding of
·
elevated VO2 elevated heart rate, and altered heart rate variability within sleep stages
strengthened the case that the elevated levels of arousal were not simply a by-prod-
uct of poor sleep. Finally, elevated metabolic rate in patients with SSM showed that
these patients truly do have an objective, physiological problem as the basis of their
complaint despite the fact that their sleep stage distributions were normal. These
physiological findings were supported very recently by a spectral analysis of EEG
of patients with SSM (26a), which showed increased higher frequency EEG in these
patients. Such physiological findings support underlying hyperarousal as a causal
mechanism in the sleep complaints presented. The findings of significant changes
in heart rate variability in patients with insomnia also are consistent with elevated
sympathetic nervous system activity and decreased parasympathetic nervous sys-
tem activity.
As an entity, insomnia is infrequently viewed as a significant medical problem.
However, if insomnia is associated with chronic sympathetic hyperactivity, long-
term consequences of the sympathetic activation associated with the insomnia may
exist. Many risk factors for coronary heart disease are related to increased sympa-
thetic activity. For example, hypertension; elevated plasma insulin (27) and its
related decrease in high-density lipoprotein (HDL) cholesterol and increase in trig-
lycerides and cholesterol (28); increased hematocrit (29); decreased plasma vol-
ume (30); increased plasma thromboglobulin (31); increased plasma angiotensin
(32); and increased cardiac arrhythmias (33,34) are all signs of increased sympa-
thetic and decreased parasympathetic tone. It remains to be determined if patients
with chronic insomnia are also at increased risk for these disorders.

Effects of Physiological Activation

In addition to poor sleep, it has been established that many patients with insom-
nia will report daytime fatigue or dysphoria, have normal or longer than normal
MSLT values, report increased stress, have abnormal MMPI values, and subjec-
tively misperceive their sleep process. These findings are summarized in Table 2.
Because patients with insomnia typically display both mood alteration and evi-
dence of physiological arousal, differentiation of cognitive vs physiological pathol-
ogy as the primary causal factor has been difficult. Production of consistent and
long-lasting mood changes in normal individuals to test the effect of mood change
on sleep and daytime function is difficult. However, in one study, it was possible to
produce a state of chronic physiological activation and to follow these hyperaroused
normal individuals for the development of both nocturnal and daytime symptoms
of insomnia (35).
In that study (35), 400 mg of caffeine was given three times a day to 12 normal
young adult sleepers for 1 week as a means of increasing physiological arousal, and
Physiological Basis of Insomnia 29

Table 2
Variables that Differentiate Insomnia Patients vs Normal Sleepers Given
Caffeine or the Sleep on an Insomnia Patient. Data from Normal Sleepers
Who Had Situational Insomnia are also Reported.
“Yoke”
Hyperaroused insomnia
True normal normal Situational
insomnia subjects subjects insomnia
MSLT Increased Increaseda Decreasedb Increasedc
Metabolic rate/ Increased Increaseda Increased PMb; Increasedc
heart rate decrease AM
Body Increased Increased Decreasedb No measure
temperature
Mood (tension, Increased Increaseda Decreasedb No change
confusion)
Vigor Decreased Decreaseda Decreasedb No change
Personality Increased Increased No change No change
disturbance MMPI PTa
Subjective sleep Overestimated Mild No change No change
latency/wake overestimation
aSignificantdifferences reported in ref. 35.
bSignificant differences reported in ref. 36.
cSignificant differences reported in ref. 45; MSLT, Multiple Sleep Latency Tests; MMPI PT,

Minnesota Multiphasic Personality Inventory Psychasthenia (Anxiety) Scale.

standard insomnia outcome variables were measured. As expected, chronic use of

caffeine significantly increased whole body metabolic rate, which was used as the
objective measure of arousal level, and sleep efficiency declined significantly.
It is well known that caffeine can produce poor sleep. However, the major ques-
tion in this study was whether caffeine would also produce the other secondary
effects seen in chronic psychophysiological insomnia.
Responses from the Profile of Mood States (POMS) suggested increasing dys-
phoria as caffeine administration progressed (see Table 2 for a summary of caffeine
effects). Significant main effects for condition were found for all six POMS scales.
Initial caffeine administration produced an immediate significant increase in vigor
and tension (anxiety), followed by a decrease as caffeine administration continued
(significant for vigor). Fatigue was significantly increased at the end of caffeine
administration compared to placebo. These results were of considerable interest
because they showed that the chronic daytime dysphoria and fatigue reported by
patients with insomnia could be paradoxically produced by unrelenting physiologi-
cal arousal.
The MSLT data revealed that SLs were significantly increased throughout caf-
feine administration compared to baseline and withdrawal, which did not differ.
The mean SL after early caffeine use was significantly longer than the SL after
30 Bonnet and Arand

chronic caffeine use. Respective means for baseline, early caffeine, late caffeine,
and withdrawal were 10.7, 17.9, 13.4, and 11.3 minutes, respectively. Again, these
increased SLs were similar to those seen in insomnia patients compared with nor-
mal subjects.
The MMPI is a nontransparent measure of relatively stable personality charac-
teristics. It was administered before caffeine use and at the end of the caffeine ad-
ministration primarily because it has been used as a measure in many previous
insomnia studies. At baseline, as expected, all of the MMPI values were character-
istic of normal young adults. However, after 1 week of caffeine administration,
there was movement toward increased pathology on all the clinical scales except
masculine–feminine scale, and the change was statistically significant for the Psy-
chasthenia (anxiety) scale. These findings were also surprising because they indi-
cated that even stable aspects of personality could shift significantly toward
pathology in a short period secondary to a relatively simple physiological manipu-
lation.
As can be seen in Table 2, subjects given caffeine had significant changes in the
direction of patients with chronic insomnia on MSLT, metabolic rate, negative
moods, and personality. The data indicate that chronic hyperarousal with no predis-
posing psychological component can produce the typical pattern of poor sleep,
mood change, and personality change commonly seen in patients with psychophysi-
ological insomnia. However, it could not be determined from these data if the mood
and personality symptoms were produced by the hyperarousal or were secondary
from the poor sleep also produced.

Effects of Poor Sleep

It has been implied that increased physiological arousal, possibly even as an
innate phenomenon, produces an environment in which an individual is prone to
report insomnia. Many patients with insomnia, however, feel that their sleep is the
central problem, and that poor sleep leads to symptoms of fatigue and dysphoria.
To test whether the insomnia sleep pattern by itself could produce hyperarousal and
the other symptoms of primary insomnia, the poor sleep found in patients with
insomnia was produced for 1 week in normal young adults, and subjects were fol-
lowed for the development of insomnia symptoms (36). Patients with primary
insomnia were identified based on the same report of poor sleep and poly-
somnographic criteria as used for insomnia patients who participated in the meta-
bolic studies reported earlier and the sleep parameters of those patients were used
in a yoke control fashion to produce comparable sleep in a group of matched nor-
mal sleepers. It was hypothesized that if the yoked normal sleepers developed the
spectrum of secondary symptoms seen in the patients with “true” insomnia after
sleeping like the patients, then those symptoms could be seen as secondary to the
poor sleep. On the other hand, if the yoked normal sleepers did not develop the
symptoms seen in the true patients with insomnia, then some factor other than poor
sleep itself would be responsible for those secondary symptoms.
Physiological Basis of Insomnia 31

In this study, the EEG sleep characteristics of patients with primary insomnia
were reproduced in matched normal sleepers for a week. Sleep patterns were
matched by making experimental arousals and awakenings throughout the night in
normal sleepers to match the pattern of wake time and arousals seen in the patients
with insomnia. Because the EEG sleep produced in the study was similar to that
found in patients reporting insomnia, changes in the outcome variables should have
reflected the consequences of pure “poor” sleep. Table 2 provides a summary of
typical findings for patients with insomnia and compares those findings with the
results of this yoke control study.
Changes secondary to the poor sleep produced in the yoke control study were
clearly different from the symptoms most frequently reported by patients with
insomnia. Patients with insomnia typically have difficulty falling asleep both at
night and during the MSLT (20–22,24). However, both SL and MSLT data from
the yoke control study supported significantly increasing ease of falling asleep as
the nights of insomnia increased.
Patients with insomnia frequently have elevated body temperature and whole
body metabolic rate (6,14,24). Except for an increase in nocturnal metabolic rate
probably associated with the experimental sleep disturbance itself (37), the trends
in the yoke control study showed lower metabolic rate and decreased body tem-
perature during the day. Patients with insomnia typically report increased stress,
anxiety, or depression (1,24). However, in the yoke control study, the state mea-
sures of tension and depression decreased significantly during the study. Patients
with insomnia typically have elevated MMPI scales, but the MMPI measures were
unchanged in this study. Patients with insomnia report increased fatigue and de-
creased vigor, and similar changes were found in the yoke control study. However,
these changes are also found during simple sleep deprivation.
Finally, patients with insomnia overestimate their time spent awake during the
night. Despite increased awakenings and wake time in the yoke control study, the
normal sleepers continued to correctly estimate their wake time during the night.
The most parsimonious explanation for the results was that the insomnia sleep
pattern resulted only in partial sleep deprivation when imposed on normal sleepers.
This interpretation is supported by rebounds of REM and SWS during the recovery
night after the 7 nights of yoke insomnia and by decreasing MSLT values. These
changes are classic signs of sleep loss. Decreases in vigor and body temperature
also suggested simple sleep loss. Because TST in the study was reduced to 6 hours
each night for a week, this could easily have resulted in partial sleep deprivation.
For example, a study by Rosenthal et al. (38) showed increased sleepiness on the
MSLT after just 1 night of 5.6 hours of sleep.
The data from the yoke control study support the contention that some patients
with insomnia may suffer from mild partial sleep deprivation. As in normal sub-
jects, however, the degree of deficit should be related to the amount of sleep lost
and should typically recover after an occasional night of improved sleep. In fact,
one could hypothesize that poor sleep in response to hyperarousal is an adaptive
32 Bonnet and Arand

response that acts as a homeostatic mechanism to cause partial sleep deprivation

and reduce the impact of hyperarousal. Unfortunately, in patients with chronic in-
somnia, a night of relatively good sleep would remove a portion of the chronic
partial sleep deprivation and leave the patient more susceptible to the effect of
hyperarousal. This situation leaves patients in the uncomfortable situation of suf-
fering either from hyperarousal or from hyperarousal masked by sleep deprivation.
If the poor sleep of patients with insomnia produces only mild sleep loss in
matched normal sleepers, how does one explain the consistent secondary symp-
toms reported by patients with insomnia? As can be seen from Table 2, the second-
ary symptoms of patients with insomnia appear in normal sleepers who are
hyperaroused (35), but not in normal sleepers actually given the poor sleep experi-
enced by patients with insomnia. The major implication of such data is that it is the
increased arousal and not the poor sleep per se that is responsible for the symptoms.
Is it possible, however, that the development of symptoms in patients with insom-
nia is actually dependent on poor sleep interacting with personality variables in the
patients with insomnia? If this is the case, then one would expect that patients with
insomnia who have particularly poor nights of sleep would experience an exacerba-
tion of their insomnia symptoms.
In another study (39), it was hypothesized that, if nocturnal sleep parameters
produced the daytime dysphoria reported by patients with insomnia, then patients
with sleep maintenance insomnia who were kept awake even longer than usual
during the night should have had increased dysphoria during the following day. To
test this hypothesis, patients with sleep maintenance insomnia were allowed only
80% of their already reduced TST each night for 7 consecutive nights. This sleep
reduction was accomplished by waking patients up at the end of each quarter of the
night if they accumulated more than 80% of their baseline sleep for that quarter of the
night (while holding TIB for the entire night at the baseline level). This paradigm
produced very poor sleep (average TST of 4.2 hours on each night for the week).
This reduction of TST by experimental awakenings resulted in a significant de-
crease in daytime MSLT values for these insomnia patients. After 7 nights of 4.2
hours of sleep, MSLT values decreased from 15.6 to 11.1 minutes. Although this
reduction was statistically significant, the 11.1-minute value was still within the
normal range for the test.
In a study in which total sleep was reduced to 5 hours per night in normal young
adults (40), MSLT was reduced to 41% of baseline compared to a reduction to 71%
of baseline that was found for the patients with insomnia. These results indicated
that when the sleep of insomnia patients was experimentally reduced, they dis-
played some increased sleepiness during the day, in agreement with the expectancy
in normal sleepers, but not the increased latency typical in patients with insomnia
as their nocturnal sleep worsens. Despite the large reduction in TST, the patients
with insomnia did not become pathologically sleepy on the MSLT, and this prob-
ably indicated the degree to which their hyperarousal was successful in masking
Physiological Basis of Insomnia 33

their sleep tendency. Of equal interest, patients did not report significant decreases
in their sleep quality or show changes in personality or physiological parameters
consistent with more severe insomnia when their wake time during the night was
increased by 2 hours.
One conclusion from such data is that the reports of poor sleep quality and day-
time dysphoria from patients with insomnia are not directly related to their EEG
sleep, but rather to their level of arousal (41). In support of these results, Chambers
and Kim (42) reported a significant negative correlation between state anxiety at
bedtime and reports of feeling rested on the next day for patients with insomnia
despite the fact that neither anxiety nor reports of feeling rested were significantly
correlated with sleep values.

Level of Arousal and the Perception of Sleep

Insomnia patients commonly overestimate how long it takes to fall asleep at
night and underestimate their TST. Is such misperception related to personality or
to underlying physiology? We decided to look at several physiological manipula-
tions to determine if they produced changes in the perception of sleep onset (43).
Patients with insomnia subjectively estimate that it takes much longer to fall
asleep than EEG measures indicate (44). One means of examining this phenom-
enon is to divide the subjective estimate of SL by the EEG estimate to derive a
unitless indicator of degree of estimation difference. For example, sleep depriva-
tion or the use of benzodiazepines decreases the level of arousal and was hypoth-
esized to decrease this subjective to objective ratio of SLs. Conversely,
administration of caffeine, which increases arousal level, or sleep during the day-
time, when level of arousal is higher, should increase the ratio.
Specifically, results from several studies (43) indicated that the ratio of subjec-
tive to objective SL decreased when subjects were given triazolam or diazepam to
decrease level of arousal, and the decreases tended to be dose related. Similarly, the
ratio of subjective to objective SL decreased during sleep deprivation; again, the
decreases were related to the amount of sleep lost. In two tests of increased arousal,
the ratios of subjective to objective SLs increased after an initial night of caffeine
consumption and were greater during sleep periods that began midday than in sleep
periods that began later in the evening. These data supported the contention that the
perception of falling asleep was related to the level of physiological arousal at sleep
onset. The consistency of the findings with six different experimental manipula-
tions supports the argument that estimates of SL may also be dependent on level of
physiological arousal.
These data support the idea that subjectively reported poor sleep or insomnia is
a physiological phenomenon that can be controlled by varying the level of arousal.
The point is that poor sleep, whether it is acute or chronic, is a physiological (as
opposed to a psychological) event that is amenable to physiological exploration
and modification.
34 Bonnet and Arand

The Development of Insomnia

It is well known that the incidence of insomnia increases with age. This increase
could be associated with increasing sympathetic nervous system dominance that is
also associated with age or with cognitive or behavioral changes. Unfortunately,
very little empirical work has examined how insomnia starts or develops. One
theory holds that individuals placed in a situation of temporary stress develop poor
sleep hygiene or inappropriate conditioned responses to their sleep environment.
Then, the poor hygiene or inappropriate responses continue to produce poor sleep
after the period of stress passes.
If this is true, one way to understand the development of insomnia would be to
take normal young adults, expose them to a temporary stress, and evaluate the
insomnia produced.
We specifically followed this methodology in a recent study of 50 normal sleep-
ers exposed to a series of stressful experiences, including first night in a sleep labo-
ratory, 3-hour phase advance of sleep time, 6-hour advance of sleep time, and sleep
following administration of 400 mg of caffeine 30 minutes prior to bedtime (45,46).
It was found that there was both wide variability and remarkable consistency in
the responses seen. The variability was in the between-subject response to the situ-
ational stress—some subjects continued to have nearly normal nights of sleep even
after a 6-hour phase advance of bedtime or caffeine ingestion, whereas other indi-
viduals had poor sleep following all of the stresses. This study involved so many
participants that it was possible to form “extreme” groups—in this case the 25% of
the population that slept best on the first night in the laboratory (super sleepers) and
the 25% who had the worst sleep on that night (situational insomnia [SI]). Signifi-
cant correlations were found between sleep efficiency on the first night and on the
other stress nights in the complete data set and also by comparing sleep values in
the extreme groups.
Subjects who had poor sleep on their laboratory adaptation night (and were there-
fore called the SI group) also had increased MSLT on the day that followed. They
had normal sleep on the baseline night that followed, but then had significantly
worse sleep on the phase-advance nights and after caffeine administration. Their
sleep was so bad after the 6-hour phase advance (about 4.5 hours compared with
about 7 hours for the super sleepers) that their MSLTs were significantly reduced
on the day that followed. The SI group also had very poor sleep after caffeine ad-
ministration but surprisingly, the MSLTs after caffeine administration were signifi-
cantly increased. The super sleep group did not have any significant changes in
MSLT throughout the study. The implication is that the SI group was not only more
sensitive to all of the stresses in terms of the production of poor sleep, but also was
more sensitive to the arousing effect of caffeine.
This study also examined other differences between the SI and good sleeping
groups (see Table 2). No significant differences were found on the MMPI or mood
measures. Whole body metabolic rate was nonsignificantly increased in the SI
group. The SI group was found to have increased heart rate, increased LFP and
Physiological Basis of Insomnia 35

decreased HFP compared to the good sleepers. These physiological findings in

“preinsomnia” patients suggest that their existing hyperreactivity to sleep-related
stress and caffeine could be secondary to elevated sympathetic nervous system activ-
ity, and this could be a marker for the development of chronic insomnia at a later date.
The finding of elevated physiological activity prior to mood change, personality
change, or complaint of chronic insomnia provides another clue that underlying physi-
ology could be the key to the later development of additional insomnia symptoms.

DISCUSSION
It is generally accepted that there are changes in several physiological systems
in association with psychophysiological insomnia. The current experiments
attempted to refine our understanding of the relationship among physiological
arousal, poor EEG sleep, psychological status, and subjective report of insomnia.
The finding that experimentally produced chronic physiological arousal in normal
young adults produces the mood and personality changes seen in patients with
insomnia provides a compelling description of how chronic insomnia could develop
in physiologically susceptible individuals. The studies showing that, by itself the
poor sleep of patients with insomnia does not produce the arousal, mood, and per-
sonality characteristics of patients and that the production of much worse EEG
sleep in patients with insomnia does not magnify symptoms leads to the conclu-
sions that the symptoms produced by chronic physiological arousal were not medi-
ated by the poor sleep that was produced and the symptom complex that was
associated with psychophysiological insomnia is not really a sleep disorder, but
rather an arousal disorder. Finally, the importance of physiological arousal as the
harbinger of insomnia was enhanced by the finding of elevated heart rate and
abnormal cardiac spectral activity in normal subjects with no sleep complaint who
were found to have EEG-defined SI. These several approaches identify tangible
physiopathology that should be open to identification and amenable to treatment.
We have recognized for many years that some patients have lifelong problems
with excessive sleepiness secondary to disorders such as narcolepsy or idiopathic
hypersomnolance. The extent to which these disorders demonstrate a failure of the
sleep system vs a failure of the arousal system can be debated. Certainly, these
disorders are commonly treated with medications that have direct impact by
increasing central nervous system arousal. Recognition that another group of
patients suffers from the opposite lifelong problem (hyposomnolence or
hyperarousal) has been more difficult. At this point, much work has identified the
physiological markers of chronic hyperarousal in patients. Behavioral relaxation
techniques can provide effective help for patients with some situational
hyperarousal, but as behavioral techniques such as sleep extension eventually fail
in patients with idiopathic hypersomnolance, behavioral techniques may also fail
in patients suffering from chronic hyperarousal. Identifying arousal disorders as a
major component of both hypersomnolance and insomnia can help direct research
toward more effective pharmacological control of the underlying physiologic
arousal disorder.
36 Bonnet and Arand

ACKNOWLEDGMENT
This chapter was supported by the Dayton Department of Veterans Affairs Medi-
cal Center, Wright State University School of Medicine, and the Sleep–Wake Dis-
orders Research Institute.

REFERENCES
1. Kales, J. D., Kales, A., Bixler, E. O., et al. (1984) Biopsychobehavioral correlates of insomnia,
V: Clinical characteristics and behavioral correlates. Am. J. Psychiatry 141, 1371–1376.
2. Tan, T. L., Kales, J. D., Kales, A., Soldatos, C. R., and Bixler, E. O. (1984) Biopsychobehavioral
correlates of insomnia. IV: Diagnosis based on DSM-III. Am. J. Psychiatry 141, 357–362.
3. Kales, A., Caldwell, A. B., Soldatos, C. R, Bixler, E. O., and Kales, J. D. (1983)
Biopsychobehavioral correlates of insomnia. II. Pattern specificity and consistency with the
Minnesota Multiphasic Personality Inventory. Psychosom. Med. 45, 341–355.
4. Hauri, P. J. (1983) A cluster analysis of insomnia. Sleep 6, 326–338.
5. Healey, E. S., Kales, A., Monroe, L. J., Bixler, E. O., Chamberlin, K., and Soldatos, C. R. (1981)
Onset of insomnia: Role of life-stress events. Psychosom. Med. 43, 439–451.
6. Monroe, L. J. (1967) Psychological and physiological differences between good and poor sleep-
ers. J. Abnorm. Psychol. 72, 255–264.
7. Haynes, S. N., Follingstad, D. R., and McGowen, W. T. (1974) Insomnia: Sleep patterns and
anxiety level. J. Psychosom. Res. 18, 69–74.
8. Freedman, R. R. and Sattler, H. L. (1982) Physiological and psychological factors in sleep-onset
insomnia. J. Abnorm. Psychol. 91, 380–389.
9. Freedman, R. R. (1986) EEG power spectra in sleep-onset insomnia. Electroencephal. Clin.
Neurophysiol. 63, 408–413.
10. Haynes, S. N., Adams, A., and Franzen, M. (1981) The effects of presleep stress on sleep-onset
insomnia. J. Abnorm. Psychol. 90, 601–606.
11. Bonnet, M. H. and Arand, D. L. (1998) Heart rate variability in insomniacs and matched normal
sleepers. Psychosom. Med. 60, 610–615.
12. Johns, M. W., Gay, T. J. A., Masterton, J. P., and Bruce, D. W. (1971) Relationship between sleep
habits, adrenocortical activity and personality. Psychosom. Med. 33, 499–508.
13. Mendelson, W. B., Garnett, D., Gillin, C. G., and Weingartner H. (1984) The experience of in-
somnia and daytime and nighttime functioning. Psychiat. Res. 12, 235–250.
14. Adam, K., Tomeny, M., and Oswald, I. (1986) Physiological and psychological differences be-
tween good and poor sleepers. J. Psychiatr. Res. 20, 301–316.
15. Frankel, B., Buchbinder, R., Coursey, R., and Snyder, F. (1973) Sleep patterns and psychological
test characteristics of chronic primary insomniacs. Sleep Res. 2, 149.
16. Borkovec, T. D. (1982) Insomnia. J. Cons. Clin. Psychol. 50, 880–895.
17. Mendelson, W. B., James, S. P., Garnett, D., Sack, D. A., and Rosenthal, N. E. (1986) A psy-
chophysiological study of insomnia. Psychiatry Res. 19, 267–284.
18. Seidel, W. F., Ball, S., Cohen, S., Patterson, N., Yost, D., and Dement, W. C. (1984) Daytime
alertness in relation to mood, performance, and nocturnal sleep in chronic insomniacs and
noncomplaining sleepers. Sleep 7, 230–238.
19. Bonnet, M. H. (1986) Effect of 64 hours of sleep deprivation upon sleep in geriatric normals and
insomniacs. Neurobiol. Aging 7, 89–96.
20. Stepanski, E., Zorick, F., Roehrs, T., Young, D., and Roth, T. (1988) Daytime alertness in pa-
tients with chronic insomnia compared with asymptomatic control subjects. Sleep 11, 54–60.
21. Haynes, S. N., Fitzgerald, S. G., Shute, G. E., and Hall, M. (1985) The utility and validity of
daytime naps in the assessment of sleep-onset insomnia. J. Behav. Med. 8, 237–247.
Physiological Basis of Insomnia 37

22. Schneider-Helmert, D. (1987) Twenty-four-hour sleep-wake function and personality patterns in

chronic insomniacs and healthy controls. Sleep 10, 452–462.
23. Mendelson, W. B., Garnett, D., and Linnoila, M. (1984) Do insomniacs have impaired daytime
functioning? Biol. Psychiatry 19, 1261–1264.
24. Bonnet, M. H. and Arand, D. L. (1995) 24-Hour metabolic rate in insomniacs and matched nor-
mal sleepers. Sleep 18, 581–588.
25. Bonnet, M. H. and Arand, D. L. (1997) Physiological activation in patients with sleep state
misperception. Psychosom. Med. 59, 533–540.
26. Stepanski, E., Glinn, M., Zorick, F. J., Roehrs, T., and Roth, T. (1994) Heart rate changes in
chronic insomnia. Stress Med. 10, 261–266.
26a. Krystal, A. D., Edinger, J. D., Wohlgemuth, W. K., and Marsh, G. R. (2002) NREM sleep EEG
frequency spectral correlates of sleep complaints in primary insomnia subtypes. Sleep 25, 630–640.
27. Deibert, D. C. and DeFronzo, R. A. (1980) Epinephrine-induced insulin resistance in man. J.
Clin. Invest. 65, 717–721.
28. DeFronzo, R. A. and Ferrannini, E. (1991) Insulin resistance: A multifacted syndrome respon-
sible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular dis-
ease. Diabetes Care 14, 173–194.
29. Julius, S. (1994) Abnormalities of autonomic nervous control in human hypertension. Cardiovas-
cular Drugs and Therapy 8, 11–20.
30. Cohn, J. N. (1966) Relationship of plasma volume changes to resistance and capacitance vessel
effects of sympathomimetic amines and angiotensin in man. Clin. Sci. 30, 267–278.
31. Kjeldsen, S. E., Gjesdal, K., Eide, I, et al. (1983) Increased beta-thromboglobulin in essential
hypertension: interactions between arterial plasma adrenaline, platlet function and blood lipids.
Acta Med. Scand. 213, 369–373.
32. Esler, M., Julius, S., Zweifler, A., et al. (1977) Mild high-renin essential hypertension: Neuro-
genic human hypertension. N. Engl. J. Med. 296, 405–411.
33. Schwartz, P. J., Vanoli, E., Stramba-Badiale. M., Ferrari, G. M., Billman, G. E., and Foreman, R.
D. (1993) Autonomic mechanisms and sudden death - new insights from analysis of baroreceptor
reflexes in conscious dogs with and without a myocardial infarction. Circulation 78, 969–979.
34. Billman, G. E. (1990) Effect of carbachol and cyclic GMP on susceptibility to ventricular fibril-
lation. FASEB 4, 1668–1673.
35. Bonnet MH, Arand DL. (1992) Caffeine use as a model of acute and chronic insomnia. Sleep 15,
526–536.
36. Bonnet, M. H. and Arand, D. L. (1996) The consequences of a week of insomnia. Sleep 19, 453–461.
37. Bonnet, M. H., Berry, R. B., and Arand, D. L. (1991) Metabolism during normal sleep, frag-
mented sleep, and recovery sleep. J. App. Physiol. 71, 1112–1118.
38. Rosenthal, L., Roehrs, T. A., Rosen, A., and Roth, T. (1993) Level of sleepiness and total sleep
time following various time in bed conditions. Sleep 16, 226–232.
39. Bonnet, M. H. and Arand, D. L. (1998) The consequences of a week of insomnia II: Patients with
insomnia. Sleep 21, 359–378.
40. Carskadon, M. A. and Dement, W. C. (1981) Cumulative effects of sleep restriction on daytime
sleepiness. Psychophysiology 18, 107–113.
41. Bonnet, M. H. (1990) The perception of sleep onset in normals and insomniacs. In: Sleep and Cog-
nition (Schacter, D., ed.), American Psychological Association, Washington, DC, pp. 148–159.
42. Chambers, M. J. and Kim, J. Y. (1993) The role of state-trait anxiety in insomnia and daytime
restedness. Behav. Med. 19, 42–46.
43. Bonnet, M. H. and Arand, D. L. (1994) The impact of level of physiological arousal on estimates
of sleep latency. In: Sleep Onset: Normal and Abnormal Processes (Ogilvie, R. D. and Harsh, J.
R., eds.), American Psychological Association, Washington, DC, pp. 127–140.
44. Moore, S. E. (1981) Estimates of sleep latency and of other temporal intervals in insomniac and
normal sleepers. University of Cincinnati Masters Thesis, 92.
38 Bonnet and Arand

45. Bonnet, M. H. and Arand, D. L. (2002) Situational insomnia: in the situation or in the patient?
Sleep 25, A32.
46. Bonnet, M. H. and Arand, D. L. (2003) Physiological activation in situational insomnia. Sleep 26,
A289.
Differential Diagnosis of Insomnia 39

4
Differential Diagnosis of Insomnia

Hrayr P. Attarian

Not poppy, nor mandragora,

Nor all the drowsy syrups of the world,
Shall ever medicine thee to that sweet sleep
Which thou owedst yesterday.
—William Shakespeare (1564–1616) “Othello. Act iii. Sc. 3”

DEFINITION
Insomnia is the inability to obtain sleep of sufficient length or quality to produce
refreshment the following morning. It is not defined by total sleep time per 24 hours.
For example, a person who needs only 4 hours of sleep does not have insomnia if he
or she is refreshed in the morning after having 4 hours of sleep, whereas someone
who needs 10 hours of sleep may have insomnia if he or she does not feel refreshed
even after 8 hours of sleep (1). Contrary to popular belief, psychiatric or psycho-
logical factors are not the most common causes of insomnia (1). In fact, untreated
insomnia, itself, is a risk factor for the subsequent development of clinical depres-
sion and psychiatric distress (2).
Insomnia is not a diagnosis in and of itself. It should be thought of as a constitu-
tional symptom, not unlike pain, fever, or weight loss, requiring identification of an
underlying cause before diagnosis and a treatment plan are established (1).

TYPES OF INSOMNIA AND UNDERLYING CAUSES

Disorders causing insomnia can be divided into two major categories: primary
and secondary. Primary insomnia is when the insomnia is the major or sole symp-
tom of a disorder. Insomnia is considered secondary when it is a symptom of an
underlying medical or psychiatric illness (Table 1).

From: Current Clinical Neurology: Clinical Handbook of Insomnia

Edited by: H. P. Attarian © Humana Press Inc., Totowa, NJ

39
40 Attarian

Table 1
Types of Insomnias
Primary insomnias Secondary insomnias
Psychophysiologic, or conditioned, insomnia Insomnia in psychiatric illnesses
Idiopathic, or childhood-onset, insomnia Insomnia in other sleep disorders
Sleep state misperception insomnia Insomnia in neurological disorders
Poor sleep hygiene insomnia Insomnia in medical disorders
Other extrinsic insomnias Medication-induced insomnia
Fatal familial insomnia Menopause-related insomnia
Environmentally induced insomnia
Restless legs syndrome

Psychophysiological, or Conditioned, Insomnia

This is the most common form of insomnia and is typically acquired during a
period when other factors (e.g., stress) are at work. After a few days of sleeping
poorly, the patient becomes concerned and begins trying harder to get to sleep. The
result is arousal and aggravation of the insomnia. Stimuli surrounding bedtime (e.g.,
the bedroom, the bed itself) may become triggers to arousal. Thus, such patients
may have severe problems with sleep in their own bedrooms but may sleep remark-
ably well in other locations (e.g., on the living room couch, in a motel, in a sleep
laboratory). The essence of psychophysiological insomnia is that attention is fo-
cused on the inability to sleep. Insomnia is perceived as the only source of distress,
and other emotional or mental concerns are minimized. Typically, patients repress
or deny awareness of stress factors and see the insomnia as occurring without any
reason.
In some patients with psychophysiological insomnia, no precipitating stress is
found. Rather, poor sleep may have gradually developed as an occasionally occur-
ring disturbed night leads to increased concern, causing sleep to deteriorate until it
becomes the patient’s chief concern. There is clear evidence for the role of familial
inheritance in the tendency to develop insomnia (3).

Idiopathic, or Childhood-Onset, Insomnia

This rare condition presents as a chronic, serious inability to initiate and main-
tain sleep, which can often be traced back to the first few weeks of life. Sleep
latency (i.e., the time it takes to fall asleep after going to bed) may be very long, and
sleep is riddled with awakenings. Daytime features typically include decreased at-
tention and vigilance, low levels of energy and concentration, and deterioration of
mood that is usually described as grim and subdued rather than obviously depressed
or anxious. The presumed underlying neurological abnormality (either hyperactiv-
ity in the arousal system or hypoactivity in the sleep system) may vary from mild to
severe, so the range of insomnia encountered also may vary from mild (essentially,
the patient is a light sleeper) to severe and incapacitating (4). In mild or moderate
Differential Diagnosis of Insomnia 41

idiopathic insomnia, psychological functioning is remarkably intact. In severe

cases, daytime functioning may be severely disrupted, and affected patients may be
unable to hold a job. During childhood and adolescence, idiopathic insomnia is
often associated with dyslexia and hyperactivity. In many cases, diffuse, nonspe-
cific abnormalities are seen on an electroencephalogram (EEG) (4,5). There is no
direct human evidence for structural neuropathology. Although idiopathic insom-
nia appears in childhood, not all childhood insomnia is idiopathic (6).

Sleep State Misperception Insomnia

In this fascinating disorder, complaints of insomnia occur without any objective
evidence of sleep disturbance. Patients may report that they have not slept at all in
weeks, months, or years. However, on objective sleep studies, they sleep several
hours per night (7). When results of sleep evaluation are presented, patients with
sleep state misperception (SSM) may vehemently insist that the studies are in error
because they are convinced that they sleep very little, if at all.

Poor Sleep Hygiene

In some patients, insomnia is the result of lifestyle. In others, poor sleep hygiene
develops as a result of chronic insomnia. For example, in the latter case, patients
may begin to drink more coffee to remain awake during the day and more alcohol to
fall asleep at night. They may stay in bed for extended periods in an attempt to get
more sleep. However, such ploys only serve to perpetuate the insomnia (5).

Fatal Familial Insomnia

This hereditary condition, with autosomal-dominant transmission, is character-
ized clinically by progressive insomnia, dysautonomia, dysphagia, dysarthria,
diplopia changes in circadian rhythm of hormone secretion, motor signs, myoclo-
nus, and slight to moderate deterioration of cognition. The usual age of onset is
between 35 and 60 years, and the course of the illness is between 7 and 32 months.
In this condition, an abnormal prion protein (PrPsc) is present in the brain, and
there is mutation of gene coding for PrPsc. The fatal nature of this illness is due to
neurological degenerative changes, not to the insomnia itself (8, 9).

Restless Legs Syndrome and Periodic Limb Movement Disorder

These familial, common, and related conditions are found in varying degrees in
up to 10% of the population (10). The prevalence of periodic limb movement disor-
der (PLMD) is 3.9% and restless legs syndrome (RLS) is 5.5% (11). The four car-
dinal symptoms of RLS are a desire to move the legs, accompanying paresthesias
that are characterized as uncomfortable or indescribable, motor restlessness, and
worsening of symptoms at night and at rest (12). Symptoms of RLS may worsen
with administration of antidepressants (13,14) and during pregnancy (15). Periodic
limb movements (PLMs) occur in 80% of patients with RLS (16). They are repeti-
tive, stereotyped movements recurring at 5- to 90-second intervals lasting usually
42 Attarian

15 to 40 seconds. PLMs are not considered abnormal unless they lead to severe
sleep disturbance or excessive daytime sleepiness, or both, in which case they form
a separate intrinsic sleep disorder, PLMD (10). RLS can be easily differentiated
from primary insomnias by history due to the characteristic symptoms with which
it presents. Insomnia as a result of PLMD may require the aid of a polysomnogram
(PSG; see later) to make the correct diagnosis.

Other Sleep Disorders

Occasionally, insomnia is the presenting complaint in obstructive sleep apnea
(OSA) syndrome. In a group of older adults with insomnia, a respiratory distur-
bance index (RDI) of at least 15 per hour was found in 29% of patients (17). In
another study of a large group of patients with insomnia, RDI of at least 30 per hour
was found in 2.3% of patients vs 1.3% of controls (18). The presence of excessive day-
time sleepiness, snoring, and observed apneas raises the possibility of OSA syndrome.
In circadian rhythm abnormalities, patients sleep well but not at socially accept-
able times (5). Those with the advanced sleep-phase syndrome have excessive
sleepiness in the evening and undesired early morning awakening. Those with the
delayed sleep-phase syndrome have sleep-onset insomnia, excessive daytime
sleepiness (particularly in the morning), or both. Other circadian rhythm abnor-
malities presenting with a variety of insomnia symptoms include irregular sleep–
wake cycle, non-24-hour sleep–wake syndrome and sleep disturbances in blind
individuals, and those resulting from social circumstances: jet lag and shift-work
sleep disorder (19). Having patients fill out sleep diaries or sleep logs during a 1- or
2-week period when they are free of social restrictions of their bedtime and wake
time (going to bed whenever they are sleepy and getting up on their own without an
alarm) helps make the diagnosis of circadian rhythm abnormalities.
Occasionally, narcolepsy presents as insomnia because 50% of patients with
narcolepsy have disrupted sleep at night (20,21). Again, excessive daytime sleepi-
ness and ancillary symptomatology (sleep paralysis, hypnic hallucinations, and
cataplexy) differentiate insomnia resulting from narcolepsy from the primary
insomnias.

Neurologic and Medical Conditions

Conditions that can cause insomnia, among other symptoms, include neuro-
degenerative diseases (22), pain, allergies (23), gastroesophageal reflux (24), and
asthma (25). All of these can be easily differentiated from primary insomnias by
history and physical exam.

Menopause-Related Insomnia
There is a high level of sleep disturbance occurring in about 42% of middle-aged
women (26). Although cross-sectional analyses indicate that sleep disturbance may
be independent of menopausal status, transition into postmenopausal status is asso-
ciated with deleterious changes in sleep among women not receiving hormone
replacement therapy (26,27).
Differential Diagnosis of Insomnia 43

Psychiatric Conditions
When anxiety permeates most aspects of functioning in patients with insomnia,
generalized anxiety disorder is the usual diagnosis. In contrast, if anxiety is focused
almost exclusively on poor sleep and its consequences on daytime functioning, psy-
chophysiological insomnia is the typical diagnosis (28)
Insomnia due to affective disorders is sometimes difficult to differentiate from
psychophysiological insomnia because a dysphoric mood, ascribed to the effects of
poor sleep, often accompanies psychophysiological insomnia. The two conditions
can often be distinguished on the basis of other “vegetative” signs, such as loss of
appetite or libido or the typical diurnal fluctuation (worse in the morning) of depres-
sion (28). In general, a diagnosis of psychophysiological insomnia is inappropriate if
the patient fulfills criteria for any other Axis I or II diagnosis in the fourth edition of
the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (29).

Medication-Induced Insomnia
Selective serotonin reuptake inhibitors (30), stimulants, theophylline, pred-
nisone, and two of the newer anticonvulsants, felbamate (31) (Felbatol) and
lamotrigine (32) (Lamictal), may cause insomnia. Other medication or chemically
related causes of insomnia include withdrawal from sedative agents, idiosyncratic
reactions to other medications, and toxin-related reactions (e.g., alcohol, carbon
monoxide [33], inorganic mercury [34], recreational drugs). A thorough list of the
patient’s medications and chemical exposures is essential for the evaluation of
insomnia.

DIAGNOSTIC TOOLS
PSG and Multiple Sleep Latency Test
The PSG is a polygraph of EEG findings, eye movements, electromyography
readings, oxygen saturation, limb movements, airflow, and chest and abdominal
movements taken during sleep, usually for the entire night. According to the Ameri-
can Sleep Disorders Association (now the American Academy of Sleep Medicine),
practice parameters polysomnography is not indicated in routine evaluation of
insomnia, except when the diagnosis is uncertain and a primary sleep disorder is
suspected and when insomnia does not respond to appropriate behavioral and phar-
macological treatments (35).
A Multiple Sleep Latency Test (MSLT) is a series of four or five opportunities,
each separated by a 2-hour interval, to take a 15- to 20-minute nap. It is used to
assess sleep latency and the possibility of such sleep disorders as OSA and narco-
lepsy. In primary insomnia, results of the MSLT are usually normal (36).

Sleep Logs
A sleep log (Fig. 1) is a graph on which, for 2 to 3 weeks, the patient records
bedtime, approximate sleep time, times and duration of awakenings during the sleep
 44
44

Attarian
Fig. 1. Example of a 1-week sleep log. Shaged areas indicate sleep; open areas indicate wakefulness.
Differential Diagnosis of Insomnia 45

Fig. 2. Picture of an actigraph. (Used with permission. Courtesy of Mini Mitter® Co. Inc.)

period, final awakening time, and naps taken during the day. Although subjective,
this record summarizes the patient’s perception of the amount and quality of sleep
he or she is getting (37).

Actigraphy
Actigraphy is a recently developed technique to record activity during waking
and sleeping without application of any electrodes. An actigraph (Fig. 2) is worn on
the wrist and is about the size of a watch. It consists of a movement detector and
considerable memory so it can record movement and nonmovement data plotted
 46
46

Fig. 3. One-week printout of an actigraph. High bars show wakefulness; low bars show sleep. (Used with permission. Courtesy of Mini
Mitter® Co. Inc.)

Attarian
Differential Diagnosis of Insomnia 47

against time for 1 or 2 weeks. The patient can wear it continuously during sleep and
as he or she goes about routine daily activities. Actigraphy is ideal for extended
examination of the sleep–wake cycle in the patient’s home environment. It is conve-
nient and readily accepted by patients. It can be used to supplement sleep logs and to
evaluate unusual complaints, such as, “I have not slept for several nights” (1).
In general, patients have fewer limb movements during sleep than while awake.
There is a very close correlation between the rest–activity findings recorded by the
actigraph and the sleep–wake pattern as determined by a PSG. Several investiga-
tors used actigraphy in groups of controls of different ages and found minute-by-
minute agreement in sleep–wake scoring between polysomnography and actigraphy
to exceed 90% (38).
Figure 3 depicts a 1-week printout of an actigraph.

Laboratory Evaluation
In patients with RLS, a serum ferritin level of less than 50 µg/L is associated
with increased severity of symptoms, which may exacerbate insomnia (39,40).

Diagnostic Workup
Insomnia is usually diagnosed by a thorough clinical history-taking. If anxiety
permeates most aspects of functioning in patients with insomnia, then generalized
anxiety disorder, rather than primary insomnia, is the usual diagnosis. Affective
disorders can be differentiated from primary insomnia on the basis of other “veg-
etative” signs, such as loss of appetite or libido or the typical diurnal fluctuation
(worse in the morning) of depression. In these situations, the patient should be first
evaluated by a psychiatrist. If a history of significant dysesthesias interfering with
sleep is elicited during history-taking, then the diagnosis of RLS should be consid-
ered, serum ferritin checked, and treatment initiated accordingly. The complaint of
excessive daytime sleepiness manifested by falling asleep unintentionally or hav-
ing a hard time staying awake in sedentary situations, is generally indicative of
another primary sleep disorder, because patients with insomnia are hyposomnolent
and often complain bitterly of the inability to take naps (36). Patients reporting
episodes of falling asleep unintentionally during the day should be evaluated with a
PSG and an MSLT to rule out primary sleep disorders. Taking a history of the
patient’s sleep habits is essential in identifying sleep hygiene issues or circadian
rhythm abnormalities. If the patient is unable to fall asleep at a desired time but is
able to fall asleep much later and is unable to wake up at a desired time then the
diagnosis of delayed sleep phase should be considered. If the patient is waking up
very early in the morning and is unable to go back to sleep but cannot stay awake
past early evening, then advanced sleep-phase syndrome should be entertained as a
diagnosis. In short, if the patient is able to fall asleep but not at socially acceptable
times, then the most likely cause of the complaint of insomnia is circadian rhythm
abnormalities that can be treated with a combination of chronotherapy, photo-
therapy, and melatonin. A history of other medical problems, exposure to toxins,
48 Attarian

Fig. 4. Algorithm. (Used with permission. Courtesy of Primary Care Reports/American

Health Consultants [41].) Abbreviations: PSG, plysomnograph; MSLT, Multiple Sleep La-
tency Tests.

and a list of medication the patient is taking is also important because many chemi-
cals, either pharmaceutical or toxic, can affect sleep and cause insomnia. If the
diagnosis of persistent primary insomnia is made, then sleep diaries are essential in
tailoring treatment to the individual patient’s needs. An actigraph is an essential
tool in primary insomnia; both in providing an objective measure of the true extent
of the insomnia and for gauging response to treatment. In patients with intermittent
situational insomnia, such as Sunday night insomnia, the use of hypnotic medica-
tion as the sole method of treatment is encouraged. This is to prevent the intermit-
tent insomnia from perpetuating itself through conditioning and poor sleep hygiene
to become persistent and more difficult to treat (Fig. 4 presents an algorithm).
Differential Diagnosis of Insomnia 49

REFERENCES
1. Mahowald, M. W., Kader, G., and Schenck, C. H. (1997) Clinical categories of sleep disorders I.
Continuum 3(4), 35–65.
2. Katz, D. A. and McHorney, C. A. (1998) Clinical correlates of insomnia in patients with chronic
illness. Arch. Intern. Med. 158(10), 1099–1107.
3. Bastien, C. H. and Morin, C. M. (2000) Familial incidence of insomnia. J. Sleep Res. 9(1), 49–54.
4. Hauri, P. and Olmstead, E. (1980) Childhood-onset insomnia. Sleep 3(1), 59–65.
5. Hauri, P. J. (1998) Insomnia. Clin. Chest Med. 19(1), 157–168.
6. Attarian, H. (2002) Idiopathic insomnia. In: MedLink Neurology (Gilman, S., Goldstein, G. W.,
Waxman, S. G., eds.), Arbor Publishing, San Diego, CA, pp.
7. Bonnet, M. H. and Arand, D. L. (1997) Physiological activation in patients with Sleep State
Misperception. Psychosom. Med. 59(5), 533–540.
8. Reder, A. T., Mednick, A. S., Brown, P., et al. (1995) Clinical and genetic studies of fatal familial
insomnia. Neurology 45(6), 1068–1075.
9. Montagna, P. (1999) [Fatal familial insomnia: clinical, laboratory and pathological features]. Rev.
Neurol. 29(11), 1006–1009.
10. Bara-Jimenez, W., Aksu, M., Graham, B., Sato, S., and Hallett, M. (2000) Periodic limb movements
in sleep: state-dependent excitability of the spinal flexor reflex. Neurology 54(8), 1609–1616.
11. Ohayon, M. M. and Roth, T. (2002) Prevalence of restless legs syndrome and periodic limb move-
ment disorder in the general population. J. Psychosom. Res. 53(1), 547–554.
12. Allen, R. P. and Earley, C. J. (2001) Restless legs syndrome: a review of clinical and pathophysi-
ologic features. J. Clin. Neurophysiol. 18(2), 128–147.
13. Sanz-Fuentenebro, F. J., Huidobro, A., and Tejadas-Rivas, A. (1996) Restless legs syndrome and
paroxetine. Acta Psychiatr. Scand. 94(6), 482–484.
14. Glasauer, F. E. (2001) Restless Legs Syndrome. Spinal Cord 39(3), 125–133.
15. Lee, K. A., Zaffke, M. E. and Baratte-Beebe, K. (2001) Restless legs syndrome and sleep distur-
bance during pregnancy: the role of folate and iron. J. Womens Health Gend. Based Med. 10(4),
335–341.
16. Silber, M. H. (1997) Restless legs syndrome. Mayo Clin. Proc. 72(3), 261–264.
17. Lichstein, K. L., Riedel, B.W., Lester, K. W., and Aguillard, R. N. (1999) Occult sleep apnea in
a recruited sample of older adults with insomnia. J. Consult Clin. Psychol. 67(3), 405–410.
18. Vgontzas, A. N., Kales, A., Bixler, E. O., Manfredi, R. L., and Vela-Bueno, A. (1995) Usefulness
of polysomnographic studies in the differential diagnosis of insomnia. Int. J. Neurosci. 82(1–2),
47–60.
19. Zisapel, N. (2001) Circadian rhythm sleep disorders: pathophysiology and potential approaches
to management. CNS Drugs 15(4), 311–328.
20. Parkes, J. D., Chen, S. Y., Cleft, S. J., Dahletz, M. J., and Dunn, G. (1998) The clinical diagnosis
of the narcoleptic syndrome. J. Sleep Res. 7(1), 41–52.
21. Overeem, S., Mignot, E., vanDijk, J. G., and Lammers, G. J. (2001) Narcolepsy: clinical features,
new pathophysiologic insights, and future perspectives. J. Clin. Neurophysiol. 18(2), 78–105.
22. Boeve, B. F., Silber, M. H. and Ferman, T. J. (2002) Current management of sleep disturbances in
dementia. Curr. Neurol. Neurosci. Rep. 2(2), 169–177.
23. Sutton, D. A., Moldofsky, H. and Badley, E. M. (2001) Insomnia and health problems in Canadi-
ans. Sleep 24(6), 665–670.
24. Raiha, I., Impivaara, O., Seppala M., Knuts, L. R., and Sourander, L. (1993) Determinants of
symptoms suggestive of gastroesophageal reflux disease in the elderly. Scand. J. Gastroenterol.
28(11), 1011–1014.
25. Dodge, R., Cline, M. G., and Quan, S. F. (1995) The natural history of insomnia and its relation-
ship to respiratory symptoms. Arch. Intern. Med. 155(16), 1797–800.
26. Owens, J. F. and Matthews, K. A. (1998) Sleep disturbance in healthy middle-aged women.
Maturitas 30(1), 41–50.
50 Attarian

27. Polo-Kantola, P., Erkkola, R., Helenius, H., Irjala, K., and Polo, O. (1998) When does estrogen
replacement therapy improve sleep quality? Am. J. Obstet. Gynecol. 178(5), 1002–1009.
28. ASDA. (1997) International classification of sleep disorders: diagnostic and coding manual.
American Sleep Disorders Association, Rochester, MN.
29. APA. (1994) Diagnostic and statistical manual of mental disorders. 4th ed. American Psychiatric
Association, Washington DC.
30. Zajecka, J., Amsterdam, J. D., Quitkin, F. M., et al. (1999) Changes in adverse events reported by
patients during 6 months of fluoxetine therapy. J. Clin. Psychiatry 60(6), 389–394.
31. Leppik, I. E. (1995) Felbamate. Epilepsia 36(Suppl 2), S66–S72.
32. Sadler, M. (1999) Lamotrigine associated with insomnia. Epilepsia 40(3), 322–325.
33. Pappenheimer, J. R. (1984) Hypoxic insomnia: effects of carbon monoxide and acclimatization.
J. Appl. Physiol. 57(6), 1696–1703.
34. Rossini, S. R., Lefevre, B. H., and Medrado-Faria, M. A. (2000) Chronic insomnia in workers
poisoned by inorganic mercury: psychological and adaptive aspects. Arq. Neuropsiquiatr. 58(1),
32–38.
35. Sateia, M. J., Doghramji, K., Hauri, P. J., Morin, C. M. (2000) Evaluation of chronic insomnia.
An American Academy of Sleep Medicine review. Sleep 23(2), 243–308.
36. Bonnet, M. H. and Arand, D. L. (2000) Activity, arousal, and the MSLT in patients with insom-
nia. Sleep 23(2), 205–212.
37. Mahowald, M. W. (1996) Diagnostic testing. Sleep disorders. Neurol. Clin. 14(1), 183–200.
38. Sadeh, A., Lavie, P., Soher, A., Tiroash, E., and Epstein, R. (1991) Actigraphic home-monitoring
sleep-disturbed and control infants and young children: a new method for pediatric assessment of
sleep-wake patterns. Pediatrics 87(4), 494–499.
39. Chesson, A. L., Jr., hartse, K., Anderson, W. M., et al. (1999) Practice parameters for the treat-
ment of restless legs syndrome and periodic limb movement disorder. An American Academy of
Sleep Medicine Report. Standards of Practice Committee of the American Academy of Sleep
Medicine. Sleep 22(7), 961–968.
40. Sun, E. R., Chen, C. A., Ho, G., Eearley, C. J., and Allen, R. P. (1998) Iron and the restless legs
syndrome. Sleep 21(4) 371–377.
41. Attarian, H. (2001) Practical Approaches to Insomnia. Primary Care Reports 20(7), 171–178.
Insomnia in Children and Adolescents 51

II The Primary Insomnias

52 Garcia
Insomnia in Children and Adolescents 53

5
Insomnia in Children and Adolescents

John Garcia

Insomnia affects youth from the cradle to college. Diagnosis and management
of insomnia relies on an understanding of normal childhood sleep development.
Using a developmental approach, this chapter describes insomnia in infants, tod-
dlers, school-aged children, adolescents, and children with developmental disabili-
ties. The treatment of insomnia in youth is driven by the diagnosis. Treatment,
either behavioral or pharmacological, is described for each developmental group.

INSOMNIA IN THE INFANT AND TODDLER

The incidence of insomnia in the infant and toddler is 23–33% (1-7). Under-
standing the importance of the internal biological clock or circadian rhythm is fun-
damental to the understanding of insomnia in the infant. Circadian rhythms refer to
the intrinsic biological clock, which influences hundreds of physiological variables
in humans. At birth, humans have a complete loss of all circadian rhythms (8,9).
There is a random distribution of sleep and wake throughout the 24-hour period.
The newborn is essentially a blank slate relying on external cues or zeitgebbers,
German for time-giver, to set the biological clock. The primary zeitgebber is light.
With the appropriate influence of light, month 3 of life brings more consolidation
of sleep with two-thirds of children having at least 5 hours of nocturnal sleep (10).
The classic pattern of nap in the morning, nap in the afternoon, and nocturnal sleep
begins between 3 and 6 months of age (11). By 6 months of age, the infant brain has
the capacity to maintain 6 hours of consolidated sleep (12,13). By approximately
18 months old, the toddler gives up the morning nap and transitions to a sleep pat-
tern that usually includes one mid-day nap with the rest of sleep consolidated in the
nocturnal hours.
Infants and toddlers may become fixed at an earlier developmental stage. For
example, a 12-month-old may continue to wake several times a night. When a par-
ent intervenes to help the child back to sleep, the opportunity for learning the nec-
essary skill of putting oneself back to sleep is lost. The well-meaning parent may,
among many behaviors, breastfeed, bottlefeed, or rock the child back to sleep. The
child then associates the parent’s behaviors with a return to sleep. This conditioned
From: Current Clinical Neurology: Clinical Handbook of Insomnia
Edited by: H. P. Attarian © Humana Press Inc., Totowa, NJ

53
54 Garcia

association is known as sleep-onset association disorder. The common marker in

these behaviors is that they are not things that the infant can do for him or herself.
Treatment involves substituting an unacceptable association for an acceptable
one and/or adapting the parent’s response. For example, if a child demands a paci-
fier in order to sleep, parents may at first provide both the pacifier and a transitional
object, such as a light blanket, that the child can get for him or herself. Then, the
pacifier is provided as the second response for a while until it is finally forgotten.
Gradual extinction has also been advocated by some researchers (14). The empha-
sis here is on teaching the child self-calming skills and not “letting them cry it out.”
In this case, the child is put to bed drowsy but awake. Parents decide together how
long to wait before intervening once the child begins to cry. Any amount of time is
acceptable. If parents feel they can wait no longer than 20 seconds, they can begin
there. When a parent enters the room, the goal is to help the child return to sleep as
independently as possible. A transitional object may be offered. The child’s back
may be stroked for a brief time. Picking the child up, rocking, nursing or
bottlefeeding until the child falls asleep must be avoided. Parents then increase the
time they wait to intervene and decrease the time spent in the child’s room as the
child begins to learn self-calming skills. Consistency is important. The same plan is
pursued during middle-of-the-night wakings. It is necessary for all caretakers to
participate. Deviation by one caretaker can confuse the child and sabotage the learn-
ing opportunity. Generally, over several days to weeks, depending on the duration
of the problem and the child’s age, the child learns to go to and return to sleep
independently.
Early treatment of children waking at night prevents symptoms from becoming
a chronic problem. Conversely, studies have revealed that nocturnal waking that
remains unaddressed after 17 months of age has an increased incidence of becom-
ing a chronic disorder. Furthermore, children who continue to have persistent noc-
turnal wakings at 29 months have been found to have mothers who report feelings
of being ineffective parents (15).

Case 1
Amanda is a 2-year-old female with a history from both parents of “she wakes
up several times a night screaming.” Amanda was born 2 months premature
and was sent home on an apnea monitor. Her parents were very vigilant during
her first few months of life. They would often check to make sure she was
breathing. Her apnea monitor was discontinued when she was 5 months old.
Amanda’s parents report that afterward, Amanda began having several nightly
nocturnal arousals. The arousals would begin 90 minutes after Amanda’s sleep
onset and continue every 2 to 3 hours until she awoke for the day at 7 AM. Her
parents often would bottlefeed and rock Amanda back to sleep. In fact, Amanda
demanded the bottle and rocking in order to return to sleep after nocturnal arous-
als. There was no evidence of sleep-disordered breathing, reflux, or stereotypic
movements.
Insomnia in Children and Adolescents 55

The intervention in cases like Amanda’s involves identifying the predispos-

ing factors, explaining normal infant sleep physiology, and helping parents to
do what they can. Amanda might be diagnosed with vulnerable child syn-
drome (1). Amanda’s history of prematurity caused her parents to perceive
her as being vulnerable. With the best intentions, Amanda’s parents became
overly responsive to her normal arousals.
It is helpful to explain to parents that all children have brief arousals several
times a night. Although these arousals are spontaneous, return to sleep can be
hindered if parents intervene. Furthermore, Amanda’s parents were gently
reminded that at 2 years of age, Amanda was no longer at risk for Sudden
Infant Death Syndrome.
The solution in cases like Amanda’s is to gradually and gently decrease the
amount of parental intervention. Additionally, in Amanda’s case, the bedtime
routine was changed. She was offered a cup of milk 1 hour before sleep onset.
She was put to bed drowsy but still awake. When she cried out in the middle
of the night, a parent would come to her bedside but would avoid picking her
up, rocking her, turning on the light, talking to her, or providing things she
could not get for herself such as the bottle. After several weeks of disciplined
restraint by her parents, Amanda’s behaviors during the night resolved.

Limit-setting sleep disorder is seen in children whose parents provide little or

inconsistent bedtime routines. It is commonly seen in 2- to 6-year-olds. Bedtime
struggles intensify with the child evading bedtime by stalling, whining, requesting
snacks, and so on. This disorder ultimately leads to prolonged sleep-onset latency.
Resolution occurs when parents communicate first with each other about a consis-
tent bedtime practice and then implement this reliably with the child.
Differential diagnosis of the sleepless infant involves circadian issues, organic
disorders, and parental stresses. Many children presenting with sleep-onset diffi-
culties have a circadian rhythm that does not fit parental expectations. For example,
a toddler with a biologically driven sleep-onset time of 9:30 PM is not going to adapt
to a 7:30 PM bedtime no matter what behavioral modification tool is brought to bear.
Using a sleep log (see Fig. 1) helps one to determine the child’s intrinsic circadian
rhythm.
There are several organic conditions seen in infants and toddlers that may inter-
fere with initiating or maintaining sleep. Among the most common are reflux, milk-
protein intolerance, and asthma. Reflux should be considered in infants who awaken
fully and have difficulty returning to sleep (16). Milk-protein intolerance can mani-
fest as insomnia in infants. These children have elevated Immunoglobulin E levels
and positive radioallergosorbent testing (16). One study of infants averaging 4
months old with milk-protein intolerance identified frequent arousals (8–22 per
night) and short sleep cycles that resolved when milk protein was eliminated from
the diet (17).
 56
56

Garcia
Fig. 1. A sleep log used in children.
Insomnia in Children and Adolescents 57

Some children with asthma suffer from insomnia. Children with asthma have
more frequent arousals and earlier final wake times (18). Sleep-onset insomnia is
rarely the problem. Most asthma attacks in children occur in the last two-thirds of
the night (19). This coincides with the poorest lung function occurring during the
24-hour cycle. Peak flow is 50% of waking maximum and oxygen saturations may
fall 10% (20,21). The nocturnal arousals associated with asthma have been found
to have consequences for school performance. Increases in daytime sleepiness as
measured using the epworth sleepiness scale, variable attention in school, and in-
creased daydreaming as measured by neuropsychological tests. These tests mea-
sure both errors of commission that correlate with hyperactivity and omission that
correlate with distractibility (22).
Finally, although bruxism is not a cause of sleeplessness, it may be a symptom.
Children who grind their teeth as a self-calming mechanism do so less when time in
bed is decreased (23).

INSOMNIA IN THE SCHOOL-AGED CHILD

School age includes the ages between 5 years and adolescence. The incidence of
sleep disorders decreases in school-age children (24). Fears and anxieties both at
sleep onset and in the middle of the sleep period are the most common complaint in
this age group. Often, these are short-term anxieties manifesting as insomnia. This
is often termed adjustment sleep disorder. In other cases, anxieties may be a mani-
festation of more lasting emotional, psychological, or psychiatric disorders such as
depression and posttraumatic stress disorder (25). One must be aware that insomnia
also may be a symptom of child sexual abuse (26). Insomnia is commonly reported
in children with attention deficit hyperactivity disorder (ADHD). Parents commonly
report that these children have difficulty falling asleep, are restless sleepers, and
awaken early (27,28). Additionally, treatment for ADHD with stimulant medica-
tions may worsen sleep (29).

SLEEP DISORDERS IN ADOLESCENCE

Adolescence sees the emergence of circadian rhythm disorders. Even teens with-
out a circadian rhythm disorder have a tendency toward later sleep onset, increased
total sleep requirement, and an increase in daytime sleepiness when compared to
preadolescents (30,31). Adolescents are predisposed to a delayed sleep onset. This
is caused by a change in their biological clock. In reference to biological clocks, the
term period refers to the length of the circadian cycle and is approximately, but not
exactly, 24 hours. In the general population, the circadian period is approximately
24.5 hours, explaining why it is easier to stay up later than go to bed earlier for most
people. In adolescence, the period becomes prolonged. In some teens, it may exceed
25 hours (30,31). The biological phenomenon of delayed sleep phase driven by the
adolescent circadian clock has been separated from the social pressures on teens to
stay up later. Work by Carskadon et al. has emphasized that the tendency is biologi-
cal and not merely a preference or effect of social pressures (31). This emphasizes
58 Garcia

the reality that the tendency toward delayed sleep-phase syndrome seen in teens is
biologically driven by the circadian system.
The treatment of circadian rhythm disorders in children and adolescents can be
discussed in three groups: chronotherapy, phototherapy, and pharmacotherapy. A
review of the sleep log helps to set the context for discussion of chronotherapy or
sleep–wake scheduling. A common method of chronotherapy is known as sleep-
phase advancement (32–34). Taking into account the youth’s social expectations
and requirements, a reasonable wake time is agreed upon. The agreed upon earlier
wake time drives the sleep-onset time earlier. There is often a 3- to 5-day delay as
the sleep phase advances. The teen may be advised that during this time, he or she
may feel tired. It is emphasized that over the next 2 to 3 months, strict wake and
bedtimes must be adhered to 7 days a week. Once a more appropriate sleep phase
has been established, relaxing the schedule once or twice a week may be allowed if
it does not throw the teen back into a delayed sleep phase. Alternatively, some
physicians prefer to delay the sleep onset and wake time by several hours each day
until the sleep-onset and wake times have been delayed to a phase consistent with
the teen’s social expectations. This form of chronotherapy is known as sleep-phase
delay. For example, the teen falling asleep at 3 AM and waking at noon is asked to
delay sleep onset until 6 AM. The wake time is proportionately delayed until 3 PM.
On the second day, sleep onset is at 9 AM and wake time is at 6 PM. The sleep-onset
time is delayed 3 hours each day until sleep onset is at 9 PM and wake time is at 6
AM. Thereafter, the sleep phase is fixed again for several months. One may choose
to emphasize the nature of the relationship at this point. The physician is often seen
as a coach. This places responsibility and control in the hands of adolescent.
Phototherapy is the second fundamental treatment in children with circadian
rhythm disorders (35–37). The goal is to decrease the evening light and increase
exposure to waking bright light. It is important that the teen’s exposure to bright
light, including television and computer monitors is eliminated after 9 PM. In the
morning, early morning bright light exposure with a light box or ambient light is
effective in resetting the biological clock. Generally, 10,000 lux is necessary. Pre-
cautions should be taken to avoid exposure to ultraviolet spectrum (38) light. Use
of light therapy should be avoided in patients with a history of bipolar disease as it
can trigger mania. It should be emphasized that the patient need not look directly at
thea light box; the direction of gaze may deviate 15°. It is recognized that children
often have difficulty using a light box and integrating the light box into their morn-
ing routine is often a challenge. Some children choose to put the light box on the
breakfast table or where they do their homework in the morning.
Medication therapy is mentioned last because it is rarely effective without
simultaneously using sleep–wake scheduling and/or phototherapy. Two groups of
medication have been described. The first is the sleep-inducing medications includ-
ing the benzodiazepines and zolpidem. These medications are most effective when
there is a pre-existing sleep debt. The second is melatonin. Melatonin has been shown
to advance the sleep phase in some patients with delayed sleep-phase syndrome (39–
Insomnia in Children and Adolescents 59

42). Melatonin must be taken approximately 3 to 4 hours before the desired sleep-
onset time (43). Many providers, including this author, are hesitant to use melatonin
because it is not approved by the Food and Drug Administration. Additionally, it is a
hormone. Possible effects during puberty have not been thoroughly studied.

Case 2
Josh is a 17-year-old male with a 5-year history of problems falling asleep.
He is very clear that although he lies down in bed with the lights out at 11 PM
most nights, he has difficulty falling asleep before 2 AM (see Fig. 2). On school
days, he needs to be awakened at 6 AM. Waking him requires many calls and
physical shaking. His first class begins at 7:15 AM. He admits to falling asleep
daily in his first four classes. He feels that he becomes more alert after lunch.
Once a week, he will take a 3- to 4-hour nap after school. On the weekends,
he feels a sense of exhilaration and stays up until between 3 and 5 AM and
awakens in the early afternoon. During summer vacation and holiday breaks,
he follows a similar routine. He is quite motivated to improve his sleep–wake
schedule. Family history reveals that Josh’s mother also has a strong biologi-
cal drive for late morning rising. In fact, she has chosen a job as a night-shift
nurse accommodating her biological drive.
Intervention with Josh could be assigned to three categories: phototherapy,
sleep–wake scheduling, and medication management. With regard to photo-
therapy, Josh agreed to use a light box on weekdays for 20 minutes after
waking in the morning. It was emphasized that he did not need to stare directly
at the light box. He could set it up so he was looking within 15° of his direct
line of vision while he was finishing his homework in the morning, eating
breakfast, or watching TV. On the weekends, he agreed to walk the family
dogs in the morning upon waking, thus exposing his eyes to bright ambient
light. Additionally, evening bright light exposure needed to be minimized.
Exposure to television and computer screens after 9 PM was discouraged.
Regarding sleep–wake scheduling, Josh agreed to awaken at 8 AM on week-
ends. Additionally, he agreed to minimize his afternoon naps. He was more
amenable to this portion of the plan after it was explained to him that the drift
toward later sleep onset and wake times on the weekends was sabotaging the
progress he made during the week.
Many teens with delayed sleep-phase syndrome find that the early morning
school start time is simply not compatible with their biological clock. In
Josh’s case, the biological underpinnings of his disorder were explained to
school officials. The school adapted his schedule, allowing for a start time of
9 AM. Finally it was explained that medications are the least effective of the
three management tools. Some people with the delayed sleep-phase syndrome
who continue to have difficulty with sleep-onset insomnia despite all efforts,
require changes in their external environment. This may mean considering
evening school opportunities.
 60
60

Fig. 2. Actigraph recording in a patient with delayed sleep syndrome (see Case 2).

Garcia
Insomnia in Children and Adolescents 61

INSOMNIA IN CHILDREN
WITH DEVELOPMENTAL DISABILITIES
Insomnia is seen commonly in children with developmental disabilities (44).
One study of 214 children ages 1–18 with severe mental retardation found that 86%
exhibited difficulties with sleep (45). Sleep disorders in children with disabilities
stress a sometimes already burdened family system. One study found that in chil-
dren with disabilities without a sleep disorder, 21% of parents had daytime sleepi-
ness. Of parents with children with disabilities and a sleep disorder, 64% of the
parents complained of daytime sleepiness (46).
Sleep disorders impact daytime behaviors in children with developmental dis-
abilities. Irritability and mood lability are also increased (47,48). The aberrant
behavior checklist, used to quantify difficult behaviors in children with disabilities,
was found to be increased when difficulties with sleep were identified (49). There
is an increase in self-injurious behavior in children found to have difficulties with
sleep. Interestingly, worsening mental handicap does not predict increased inci-
dence of sleep disorders.
Some syndromes are associated with an increased incidence of sleep difficulties
including autism, Prader-Willi, Angelman, Smith-Magenis, Sanfilippo, Rett syn-
drome, and cerebral palsy. Of children with autism, 63–72% are identified as hav-
ing sleep difficulties (50–52). These problems are often severe. Sleep problems
include prolonged sleep latencies (the length of time between going to bed and
going to sleep), prolonged periods of nocturnal wakefulness, shortened total sleep
time, and early morning waking. Children with autism are more likely to suffer
from sleep disorders than other children with developmental delays, with the most
common problem being early waking (53). Of children with Sanfilippo syndrome,
78% have problems with sleep; 46% of which are severe enough to warrant medi-
cation management (54). Of children with Smith-Magenis syndrome, 59% suffer
from sleep problems (55).
Treatment begins with the same basic principles used in children without devel-
opmental disabilities. For example, one study found that the gradual extinction tech-
nique described for sleep-onset association disorder resulted in quick and lasting
reductions in sleep disorder symptoms in children with developmental disabilities
(56). Sleep–wake scheduling, or chronotherapy, has been found to be effective in
children with developmental disabilities. In this case, the wake time is fixed. The
nap time is minimized. Using a sleep log (see Fig. 1 for an example of a sleep log)
the individual’s average sleep requirement is determined.
The bedtime is then approximated and increased or decreased until a 90% sleep
efficiency is achieved (57). A combination of sleep–wake scheduling and photo-
therapy was effective in one study (58). Finally, medication management is often
required in this population. The benzodiazepines may not be effective in this popu-
lation. (59). Some authors have recommended choral hydrate (60). Melatonin has
been used effectively in a population of blind children with developmental disabili-
ties (59,61,62). Melatonin has been used in sleep disorders associated with
62 Garcia

neurodevelopmental disabilities including Rett syndrome (63), tuberous sclerosis,

(64), autism (65), and Asperger syndrome (51). Again, the reservations previously
discussed in the treatment of circadian rhythm disorders apply here. Many sleep-
inducing medications have been used, but in general, the literature is incomplete in
measuring which medications are most effective. Further research is necessary.

Case 3
Erin is a 5-year-old girl with autism. Her sleep-onset time and wake times are
variable. Her sleep-onset time ranges from 9 PM to 1 AM. Her wake time ranges
from 4 AM to 9:30 AM. Additionally, she has difficulty maintaining her sleep.
Several times a week she will be fully alert for 1 to 2 hours between 1 AM and
3 AM. Her daytime behavior deteriorates when she has nights of shorter total
sleep time. She has no history of snoring. She takes a 1- to 2-hour afternoon
nap when cared for by her grandmother 3 days a week.
Intervention for Erin involved sleep–wake scheduling and medication man-
agement. Her afternoon nap was gradually eliminated over a 3-week period.
A regular wake time of 7 AM was initiated. Several weeks after the regular
wake time was established, her middle-of-the-night arousals decreased to
once every 2 or 3 weeks. It became clear that although most nights she was
asleep by 10 PM, once or twice a week she continued to be awake after mid-
night. Her parents had already tried over-the-counter melatonin without much
success. Doxepin (10 mg/1 mL) 2 mL (20 mg) was given when she was not
asleep by 10:30 PM. This helped to further regularize her sleep phase.

CONCLUSIONS
A developmental approach to the diagnosis of youth with insomnia makes this
difficult issue more approachable. Treatment is driven by the diagnosis. Careful
patient- and family-specific treatments provide enormous benefits. Childhood treat-
ment leads to the prevention of lifelong insomnia. Treatment of the child with a
neurodevelopmental diagnosis provides relief to the family as well as the child.

REFERENCES
1. Ragins, N. and Schachter, S. (1957) A study of sleep behavior in two-year-old children. J. Am.
Acad. Child Psychiatry 10, 464–480.
2. Bax, M. (1980) Sleep disturbance in the young child. Br. Med. J. 280, 1177–1179.
3. Bernal, J. (1973) Night waking in infancy during the first 14 months. Dev. Med. Child Neurol. 15,
760–769.
4. Blurton Jones, N., Ferreira, M. C., Farquar, M., and Macdonald, B. L. (1978) The association
between perinatal factors and later night waking. Dev. Med. Child Neurol. 20, 427–434.
5. Richman, N. (1984) Sleep problems in young children. Arch. Dis. Child 56, 491.
6. Van Tassel, E. (1985) The relative influence of child and environmental characteristics on sleep
disturbances in the first and second years of life. J. Dev. Behav. Pediatr. 6, 81.
7. Roberts, K. (1951) Eating, sleeping, and elimination practices of a group of two and one half year
old children. Am. J. Dis. Child 82, 121.
Insomnia in Children and Adolescents 63

8. Meier-Koll, A., Hall, U., hellwig, U., Kott, G., and Meler-Koll, V. (1978) A biological oscillator
system and the development of sleep–waking behavior during early infancy. Chronobiologia 5, 425.
9. Kleitman, J. and Engleman, H. M. (1953) Sleep characteristics of infants. J. Appl. Physiol. 6, 269.
10. Weinert, D., Sitka, U., Minors, D. S., and Waterhouse, J. M. (1994) The development of circadian
rhythmicity in neonates. Early Hum. Dev. 36, 117–126.
11. Armstrong, K., Quinn, R., and Dadds, M. (1994) The sleep patterns of normal children. Med. J.
Aust. 161(3), 202–206.
12. Tomioka, K. and Tomioka, F. (1991) Development of circadian sleep wakefulness rythmicity o f
three infants. J. Interdiscipl Cycle Res. 22, 72–80.
13. Coons, S. and Guilleminault, C. (1984) Development of consolidated sleep and wakeful periods
in relation to the day/night cycle in infancy. Dev. Med. Child Neurol. 26, 169–176.
14. Ferber, R. (1985) Solve your child’s sleep problem. Simon and Schuster, New York.
15. Touchette, E., Petit, D., Paquet, J., Gosselin, N., and Montplaisic, J. (2002) Do Factors Associ-
ated with Consolidated Sleep Change Wen the Child Grows Up? in Associated Professional Sleep
Societies. Seattle.
16. Ferber, R. (1995) Sleeplessness in children. In: Principles and Practice of Sleep Medicine in the
Child (Ferber, R. and Kryger, M., eds.), W.B. Saunders, Philadelphia, PA, pp. 79–89.
17. Kahn, A., Francois, G., Sottiaux, M., et al. (1988) Sleep characteristics in milk-intolerant infants.
Sleep 11(3), 291–297.
18. Kales, A., Kales, J., and Sly, R. (1970) Sleep patterns of asthmatic children. J. Allergy 46, 300–
308.
19. Montplaisir, J., Walsh, J., and Malo, J. (1982) Nocturnal asthma: features of attacks, sleep and
breathing patterns. Am. Rev. Resp. Dis. 125, 18–22.
20. Hetzel, M. and Clark, T. (1980) Comparison of normal and asthmatic circadian rhythms in peak
expiratory flow rate. Thorax 35, 732–738.
21. Clark, T. and Tetzel, M. (1977) Diurnal variation of asthma. Br. J. Dis. Chest 71, 87–92.
22. Glaze, D., Glaze, D., Rais, M., et al. (2002) Sleep disturbance and associated cognitive problems
in children with nocturnal asthma. Sleep 25, 54.
23. Ferber, R. (2002) Recognizing & treating pediatric parasomnias. in APSS meeting. Seattle.
24. Klackenberg, G. (1982) Sleep behavior studied longitudinally. Data from 4–16 years on duration,
night-awakening and bedsharing. Acta Paediatr. Scand. 71, 501–506.
25. Sadeh, A., McGuire, J. P., Sachs, H., et al.(1995) Sleep and psychological characteristics of chil-
dren on a psychiatric inpatient unit. J. Am. Acad. Child Adolesc. Psychiatry 34, 813–819.
26. Glod, C., et al. (1997) Increased nocturnal activity and impaired sleep maintenance in abused
children.
27. Salzarulo, P. and Chevalier, A. (1983) Sleep problems in children and their relationship with
early disturbances of the waking–sleeping rhythms. Sleep 6, 47–51.
28. Kaplan, B. M., McNicol, J., Conte, R. A., and Moghadan, N. K. (1987) Sleep disturbances in
preschool-age to hyperactive and nonhyperactive children. Pediatrics 80, 839–844.
29. Stein, D. A. P.-H., Blank, R., Dagan, S., Barak, Y., Toram, Gumpuel, T. (2002) Sleep distur-
bances in adolescents with symptoms of attention deficit/hyperactivity disorder. J. Learning Dis.
35, 268–275.
30. Carskadon, M., Harvey, K., Duke, P., Andus, T. F., Litt, I. F., and Dement, W. C. (1980) Pubertal
changes in daytime sleepiness. Sleep 2, 453–460.
31. Carskadon, M., Vieera, C., and Acebo, C. (1993) Association between puberty and delayed phase
preference. Sleep 16, 258–262.
32. Ferber, R. and Boyle, M. (1983) Phase shift dyssomnia in early childhood. Sleep Res. 12, 239.
33. Ferber, R. (1990) Childhood insomnia. In: Handbook of Sleep Disorders (Thorpy, M., ed.), Marcel
Dekker, New York.
34. Ferber, R. (1987) Circadian and schedule disturbances. In: Sleep and Its Disorders in Children
(Guilleminalult, C., ed.), Raven Press, New York, pp. 165–175.
64 Garcia

35. Czeisler, C., kronauer, R. E., Allan, J. S., et al. (1989) Bright light induction of strong resetting of
the human pacemaker. Science 244, 1328–1333.
36. Eastman, C. (1991) Squashing versus nudging circadian rhythms with artificial bright light: solu-
tions for shift work? Perspect. Biol. Med. 34, 181–195.
37. Rosenthal, N., Joseph-Vanderpool, J. R., Levendosky, A. A., et al. (1990) Phase-shifting effects
of bright morning light as treatment for delayed sleep phase syndrome. Sleep 13, 354–361.
38. Terman, M., Williams, J., and Terman, J. (1991) Light therapy for winter depression: a clinician’s
guide. In: Innovations in Clinical Practice: A Source Book (Keller, P., ed.), Professional
Resource Exchange, Sarasota, FL.
39. Kayumov, L., Brown, G., Jindal, R., Buttoo, K., and Shapiro, C. M. (2001) A randomized, double-
blind, placebo-controlled crossover study of the effect of exogenous melatonin on delayed sleep
phase syndrome. Psychosom. Med. 63(1), 40–48.
40. Yang, C.-M., Spielman, A. J., D'Ambrosio, P., Serizanoi, S., Nunes, J., and Birnbaum, J. (2001)
A single dose of melatonin prevents the phase delay associated with a delayed weekend sleep
pattern. Sleep 24(3), 272–281.
41. Nagtegaal, J., kerkhot, G. A., Smits, M. G., Swart, A. C., and Van Der Meer, Y. G. (1998) Delayed
sleep phase syndrome: a placebo-controlled cross-over study on the effects of melatonin admin-
istered five hours before the individual dim light melatonin onset. J. Sleep Res. 7, 135–143.
42. Dagan, Y., Yovel, I., Hallis, D., Eisenstein, M., and Raichik, I. (1998) Evaluating the role of
melatonin in the long-term treatment of delayed sleep phase syndrome. Chronobiol. Int. 15(2),
181–190.
43. Tzischinsky, O., Pal, I., Epstein, R., Dagan, Y., and Lavie, P. (1992) The importance of timing in
melatonin administration in a blind man. J. Pineal. Res. 12, 105–108.
44. Richman, N. Douglas, J., Hunt, H., Lansdown, R., and Levere, R. (1985) Behavioral methods in
the treatment of sleep disorders: A pilot study. J. Child Psychol. Psychiatry 26, 581–590.
45. Bartlett, L., Rooney, V., and Spedding, S. (1985) Nocturnal difficulties in a population of men-
tally handicapped children. Brit J. Mental Subnormality 31 54–59.
46. Wiggs, L. and Stores, G. (1996) Severe sleep disturbances and daytime challenging behavior in
children with severe learning disabilities. J. Intellect. Disabil. Res. 40, 518–528.
47. Richman, N. (1981) A community survey of characteristics of 12-year-olds with sleep disruption.
J. Am. Acad. Child Psych. 20, 281–291.
48. Quine, L. (1991) Sleep problems in children with a mental handicap. J. Ment. Def. Res. 35, 269–290.
49. Aman, M., Singh, N. N., Stewart, A. W., and Field, C. J. (1985) The aberrant behavior checklist: the
behavior rating scale for the assessment of treatment effect. Am. J. Mental Defic. 89, 492–502.
50. Inanuma, K. (1984) Sleep wake patterns in autistic children. Japanese J. Child and Adolescent
Psych. 25, 205–217.
51. Patzold, L. M., Richdale, A. L., and Tonge, B. (1998) Investigation into sleep characteristics of
children with autism and Asperger disorders. J. Paediatr. Child Health 34, 528–533.
52. Hering, E., Epstein, R., Elroy, S., Iancu, D. R., and Zelnik, N. (1999) Sleep patterns in autistic
children. J. Autism Dev. Disord. 29 143–147.
53. Richdale, A. and Prior, M. R. (1995) The sleep/wake rhythm in children with autism. Eur. Child
Adoles. Psychiatry 4, 175–186.
54. Colville, G., Waters, J. P., Yule, W., and Box, M. (1996) Sleep problems in children with
Sanfilippo syndrome. Dev. Med. Child Neurol. 38, 538–544.
55. Smith, A., Dykens, E., and Greenberg, F. (1998) Sleep disturbance in Smith-Magenis syndrome.
Am. J. Med. Genet. 81(2), 186–191.
56. Didden, R., Curfs, L. M., Sikkema, S. P., and de Morr, J. (1998) Functional assessment and
treatment of sleeping problems with developmentally disabled children: six case studies. J. Behav.
Ther. Exp. Psychiatry 29, 87–95.
57. Espie, C. and Wilson, A. (1993) Improving sleep wake schedules amongst peoples with mental
handicap: some preliminary case material. Behav. Psychother. 21, 51–55.
Insomnia in Children and Adolescents 65

58. Guilleminault, C., McCann, C. C., Quera-Slave, M., and Cetel, M. (1993) Light therapy as treat-
ment of dyschronosis in brain impaired children. Eur. J. Pediatr. 152, 754–759.
59. Mohemmed, M. and Jan, S. (2000) Melatonin for the treatment of handicapped children with
severe sleep disorders. Pediatric Neurol. 23, 229–232.
60. Ferber, R. M. and Kryger, M. M. (1995) Principles and Practice of Sleep Medicine in the Child.
W.B. Saunders, Philadelphia, PA.
61. Palm, L., Blennow, G., and Wetterberg, L. (1991) Correction of non-24-hour sleep/wake cycle by
melatonin in a blind retarded boy. Am. Neuro. Assoc. 29(3), 336–339.
62. Palm, L., Blennow, G. and Wetterberg, L. (1997) Long-term melatonin treatment in blind children
and young adults with circadian sleep-wake disturbances. Dev. Med. Child Neurol. 39, 319–325.
63. Miyamoto, A., Oki, J., Takahashi, S., and Okuno, A. (1999) Serum melatonin kinetics and long
term melatonin treatment for sleep disorders in Rett Syndrome. Brain Dev. 21, 59–62.
64. O’Callaghan, F. J., Clarke, A. A., hancock, E., hunt, A., and Osborne, J. P. (1999) Use of melato-
nin to treat sleep disorders in tuberous sclerosis. Dev. Med. Child Neurol. 41, 123–126.
65. Etzioni, A., Luboshitzky, R., Tiosano, D., Ben-Harush, M., Goldsher, D., Lavie, P. (1996) Melatonin
replacement corrects sleep disturbances in a child with pineal tumor. Neurology 46, 261–263.
66 Garcia
Psychophysiological Insomnia 67

6
Psychophysiological Insomnia

Hrayr P. Attarian

O sleep! O gentle sleep! Nature’s soft nurse, how have I frightened thee, That
thou no more wilt weigh my eyelids down and steep my senses in forgetfulness?
—William Shakespeare (King Henry IV part 2 Act III Scene I)

DEFINITION
The International Classification of Sleep Disorders defines psychophysiologi-
cal insomnia as “a disorder of somatized tension and learned sleep-preventing asso-
ciations that results in a complaint of insomnia and associated decreased functioning
during wakefulness” (1). Psychophysiological insomnia is included under the cat-
egory of primary insomnias in the fourth edition of the Diagnostic and Statistical
Manual of Mental Disorders (DSM-IV) (2). It is also commonly referred to as
learned or conditioned insomnia and less commonly as functionally autonomous or
internal arousal insomnia.

HISTORICAL PERSPECTIVES
The suspicion that maladaptive learning coupled with poor sleep hygiene can
cause insomnia was first mentioned in landmark publications by Betollo in 1931
(3) and Strauss in 1948 (4). The diagnostic category of persistent psychophysi-
ological insomnia was first created in the 1979 Diagnostic Classification of Sleep
and Arousal Disorders published by the Association of Sleep Disorders Centers. It
was defined as “insomnia that develops as a result of the mutually reinforcing fac-
tors of chronic, somatized tension anxiety and negative conditioning to sleep” (5).
In 1983, Peter Hauri published a paper showing that a cluster analysis could iden-
tify psychophysiological insomnia on the basis of polysomnographic variables, psy-
chological questionnaires such as the Minnesota Multiphasic Personality Inventory
(MMPI), and a sleep history (6). In another seminal study, Hauri and Fisher com-
pared psychophysiological insomniacs, normal sleepers, and insomniacs with dys-
thymic disorder. The two insomnia groups (psychophysiological and dysthymic)

From: Current Clinical Neurology: Clinical Handbook of Insomnia

Edited by: H. P. Attarian © Humana Press Inc., Totowa, NJ

67
68 Attarian

showed similar degrees of sleep impairment. Psychologically, however, patients

with persistent psychophysiological insomnia were similar to normal sleepers and
different from dysthymic patients, except that psychophysiological patients were
more likely to be repressors or sensation avoiders than normal subjects. Addition-
ally, psychophysiological patients suffered more than either normal subjects or
dysthymics from tension-related symptoms such as muscle tension headaches (7).

EPIDEMIOLOGY
The exact incidence and prevalence of psychophysiological insomnia is un-
known. In a study of 216 patients with insomnia from five centers, psychophysi-
ological insomnia was the primary diagnosis in 12.5% of all cases and a secondary
diagnosis in another 27.2% (8). A different study found that of 113 subjects com-
plaining of insomnia, 11.3% had psychophysiological insomnia (9). According to a
third study of 8000 patients seeking help for insomnia at multiple sleep centers,
about 15% were diagnosed with psychophysiological insomnia (10). Psychophysi-
ological insomnia is often diagnosed as a secondary problem because learned asso-
ciations often prevent or disrupt sleep in many other forms of chronic insomnia.

ETIOLOGY
A few nights of disturbed sleep due to stress such as psychological distress,
physical pain, or any other acute internal or external event, is a universal human
experience. In other words, anyone can have a few bad nights of sleep. In the
majority of cases, the trouble is short-lived. People suffering from psychophysi-
ological insomnia, however, continue to have poor sleep despite the resolution of
the acute event. In the development of pyschophysiological insomnia there are three
factors playing a role:
1. Predisposition: being an excessive worrier (11), being physiologically hyperaroused
(12), and familial inheritance of the tendency to develop insomnia (13).
2. Precipitant: a transient stressor.
3. Perpetuating factors: the individual’s expectation of a poor night’s sleep that becomes
a self-fulfilling prophecy and the counterproductive trials to sleep (11).
In some patients with psychophysiological insomnia, either a precipitant is not
found or the stressor is so minor that it has been forgotten. Rather, poor sleep may
have gradually developed as an occasionally occurring disturbed night leads to
increased concern, causing sleep to deteriorate in a snowball fashion, until it
becomes the patient’s chief concern (12).

PATHOGENESIS AND PATHOPHYSIOLOGY

The role of organic components in the pathophysiology of insomnia is well docu-
mented. There is growing evidence that shows the biological basis of psychophysi-
ological insomnia to be moderate physiological hyperarousal or an imbalance of
the sleep–wake system toward alertness. Physiological hyperarousal is documented
in many other types of primary insomnia as well (14,15).
Psychophysiological Insomnia 69

Insomniacs display faster heart rates (16), higher 24-hour metabolic rates (14),
higher body temperatures (17), and higher resting electromyogram activities (lead-
ing to an inability to relax) (18). They are also as or more alert than controls during
the day; their Multiple Sleep Latency Tests show increased sleep latency (SL) as
compared to controls (19). By electroencephalography (EEG) criteria, insomniacs
tend to have a higher percentage of faster frequencies both in waking and in sleep-
ing (18,20). Lamarche and Ogilvie compared patients with psychophysiological
insomnia to patients with psychiatric insomnia and to normal controls. EEG activ-
ity showed higher cortical arousal in the psychophysiological insomniacs vs the
other two groups, which did not differ from each other significantly. Psychophysi-
ological insomniacs had less α during the first part of the sleep-onset period and did
not show the dramatic drop in α across the sleep-onset period that characterizes
normal sleep (21). Vgontzas and colleagues discovered a positive correlation
between objective sleep disturbance and the activity of both limbs of the stress
system (the hypothalamic–pituitary–adrenal axis and the sympathetic system) and
increased serum levels of adrenocorticotropic hormone and cortisol in a group of
chronic insomniacs (22).

CLINICAL MANIFESTATIONS
Patients with psychophysiological insomnia usually give a history of being light
sleepers even before the development of persistent difficulty initiating or maintain-
ing sleep.
Patients suffering from psychophysiological insomnia focus attention on inability
to sleep. The insomnia becomes the only perceived source of distress. Other emo-
tional or mental concerns are either minimized or are absent. Stress factors involved
in the development of the insomnia are either forgotten or patients typically deny
awareness of these factors, unable to find any reason for the insomnia (12).
Psychophysiological insomnia is typically acquired during a period when other
factors, such as stress, can cause insomnia. After a few days of sleeping poorly, the
patient becomes concerned about his or her inability to sleep, trying harder to get to
sleep, which causes arousal and aggravates the insomnia. The stimuli surrounding
the bedtime event (such as the bed itself, the bedroom, etc.) may become condi-
tioned triggers to arousal (12). Thus, such patients may have severe problems sleep-
ing in their own bedrooms but often sleep remarkably well in other situations, such
as on the living room couch, in a motel, or in a laboratory.
The sleep disturbance in persistent psychophysiological insomnia ranges from
mild to severe. Characteristically, the polysomnogram (PSG) reveals increased SL,
increased percentage of stage 1 sleep, and increased number of brief arousals; oth-
erwise the sleep architecture is within normal limits (23). However, these features
are simply the hallmarks of poor sleep in general and they are not specifically diag-
nostic of psychophysiological insomnia.
Maladaptive behaviors also contribute to the development of the psychophysi-
ological insomnia. Common maladaptive behaviors include laying awake in bed
for hours on end trying to go to sleep, which of course increases frustration and
70 Attarian

agitation and hence the arousal and aggravates the insomnia; watching the clock
and counting the hours left before one has to get up; sleeping in in the mornings in
order to “catch up”; doing housework, homework, or office work while awake at
night; and, in rare cases, napping during the day. All these behaviors are engaged in
“in good faith” but tend to exacerbate the problem rather than alleviate it.
A deterioration of mood and motivation as well as problems with attention, vigi-
lance, and concentration are associated with psychophysiological insomnia (1).
Studies have shown that these symptoms are secondary to central nervous system
arousal and not to poor sleep per se (24).
Of note, patients with psychophysiological insomnia complain bitterly of fatigue
and difficulty with concentration and attention but almost never give a history of
falling asleep unintentionally during the day. Only rarely are they able to even nap
in the daytime.
Within the limits of a normal personality profile, patients with psychophysi-
ological insomnia tend to be more tense, generally less satisfied, and are typically
emotional repressors and deny problems (12, 25). There usually is a positive family
history of insomnia and/or light sleepers.
Acute physical and psychological stressors tend to exacerbate insomnia, as does
shift work (26). Pregnancy may aggravate psychophysiological insomnia as well,
especially in the first and third trimester (27).
According to the ICSD, the following criteria must be satisfied to diagnose psy-
chophysiological insomnia: (1) a complaint of insomnia and a complaint of
decreased functioning during wakefulness; (2) indications of learned, sleep-pre-
venting associations, such as trying too hard to sleep or showing conditioned arousal
to the bedroom; (3) evidence for increased somatized tension, such as agitation,
high muscle tension as manifest in tension headaches, or increased sympathetic
tone; (4) the PSG, if used, shows disturbed sleep; (5) no other medical or psychiat-
ric disorder can account for the severity of the sleep disturbance, although most
patients with psychophysiological insomnia are somewhat anxious and dysphoric;
and (6) other sleep disorders may co-exist with the insomnia (e.g., poor sleep
hygiene and obstructive sleep apnea [OSA]) (1).
Case 1
K is a 41-year-old woman who presented to the sleep center outpatient
clinic for initial evaluation of a year’s history of sleep-onset and sleep main-
tenance insomnia. K was always a light sleeper, but about 1 year ago, after
the death of her mother, she started having trouble falling and staying asleep.
Prescription sleep aids help her go to sleep within a reasonable time, but she
wakes up at 4 AM unable to return to sleep.
She has tried napping during the day, but cannot. She does not fall asleep
unintentionally, although she feels fatigued during the day. At night when
she is awake, she tosses and turns in bed and never leaves the bed or the
bedroom. Currently, she is between jobs, so in the morning when she wakes
Psychophysiological Insomnia 71

up around 4:30–5 AM she stays in bed, dozing on and off until about 11 AM.
Prior to this, she used to go to bed around 10–11 PM, fall asleep within an hour
or so, and then wake up at 4 AM and stay in bed tossing and turning until about
7 AM when she had to get up to go to work. She tried drinking alcohol just
before bedtime to help her fall asleep. She does not use caffeine during the
day. She denies snoring, observed apneas, cataplexy, sleep paralysis, hypna-
gogic hallucinations, and choking spells. She denies waking up gasping for
air. She denies symptoms of restless legs.

DIFFERENTIAL DIAGNOSIS
Psychophysiological insomnia lies on a continuum with a number of other diag-
nostic categories.
Idiopathic insomnia is diagnosed if the predisposition toward poor sleep by itself
is severe enough to cause insomnia. Psychophysiological insomnia is assumed to
start with a somewhat milder predisposition toward poor sleep that usually devel-
ops into insomnia only with the occurrence of some other, identifiable stressor act-
ing as the trigger (1).
A sleep state misperception (SSM) is when the patient sleeps adequately but
does not perceive it as sleep (28). In this disorder, complaints of insomnia occur
without any objective evidence of sleep disturbance. Patients may report that they
have not slept at all in weeks, months, or years. However, on objective sleep stud-
ies, they sleep several hours per night. When results of sleep evaluation are pre-
sented, patients with SSM may vehemently insist that the studies are in error
because they are convinced that they sleep very little, if at all.
Idiopathic, or childhood-onset, insomnia is a rare condition presenting as a
chronic, serious inability to initiate and maintain sleep, which can often be traced
back to the first few weeks of life.
Circadian rhythm abnormalities occur when the patient sleeps well but not at
socially acceptable times (28). Those with the advanced sleep-phase syndrome have
excessive sleepiness in the evening and undesired early morning awakening. Those
with the delayed sleep-phase syndrome have sleep-onset insomnia, excessive day-
time sleepiness (particularly in the morning), or both.
Inadequate sleep hygiene is the diagnosis when insomnia is maintained prima-
rily by neglecting sleep hygiene and engaging in behaviors that are not conducive for
sleep (e.g., drinking too much coffee, exercising too close to bedtime, napping, stay-
ing in bed too long, drinking alcohol too close to bedtime). To the extent that the
insomnia is independent of the precipitating causes and also independent of the qual-
ity of sleep hygiene, psychophysiological insomnia is the preferred diagnosis (28).
Generalized anxiety disorder is the preferred diagnosis when anxiety permeates
most aspects of a patient’s functioning (anxiety in social interactions, about job
performance, etc.). Psychophysiological insomnia is preferred when the anxiety is
focused almost exclusively on poor sleep and its consequences on daytime func-
tioning (28).
72 Attarian

Affective disorder is sometimes difficult to separate from psychophysiological

insomnia because a dysphoric mood that is ascribed to the effects of poor sleep
often accompanies psychophysiological insomnia. It is especially difficult to dis-
tinguish dysthymia from psychophysiological insomnia in cases of “masked”
depression (i.e., when the patient denies overt sadness or hopelessness). Often, the
discrimination can be made on other “vegetative signs,” such as loss of appetite or
libido or the typical diurnal fluctuation of depression (morning being worse). In the
final analysis, the diagnostician’s sense is important whether depression is still driv-
ing the insomnia, or whether the insomnia is driven by maladaptive sleep habits
learned during a previous depression. Also, dysthymic patients may typically show
depressive traits before the insomnia developed (1).
In general, a diagnosis of psychophysiological insomnia should not be made if
the patient fulfills criteria for any other Axis I or II diagnosis in the DSM-IV (2).
Medical causes of insomnia include propriospinal myoclonus (29); restless legs
syndrome, which is a common condition characterized by a desire to move the legs;
accompanying paresthesias that are characterized as uncomfortable or indescrib-
able that interfere with sleep; cardiorespiratory disorders; pain; degenerative disor-
ders; prostatic hypertrophy (30); OSA disorder (31,32); and HIV infection (33).
Medications, recreational drugs, and toxins can also cause insomnia and a full
list of medications, ingested substances, and chemical exposures should be
obtained. Among medications causing insomnia, the most common are stimulants,
theophylline, prednisone, and selective serotonin reuptake inhibitors. Withdrawal
from sedative medication can also cause insomnia in addition to idiosyncratic reac-
tions to other medications such as the anticonvulsants, felbamate (34) and
lamotrigine (35). Substances such as alcohol or other recreational drugs can cause
insomnia (10), as can environmental toxins such as carbon monoxide or inorganic
mercury (36,37).

MENOPAUSE-RELATED INSOMNIA
There is a high level of sleep disturbance occurring in about 42% of middle-aged
women (38). Although cross-sectional analyses indicate that sleep disturbance may
be independent of menopausal status, transition into postmenopausal status is asso-
ciated with deleterious changes in sleep among women not receiving hormone
replacement therapy (38,39).
The prion diseases of Creutzfeld Jacob and Fatal Familial Insomnia can be
extremely rare causes of insomnia. More commonly, Alzheimer’s disease,
Parkinson’s disease, and other degenerative neurologic conditions can have prominent
symptoms of insomnia. Rarely, brain stem lesions can also produce insomnia (40).

DIAGNOSTIC WORKUP
The diagnosis of psychophysiological insomnia is typically and often made by
history and observation. Eliciting an account of learned associations preventing
sleep and paying attention to the patient’s display of somatized tension are key in
making the diagnosis. To rule out other causes one needs to perform the following:
Psychophysiological Insomnia 73

1. A brief psychiatric interview specifically looking for neurovegetative symptoms of

affective disorders and/or anxiety permeating daily activities other than sleep. Occa-
sionally, psychological tests such as the MMPI and Profile of Mood States are used,
looking for a profile of malaise, guardedness, sensation avoidance, repression, and
denial. (The abnormalities on the psychological tests may be either the cause or the
result of insomnia.)
2. A general medical evaluation to rule out physical problems, such as other medical or
neurologic disorders, medication effects, or substance abuse (10).
3. According to the American Academy of Sleep Medicine practice parameters,
polysomnography is not indicated in the routine evaluation of insomnia, except when
another sleep disorder is suspected and when insomnia does not respond to appropriate
treatment.
4. A sleep log is a graph on which, for 2 to 3 weeks, the patient records bedtime, approxi-
mate sleep time, times and duration of awakenings during the sleep period, final awak-
ening time, and naps taken during the day. This record summarizes the patient’s
perception of the amount and quality of sleep he or she is getting.
5. Actigraphy is an invaluable tool for evaluating insomnia, especially in patients with
unusual complaints, such as “I don’t sleep at all.” It supplements subjective sleep logs.
An actigraph is a small, wrist-mounted device that records the activity plotted against
time, usually 1 or 2 weeks at a time. There is a close correlation between the rest
activity recorded by the actigraph and the wake–sleep pattern as determined by the
PSG (41). Certain standardized questionnaires are sometimes used to screen for in-
somnia and determine its severity (42,43).

PREVENTION
In early and aggressive treatment of transient insomnia, both with hypnotics and
a discussion of good sleep hygiene, addressing the acute stressor may prevent the
development of the learned maladaptive associations leading to psychophysiologi-
cal insomnia (11).

PROGNOSIS AND COMPLICATIONS

If untreated, psychophysiological insomnia can continue for decades. In some
cases, it gradually worsens as a vicious cycle of insomnia develops. Overall quality
of life, as measured by the SF-36 Health Status Survey, is greatly impaired by
chronic insomnia (44). Complications, as in any serious insomnia, include exces-
sive use of hypnotics, self-treatment with alcohol, treatment of ensuing daytime
somnolence by stimulants, and daytime tension with tranquilizers (45). Untreated
insomnia is a risk factor for the subsequent development of clinical depression and
psychiatric distress (30,46). Other psychological complications include a passive
and defeatist attitude (1) and cognitive, particularly memory, impairment (47,48).
Chronic insomnia is also associated with an increase in motor vehicle accidents and
a decrease in job performance (49).

MANAGEMENT
There are two main categories of treatment modalities for psychophysiological
insomnia: behavioral and pharmacological. The best management strategy is com-
bining hypnotic medication and behavioral methods (50). Although current Food
74 Attarian

and Drug Administration guidelines recommend hypnotic medication only for

short-term use, studies have shown that the risk of tolerance, addiction, depen-
dence, and rebound insomnia are minimal (51–53). Hypnotics that have clinically
proven efficacy include the newer nonbenzodiazepine hypnotics, zolpidem (54,55),
zopiclone (56) (not available in the United States), and zaleplon (57,58); the benzo-
diazepines; and low-dose trazodone. Two studies have shown efficacy of valerian
root in the treatment of insomnia, comparable, according to one of the studies, to
that of oxazepam (a benzodiazepine) (59,60). Tricyclic antidepressants and antihis-
tamines (including over-the-counter [OTC] sleep aids) are rarely indicated because
of a poor side-effect profile and unproven value as hypnotics. There is paucity of
data on the efficacy of antidepressants and OTC sleep aids in the treatment of
insomnia. Additionally, the risk of serious adverse effects with these medications is
well documented (52,61). There is also growing evidence that the benefits of ben-
zodiazepine treatment outweighs the risks in the vast majority of patients. Despite
these facts, there has been a significant increase over the past several years in the
use of antidepressants and OTC sleep aids in the treatment of insomnia with a con-
comitant decrease in the use of hypnotics (52). A recent study showed that long-
term use of zolpidem is safe, well-tolerated, and effective in the treatment of chronic
insomnia (62).
Behavioral methods include sleep restriction consolidation, sleep hygiene edu-
cation, relaxation therapy, and stimulus control therapy (63,64). These behavioral
methods are effective in increasing the total sleep time by 13%, reducing SL by
65%, and reducing the wake time after sleep by 48% (65–67).

Case 2
A 42-year-old woman referred with the chief complaint of sleep mainte-
nance for approximately 10 years. She is able to initiate sleep, but, a few
hours later she wakes up and is unable to return to sleep. Typically, she wakes
up in the middle of the night to go to the bathroom, and then is wide awake.
She is awake for several hours and lays in bed trying to go back to sleep but
tends to worry about issues relating to work, home, and family. Occasionally,
she sleeps for brief periods of time throughout the rest of the night. This prob-
lem has gradually been worsening over a 10-year period. She stopped drink-
ing caffeine approximately 2–3 years ago, which helped slightly, but did not
have a significant impact. She had been taking Tylenol PM for a year or so
approximately 4 years ago, which initially helped, but after a while the medi-
cation stopped helping her sleep through the night. She has tried not taking
Tylenol PM and she said her insomnia became much worse. She most re-
cently has been taking temazepam about once or twice a week when she feels
particularly anxious and fears that she will not be able to fall asleep at all. She
says this is quite effective and she tends to sleep through most of the night.
Although this has been going on for some time, she has just recently sought
medical attention because of her recent problems with fatigue and a difficulty
 Psychophysiological Insomnia
75

75
Fig. 1. Sleep log prior to treatment.
 76
76

Attarian
Fig. 2. Sleep log after treatment.
Psychophysiological Insomnia 77

concentrating. Overall, during the day she feels fatigued, but does not nap
and does not fall asleep unintentionally during the day. She states that she has
been a light sleeper for most of her life but cannot remember a particular
event that triggered the insomnia 10 years earlier. She has a positive family
history of insomnia in two siblings.
She was asked to keep sleep diaries for two weeks and bring them in dur-
ing her followup visit. (Figure 1 reproduces one of those logs.)
She was placed on a nightly dose of temazepam and also on a sleep restric-
tion consolidation program restricting her time in bed to 5 hours. She was
also asked to continue keeping sleep logs and fax them in every 3 weeks, at
which point her time in bed would be adjusted according to her overall sleep
efficiency.
Six months after she was averaging 7–8 hours of sleep at night, she was
gradually tapered off the temazepam. Figure 2 illustrates one of her last sleep
logs after the discontinuation of the temazepam.

REFERENCES
1. American Sleep Disorders Association. (1997) International classification of sleep disorders:
diagnostic and coding manual. American Sleep Disorders Association, Rochester, MN.
2. American Psychiatric Association. (1994) Diagnostic and statistical manual of mental disorders
(4th ed.). American Psychiatric Association, Washington DC.
3. Bettolo, A. (1931) L’insonnia e sua importanza clinica: le sue cause predisponenti e determinanti,
i suoi caratteri nelle diverse malattie, la sua importanza prognostica ed il suo trattamento generale
e speciale. Studium 21, 54–65.
4. Strauss, E. (1948) Insomnia. St. Barts Hosp. J. 52, 163–168.
5. Association of Sleep Disorders Centers. (1979) Disorders Centers. Diagnostic classification of
sleep and arousal disorders (1st ed.). Sleep 2, 1–137.
6. Hauri, P. J. (1983) A cluster analysis of insomnia. Sleep 6(4), 326–338.
7. Hauri, P. and Fisher, J. (1986) Persistent psychophysiologic (learned) insomnia. Sleep 9(1), 38–53.
8. Buysse, D. J., Reynolds, C. F., III, Kupfer, D. J., et al. (1994) Clinical diagnoses in 216 insomnia
patients using the International Classification of Sleep Disorders (ICSD), DSM-IV and ICD-10
categories: a report from the APA/NIMH DSM-IV Field Trial. Sleep 17(7), 630–637.
9. Edinger, J. D., Fins, A. I., Goeke, J. M., et al. (1996) The empirical identification of insomnia
subtypes: a cluster analytic approach. Sleep 19(5), 398–411.
10. Sateia, M. J., Doghramji, K., Hauri, P. J., and Morin, C. M. (2000) Evaluation of chronic insom-
nia. An American Academy of Sleep Medicine review. Sleep 23(2), 243–308.
11. Spielman, A. J., Nunes, J., and Glovinsky, P. B. (1996) Insomnia. Neurol. Clin. 14(3), 513–543.
12. Bonnet, M. H. and Arand, D. L. (1999) Diagnosis and treatment of insomnia. Respir. Care Clin.
N. Am. 5(3), 333–348.
13. Bastien, C. H. and Morin, C. M. (2000) Familial incidence of insomnia. J. Sleep Res. 9(1), 49–54.
14. Bonnet, M. H. and Arand, D. L. (1995) 24-hour metabolic rate in insomniacs and matched normal
sleepers. Sleep 18(7), 581–588.
15. Pavlova, M., Berg, O., Gleason, R., Walker, F., Roberts, S., and Regestein, Q. (2001) Self-re-
ported hyperarousal traits among insomnia patients. J. Psychosom. Res. 51(2), 435–441.
16. Bonnet, M. H. and Arand, D. L. (1998) Heart rate variability in insomniacs and matched normal
sleepers. Psychosom. Med. 60(5), 610–615.
17. Lushington, K., Dawson, D., and Lack, L. (2000) Core body temperature is elevated during con-
stant wakefulness in elderly poor sleepers. Sleep 23(4), 504–510.
78 Attarian

18. Bonnet, M. H. and Arand, D. L. (2001) Impact of activity and arousal upon spectral EEG param-
eters. Physiol. Behav. 74(3), 291–298.
19. Bonnet, M. H. and Arand, D. L. (2000) Activity, arousal, and the MSLT in patients with insom-
nia. Sleep 23(2), 205–212.
20. Merica, H., Blois, R. and Gaillard, J. M. (1998) Spectral characteristics of sleep EEG in chronic
insomnia. Eur. J. Neurosci. 10(5), 1826–1834.
21. Lamarche, C. H. and Ogilvie, R. D. (1997) Electrophysiological changes during the sleep onset
period of psychophysiological insomniacs, psychiatric insomniacs, and normal sleepers. Sleep
20(9) 724–733.
22. Vgontzas, A. N., Zoumakes, M., Papanicolaou, D. A., et al. (2001) Chronic insomnia is associ-
ated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implica-
tions. J. Clin. Endocrinol. Metab. 86(8), 3787–3794.
23. Salin-Pascual, R. J., Roehrs, T. A., Merlotti, L. A., Zorick, F., and Roth, T. (1992) Long-term
study of the sleep of insomnia patients with sleep state misperception and other insomnia pa-
tients. Am. J. Psychiatry 149(7), 904–908.
24. Bonnet, M. H. and Arand, D. L. (1998) The consequences of a week of insomnia. II: Patients with
insomnia. Sleep 21(4), 359–368.
25. Hauri, P. (2000) Primary insomnia. In: Principles and Practice of Sleep Medicine (Kryger, R. A.
D., ed.), W.B. Saunders, Philadelphia, PA, pp. 633–639.
26. Dumont, M., Montplaisir, J., and Infante-Rivard, C. (1997) Sleep quality of former night-shift
workers. Int. J. Occup. Environ. Health 3(Suppl 2), S10–S14.
27. Suzuki, S., Dennerstein, L., Greenwood, K. M., Armstrong, S. M., and Satohesa, E. (1994) Sleeping
patterns during pregnancy in Japanese women. J. Psychosom. Obstet. Gynaecol. 15(1), 19–26.
28. Hajak, G. (2000) Insomnia in primary care. Sleep 23(Suppl 3), S54–S63.
29. Montagna, P., Provini, F., Plazzi, G., Liguori, R., and Lugaresi, E. (1997) Propriospinal myoclo-
nus upon relaxation and drowsiness: a cause of severe insomnia. Mov. Disord. 12(1), 66–72.
30. Katz, D. A. and McHorney, C. A. (1998) Clinical correlates of insomnia in patients with chronic
illness. Arch. Intern. Med. 158(10), 1099–1107.
31. Lichstein, K. L., Riedel, B. W., Lester, K. W., and Aguillard, R. N. (1999) Occult sleep apnea in
a recruited sample of older adults with insomnia. J. Consult. Clin. Psychol. 67(3), 405–410.
32. Hopf, R. and Moller, A. (2000) [Disturbed sleep caused by sleep apnea. To the sleep laboratory
for diagnosis?]. MMW Fortschr. Med. 142(12), 31–33.
33. Rubinstein, M. L. and Selwyn, P. A. High prevalence of insomnia in an outpatient population
with HIV infection. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 19(3), 260–265.
34. Leppik, I. E. (1995) Felbamate. Epilepsia 36(Suppl 2), S66–S72.
35. Sadler, M. (1999) Lamotrigine associated with insomnia. Epilepsia 40(3), 322–325.
36. Satoh, H. (2000) Occupational and environmental toxicology of mercury and its compounds. Ind.
Health 38(2), 153–164.
37. Rossini, S. R., Reimao, R., LeFevre, B. H., and Medrado-Faria, M. A. (2000) Chronic insomnia
in workers poisoned by inorganic mercury: psychological and adaptive aspects. Arq.
Neuropsiquiatr. 58(1), 32–38.
38. Owens, J. F. and Matthews, K. A. (1998) Sleep disturbance in healthy middle-aged women.
Maturitas 30(1), 41–50.
39. Dennerstein, L., Dudley, E. C., Hopper, J. L., Guthrie, J. R., and Burger, H. G. (2000) A prospec-
tive population-based study of menopausal symptoms. Obstet. Gynecol. 96(3), 351–358.
40. Autret, A., Lucas, B., Mondon, K., et al. (2001) Sleep and brain lesions: a critical review of the
literature and additional new cases. Neurophysiol. Clin. 31(6), 356–375.
41. Attarian, H. P. (2000) Helping patients who say they cannot sleep. Practical ways to evaluate and
treat insomnia. Postgrad. Med. 107(3), 127–130, 133–137, 140–142.
42. Bastien, C. H., Vallieres, A., and Morin, C. M. (2001) Validation of the Insomnia Severity Index
as an outcome measure for insomnia research. Sleep Med. 2(4), 297–307.
Psychophysiological Insomnia 79

43. Smith, S. and Trinder, J. (2001) Detecting insomnia: comparison of four self-report measures of
sleep in a young adult population. J. Sleep Res. 10(3), 229–235.
44. Leger, D., Scheuermaier, K., Philip, P., Paillard, M., and Guilleminault, C. (2001) SF-36: evalu-
ation of quality of life in severe and mild insomniacs compared with good sleepers. Psychosom.
Med. 63(1), 49–55.
45. Roehrs, T., Papineau, K., Rosenthal, L., and Roth, T. (1999) Ethanol as a hypnotic in insomniacs:
self administration and effects on sleep and mood. Neuropsychopharmacology 20(3), 279–286.
46. Chang, P. P., Ford, D. E., Mead, L. A., Cooper-Patrick, L., and Klag, M. J. (1997) Insomnia in
young men and subsequent depression. The Johns Hopkins Precursors Study. Am. J. Epidemiol.
146(2), 105–114.
47. Roehrs, T. and Roth, T. (2000) Sleep-wake state and memory function. Sleep 23(Suppl 3), S64–S68.
48. Szelenberger, W. and Niemcewicz, S. (2000) Severity of insomnia correlates with cognitive im-
pairment. Acta Neurobiol. Exp. (Warsz) 60(3), 373.
49. Hajak, G. (2001) Epidemiology of severe insomnia and its consequences in Germany. Eur. Arch.
Psychiatry Clin. Neurosci. 251(2), 49–56.
50. Vgontzas, A. N. and Kales, A. (1999) Sleep and its disorders. Annu. Rev. Med. 50, 387–400.
51. Schenck, C. H. and Mahowald, M. W. (1996) Long-term, nightly benzodiazepine treatment of
injurious parasomnias and other disorders of disrupted nocturnal sleep in 170 adults. Am. J. Med.
100(3), 333–337.
52. Walsh, J. K. and Schweitzer, P. K. (1999) Ten-year trends in the pharmacological treatment of
insomnia. Sleep 22(3), 371–375.
53. Doghramji, K. (2000) The need for flexibility in dosing of hypnotic agents. Sleep 23(Suppl 1),
S16–S20; discussion S21–S2.
54. Darcourt, G., Pringuey, D., Salliere, D., and Lavoisy, J. (1999) The safety and tolerability of
zolpidem—an update. J. Psychopharmacol. 13(1), 81–93.
55. Holm, K. J. and Goa, K. L. (2000) Zolpidem: an update of its pharmacology, therapeutic efficacy
and tolerability in the treatment of insomnia. Drugs 59(4), 865–889.
56. Hajak, G. (1999) A comparative assessment of the risks and benefits of zopiclone: a review of 15
years’ clinical experience. Drug Saf. 21(6), 457–469.
57. Elie, R., Ruther, E., Farr, I., Emilien, G., and Salenas, E. (1999) Sleep latency is shortened during
4 weeks of treatment with zaleplon, a novel nonbenzodiazepine hypnotic. Zaleplon Clinical Study
Group. J. Clin. Psychiatry 60(8), 536–544.
58. Hedner, J., Yaeche, R., Emilieu, G., Farr, I., and Salinas, E. (2000) Zaleplon shortens subjective
sleep latency and improves subjective sleep quality in elderly patients with insomnia. The
Zaleplon Clinical Investigator Study Group. Int. J. Geriatr. Psychiatry 15(8), 704–712.
59. Dominguez, R. A., Bravo-Valverde, R. L., Kaplavitz, B. R., and Cott, J. M. (2000)Valerian as a
hypnotic for Hispanic patients. Cultur. Divers. Ethni. Minor Psychol. 6(1), 84–92.
60. Dorn, M. (2000) [Efficacy and tolerability of Baldrian versus oxazepam in non-organic and non-
psychiatric insomniacs: a randomised, double-blind, clinical, comparative study]. Forsch.
Komplementarmed. Klass. Naturheilkd. 7(2), 79–84.
61. Weiler, J. M., Bloomfield, J. R., Woodworth, G. G., et al. (2000) Effects of fexofenadine, diphen-
hydramine, and alcohol on driving performance. A randomized, placebo-controlled trial in the
Iowa driving simulator. Ann. Intern. Med. 132(5), 354–363.
62. Hajak, G., Cluydts, R., Declerck, A., et al. (2002) Continuous versus non-nightly use of zolpidem
in chronic insomnia: results of a large-scale, double-blind, randomized, outpatient study. Int.
Clin. Psychopharmacol. 17(1), 9–17.
63. Beullens, J. (1999) [Determinants of insomnia in relatively healthy elderly. A literature review].
Tijdschr. Gerontol. Geriatr. 30(1), 31–38.
64. Morin, C. M., Mimeault, V., and Gagne, A. (1999) Nonpharmacological treatment of late-life
insomnia. J. Psychosom. Res. 46(2), 103–116.
80 Attarian

65. Perlis, M., Aloia, M., Millikan, A., et al. (2000) Behavioral treatment of insomnia: a clinical case
series study. J. Behav. Med. 23(2), 149–161.
66. Espie, C. A., Inglis, S. J., and Harvey, L. (2001) Predicting clinically significant response to
cognitive behavior therapy for chronic insomnia in general medical practice: analysis of outcome
data at 12 months posttreatment. J. Consult. Clin. Psychol. 69(1), 58–66.
67. Edinger, J. D., Wohlgemuth, W. K., Radtke, R. A., Marsh, G. R., and Quillian, R. E. (2001)
Cognitive behavioral therapy for treatment of chronic primary insomnia: a randomized controlled
trial. JAMA 285(14), 1856–1864.
Idiopathic Insomnia 81

7
Idiopathic Insomnia

Hrayr P. Attarian

You know I can’t sleep, I can’t stop my brain

You know it’s three weeks, I’m going insane.
You know I’d give you everything I’ve got for a little peace of mind.
—The Beatles (I’m so tired)

DEFINITION
The International Classification of Sleep Disorders (ICSD) defines idiopathic
insomnia, or childhood-onset, insomnia as a lifelong inability to get adequate
amounts of sleep.
This is presumably due to an abnormality in the neurological control of the sleep–
wake system (1). However, not everyone agrees that this disorder is a separate and
unique type of insomnia. For example, the fourth edition of the Diagnostic and
Statistical Manual of Mental Disorders (DSM-IV) regards the apparent neurologi-
cal predisposition toward insomnia described here as a component of a broader
entity named primary insomnia that includes idiopathic insomnia, psychophysi-
ological insomnia, and sleep state misperception (SSM) (2,3).

HISTORICAL NOTE
The Association of Sleep Disorders Centers (now the American Academy of
Sleep Disorders) developed and published Sleep Nosology in 1979. In that publica-
tion, a new category entitled “childhood-onset insomnia” was presented. It was
described as “sleep-onset and sleep maintenance insomnia, resulting in daytime
symptoms of inadequate sleep, that is characterized by a distinctive history of
(unexplained) development before puberty, and persistence into adulthood.” It was
postulated that this new entity represented “a CNS [central nervous system] shift or
dysfunction of the sleep-arousal equilibrium” (4). The existence of this disorder

From: Current Clinical Neurology: Clinical Handbook of Insomnia

Edited by: H. P. Attarian © Humana Press Inc., Totowa, NJ

81
82 Attarian

was confirmed by research done in the 1980s. It was also documented that this is a
distinct form of insomnia by showing that childhood-onset insomnia was different
from adult-onset insomnia on polysomnographic grounds (5) and that it could be
distinguished from other types of insomnia in a cluster analysis (6).

EPIDEMIOLOGY
Idiopathic insomnia is rarely seen in its pure form. Chronic and serious insom-
nia over a lifetime almost always leads to other factors such as maladaptive behav-
iors; poor sleep hygiene, and emotional disturbances that further complicate the
picture (7). A predisposition toward poor sleep exists in many insomniacs. How-
ever, in its pure form, idiopathic insomnia represents less than 5% of all insomniacs
(8). Evidence shows that idiopathic insomnia often, but not always, has familial
patterns of inheritance (1).

ETIOLOGY
Idiopathic insomnia may be due to some dysfunction in the brain’s sleep–wake
center. It may represent either hyperactivity in the wake center or hypoactivity in
the sleep center (5,9). Another, and more commonly accepted theory, is that patients
with idiopathic insomnia are just simply organically hyperaroused (10).

PATHOGENESIS AND PATHOPHYSIOLOGY

Sleep–wake centers include the sleep-promoting center present in the anterior
hypothalamus, the raphe nuclei, and medial forebrain area, and the wake-promot-
ing center in the ascending reticular-activating system including the posterior
hypothalamus (7,9). Whether a person is awake or asleep depends on the neuro-
physiological balance between the reticular-activating system and the sleep-induc-
ing maintenance systems (11). Idiopathic insomnia presumably is due to a shift of
this balance toward arousal. Either hyperactivity in the arousal system or
hypoactivity in the sleep system may cause idiopathic insomnia (9). Patients suffer-
ing from idiopathic insomnia may have a neurochemical, neuroanatomical, or neu-
rophysiological dysfunction or lesions interfering with normal sleep (11). Idiopathic
insomniacs are often hyperaroused during wakefulness on questionnaires, auditory-
evoked potentials, and electroencephalogram (EEG) (12). Physiological
hyperarousal in many systems (cardiac, core temperature, corticosteroids, etc.) is
not confined to patients with idiopathic insomnia but is frequently found in all pri-
mary insomniacs (10). Despite animal data showing the creation of insomniac ani-
mals with medial forebrain and the medial preoptic area (13), no direct human
evidence for structural neuropathology exists (14). Difficult birth and prematurity
are likely risk factors for the development of idiopathic insomnia (1).

CLINICAL MANIFESTATIONS
Idiopathic insomnia is a chronic and serious inability to initiate and maintain
sleep that can often be observed as early as the first few weeks of life. Parents often
Idiopathic Insomnia 83

report that these patients slept much less, or required less sleep, than their siblings
when they were infants. Sleep latency is long. Sleep is riddled with many awaken-
ings and may show sleep-stage abnormalities, such as rapid eye movement (REM)
sleep with few eye movements or ill-formed sleep spindles during stage 2 sleep (5).
Paradoxically, idiopathic insomniacs may show fewer body movements per unit of
sleep than do normal sleepers (14). The spectrum of severity of insomnia in this
condition varies from mild (essentially a light sleeper) to severe and incapacitating,
as the presumed underlying neurological abnormality varies from mild to severe
(14). Daytime features typically include decreased attention and vigilance, low lev-
els of energy and concentration, and a deterioration of mood commonly described
as grim and subdued, rather than obviously depressed or anxious. In mild or moder-
ate idiopathic insomnia, psychological functioning is remarkably intact. In severe
cases, daytime functioning may be severely disrupted and affected patients may be
unable to hold a job. During childhood and adolescence, idiopathic insomnia is
often associated with soft neurological signs (i.e., as dyslexia or hyperactivity).
Many cases show diffuse nonspecific abnormalities on the EEG (1).
The ICSD’s diagnostic criteria for idiopathic insomnia are (1) a complaint of
insomnia combined with a complaint of decreased functioning during wakefulness;
(2) long-standing insomnia, typically beginning in early childhood or soon after
birth; (3) relentless insomnia during periods of both poor and good emotional
adjustment; (4) one or more of the following polysomnography: increased sleep
latency, reduced sleep efficiency, and increased number and duration of awaken-
ings often a reversed first-night effect (best sleep on the first night); (5) the diagno-
sis cannot be made if medical or psychiatric disease or stress can explain the early

Case 1
Mr. T. is a 53-year-old man with lifelong history of insomnia. Mr. T. stated
that his mother told him that he had trouble sleeping even during his infancy.
He stated that as far back as he could remember he has had insomnia. Around
age 10 or 11 he started having some anxiety associated with his inability to
sleep. He stated that when he has a decent night’s sleep for several nights in a
row, he really does not feel depressed and anxious; but not getting a good
night’s sleep creates anxiety over the inability to sleep, which then becomes
reinforced when he does not sleep easily the following night.
For reasons unknown, he did not seek medical attention for his problem
until about 1 year ago when he mentioned it to his primary care physician. He
was tried on Xanax, Ambien, Trazodone, Remeron, and over-the-counter
Tylenol PM. Few medications had any impact on his sleep. Even with medi-
cation, he had only one good night every 2–3 weeks, during which he would
sleep 6–7 solid hours.
Most of the time, Mr. T. goes to bed between 11 PM and midnight feeling
sleepy and tired, but when he lays down he is awake for at least 1 hour, some-
84 Attarian

times worrying about the day’s events or sometimes just laying there. He then
manages to fall asleep, only to wake up several times in the middle of the
night, staying awake each time for 30–40 minutes. His total awake time in the
middle of the night, he reports, is about 2 hours. He wakes up between 8 and
8:30 AM feeling fatigued and not restored. Despite his fatigue, he is not sleepy
during the day, does not fall asleep unintentionally, and does not take naps.
He has no other sleep complaints, and he does not have any family history of
insomnia. Physical exam is normal.

onset of this insomnia; and (6) other sleep disorders causing insomnia can occur
simultaneously (e.g., adjustment sleep disorder). Minimal criteria: 1, 2, and 5 (1).

DIFFERENTIAL DIAGNOSIS
Not all insomnia in childhood is idiopathic or childhood-onset insomnia.
Although the complaints of insomnia are seen in up to 41% of children (15), as
mentioned previously, idiopathic insomnia in its pure form is rarely seen. Idio-
pathic insomnia is diagnosed when insomnia predates the development of the other
complicating factors (emotional problems, ill adaptive associations, or poor sleep
hygiene) and when the imbalance of the sleep–wake system plays a paramount role (1).
Idiopathic insomnia should be differentiated from other common childhood
insomnias such as sleep-onset association disorder and limit-setting sleep disorder.
In the former, habits, objects, or conditions become associated with the transition
to sleep and need to be re-established throughout the night to permit return to sleep
after normal awakenings, otherwise periods of waking are prolonged (16). The lat-
ter is a disorder of childhood characterized by normal sleep ability and deliberate
attempts to remain awake at bedtime and, sometimes, after nighttime awakenings
using a variety of requests, demands, and stalling tactics (stories, drinks, bathroom
trips, blanket adjustments, television) (16). A careful history of the child’s bedtime
behavior enables one to distinguish these disorders from idiopathic insomnia.
Idiopathic insomnia is differentiated from short sleepers by the accompanying
fatigue and daytime performance impairment, whereas short sleepers feel and func-
tion well during waking hours.
Idiopathic insomnia is difficult to distinguish from psychophysiological insom-
nia, which is also accompanied by an innate predisposition toward poor sleep. In
idiopathic insomnia, the presumed sleep–wake imbalance is enough to cause the
insomnia by itself; in psychophysiological insomnia, the inherent sleep–wake dis-
turbance is weaker, needing the addition of the stress of maladaptive conditioning
to trigger the insomnia (1).
Psychologically, most patients with idiopathic insomnia are remarkably healthy,
given their chronic lack of sleep (1). However, as in other primary insomnias,
patients with idiopathic insomnia tend to be emotional repressors (7). Although the
insomnia is persistent, relentless, and almost unvaried through both poor and good
Idiopathic Insomnia 85

periods of emotional adaptation (1), patients do experience occasional worsening

of their sleep under stressful situations (7).

DIAGNOSTIC WORKUP
Idiopathic insomnia is a diagnosis of exclusion. A careful history identifies the
exact onset of the insomnia and is important in defining any maladaptive behaviors,
sleep hygiene issues, and extrinsic factors. A thorough psychiatric interview reveals
no psychological reason severe enough to explain the insomnia. Specifically, no
psychological distress explains the early onset. A general medical evaluation reveals
no causative medical factors such as allergies, pain, or thyroid abnormalities that
might have been operative since early childhood. A polysomnogram (PSG), if per-
formed, reveals severely impaired sleep, and sleep stages may be difficult to score
according to accepted criteria. However, because idiopathic insomniacs often show
a “reverse first night effect” (6), more than one night in the sleep laboratory may be
necessary. Another way of bypassing the reverse first night effect is doing actigraphy.
Actigraphy is an invaluable tool in evaluating insomnia, especially in patients with
unusual complaints, such as “I don’t sleep at all.” It supplements subjective sleep
logs. An actigraph is a small wrist-mounted device that records the activity plotted
against time, usually 1 or 2 weeks at a time. A close correlation exists between the
rest activity recorded by the actigraph and the wake–sleep pattern as determined by
the PSG (17). Nonspecific EEG abnormalities may be seen, but are highly idiosyn-
cratic and are not diagnostic of idiopathic insomnia. Overall, PSGs add little of
diagnostic value in idiopathic insomnia.

PROGNOSIS AND COMPLICATIONS

The suspected neurological abnormality underlying the idiopathic insomnia is
presumably lifelong. Therefore, the symptom of insomnia to a certain degree per-
sists for the person’s entire life. Complications, like with other primary insomnias,
include depression (18), attempts to treat the condition either by self-medication
(such as with alcohol) or by prescriptions (high doses of benzodiazepines or barbi-
turates), excessive use of stimulants to promote alertness (1), and, as mentioned
previously, the development of maladaptive behaviors and poor sleep hygiene.

MANAGEMENT
No guidelines for a consistent treatment approach to childhood-onset insomnia
are available. Impeccable sleep hygiene is essential, including regular, somewhat
curtailed sleep hours, excellent relaxation skills, and active waking lifestyles (11).
Behavioral treatments such as sleep restriction consolidation, biofeedeback, and the
like, also can be helpful. Pharmacologically, benzodiazepines and zolpidem are effective
as hypnotics (9). Long-term use of drugs has raised the question of tolerance and
dependence (9). Recent studies, however, have shown that the risk for tolerance, de-
pendence, and addiction is minimal in patients using long-term benzodiazepines for
86 Attarian

insomnia or for other sleep disorders (19–21). Another problem with the use of ben-
zodiazepines in patients with idiopathic insomnia is the tendency among such pa-
tients to have atypical reactions to medications (7); for example, little sedation from
large doses of sedative/hypnotics (7). According to sporadic case reports, some pa-
tients with idiopathic insomnia have responded to low-dose tricyclics, antipsy-
chotic medications, or opiates (7,22). More recently, 5 mg of melatonin has been
shown to be helpful in treating chronic insomnia in school-age children (23).

Case 2
A 36-year-old man presented to the sleep center clinic for a first-time
evaluation concerning his long-standing inability to fall or stay asleep. He
stated that as far back as he could remember, even as a child in grade school,
he had trouble falling asleep. His mother told him that even as a newborn he
slept much less than his siblings had. He went to bed around 10 PM and tossed
and turned for an hour or so before falling asleep. He stated that his sleep was
very light, and he tended to wake up once or twice in the middle of the night
and stayed awake an undetermined amount of time, tossing and turning in
bed. Whenever he was unable to fall asleep, he became restless, constantly
watching the digital clock on his bedside table and only rarely getting out of
bed to watch TV. He went to bed every night anticipating not falling asleep.
As a result, he got about 4–5 hours of sleep a night, and did not feel refreshed.
Sometimes, after a few bad nights during which he would hardly get any
sleep, he would sleep 1 night for about 7 hours, and then would feel signifi-
cantly better and refreshed in the morning. He denied excessive daytime
sleepiness, and denied falling asleep in inappropriate situations. He denied
being able to take naps. He stated that whether he slept at home or somewhere
else, he was still unable to fall asleep and had the same trouble falling and
staying asleep. He denied symptoms of restless legs or of periodic limb move-
ments. He denied snoring, heartburn, cataplexy, sleep paralysis, hypnagogic
hallucinations, or symptoms of apnea. In the past, he had tried zaleplon and
trazodone. Zaleplon had not helped, and although trazodone helped him to
sleep, it produced excessive daytime tiredness, grogginess, and fatigue. He
also tried over-the-counter sleeping aids that did not make his sleep satisfac-
tory in length or quality. He did not drink caffeinated beverages after the
early afternoon, nor alcohol in the early afternoon, but he did chew tobacco
throughout the day, even into the late evening. He had no other complaints.
His family history was significant for a similar type of insomnia in his grand-
mother and mother, but not in his father or siblings. Physical exam was normal.
All-night PSG revealed increased sleep latency and poor sleep efficiency at
48% due to prolonged unexplained awakenings. An actigraph, worn for 1 week,
confirmed his subjective reports of 4–5 hours of fragmented sleep at night.
With strict compliance of sleep hygiene regulations and 1 mg of estazolam
at bedtime, he was able to improve his sleep efficiency to a considerable
degree, but not resolve his insomnia entirely (24).
Idiopathic Insomnia 87

REFERENCES
1. American Sleep Disorders Association. (1997) International classification of sleep disorders:
diagnostic and coding manual. American Sleep Disorders Association, Rochester, MN.
2. American Psychiatric Association. (1994) Diagnostic and statistical manual of mental disorders
(4th ed.). American Psychiatric Association, Washington DC.
3. Reynolds, C. F., III, Kupfer, D. J., Buysse, D. J., Colde, P. A., and Yeager, A. (1991) Subtyping
DSM-III-R primary insomnia: a literature review by the DSM-IV Work Group on Sleep Disor-
ders. Am. J. Psychiatry 148(4), 432–438.
4. Association of Sleep Disorders Centers. (1979) Diagnostic classification of sleep and arousal
disorders (1st ed.). Sleep 2, 1–137.
5. Hauri, P. and Olmstead, E. (1980) Childhood-onset insomnia. Sleep 3(1), 59–65.
6. Hauri, P. J. (1983) A cluster analysis of insomnia. Sleep 6(4), 326–338.
7. Hauri, P. (2000) Primary insomnia. In: Principles and Practice of Sleep Medicine (Kryger, R. A.
D., ed.), W.B. Saunders, Philadelphia, PA, pp. 633–639.
8. Buysse, D. J., Reynolds, C. F., III, Kupfer, D. J., et al. (1994) Clinical diagnoses in 216 insomnia
patients using the International Classification of Sleep Disorders (ICSD), DSM-IV and ICD-10
categories: a report from the APA/NIMH DSM-IV Field Trial. Sleep 17(7), 630–637.
9. Sano, H. and Itoh, H. (1998) [Idiopathic insomnia]. Nippon Rinsho 56(2), 361–364.
10. Bonnet, M. H. and Arand, D. L. (1995) 24-hour metabolic rate in insomniacs and matched normal
sleepers. Sleep 18(7), 581–588.
11. Hauri, P. J. (1998) Insomnia. Clin. Chest Med. 19(1), 157–168.
12. Regestein, Q. R., Dambrosia, J., Hallett, M., Murawski, B., and Paive, M. (1993) Daytime alert-
ness in patients with primary insomnia. Am. J. Psychiatry 150(10), 1529–1534.
13. John, J., Kumar, V. M., and Gopinath, G. (1998) Recovery of sleep after fetal preoptic transplan-
tation in medial preoptic area-lesioned rats. Sleep 21(6), 601–606.
14. Hauri, P. (1999) Idiopathic insomnia. In: MedLink Neurology (Gilman, S., Goldstein, G., and
Waxman, S., eds.), Arbor Publishing, San Diego, CA.
15. Archbold, K. H., Pituch, K. J., Panahi, P., and Chevin, R. D. (2002) Symptoms of sleep distur-
bances among children at two general pediatric clinics. J. Pediatr. 140(1), 97–102.
16. Ferber, R. (1990) Childhood insomnia. In: Handbook of sleep disorders (Thorpy, M., ed.), Marcel
Dekker, New York, pp. 435–455.
17. Mahowald, M. W. (1996) Diagnostic testing. Sleep disorders. Neurol. Clin. 14(1), 183–200.
18. Chang, P. P., Ford, D. E., Mead, L. A., Cooper-Patrick, L., and Klag, M. J. (1997) Insomnia in
young men and subsequent depression. The Johns Hopkins Precursors Study. Am. J. Epidemiol.
146(2), 105–114.
19. Schenck, C. H. and Mahowald, M. W. (1996) Long-term, nightly benzodiazepine treatment of
injurious parasomnias and other disorders of disrupted nocturnal sleep in 170 adults. Am. J. Med.
100(3), 333–337.
20. Salzman, C. (1998) Addiction to benzodiazepines. Psychiatr. Q. 69(4), 251–261.
21. Darcourt, G., Pringuey, D., Salliere, D., and Lavoisy, J. (1999) The safety and tolerability of
zolpidem—an update. J. Psychopharmacol. 13(1), 81–93.
22. Regestein, Q. R. and Reich, P. (1983) Incapacitating childhood-onset insomnia. Compr. Psychia-
try 24(3), 244–248.
23. Smits, M. G., Nagtegaal, E. E., van der Heijden, J., Coenen, A. M., and Kerkhof, G. A. (2001)
Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial. J.
Child. Neurol. 16(2), 86–92.
24. Attarian, H. (2002) Idiopathic Insomnia. In: MedLink Neurology (Gilman, S., Goldstein, G. W.,
Waxman, S. G., eds.), Arbor Publishing, San Diego, CA.
88 Attarian
Sleep State Misperception 89

8
Sleep State Misperception

Stephen Duntley

DEFINITION
Sleep state misperception (SSM) is defined by the International Classification
of Sleep Disorders (ICSD) as “a disorder in which a complaint of insomnia or
excessive sleepiness occurs without objective evidence of sleep disturbance” (1).
SSM is included under the category of primary insomnias in the fourth edition of
the Diagnostic and Statistical Manual of Mental Disorders (2). It is also referred to
as pseudoinsomnia, subjective complaint of disorder of initiating and maintaining
sleep without objective findings, and sleep hypochondriasis.

HISTORICAL PERSPECTIVES
Awareness that objective sleep findings and subjective sleep reports may differ
markedly emerged with the appearance of polysomnography as a research tool in
the late 1950s. In 1959, a case study was published reporting a marked discrepancy
between a patient’s subjective complaint of severe insomnia and objective sleep in
the laboratory (3). A 1976 study of 122 patients with chronic insomnia found wide-
spread differences between subjective and objective sleep parameters (4). The dis-
crepancy between subjective complaints of excessive sleepiness and objective
findings was noted after the adoption of the Multiple Sleep Latency Test (MSLT)
as an objective, validated test of daytime sleepiness (5). In 1990, the term sleep
state misperception was adopted as a diagnostic term in the ICSD, replacing the
terms subjective insomnia complaint without objective findings and subjective
sleepiness without objective findings (1).

EPIDEMIOLOGY
The population-based incidence and prevalence of SSM is unknown. In one large
series of patients presenting to a sleep disorders center, 9% of patients with insom-
nia and 5% of patients with excessive daytime sleepiness were classified as having
SSM (6). A more recent multicenter evaluation of the ICSD and DSM-IV classifica-
From: Current Clinical Neurology: Clinical Handbook of Insomnia
Edited by: H. P. Attarian © Humana Press Inc., Totowa, NJ

89
90 Duntley

tion systems found that SSM was a primary or secondary diagnosis in 6.6% of 216
patients with consecutive insomnia (7).

ETIOLOGY
The etiology of SSM is not known. Some discrepancy between subjective sleep
reports and polysomnographically recorded sleep is found in normal sleepers. For
instance, in one study of normal sleepers, 4–8 minutes after the first sleep spindle,
only 60% of individuals were aware of sleep onset, and at 16 minutes, 10% were
still unaware of sleep onset (8). Similarly, individuals are often unaware of being
asleep when awakened from stage 4 sleep (9). An attempt has been made to corre-
late multiple electroencephalogram (EEG) measures such as sleep stage, sleep-on-
set latency, waking time and arousal frequency, total sleep time, and sleep spindle
density with the perception of sleep. It is clear that no single factor or combination
of factors has been found to strongly relate EEG, behavioral, and subjective in-
dexes of sleep (10). Patients with insomnia tend to report more discrepancies than
normal sleepers, typically overestimating sleep latency (SL) and waking time (4,11–
13). How this discrepancy becomes further exaggerated to a clinically significant
SSM is unknown.
Salin-Pascual et al. noted that although sleep continuity measures did not differ
between patients with SSM and normal controls, the sleep-stage distribution of pa-
tients with SSM was similar to that of other patients with insomnia with more stage
1 and 2 sleep and less stage 3 and 4 sleep (14). Because of this finding, they sug-
gested that SSM might represent a transitional state between normal sleep and a
more extreme insomnia condition. Arguing against this view is the observation that
patients with psychophysiological insomnia rarely report a history of the complete
insomnia, which is so characteristic of patients with SSM. The authors also pro-
posed that SSM may represent a distinct subclassification of primary insomnia. It
has also been proposed that the hyperarousal seen in insomnia is not a unitary phe-
nomenon but consists of three components: somatic, cognitive, and central nervous
system (CNS) arousal. These three components can occur in varying degrees in
different patients. According to this theory, in SSM, CNS hyperarousal is dispro-
portionately present with relatively little of the cognitive or somatic hyperarousal,
which would lead to the polysomnographic changes found in psychophysiological
insomnia (15).

PATHOGENESIS AND PATHOPHYSIOLOGY

The biological basis of SSM is not known. Suggested possibilities include the
presence of a pre-sleep cognition that interferes with perception of sleep (16),
excessive mentation during sleep (17), or attenuation in the mesograde amnesia
that accompanies sleep (18). It is also possible that a physiological abnormality
exists in these patients that is not detected by standard polysomnography. For
instance, it has been shown that auditory stimuli sufficient to increase arterial blood
pressure or heart rate can result in daytime sleepiness despite the absence of EEG
Sleep State Misperception 91

arousals during the stimulus (19). Patients with SSM have been shown to have
elevated levels of physiological arousal as measured by 24-hour metabolic rate,
although the increase was less than observed in psychophysioligical insomnia (20).
Patients with SSM have demonstrated increased activity on actigraphy during sleep
(21). The tendency toward mislabeling sleep as wakefulness in insomnia may reflect
elevated levels of CNS arousal, and frequencies that are not normally quantified in
standard polysomnography may be important markers for this elevated arousal. In
one study, patients with insomnia who have low EEG α frequency activity during
sleep were more likely to underestimate total sleep time and overestimate awaken-
ings compared to patients with insomnia who have higher amounts of α frequency
EEG activity (22). It has also been demonstrated that increased β/γ activity is corre-
lated with the perception of wakefulness during sleep (23).
Another potential cause of SSM is the misperception or mislabeling of another
bodily state such as fatigue or depression. For instance, in two recent studies, both
nefazodone and fluoxetine alleviated depression and resulted in improvements in
subjective sleep quality, although patients given fluoxetine showed significant
declines in objective sleep characteristics such as increased number of awakenings
and decreased sleep efficiency (24,25). Similarly, no group difference in sleep diary
measures of sleep quality was seen between patients given nefazodone or
paroxetine, despite the declines in objective sleep measures in the patients given
paroxetine (26). Some patients may attribute daytime cognitive difficulties such as
trouble concentrating or memory problems to a poor night’s sleep or sleepiness,
when sleep is adequate and true sleepiness is not present.
Smith and Trinder were able to simulate SSM in 20 healthy volunteers who did
not have insomnia by causing microarousals from sleep through the manipulation
of the sleep environment. The same individuals did not have any misperception
when they were restudied on other nights when the sleep environment was not ma-
nipulated to cause the above mentioned arousals. Hence, the researchers postulated
that the cause of SSM in insomniacs is due at least partly to the increased number of
brief arousals from sleep (27). This sleep misperception as being awake also leads
to the perpetuation of the insomnia because of previous sleep being perceived as
wake time (13).

CLINICAL MANIFESTATIONS
Patients with SSM complain of either longstanding insomnia with difficulty ini-
tiating or maintaining sleep, nonrestorative sleep, or excessive daytime sleepiness
that is not documented by polysomnography and MSLT. The patient must report
that the symptoms were present during the testing. Unique to SSM is the tendency
for patients to report virtually no sleep for days, weeks, or even years. They often
vehemently claim that the essentially normal polysomnographic recordings are in
error. Like other forms of insomnia, clinically significant complaints are accompa-
nied by reports of waking dysfunction, such as fatigue that impairs social or occu-
pational function and that the patient believes will improve with treatment.
92 Duntley

Case 1
A 36-year-old female presented to the sleep center outpatient clinic for
initial evaluation of a lifelong history of insomnia. She stated that as far back
as she could remember, which is as young as 4 years old, she had a problem
with insomnia. She stated that over the past several years her problem had
worsened. There were nights when she did not sleep at all. Most nights she
went to bed between 8:30 and 11 PM, and it took her 3–4 hours to actually fall
asleep. She reported that she woke up after 45 minutes to 3 hours. The most
she slept in a 24-hour period was 3 hours. The next day she would feel se-
verely exhausted. She had tried and failed four different hypnotics. Despite
being fatigued, she could not take naps during the day. She did not fall asleep
unintentionally during the day in any situation. She denied gasping for air or
symptoms of restless legs or any pains, anxieties, or worries at night. She
stated that her daughter mentioned that she rarely snored. She denied any
morning headaches or dry mouth. She denied cataplexy symptoms and hyp-
nagogic hallucinations, but endorsed rare episodes (three in her entire life) of
sleep paralysis. She had no allergies, was not on any medications, and had a
past medical history of head banging and rocking sleep disorder as a child
and a teenager. She also had a severe febrile illness as an infant. Her family
history is significant for delayed sleep phase in her sister. Her social history
is significant for considerable amounts of caffeine intake in the form of cof-
fee and chocolate. A review of her systems was negative and her exam was
normal.
She came in for an overnight polysomnogram (PSG). The PSG revealed
6.8 hours of sleep with 7.9 brief arousals for no apparent reason per hour of
sleep. When questioned the next day as to how much she thought she had
slept, she mentioned that at best 2 hours.
She was set up with an actigraph and asked to fill out concomitantly sleep
logs.
Figure 1 shows her subjective perception of sleep on the sleep logs.
Figure 2 shows the objective amount of sleep she actually got as measured
by the actigraph.
The results were discussed with the patient and she was reassured. She
was accepting of the diagnosis. Unfortunately she was lost to followup.

DIFFERENTIAL DIAGNOSIS
The presenting symptoms of SSM may be difficult to distinguish from other
forms of insomnia. SSM shares many features with psychophysiological insomnia
and the underlying pathophysiology may be related. The longstanding, unremitting
character of the complaint may resemble idiopathic insomnia. Inadequate sleep
hygiene, generalized anxiety disorder, affective disorder, circadian rhythm disor-
ders, and medication use and abuse may co-exist with SSM, but do not explain the
 Sleep State Misperception
93

93
Fig. 1. Sleep log showing patient’s subjective perception of sleep. Shaded areas signify sleep; open areas signify wakefulness.
 94
94

Duntley
Fig. 2. The objective amount of sleep patient actually got as measured by the actigraph. High bars indicate wakefulness; low bars indicate
sleep.
Sleep State Misperception 95

marked discrepancy between objectively measured sleep and subjective reports.

Polysomnography is required because the distinguishing feature is normal SL and
continuity measures during polysomnographically measured sleep despite the
insomnia complaint. Primary sleep disorders such as sleep apnea syndrome and
periodic limb movement disorder may be associated with a perception of obtaining
virtually no sleep because the frequent arousals and awakenings in these disorders
may not allow normal perception of sleep. Unlike SSM, sleep continuity measures
in these patients are not normal, and other associated clinical symptoms usually
suggest the correct diagnosis.

DIAGNOSTIC WORKUP
As with other forms of insomnia, a thorough history and physical examination
are essential. The bedpartner should be interviewed if possible. Unlike other forms
of insomnia, however, polysomnography is essential for the diagnosis. The ICSD
(1) requires a PSG SL of less than 20 minutes, a minimum of 6.5 hours of sleep, and
a normal number of awakenings and arousals. Additionally, MSLT should show a
mean SL of greater than 10 minutes. The latter requirement is to assess for the
possibility that patients with idiopathic hypersomnia may interpret daytime sleepi-
ness as a consequence of inadequate sleep. However, because insomnia by nature
varies from night to night, occasionally bad sleepers can have a good night. There-
fore, the only way to diagnose SSM is if the individual states that he or she has not
slept well or not at all in the lab on a given night when the PSG shows normal sleep.
Although not required for diagnosis, actigraphy may be useful in establishing
the actual sleep patterns of these patients because, by definition, these indivduals
are unable to give accurate accounts of actual sleep time. Actigraphy is a recently
developed technique that records activity during waking and sleeping without
application of any electrodes. An actigraph is worn on the wrist and is about the
size of a watch. It consists of a movement detector and considerable memory, so it
can record movement and nonmovement data plotted against time for 1 or 2 weeks.
The patient can wear it continuously during sleep and as he or she performs routine
daily activities. Actigraphy is ideal for extended examination of the sleep–wake
cycle in the patient’s home environment. However, there may be a discrepancy in
some patients with SSM between actigraphy and polymsomnography, with wrist
actigraphy registering wakefulness, while the PSG shows sleep. Increased wrist
movements or similar events in these patients may be the reason they perceive them-
selves as awake when they are actually asleep.

PREVENTION
Because the cause of SSM is poorly understood, effective prevention is not pos-
sible. This disorder may share features with psychophysiological insomnia, thus, it
is possible that measures used for the prevention of psychophysiological insomnia
may also prevent SSM in some patients.
96 Duntley

PROGNOSIS AND COMPLICATIONS

The prognosis of this group is not clearly delineated. In many patients, it is
chronic and unremitting despite persistent treatment attempts. Drug dependence
may develop as patients attempt to treat either perceived insomnia or daytime sleepi-
ness with hypnotics or stimulants.

MANAGEMENT
Data on the treatment of SSM is extremely limited. Initial treatment should con-
sist of sharing with the patient the normal results of the sleep study, and educating
the patient about sleep while attempting to correct any misconceptions the patient
may have. Some patients will express relief, but many will refuse to accept the
results of the study. The same cognitive-behavioral techniques that are used to treat
psyhophysiological insomnia may be helpful for some patients. Hypnotics may pro-
vide symptomatic improvement despite the normal sleep continuity measures, but
caution should be used because of the risk of hypnotic dependence without clearly
defined benefits.

REFERENCES
1. American Sleep Disorders Association. (1990) International classification of sleep disorders:
diagnostic and coding manual. American Sleep Disorders Association, Rochester, MN.
2. American Psychiatric Association. (1994) Diagnostic and statistical manual of mental disorders
(4th ed.). American Psychiatric Association, Washington, DC.
3. Held, R., Schwartz, B., and Fischgold, H. (1959) Fausse insomnie: Etude psychoanalytique et
electroencephalographique. Presse Med. 67, 141–143.
4. Carskadon, M., Dement, W., Merrill, M., Guilleminault, C., Zarcone, V., and Spiegel, R. (1976)
Self-reports versus sleep laboratory findings in 122 drug-free subjects with complaints of chronic
insomnia. Am. J. Psychiatry 133, 1382–1388.
5. Richardson, G., Carskadon, M., Flagg, W., van den Hoed, J., Dement, W., and Mitler, M. (1978)
Excessive daytime sleepiness in man: multiple sleep latency measurement in narcoleptic and
control subjects. Electroencephalogr. Clin. Neurophysiol. 45, 621–627.
6. Coleman, R. M., Roffwarg, H. P., Kennedy, S. J., et al. (1982) Sleep wake disorders based on a
polysomnographic diagnosis. JAMA 247,997–1003.
7. Buysse, D., Reynolds, C., Kupfer, D., et al. (1994) Clinical diagnosis in 216 insomnia patients
using the International Classification of Sleep Disorders (ICSD), DSM-IV and ICD-10 catego-
ries: a report from the APA/NIMH DSM-IV Field Trial. Sleep 17, 630–637.
8. Bonnet, M. and Moore, S. (1982) The threshold of sleep: perception of sleep as a function of time
asleep and auditory threshold. Sleep 5, 267–276.
9. Switch, D. (1984) NREM sleep continuity and the sense of having slept in normal sleepers. Sleep
7,147–154.
10. Laposky, A., Anch, M., and Duntley, S. (2001) The association between EEG and sleep perception
during MSLT naps on subjects with excessive daytime sleepiness. Sleep and Hypnosis 3, 84–92.
11. Frankel, B., Coursey, R., Buchbinder, R., and Snyder, F. (1976) Recorded and reported sleep in
chronic primary insomnia. Arch. Gen. Psychiatry 33, 615–623.
12. Reynolds, C., Kupfer, D., Buysse, D., Coble, P., and Yeager, A. (1991) Subtyping DSM-III-R
primary insomnia: a literature review by the DSM-IV work group on sleep disorders. Am. J.
Psychiatry 148, 432–438.
Sleep State Misperception 97

13. Mercer, J., Bootzin, R., and Lack, L. (2002) Insomniacs’ perception of wake instead of sleep.
Sleep 25, 564–571.
14. Salin-Pascual, R., Roehrs, T., Merlotti, L., Zorick, F., and Roth, T. (1992) Long-term study of the
sleep of insomnia patients with sleep-state misperception and other insomnia patients. Am. J.
Psychiatry 149, 904–908.
15. Perlis, M., Merica, H., Smith, M., and Giles, D. (2001) Beta EEG activity and insomnia. Sleep
Med. Rev. 5, 365–376.
16. Borkovec, T. (1979) Pseudo (experiential)-insomnia and idiopathic(objective) insomnia: theo-
retical and therapeutic issues. Adv. Behav. Res. Ther. 2, 27–55.
17. Kuisk, L., Bertelson, A., and Walsh, J. (1989) Presleep cognitive hyperarousal and affect as fac-
tors in objective and subjective insomnia. Percept. Mot. Skills 69, 1219–1225.
18. Perlis, M. L., Smith, M. T., Orff, H. J., Andrews, P. J., and Giles, D. E. (2001) The mesograde
amnesia of sleep may be attenuated in subjects with primary insomnia. Physiol. Behav. 74, 71–76.
19. Martin, S., Wraith, P., Deary, I., and Douglas, N. (1997) The effect of nonvisible sleep fragmen-
tation on daytime function. Am. J. Respir. Crit. Care Med. 155, 1596–1601.
21. Bonnett, M. H. and Arand, D. L. (1997) Physiological activation in patients with sleep state
misperception. Psychosom. Med. 59(5), 533–540.
21. Hauri, P. and Wishbey, J. (1992) Wrist actigraphy in insomnia. Sleep 15, 293–301.
22. Schneider-Helmert, D. and Kumar, A. (1995) Sleep, its subjective perception, and daytime per-
formance in insomniacs with a pattern of alpha sleep. Biol. Psychiatry 37, 99–105.
23. Perlis, M., Smith, M., Orff, H., Andrews, P., and Giles, D. (2001) Beta/gamma activity in patients
with insomnia and in good sleeper controls. Sleep 24, 110–117.
24. Gillin, C., Rapaport, M., Winokur, A., and Albala, B. J. (1997) A comparison of nefazodone and
fluoxetine on mood and on objective, subjective, and clinician-rated measures of sleep in
depressed patients: A double-blind, 8-week clinical trial. J. Clin. Psychiatry 58, 185–192.
25. Rush, A. J., Armitage, R., Gillin, C., et al. (1998) comparative effects of nefazodone and
fluoxetine on sleep in outpatients with major depressive disorder. Biol. Psychiatry 44, 14.
26. Hicks, J, A., Argyropoulos, S. V., Rich, A. S., et al. (2002) Randomized controlled study of sleep
after nefazodone or paroxetine treatment in out-patients with depression. Br. J. Psychiatry 180,
528–535.
27. Smith, S. and Trinder, J. (2002) The effect of arousals during sleep onset on estimates of sleep
onset latency. J. Sleep Res. 9(2), 129–135.
28. Mercer, J. D., Bootzin, R. R., and Lack, L. C. (2002) Insomniacs’ perception of wake instead of
sleep. Sleep 25(5), 564–571.
29. Hauri, P. J. and Wisbey, J. (1992) Wrist actigraphy in insomnia. Sleep 15(4), 293–301.
98 Duntley
Sleep Hygiene 99

9
Sleep Hygiene

Hrayr P. Attarian

DEFINITION
The American Academy of Sleep Medicine (AASM; previously the American
Sleep Disorders Association [ASDA]) classifies poor sleep hygiene-induced
insomnia as one of the 13 extrinsic sleep disorders in the 1997 revised edition of the
International Classification of Sleep Disorders (ICSD) (1). Inadequate sleep
hygiene and extrinsic sleep disorders are those sleep disorders caused or main-
tained by forces outside the body, as opposed to intrinsic sleep disorders (e.g., nar-
colepsy, obstructive sleep apnea syndrome or psychophysiologic insomnia), which
are conditions where the pathophysiology depends on factors within the body. In
extrinsic sleep disorders, external factors are primarily responsible for producing
the symptoms. Removal of these factors is the first step of treatment and almost
always ameliorates if not completely resolves the disorder. Although the distinc-
tion between intrinsic and extrinsic sleep disorders is clear, the two may co-exist
and/or interact in an individual patient. Volitional extrinsic factors may initiate the
processes responsible for the development of some intrinsic sleep disorders, be-
coming internalized as the disorder develops. For example, psychophysiological
insomnia can develop after years of extrinsic sleep-destroying habits collectively
known as inadequate or poor sleep hygiene. Sleep hygiene refers to one’s engaging
in a set of behaviors that are conducive to falling asleep and staying sleep and
abstaining from behaviors that are not. For example, intake of caffeinated bever-
ages very close to bedtime produces insomnia resulting from caffeine’s stimulating
properties, thus constituting poor sleep hygiene. Setting aside relaxation or “down
time” prior to going to bed facilitates sleep, therefore making it an element of good
sleep hygiene.
The ICSD defines inadequate sleep hygiene as a sleep disorder resulting from
the performance of daily living activities that are inconsistent with the maintenance
of good-quality sleep and full daytime alertness (1).

From: Current Clinical Neurology: Clinical Handbook of Insomnia

Edited by: H. P. Attarian © Humana Press Inc., Totowa, NJ

99
100 Attarian

EPIDEMIOLOGY
There are no ethnic or racial predilections identified in poor sleep hygiene
insomnia and men and women are affected by it almost equally. Older teenagers
and young adults are one of the two groups especially affected by poor sleep hy-
giene. Manni et al. studied a large group of 17-year-old Italian high school stu-
dents. In this cohort, 19% of girls and 11.6% of boys had persistent insomnia due to
poor sleep hygiene (2). The other group especially affected is comprised of the
elderly, especially those dwelling in nursing homes (3). This is probably resulting
from the level of noise and ambient light present in this situation (4).
Patients suffering from chronic insomnia exhibit a complex interplay of internal
factors and poor sleep hygiene behaviors. It is impossible to tease out the magni-
tude of the roles each element plays in the development of the insomnia. Most
patients suffering from chronic and persistent insomnia have at least some features
of inadequate sleep hygiene admixed with the features of their primary disorder. It
is not known whether the sleep hygiene components are a result, or a partial cause,
of the main sleep problem. There is, however, evidence to suggest that sleep hygiene
education is at least partially effective in patients with primary insomnia (5,6). In a
survey conducted among 3600 adult Japanese women to identify external factors
causing insomnia, the prevalence of insomnia was found to be 11.2% (7). Most
complaints of insomnia were related to nighttime street noises.

ETIOLOGY
As discussed previously, the main cause of poor sleep hygiene insomnia is
the set of behaviors in which patients voluntary engage. These behaviors pro-
duce increased arousal or in some way disrupt normal sleep (1). These behaviors
are normal when practiced in moderation but cause insomnia when they occur in
susceptible people or in conjunction with other factors that disrupt sleep. Common
poor sleep hygiene practices include going to bed when not feeling sleepy; con-
suming moderate amounts of alcohol, caffeine, or nicotine close to bedtime; night-
to-night variability in bed and wake times; excessive napping, especially when done
in close proximity to the major sleep period; stimulation near bedtime (psychoso-
cial stress, excitement, physical exercise, stimulating mental activity, etc.) (8);
poorly regulated environmental elements such as ambient noise (7), light, or tem-
perature (8); or disturbing household members (9). A study done in community-
dwelling Japanese women found that living close to streets with high nighttime
traffic was the most important external risk factor for developing poor sleep hygiene
insomnia. Others included experiencing major life events, having children under
the age of 6 years, and having an irregular bedtime (7).

PATHOGENESIS AND PATHOPHYSIOLOGY

Not every individual who practices poor sleep hygiene develops insomnia. Per-
sons diagnosed with inadequate sleep hygiene insomnia have an underlying hyper-
Sleep Hygiene 101

Table 1
Sleep Hygiene Guidelines Used at Washington University Sleep Medicine Center
1. Go to bed only when sleepy.
2. Use the bed only for sleeping. Do not read, watch television, or eat in bed.
3. If unable to sleep, get up and move to another room. Stay up until you are definitely
sleepy and then return to bed.
4. Set the alarm and get up at the same time every morning, regardless of how much you
have slept through the night.
5. Do not nap.
6. Do not exercise just before going to bed.
7. Do not engage in stimulating activity just before bed.
8. Avoid caffeine in the afternoon.
9. Do not drink alcohol close to bedtime.
10. Eliminate clocks in the bedroom.
11. Before bedtime, schedule a period to review stressful events of the day.
12. Promote relaxation and sleep by focusing on quiescent tasks that occupy the mind such
as reading, watching television, or listening to music.

Table 2
Amount of Caffeine in Common Beverages
Beverage Amount of caffeine
1 cup of brewed coffee 100–150 mg
1 cup of instant coffee 85–100 mg
1 cup of tea 65–75 mg
12 ounces of cola 40–75 mg
1 cup of cocoa 50 mg

sensitivity to changes in their sleep schedules and minute amounts of external

stimuli. They have exaggerated physiological responses to even small amounts of
stimulants (caffeine, nicotine), alcohol, exercise, excitement, or strong environ-
mental disruptions, such as noise, shift work, and ambient light. It is thought that
these persons’ circadian control centers (suprachiasmatic nucleus) (10) also seem
to be sensitive to even minimal variations in their sleep schedules or to daytime
napping (1). Others who suffer from inadequate sleep hygiene insomnia because of
psychological or physical illness or because of an innate predisposition, may have a
particularly low tolerance to the effects of even infrequent sleep deprivation and, in
good faith, in an attempt to remedy the situation may resort to such poor sleep
hygiene behaviors as extra naps or bedtime alcohol. A combination of behaviors
that are nonconducive sleep and an innate physiological hyperarousal leads to the
development of poor sleep hygiene insomnia (11,12).
102 Attarian

CLINICAL MANIFESTATIONS
The main clinical symptom of inadequate sleep hygiene is insomnia. Other
symptoms may include dysphoric mood, fatigue, irritability, occasional
hypersomnia, and poor concentration. The time course of poor sleep hygiene-
induced sleep problems may vary from self-limiting and transient, to occa-
sional or even frequent but intermittent, or persistent. It may be the cause of
insomnia or may exacerbate an already existing one or itself may be the result
of a pre-existing primary or secondary insomnia. The insomnia may be sleep-
onset, sleep maintenance, or terminal resulting in early morning awakenings.
In some cases, it may present as irregular sleep patterns. The activities that
constitute poor sleep hygiene and lead to poor sleep hygiene insomnia usually
are common activities of daily life, which produce sleep disturbances in
people with an innate susceptibility. Behaviors that are considered
nonconducive to sleep include caffeine intake late in the afternoon or evening,
alcohol intake at night (often in an attempt to self-medicate), psychological
stress or excitement in the evening, obsessive clock watching while awake at
night, exercise or smoking late at night or close to bedtime, use of the bed for
activities unrelated to sleep (other than sex), variable bedtime and rise time,
going to bed when not sleepy, poorly regulated comfort measures in the bed-
room such as temperature, light, noise, uncomfortable bed, pets, and family
members or housemates who may engage in behaviors that are disruptive to
one’s sleep (13). Usually, in addition to an innate susceptibility, a combina-
tion of these behaviors and extrinsic factors is needed, any one of which might
be considered acceptable behavior in most people.
Case 1
A 46-year-old engineer presented with the complaint of sleep maintenance
insomnia. The patient had a bedtime between 10 and 11 PM, and had no diffi-
culty initiating sleep. He reporting awakening everyday at around 3 AM. He
subsequently was unable to return to sleep for the rest of the morning. This
problem was of about 2–3 years in duration. Over-the-counter hypnotics did
not help. The patient denied pain, worry, or anxiety at night. He had no his-
tory of snoring or witnessed apneas, falling asleep unintentionally during the
day, or any caffeine intake after an early morning cup of coffee. He denied
any neurovegetative symptoms of anxiety and depression. He was taking
Zestril and Lipitor. The patient’s exam was normal and his Beck’s Depres-
sion Inventory score was 4 (not depressed). When further questioned, he re-
vealed that he drinks on a nightly basis and over the past several years has
three glasses of wine or some other type of liquor just before going to bed. He
does this out of habit and denied having had problems falling asleep prior to
engaging in this nightly alcohol consumption. He was asked to reduce his
alcohol intake and to drink lesser amounts earlier in the evening.
At the next visit, 6 weeks later, his insomnia was resolved.
Sleep Hygiene 103

Case 2
A 26-year-old psychology student presented to the sleep medicine center’s
clinic for initial evaluation of recent sleep-onset initiation insomnia. In the
past, she had only rare problems falling and staying asleep. About 6–7 months
prior to coming to the center, the problem became persistent.
Currently, she goes to bed exhausted, sleepy, around midnight or 1 AM but is
still unable to fall asleep. She lays in bed anywhere from 30 minutes to 3–4
hours tossing and turning, but does not leave the bed or the bedroom. She usu-
ally gets up at 7 AM with an alarm and on weekends, when she doesn’t have to
go to work, she sleeps into late morning and sometimes, until early afternoon.
During the day, she takes a 45- to 90-minute nap. She also uses her bed-
room during the day to study, eat, watch television, read, and sometimes
works late into the night shortly before retiring. She does not abuse caffeine
and uses alcohol only socially. She does not abuse recreational drugs and
does not smoke. She denies cataplexy, hypnagogic hallucinations, snoring,
choking spells, falling asleep unintentionally during the day, or symptoms of
restless legs. The only symptom she states that she has experienced is rare
periods of sleep paralysis, maybe two to three times in her life time. She has
a past medical history of attention deficit hyperactivity disorder. She is tak-
ing Dexedrine and Ambien when needed. Her exam is normal and her Beck’s
Depression Inventory score is 6 (not depressed).

DIFFERENTIAL DIAGNOSIS
The differential diagnosis of poor sleep hygiene insomnia includes three main
categories of disorders. The other extrinsic sleep disorders are environmental sleep
disorder; adjustment sleep disorder; sleep-onset association disorder; nocturnal eat-
ing or drinking syndrome; limit-setting sleep disorder; food allergy insomnia;
insufficient sleep syndrome; altitude insomnia; the hypnotic-, stimulant-, and alco-
hol-dependent insomnias; and toxin-induced sleep disorder (1). Sometimes, it is
hard to differentiate individual disorders from each other because of significant
overlap among them.
The second main category is the primary insomnias, which include psychophysi-
ological insomnia, childhood-onset, or idiopathic insomnia, and sleep state
misperception insomnia (1). Any of these may co-exist with poor sleep hygiene and
may cause or be exacerbated by it.
The third category is the secondary insomnias, including insomnia due to other
sleep disorders such as obstructive sleep apnea, restless legs syndrome, periodic
limb movement syndrome, and even narcolepsy. Insomnia can be caused by a vari-
ety of neurological, psychiatric, and other medical illnesses. Degenerative neuro-
logical illnesses, anxiety disorders, asthma, and so on, are some examples. When
the symptoms of the underlying disorder are prominent, secondary insomnias are
usually suspected and diagnostic testing appropriate to the circumstance may eluci-
date the underlying cause of the insomnia.
104 Attarian

DIAGNOSTIC WORKUP
The diagnosis of inadequate sleep hygiene is best made through careful and
detailed history of the patient’s daily sleep-related habits (13). These include bed-
time, rise time, time spent in bed awake, different nonsleep-related activities in
which the patient engages in the bed and the bedroom including watching TV, read-
ing, and so on, timing of exercise, activities engaged in prior to bedtime and while
awake at night, amount and timing of caffeine or alcohol ingestion, and daytime
napping. In short, the diagnosis should try to identify any activity that is not com-
patible with sleep.
A useful diagnostic tool is a detailed sleep questionnaire completed by the patient
and the bedpartner (14,15). As in most primary insomnias, sleep diaries are essen-
tial tools in identifying sleep problems and charting their evolution and response to
treatment. In a paper published in 1998, Blake and Gomez introduced a simple but
useful questionnaire by which to measure compliance with sleep hygiene education
(16). As in most insomnias, a thorough psychiatric and medical evaluation, includ-
ing a physical exam, should be done to rule out medical or psychiatric causes of the
insomnia.
Per ASDA (now AASM) guidelines, polysomnography is not indicated in rou-
tine evaluation of insomnia, except when the diagnosis is uncertain and a primary
sleep disorder is suspected, and when insomnia does not respond to appropriate
behavioral and pharmacological treatments (17).

PROGNOSIS AND COMPLICATIONS

As in most extrinsic sleep disorders, once the underlying cause is removed, the
symptoms resolve completely. The sooner treatment is started, the more complete
the resolution of symptoms, and the better the prognosis. If poor sleep hygiene is
allowed to continue, psychophysiological insomnia may result in susceptible indi-
viduals. Some recent publications find a high correlation between poor sleep
hygiene, especially among younger drivers and high accident rates (18,19).

PREVENTION
Education is the cornerstone for the prevention of poor sleep hygiene insomnia.
Almost everyone engages in poor sleep hygiene at various times. There is also a
large number of external sleep disruptors such as noise, ambient light, and so on,
outside of one’s control. Although it is extremely important to educate people about
sleep hygiene, these rules do not strictly apply to everyone. A short daily nap is part
of the lifestyles of some cultures and does not necessarily constitute poor sleep
hygiene if it does not result in symptoms of insomnia or sleep disturbances. Simi-
larly, a cup of coffee or a drink with dinner or even reading in bed may not nega-
tively impact some people’s sleep. However, either because of their predisposition
or because of the additive effect of different factors, some people may develop
significant insomnia.
Sleep Hygiene 105

It is essential to inform people, at the first appearance of symptoms of the poten-

tial sleep problems that poor sleep hygiene can cause, and help identify and stop
them.

TREATMENT
Like all extrinsic sleep disorders, the mainstay of treatment needs to be modifi-
cation or complete removal of the external factors causing the insomnia. Sleep
hygiene must be taught and reinforced in patients suffering with this disorder (20).
It may be overwhelming for patients to follow every single sleep hygiene regula-
tion at once. This may lead to noncompliance. It is best to isolate two or three key
factors individualized to the patient and ask the patient to concentrate on those (13).
Other cognitive-behavioral treatment modalities may be helpful in select cases.
These include relaxation therapy, biofeedback, sleep-restriction consolidation, and
stimulus control therapy (13). Usually, however, sleep hygiene education is sim-
pler, easier to follow, and as effective as the more elaborate and difficult to follow
cognitive-behavioral therapy. In fact, of all the nonpharmacological/behavioral
treatments, sleep hygiene education is one of the most effective methods and one of
the easiest to follow (6).

REFERENCES
1. American Sleep Disorders Association. (1997) International classification of sleep disorders:
diagnostic and coding manual. American Sleep Disorders Association, Rochester, MN.
2. Manni, R., Ratti, M. T., Marchone, E., et al. (1997) Poor sleep in adolescents: a study of 869 17-
year-old Italian secondary school students. J. Sleep Res. 6(1), 44–49.
3. Schnelle, J. F., Cruise, P. A., Alessi, C. A., Ludlow, K., al-Smarrai, N. R., and Ouslander, J. G.
(1998) Sleep hygiene in physically dependent nursing home residents: behavioral and environ-
mental intervention implications. Sleep 21(5), 515–523.
4. Schnelle, J. F., Alessi, C., A., al-Samarrai, N. R., Fricker, R. D. Jr., and Ouslander, J. G. (1999)
The nursing home at night: effects of an intervention on noise, light, and sleep. J. Am. Geriatr.
Soc. 47(4), 430–438.
5. Martinez-Manzano, C. and Levario-Carrillo, M. (1997) [The efficacy of sleep hygiene measures
in the treatment of insomnia]. Gac. Med. Mex. 133(1), 3–6.
6. Friedman, L., Benson, K., Noda, A., et al., (2000) An actigraphic comparison of sleep restriction
and sleep hygiene treatments for insomnia in older adults. J. Geriatr. Psychiatry Neurol. 13(1),
17–27.
7. Kageyama, T., Kabuto, M., Netta, H., et al., (1997) A population study on risk factors for insomnia
among adult Japanese women: a possible effect of road traffic volume. Sleep 20(11), 963–971.
8. Onen, S. H., Onen, F., Bailley, D., and Parquet, P. (1994) [Prevention and treatment of sleep
disorders through regulation] of sleeping habits]. Presse Med. 23(10), 485–489.
9. Ulfberg, J., Carter, N., Talback, M., and Edling, C. (2000) Adverse health effects among women
living with heavy snorers. Health Care Women Int. 21(2), 81–90.
10. Ibata, Y., Okamura, H., Tanaka, M., et al. (1999) Functional morphology of the suprachiasmatic
nucleus. Front. Neuroendocrinol. 20(3), 241–268.
11. Bonnet, M. H. and Arand, D. L. (1996) The consequences of a week of insomnia. Sleep 19(6),
453–461.
12. Bonnet, M. H. and Arand, D. L. (1998) The consequences of a week of insomnia. II: Patients with
insomnia. Sleep 21(4), 359–368.
106 Attarian

13. Hauri, P. J. (1998) Insomnia. Clin. Chest Med. 19(1), 157–168.

14. Domino, G., Blair, G., and Bridges, A. (1998) Subjective assessment of sleep by Sleep Question-
naire. Percept. Mot. Skills 59(1), 163–170.
15. Buysse, D. J., Reynolds, C. F., 3rd, Monk, T. H., Berman, S. R., and Kupfer, D. J. (1989) The
Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychia-
try Res. 28(2), 193–213.
16. Blake, D. D. and Gomez, M. H. (1998) A scale for assessing sleep hygiene: preliminary data.
Psychol. Rep. 83(3 Pt 2), 1175–1178.
17. Chesson, A., Jr., Hartse, K., Anderson, W. M., et al. (2000) Practice parameters for the evaluation
of chronic insomnia. An American Academy of Sleep Medicine report. Standards of Practice
Committee of the American Academy of Sleep Medicine. Sleep 23(2), 237–241.
18. Laube, I., Seeger, R., Russi, E. W., and Bloch, K. E. (1998) Accidents related to sleepiness:
review of medical causes and prevention with special reference to Switzerland. Schweiz. Med.
Wochenschr. 128(40), 1487–1499.
19. Philip, P., Taillard, J., Guilleminault, C., Quera Salva, M. A., Boulac, B., and Ohayon, M. (1999)
Long distance driving and self-induced sleep deprivation among automobile drivers. Sleep 22(4),
475–480.
20. Lacks, P. and Rotert, M. (1986) Knowledge and practice of sleep hygiene techniques in insomni-
acs and good sleepers. Behav. Res. Ther. 24(3), 365–368.
Medical and Neurological Causes 107

III The Secondary Insomnias

108 Plotkin
Medical and Neurological Causes 109

10
Insomnia Caused by Medical
and Neurological Disorders

Kenneth E. Plotkin

Any systemic or neurological condition can cause sleep disruption. Diseases of

the central nervous system (CNS) in particular may profoundly affect sleep initia-
tion and maintenance by disrupting the structural and neurochemical substrates that
regulate sleep. Medical conditions can lead to chronic insomnia in several ways.
They may cause unpleasant stimuli, which in turn disrupt sleep continuity. They
may produce changes in systemic physiology that are vital to sleep continuity (as
with disorders of ventilation), or they may produce humoral changes that favor
awakening (as in thyroid or adrenal disease). The incidence of insomnia increases
with age as medical problems increasingly occur (1), and patients with chronic
insomnia are more likely to develop adverse health outcomes due to medical dis-
ease (2). The effects of acute and subacute sleep disruption can lead to psycho-
physiological insomnia by creating the anticipation of disturbed sleep and altering
circadian rhythms, further accentuating the disruptive effects of the underlying
medical condition. Difficulties with insomnia may persist long after the causative
medical condition has been effectively managed.
When describing the medical causes of insomnia, the most frequently recurring
theme is the disruptive influence of painful or unpleasant stimuli on sleep initiation
and maintenance. The polysomnographic appearance of sleep disturbance caused
by medical conditions is nonspecific, and most times is no different than any other
form of insomnia. The diagnosis is mostly made by clinical correlation, requiring a
thorough review of a patient’s general medical profile and a complete physical
examination. After a polysomnogram (PSG) has been recorded to evaluate for any
clear physiological causes of sleep disruption, an empirical approach to treatment
can begin.
Treatment of secondary insomnia draws on all of the commonly utilized behav-
ioral, pharmacological, and alternative medical approaches utilized in primary
insomnia. Optimizing the treatment of the underlying medical condition is the cor-
nerstone of effective insomnia management, along with attempts to improve the

From: Current Clinical Neurology: Clinical Handbook of Insomnia

Edited by: H. P. Attarian © Humana Press Inc., Totowa, NJ

109
110 Plotkin

quality of sleep. Ultimately, the treatment must also take into consideration poten-
tial complications produced by the medical condition(s), either a change in the natu-
ral course of the disease, or an untoward response to well-intended pharmacological
insomnia therapy. In cases where the medical condition has an intermittent charac-
ter, shorter term or intermittent insomnia treatment may be the best approach. In
progressive medical disorders, the management of associated insomnia may require
elaboration over time. More complicated cases should compel frequent review of
the applied management strategies, in order to avoid the maintenance of subopti-
mal therapy, the continuation of pernicious medications, and the ultimate surrender
of the patient to decline in level of function as sleep disruption becomes more pro-
found.
An attempt to comprehensively review major medical disorders is bound to leave
some conditions unaddressed. For most conditions there is, at best, anecdotal infor-
mation regarding insomnia as a feature of the disease process. Perhaps the best way
to frame the discussion is an approach to each organ system, allowing for the col-
lection of related disorders that may share a common overall effect on sleep conti-
nuity. This parallels the method used by physicians to categorize the symptomatic
profile (the Review of Systems) for a given patient, allowing for an orderly review
of potential medical issues during a general medical examination. The unique role
of each organ system in sleep disruption can be reviewed, even for disorders of
completely disparate etiology (e.g., a neoplastic vs inflammatory cause of disease),
along with the shared treatment issues.
The skin is the body’s largest organ, serving to sequester and protect the internal
environment from the outside world, and providing some of the most profound
early alerts of important environmental issues. It has the densest collection of nerve
terminals outside of the CNS. Any condition that imposes damage, pressure, or
irritation on the dermis will cause pain through dermal nerve endings, and the pain
will disturb the integrity of sleep. Infectious, allergic, or inflammatory skin condi-
tions are common potential causes of disturbed sleep initiation and maintenance.
Pain due to minor or major burns frequently delay sleep initiation, and may become
aggravated by involuntary body shifting during sleep. The acute phase of burn heal-
ing may be incredibly painful and may last several months in severe cases, and this
is the time of greatest sleep disturbance. The healing process may leave scar tissue
that is unusually sensitive or restrictive, prolonging the negative influence on sleep
quality. In a cohort suffering from herpes zoster reactivation, insomnia was one of
the most bothersome symptoms reported (25%), second only to pain (3). Lacera-
tions have a shorter healing time, but may produce nerve injury, and the subsequent
re-innervation can cause paroxysms of sharp, burning, or dull aching pain. Swell-
ing of soft tissues due to edema may be transient, intermittent, or chronic, but causes
epidermal discomfort that delays sleep onset and impairs sleep maintenance. Patho-
logical diaphoresis may be sufficiently severe to cause awakening due to cold, damp
bedclothes or sheets (4). The use of occlusive dressings, bandages, or splints may
produce discomfort and restrict movement during sleep. Oral corticosteroid medi-
Medical and Neurological Causes 111

cations may produce insomnia (5), particularly at higher doses, especially during
the initial period of use.
Amelioration of a skin condition may require a relatively short duration of treat-
ment, and therefore may cause only short-term sleep disruption. The use of hyp-
notic medication, especially shorter acting medications that are unlikely to produce
daytime sedation, may be ideally suited to a skin condition that has brief course
(such as poison ivy dermatitis) or intermittent exacerbation (such as eczema). Many
of the antihistamine medications used to reduce allergic response and itching are
sedating, improving sleep initiation and maintenance somewhat, but may cause
residual daytime effects on alertness and cognitive performance (6). The use of
medications such as amitriptyline or trazadone, which may improve the component
of insomnia caused by depression and pain, should be considered if duration and
severity of insomnia warrants their use, and if other medical conditions do not pre-
clude their use.
Problems in the nasopharynx, oropharynx, and larynx are a common cause of
sleep disruption. The most widely recognized condition that can be caused by the
pharyngeal tree is obstructive sleep apnea (OSA), which can be seen in association
with conditions such as nasal polyps, excessive submucosal oropharyngeal adipose
tissue, oropharyngeal or nasopharyngeal mass lesions, macroglossia, uvular hyper-
trophy, retrognathia, and pharyngeal muscle weakness. The neck may permit OSA
to occur if it is short, broad, restricted in motion, or has anterior adipose deposition.
Mass lesions, hyoid pathology, and cervical spine degenerative changes can also
cause OSA. Sleep apnea can produce secondary insomnia through chronic disrup-
tion of sleep continuity, and secondary insomnia in turn makes patients less toler-
ant of treatment with continuous positive airway pressure (CPAP) ventilation. The
diagnostic PSG will show worsened sleep efficiency, less deep sleep, more fre-
quent arousal from sleep, and longer arousal when OSA is complicated by insom-
nia. Upper airway resistance syndrome (UARS) may typify such a condition, where
less severely disordered breathing causes a disproportionately profound degree of
sleep disruption.
When insomnia complicates UARS and OSA, treatment with CPAP is poorly
tolerated and may require the adjunctive use of sedating medications, which will
worsen obstructive breathing to some extent. The availability of auto-titrating CPAP
and biphasic ventilation units may allow for more comfortable treatment, adjusting
the level of positive pressure required to overcome airway obstruction at any given
time. However, even the automatic changes in pressure settings may cause arousal
in a patient who suffers from insomnia. Because CPAP therapy is the most univer-
sally effective method of treating obstructive breathing during sleep, the addition
of a medication to improve sleep initiation and continuity is a reasonable option.
Shorter acting hypnotic medications (estazolam, zaleplon, zolpidem) will least
affect the overall architecture of sleep, but will only provide benefit for the initial
hours of sleep. Re-dosing of these medications may be considered, with the caveat
that patients are more likely to awaken with a “hangover” effect that mitigates some
112 Plotkin

of the therapeutic efficacy of CPAP. Longer acting hypnotic medications

(temazepam, clonazepam, diazepam, lorazepam) produce more alteration in sleep
architecture, and are more likely to have residual morning sedation as a side effect,
in addition to having more profound muscle relaxant effects that may worsen the
magnitude of obstructive breathing. Tricyclic antidepressant medications (such as
amitriptyline, nortriptyline, and trimipramine), trazadone, or a sedating antihista-
mine may help improve sleep initiation and continuity, but their side effects may
include daytime sleepiness and mucosal dryness, which aggravates the drying effect
of CPAP therapy on nasopharyngeal and oropharyngeal mucosa.
Postnasal drip caused by chronic allergic rhinitis or chronic/recurrent sinusitis
may cause frequent awakening by stimulating cough during sleep. Allergic, infec-
tious, or inflammatory pharyngitis can impair sleep continuity through the occur-
rence of local pain, which may be worsened on swallowing, or may stimulate
frequent reflexive swallowing. Sleep-related laryngospasm (7) or choking (8) has
been described, and may cause sufficient distress that the security of sleep is threat-
ened. Any painful condition affecting the airway can negatively affect the quality
of sleep, and when present for a sufficient duration or with sufficient frequency,
can cause secondary insomnia. Assessment of the head and neck may not provide
sufficient evidence of pathology in some cases. The diagnostic clue on a routine
PSG would be frequent bursts of submental myogenic activity, which in isolation
could also be interpreted as bruxism or a reflection of a nocturnal periodic move-
ment disorder. In this case, the bedpartner’s observations or the use of good quality
video/audio during PSG may help to identify the cause of sleep disruption, and help
to appropriately direct treatment.
Pulmonary disorders frequently cause some degree of sleep disruption, which
can develop over time into secondary insomnia. Asthma (9–11); chronic obstruc-
tive pulmonary disease (12,13); restrictive changes in the pulmonary bed (14);
bronchitis, pneumonitis, pleuritis, and neoplasia of the pulmonary tree can cause
disruption of ventilation, waxing/waning hypoxia (15), chest wall pain, and cough
that lead to frequent arousal and poor sleep continuity. Chronic hypoxia and
hypercarbia gradually desensitize carotid and CNS medullary chemoreceptors,
causing central apnea that can worsen the magnitude of ventilatory pathology, and
thereby the chronic nature of sleep disruption. Medications used to treat asthma,
including bronchodilators such as albuterol, the methylxanthines derivatives theo-
phylline and caffeine, and even inhaled steroid medications have an activating effect
on the CNS, prolonging sleep initiation and increasing the likelihood of arousal
from sleep. The appearance of sleep-disordered breathing in association with pul-
monary disease is well appreciated by the medical community, but optimal sleep
quality may not immediately return despite appropriate management of the pulmo-
nary problem. Medications used in the treatment of secondary insomnia due to pul-
monary dysfunction must be chosen carefully. The level of oxygenation and the
persistence of ventilatory drive may be challenged by even the short-acting hyp-
notic medications, and hypnotics with more muscle-relaxing qualities may com-
Medical and Neurological Causes 113

promise the additional ventilatory effort offered by chest wall musculature. The use
of tricyclic antidepressant medications is relatively contraindicated in asthma, due
to their propensity to aggravate bronchiolar constriction. Nonpharmacological treat-
ments (sleep restriction, light therapy) may be paired with very low doses of short-
acting hypnotic medications to enhance sleep initiation and continuity, and the
serotonin reuptake inhibitor paroxitine may have slightly sedating and anxiolytic
properties that prove useful for the treatment of secondary insomnia due to pulmo-
nary disease.
Cardiovascular diseases cause sleep disruption through nocturnal angina (16,17),
abnormal sensations such as palpitations or tachycardia (18), paroxysmal dyspnea,
or orthopnea related to congestive heart failure (CHF). More severe CHF produces
ventilatory changes during sleep as well, with periodic breathing of Cheyne-Stokes
character, or central apnea that produces frequent arousal. Orthopnea may require
that a patient recline only slightly from a sitting position, and the disturbance of
sleep continuity may be dramatic. Acute insomnia is a common sequela of myocar-
dial infarction (19). The medications used to treat cardiac disturbance may aggra-
vate sleep disruption. Vasodilating agents may produce headache that disrupts sleep
continuity, as may the rebound effects of morphine when it is used intermittently.
Digoxin may produce side effects including insomnia and headache, especially at
higher blood levels. Diuretic therapy at night causes frequent awakening to urinate.
The symptoms of cardiac disease and potentially pernicious effects of its treatment
are usually superimposed on the typical sleep fragmentation of elderly individuals,
but the chronicity and severity of cardiac disturbance will largely determine whether
secondary insomnia becomes sufficiently severe to require treatment. Once medi-
cal therapy has been optimized, the ideal approach will select therapy that has the
least chance of casing medical complications. As with severe pulmonary disease,
longer acting hypnotic medications are more likely to cause ventilatory compro-
mise. Tricyclic antidepressant medications can increase the possibility of cardiac
arrhythmia, and are relatively contraindicated. Trazadone may be somewhat less
likely to cause arrhythmia, but like the tricyclic agents, its residual effects in the
daytime may cause fatigue or hypersomnia. Creative treatment with shorter acting
hypnotic medications may be combined with efforts to maximize physical comfort
through special furniture, such as a hospital bed, to promote blocks of restful sleep
lasting a few hours at a time. Monophasic sleep may need to be sacrificed, in favor
of two or three smaller blocks of sleep that take advantage of the natural periods of
drowsiness that occur during the day. Treatment of disturbed ventilation may help
sleep continuity, avoid hypoxia, and provide more refreshing sleep, but CPAP
therapy is not well tolerated, and can actually aggravate central apnea. Biphasic
positive pressure ventilation may avoid exacerbation of central apnea, and may be
more tolerable in its promotion of normal ventilatory tidal movement.
Disorders of the gastrointestinal (GI) system may produce significant sleep dis-
turbance leading to secondary insomnia. The primary problem may remain occult,
even as PSG and attempts at therapeutic management proceed over the course of
114 Plotkin

months or years. The effects of gastroesophageal reflux disorder (GERD) (20) and
peptic ulcer disease (21) on sleep have led to their inclusion in the International
Classification of Sleep Disorders diagnositic and coding manual. GERD worsens
with reclining, especially if a person has eaten within 1 or 2 hours of sleep. GERD
is also worsened by obstructive breathing, as increased in intrathoracic pressure
produces an increase in abdominal displacement, causing more pressure within the
GI lumen and more tendancy for reflux through a hypotonic or incontinent lower
esophageal sphincter. The irritation of the esophageal mucosa causes arousal from
sleep, which appears on PSG to be spontaneous, without correlation on ventilatory
or electromyogram channels. Only the use of a nasogastric pH probe during PSG
will provide definitive diagnosis, but most sleep laboratories do not routinely per-
form such testing. Peptic ulcer disease is likely to be identified due to its typical
pattern of awakening in the early hours of sleep, with abdominal discomfort or
nausea. The untreated condition could certainly produce chronic sleep disruption,
but recurrent bouts of ulcer may eventually lead to chronic difficulties with sleep
maintenance and persistent early awakening. Pain and discomfort in association
with any infectious, inflammatory, allergic, or neoplastic intestinal disorders may
cause frequent nocturnal arousal, which may also include prolonged awakenings
for bathroom visits, requiring sleep to be reinitiated at a disadvantageous time dur-
ing the night. Milk (22) and other food allergies (23) have been suggested as a
cause of poor sleep in infants. The absence of a specific finding on PSG makes it
contingent on the clinician to infer the diagnosis from clinical history, and treat-
ment of the underlying disorder can be combined with short-term or longer term
treatment of secondary insomnia, which is likely to require at least some pharmaco-
therapy. The symptoms of esophageal reflux may be reduced by smoking cessa-
tion, weight loss, avoiding fatty/spicy foods, reducing daily caffeine intake, and
treatment with a variety of medications, including antacids, H2-receptor blockers,
proton pump inhibitors, and agents that improve gastric motility. Flexible dosing of
shorter acting hypnotic medications may be most appropriate for disorders that have
waxing and waning symptoms (inflammatory bowel disease) that appear at differ-
ent times of night. Longer acting hypnotic medications may be required when symp-
toms are more severe or enduring on a given night. Note that nearly all of the
hypnotic medications can aggravate intestinal problems by dehydrating mucosal
linings (tricyclic antidepressants, antihistamines), increasing motility (serotonin
reuptake inhibitors), or decreasing motility (benzodiazepines, barbiturates).
Urological disorders cause sleep disruption by compelling frequent awakening
for urination and frequent arousal due to pain. Progressive prostatic hypertrophy
compels frequent voiding of small urine volumes, ameliorated somewhat by medi-
cations that reduce the size of the prostate. Prostatic carcinoma may cause a similar
pattern, and resection of the prostate may produce urinary urgency and inconti-
nence, further exacerbating sleep dysfunction. Pain or discomfort related to inter-
stitial cystitis, prostatitis, bladder infection, or nephrolithiasis may cause awakening
or occult nocturnal arousal, resulting in insufficient sleep. Neurogenic bladder dys-
Medical and Neurological Causes 115

function may produce a hypotonic (overfilled) bladder that requires intermittent

catheterization to avoid overflow incontinence, or a hypertonic bladder that pro-
duces discomfort and the urge to void with the smallest amount of urine volume.
Once the cause of urological dysfunction has been identified and appropriately
addressed, the use of hypnotic medications tend to be benign, and the pharmacol-
ogy of different medications can be chosen for the most practical solution. Tricy-
clic antidepressant medications tend to cause urinary retention and increase urinary
hesitancy, and would not be an ideal choice. Chronic renal disease commonly causes
insomnia (24), worsened by electrolyte fluctuations caused by hemodialysis and
the high incidence of periodic limb movement disorder (PLMD).
The rheumatoid disorders, and musculoskeletal discomfort in general, are highly
associated with chronic sleep disruption. Rheumatoid arthritis (25,26), ankylosing
spondylitis (27), systemic lupus erythematosis (28), vasculitis, polymyalgia
rheumatica, and fibromyalgia (29) can produce sleep disruption, which may become
a very debilitating aspect of the disease, complicating functional recovery. Day-
time pain is reported to be worse following unrefreshing sleep (30). The pain cer-
tainly is a profound trigger of sleep disturbance, as are the effects of glucocorticoid
medications (31) commonly used to treat the rheumatoid diseases. The electroen-
cephalogram (EEG) during non-rapid eye movement (NREM) sleep may include
considerable alpha range activity, even in deep sleep (the “alpha-delta” sleep pat-
tern), but alpha intrusion is not specific to the rheumatoid disorders. The same pat-
tern may be seen in chronic fatigue syndrome (32), with its cardinal symptoms of
idiopathic fatigue, headache, arthralgia, myalgia, and insomnia (33). Osteoarthritis
may become more symptomatic as the morning approaches, after a night of relative
immobility, and may result in early awakening. Degenerative change of the spine,
scoliosis, and scleroderma may cause impaired ventilation, which causes frequent
arousals and impaired sleep.
Various endocrine disturbances cause insomnia, because of either the activating
effects of the hormones or the somatic discomfort produced by their imbalances.
Insomnia is more prevalent in hyperthyroidism, in association with a globally acti-
vated behavioral state, and sleep studies have shown an overall increase in the per-
centage of deep sleep (34) once difficulties with sleep initiation are overcome. The
return to a serological and clinical euthyroid state may not guarantee the resolution
of insomnia. Hypothyroidism more commonly causes fatigue and lethargy, and PSG
has shown an associated decrease in deep sleep. Adrenal dysfunction causing
catacholamine secretion will cause sympathetic activation and insomnia, and ex-
cessive glucocorticoid levels also cause insomnia (5,31). It has been suggested that
elevated glucocorticoid levels may alter the production of endogenous γ-
aminobutyric acid (GABA)-related steroid production (35), causing some of the
observed insomnia. Disruption of the hypothalamic–pituitary–adrenal axis has been
found in association with chronic insomnia, although it is not clear whether the
disruption of hormonal secretion is cause or effect of insomnia (36,37). There is
considerable clinical reporting of insomnia during menses (38), with or without
116 Plotkin

associated somatic discomfort, and during menopause (39). Insomnia is reported in

up to one-third of patients with diabetes mellitus (40). Treatment of sleep disrup-
tion in endocrine disturbance may be complicated by hormonal fluctuations and
potential medical complications of therapy, and may require multiple modalities,
spanning the pharmacological, behavioral, and alternative therapeutic realms.
Pregnancy may induce changes in sleep, which are observed to be most pro-
found in the first and third trimesters (41). The insomnia seen in the first trimester
of pregnancy may be related to hormone fluctuations, whereas the insomnia associ-
ated with the third trimester is typically caused by physical discomfort including a
firm, enlarged abdomen, urinary frequency, backache, hip ache, and fetal move-
ments (42). One study found that insomnia was reported more frequently in multi-
parous (vs nulliparous) women (43). Changes in sleep architecture have been shown
to include increased waking after sleep onset (WASO) and lower sleep efficiency,
along with decreased percentage of REM sleep (44). Sleep problems during preg-
nancy are frequently followed by postpartum sleep disruption caused by a
polyphasic sleeper (the neonate), and the incidence of maternal insomnia and de-
pression has been shown to increase when an infant has significant sleep problems
(45). Treatment of insomnia during pregnancy and breastfeeding provides a thera-
peutic challenge. Concerns must include the health of the developing child, to whom
some amount of medication is inevitably transferred, potentially affecting the
developing CNS (46). In most cases of pregnancy and lactation, it is best to apply
conservative behavioral and environmental treatment measures (47). In severe cases
of insomnia, pharmacological options can be used with the recognition that most
have an unknown effect on human fetal development, and some actually are con-
traindicated. In one study (48), benzodiazepines were shown to account for the
greatest number of psychotropic medication exposures during pregnancy. They
were mostly utilized to treat anxiety and insomnia, and no clustering of fetal mal-
formation was observed in the population studied.
Cancer may produce insomnia due to pernicious effects on systemic physiology,
painful tissue changes, therapeutic efforts, or the anxiety and depression accompa-
nying the diagnosis. Insomnia has been found to occur in more than half (53%) of
the patients with newly diagnosed lung cancer, and was felt to be a severe symptom
in more than one-quarter (49). Insomnia occurred in 19% of women with breast
cancer, and was of chronic character 95% of the time (50). Insomnia has been
examined in a variety of cancer types (51), and has been found to occur in about
one-third of cases, along with reports of fatigue, leg restlessness, and excessive
sleepiness. The fatigue associated with cancer treatment may in part be due to
insomnia (52). The claudication associated with hematologic disorders such as
sickle cell anemia causes severe intermittent sleep disruption (53), made worse by
occult sleep-disordered breathing and PLMD. Treatment should take into consider-
ation the anticipated duration of the underlying disease, and any potential medical
issues that could complicate pharmacotherapy. Insomnia therapy should be directed
to preserve the quality of daytime function, improving sleep with a minimum of
Medical and Neurological Causes 117

residual cognitive dulling, lingering hypnotic effects, or uncomfortable side effects.

There may be a role for medications that have antidepressant or anxiolytic charac-
teristics, especially in the early stages following cancer diagnosis. Chronic treat-
ment may be better achieved by nonpharmacologic interventions (54,55) such as
cognitive therapy, relaxation therapy, biofeedback, and behavioral approaches to
improve sleep quality.
Degenerative conditions of the CNS alter the chemical and structural substrates
that regulate sleep; most of these produce fragmented sleep, with or without day-
time hypersomnia. Disrupted sleep patterns are common in Alzheimer’s Dementia
(56), and the difficulties produced by perceptual impairment may aggravate noctur-
nal behaviors and confusion (57,58), characterized as a “sundown” syndrome. Cho-
linergic agonists or cholinesterase inhibitors utilized to treat Alzheimer’s Dementia
may aggravate difficulties with sleep initiation, by augmenting cholinergic tone in
the basal forebrain and cerebral cortex, favoring the maintenance of wakefulness.
Parkinson’s disease (PD) may disrupt sleep by way of tremor, dystonia, or periodic
nocturnal movements, whereas the dopamine agonist medications used for treat-
ment of PD may also cause insomnia, dystonia, or dyskinesia. Thus, inadequate
symptomatic treatment at night or the side effects of treatment may cause sleep
disruption by similar mechanisms. The dopamine agonists tend to enhance dream-
ing, and many patients report increased nightmares in association with bedtime
doses of levodopa and pergolide. These medications may also cause increased motor
activity during dreams. Lewy body dementia has a high incidence of REM behavior
disorder and sleep fragmentation (58a). The EEG in progressive supranuclear palsy
has been observed to include more elemental changes in sleep architecture, with
decreased total sleep time, decreased sleep spindles, and diminished REM sleep
(59,60). Multiple systems atrophy also produces considerable sleep disruption, with
increased arousal and diminished slow wave sleep (61). Huntington’s chorea has
been associated with decreased sleep efficiency, and sleep may become dramati-
cally fragmented as behavioral symptoms increase. Fatal Familial Insomnia is a
rare prion-associated spongeform encephalopathy with rapid progression through
fulminant insomnia to dementia and death over the course of months (62). Insom-
nia is also commonly seen in association with Creutzfeldt-Jakob disease (63,64),
especially when the thalamic degeneration is disproportionately observed.
Neuropathy and radiculopathy are associated with chronic pain, fasciculations,
and muscle spasms that cause impaired sleep initiation/maintenance, and periodic
limb movements of sleep are augmented in peripheral nerve disorders, further
exacerbating difficulties with sleep maintenance. Muscular dystrophy and inflam-
matory myopathies can cause insomnia by similar mechanisms, in addition to their
effects on ventilatory and pharyngeal musculature that lead to hypoventilation and
frequent aspiration. Most of the medications used to treat the symptoms of neur-
opathy are sedating for the majority of people who take them, but the
anticonvulsants carbamazepine and lamotrigine have been reported to cause
insomnia. Myelopathy can also cause pain, muscle spasms, spasticity, constipation,
118 Plotkin
Table 1
Causes of Secondary Insomnia
Skin conditions
Allergic, infectious, or inflammatory dermatitis
Burns
Herpes zoster reactivation (shingles)
Lacerations
Swelling
Edema
Diaphoresis
Dressings, bandages, or splints
Oral corticosteroid medications
Sleep-disordered breathing due to pathology in the nasopharynx, oropharynx, and larynx
Nasal polyps
Excessive oropharyngeal adipose tissue
Oropharyngeal or nasopharyngeal mass lesion
Macroglossia
Uvular hypertrophy
Retrognathia
Pharyngeal muscle weakness
Neck anatomy (short, broad, restricted in motion, anterior adipose deposition)
Cervical mass lesions
Hyoid pathology
Cervical spine degeneration
Other conditions affecting the pharyngeal and laryngeal tree
Postnasal drip
Chronic/recurrent sinusitis
Allergic, infectious, or inflammatory pharyngitis
Sleep-related laryngospasm, choking, or repetitive swallowing
Bruxism
Pulmonary disorders
Asthma
Chronic obstructive pulmonary disease
Restrictive/interstitial pulmonary disease
Bronchitis
Pneumonia/pneumonitis
Pleuritis
Pulmonary neoplasia
Hypoxia
Chest wall pain
Cough
Bronchodilator medications, methylxanthines derivatives, inhaled steroids
Cardiovascular diseases
Nocturnal angina
Ppalpitations, tachycardia, arrythmia
Paroxysmal dyspnea
Orthopnea

118
Medical and Neurological Causes 119
Table 1 (continued)
Congestive heart failure
Myocardial infarction
Vasodilating medications
Digoxin
Diuretics
Disorders of the gastrointestinal system
Gastroesophageal reflux disorder
Gastric and peptic ulcer disease
Infectious, inflammatory, allergic intestinal disorders
Neoplasia of the gastrointestinal tract
Milk allergy/food allergies
Urological disorders
Prostatic hypertrophy
Prostatic carcinoma
Prostatitis
Interstitial cystitis
Bladder infection
Nephrolithiasis
Neurogenic bladder
Chronic renal disease
Hemodialysis
Rheumatoid/musculoskeletal disorders
Rheumatoid arthritis
Ankylosing spondylitis
Systemic lupus erythematosis
Vasculitis
Polymyalgia rheumatica
Fibromyalgia
Pain
Chronic fatigue syndrome
Osteoarthritis
Degenerative change of the spine
Scoliosis
Scleroderma
Endocrine changes
Hyperthyroidism
Hypothyroidism
Adrenal dysfunction
Menses
Menopause
Diabetes mellitus
Pregnancy
Neoplastic or hematologic disorders
Disorders of the nervous system
Alzheimer’s dementia
Parkinson’s disease
(continued)
119
120 Plotkin

Table 1 (continued)
Lewy body dementia
Progressive supranuclear palsy
Multiple systems atrophy
Huntington’s disease
Fatal Familial Insomnia
Creutzfeldt-Jakob disease
Neuropathy/radiculopathy
Muscular dystrophy
Inflammatory myopathy
Myelopathy
Amyotrophic lateral sclerosis
Stroke
Multiple sclerosis
Antoparkinsonian medications
Cholinergic agonists
Interferon therapy
Cerebral mass lesions
Cerebral palsy
Headache
Head injury
Encephalitis/meningitis (including Lyme disease and HIV)
Epileptic syndromes

and bladder dysfunction that contribute to secondary insomnia. Restriction of body

movement by severe neuropathy or myelopathy can cause discomfort due to the
development of soreness over bony prominences, pressure sores, or arthralgia due
to malpositioned extremities. For this reason, insomnia becomes especially promi-
nent with the symptomatic progression of amyotrophic lateral sclerosis, worsening
as bulbar involvement becomes prevalent (65).
Stroke can produce impaired sleep due to structural changes in the cerebrum
(56,66), especially when ischemia has affected the thalamus, anterior hypothala-
mus, or the central pons (67). A stroke can also produce insomnia by way of its
associated physical symptoms, such as movement restriction due to paresis, sen-
sory disruption causing parasthesia/dysesthesia, or impaired pharyngeal function
causing aspiration and obstructive breathing. Multiple sclerosis may cause insom-
nia as demyelinated plaques involve more of the cortical mantle or the diencepha-
lon, and may also be aggravated by motor, sensory, or urological symptoms that
increase with the progression of the disease. Insomnia has also been reported with
various forms of interferon therapy (68). It has been seen with lesions involving the
pituitary (69) and pineal gland (70). Cerebral palsy may significantly affect sleep
Medical and Neurological Causes 121

architecture (71), and assessment by PSG may be made difficult by the significant
EEG alterations seen with more severe structural abnormalities in the brain.
Headache may occur during sleep, as in the syndromes of cluster headache (72),
paroxysmal hemicrania, and migraine headache, producing significant sleep dis-
ruption (73). These headache types may appear intermittently or in occasional flur-
ries of several nights, and are less often associated with chronic insomnia. The
rebound headache caused by analgesic overuse, drug abuse, or drug withdrawal is
more likely to cause chronic problems with awakening that impairs the quality of
sleep (74). Nocturnal headache may also reflect sleep-related pathology such as
bruxism or sleep apnea (75). Acute head injury typically produces hypersomnia,
gradually changing to insomnia over the course of weeks to months. Milder head
trauma may produce chronic insomnia of disproportionate character (76), typically
accompanied by a variety of somatic symptoms. Meningitis and encephalitis may
cause acute and chronic changes in sleep quality. The acute phase of an encephal-
itic process may produce symptoms ranging from hypersomnia to agitation and
delirium. After the resolution of acute infection, insomnia is a common sequela
(77). Insomnia may also be seen in paraneoplastic encephalitis (78). Insomnia may
be seen following CNS involvement in Lyme disease (79), and is common in
chronic HIV infection (80).
Epileptic syndromes may include nocturnal seizures of sufficient frequency to
cause sleep disruption, and cumulative sleep disruption may in turn increase the
frequency of seizures. Studies have shown that up to 45% of people with epilepsy
have their seizures mostly during the night (81). Autosomal-dominant frontal lobe
epilepsy, lesional frontal lobe epilepsy, benign partial epilepsy with centrotemporal
spikes (Benign Rolandic Epilepsy), and electrical status epilepticus of sleep pro-
duce seizures that occur mostly during sleep. Juvenile myoclonic epilepsy, tempo-
ral lobe epilepsy, and symptomatic generalized epilepsy (Lennox-Gastaut
Syndrome) may include seizures that predominate during sleep. Sleep architecture
in epilepsy may be disturbed even on nights without seizure activity, as shown in a
cohort of patients with temporal lobe epilepsy compared to normal controls (82).
Changes in sleep architecture may include decreased total sleep time, decreased
sleep efficiency, increased arousals, increased WASO, and reduced REM sleep. Of
the anticonvulsant medications, insomnia has been reported most often with mem-
brane-stabilizing agents including phenytoin, carbamazepine, oxcarbazepine,
lamotrigine, and felbatol. Anticonvulsant medications that enhance GABA tone in
the CNS, such as barbiturates, benzodiazepines, valproic acid, tiagabine,
gabapentin, and vigabatrin, are less likely to cause insomnia. Studies of sleep archi-
tecture during anticonvulsant therapy have shown a broad range of effects, includ-
ing a reduction in slow wave sleep and an increase in stages 1 and 2 of NREM sleep
(83) during chronic treatment. Some studies have shown contradictory effects, and
there has been little correlation of sleep effects with anticonvulsant drug levels.
Overall, the sleep-related benefits of improved seizure control may outweigh any
negative influence the anticonvulsant medications might have on sleep (84).
122 Plotkin

REFERENCES
1. Foley, D. J., Mojan, A., Simonsick, E. M., Wallace, R. B., and Blazer, D. G. (1999) Incidence and
remission of insomnia amoung elderly adults: an epidemiologic study of 6800 persons over three
years. Sleep 22(Suppl 2), S366–S372.
2. Katz, D. A. and McHorney, C. A. (1998) Clinical correlates of insomnia in patients with chronic
illness. Arch. Intern. Med. 158(10), 1099–1107.
3. Goh, C. L. and Khoo, L. (1997) A retrospective study of the clinical presentation and outcome of
herpes zoster in a tertiary dermatology outpatient referral clinic. Int. J. Dermatol. 36(9), 667–672.
4. Lea, M. J. and Aber, R. C. (1985) Descriptive epidemiology of night sweats upon admission to a
university hospital. South. Med. J. 78, 1065–1067.
5. Radakovic-Fijan, S., Furnsinn-Friedl, A. M., Honigsmann, H., and Tanew, A. (2001) Oral dex-
amethasone pulse treatment for vitiligo. J. Am. Acad. Dermatol. 44(5), 814–817.
6. Kay, G. G., Plotkin, K. E., Quig, M. B., Starbuck. V. N., and Yasuda, S. (1997) Sedating effects
of AM/PM antihistamine dosing with evening chlorpheniramine and morning terfenadine. Am. J.
Manag. Care 3, 1843–1848.
7. Thorpy, M. J. and Aloe, F. (1989) Sleep-related laryngospasm. Sleep Res. 18, 313.
8. Thorpy, M. J. and Aloe, F. (1989) Choking during sleep. Sleep Res. 18, 314.
9. Douglas, N. J. (1989) Asthma. In: Principles and practice of sleep medicine (Kryger, M. H.,
Roth, T., and Dement, W. C., eds.), WB Saunders, Philadelphia, PA, pp. 591–600.
10. Montplaisir, J., Walsh, J., and Malo, J. L. (1982) Nocturnal asthma features of attacks, sleep, and
breathing patterns. Am. Rev. Respir. Dis. 125, 18–22.
11. Janson, C., Gislason, T., Boman, G., Hetta, J., and Roose, B. E. (1990) Sleep disturbances in
patients with asthma. Respir. Med. 84, 37.
12. Flenley ,C. (1989) Chronic obstructive pulmonary disease. In: Principles and practice of sleep
medicine (Kryger, M. H., Roth, T., and Dement, W. C., eds.), WB Saunders, Philadelphia, PA,
pp. 601–610.
13. Fletcher, E. C., Martin, R. J., and Monlux, R. D. (1982) Disturbed EEG sleep patterns in chronic
obstructive pulmonary disease. Sleep Res. 11, 186.
14. Perez-Padilla, R., West, P., Lertzman, M., and Kryger, M. H. (1985) Breathing during sleep in
patients with interstitial lung disease. Am. Rev. Respir. Dis. 132, 224
15. Calverley, P. M., Brezinova, V., Douglas, N. J., Catterall, J. R., and Flenley, D. C. (1982) The
effects of oxygenation on sleep quality in chronic bronchitis and emphysema. Am. Rev. Respir.
Dis. 126, 206–210.
16. Nowlin, J. B., Troyer, W. G., Jr., Collins, W. S., et al. (1965) The association of nocturnal angina
pectoris with dreaming. Ann. Intern. Med. 63,1040–1046.
17. Karacan, I., Williams, R. L., and Taylor, W. J. (1969) Sleep characteristics of patients with an-
gina pectoris. Psychosomatics 10, 280.
18. Willmer, J. P. and Broughton, R. J. (1989) Neurogenic sleep related polypnea-a new disorder?
Sleep Res. 18, 322.
19. Karacan, I., Green, J. R., Taylor, W. J., et al. (1973) Sleep characteristics of acute myocardial
infarct patients in an ICU. Sleep Res. 2, 159.
20. Orr, W. C., Robinson, M. G., and Johnson, L. F. (1981) Acid clearing during sleep in the patho-
genesis of reflux esophagitis. Dig. Dis. Sci. 26, 423–427.
21. Orr, W. C. (1989) Gastrointestinal disorders. In: Principles and practice of sleep medicine (Kryger,
M. H., Roth, T., and Dement, W. C., eds.), WB Saunders, Philadelphia, PA, pp. 622–629.
22. Kahn, A., Rebuffat, E., Blum, D., et al. (1987) Difficulty in initiating and maintaining sleep
associated with cow’s milk allergy in infants. Sleep 10(2), 116–121.
23. Brigino, E. and Bahna, S. L. (1995) Clinical features of food allergy in infants. Clin. Rev. Allegry
Immunol. 13(4), 329–345.
24. Kimmel, P. L. (1989) Sleep disorders in chronic renal disease. J. Nephrol. 1, 59.
25. Nicassio, P. M. and Wallston, K. A. (1992) Longitudinal relationships amoung pain, sleep prob-
lems, and depression in rheumatoid arthritis. J. Abnorm. Psychol. 101(3), 514–520.
Medical and Neurological Causes 123

26. Bloom, B. J., Owens, J. A., McGuinn, M., Nobile, C., Schaeffer, L., and Alario, A. J. (2002)
Sleep and its relationship to pain, dysfunction, and disease activity in juvenile rheumatoid arthri-
tis. J. Rheumatol. 29(1), 169–173.
27. Tanfield, M. (1978) Ankylosing spondylitis and sleep. Lancet 1(8070), 944–945.
28. Ivanova, M. M., Blizniuk, O. I., Shchekut’ev, G. A., and Pushkova, O. V. (1991) Diagnosis of
lesions of the central nervous system in patients with systemic lupus erythematosus.
Revmatologiia 4, 6–9.
29. Hagan, K. B., Kvien, T. K., and Bjorndal, A. (1997) Musculoskeletal pain and quality of life in
patients with noninflammatory joint pain compared to rheumatoid arthritis: a population survey.
J. Rheumatol. 24(9), 1703–1709.
30. Walsh, J. K., Muelbach, M. J., Lauter, S. A., Hilliker, N. A., and Schweitzer, P. K. (1996) Effects
of triazolam on sleep, daytime sleepiness, and morning stiffness in patients with rheumatoid ar-
thritis. J. Rheumatol. 23(2), 245–252.
31. Fadeev, V. V., Gitel, E. P., and Mel’nichenko, G. A. (2001) The diurnal rhythm of adrenocortico-
tropic hormone secretion in the assessment of the adequacy of replacement therapy in primary
chronic adrenal failure. Neurosci. Behav. Physiol. 31(3), 237–242.
32. Manu, P., Lane, T. J., Matthews, D. A., Castriotta, R. J., Watson, R. K., and Abeles, M. (1994)
Alpha-delta sleep in patients with a chief complaint of chronic fatigue. South. Med. J. 87, 465.
33. Buchwald, D., Pascualy, R., Bombardier, C., and Kith, P. (1994) Sleep disorders in patients with
chronic fatigue. Clin. Infect. Dis. 18, S68.
34. Kales, J. D. and Kales, A. (1975) Nocturnal psychophysiological correlates of somatic conditions
and sleep disorders. Int. J. Psychiatry Med. 6(1-2), 43–62.
35. Sturenburg, H. J., Fries, U., and Kunze, K. (1997) Glucocorticoids and anabolic/androgenic steroids
inhibit the synthesis of GABAergic steroids in rat cortex. Neuropsychobiology 35(3), 143–146.
36. Maes, M., Meltzer, H. Y., Suy, E., Minner, B., Calabrese, J., and Cosyns, P. (1993) Sleep disor-
ders and anxiety as symptom profiles of sympathoadrenal system hyperactivity in major depres-
sion. J. Affect. Disord. 27(3), 197–207.
37. Vgontzas, A. N., Bixler, E. O., Lin, H. M., et al. (2001) Chronic insomnia is associated with
nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications. J. Clin.
Endocrinol. Metab. 86(8), 3787–3794.
38. Hart, W. G. and Russell, J. W. (1986) A prospective comparison study of premenstrual symp-
toms. Med. J. Aust. 144(9), 466–468.
39. Coope, J. (1996) Hormonal and non-hormonal interventions for menopausal symptoms. Maturitas
23(2), 159–168.
40. Sridhar, G. R. and Madhu, K. (1994) Prevalence of sleep disturbances in diabetes mellitus. Dia-
betes Res. Clin. Pract. 23(3), 183–186.
41. Baratte-Beebe, K. R. and Lee, K. (1999) Sources of midsleep awakenings in childbearing woman.
Clin. Nurs. Res. 8(4), 386–397.
42. Suzuki, S., Dennerstein, L., Greenwood, K. M., Armstrong, S. M., and Satohisa, E. (1994) Sleeping
patterns during pregnancy in Japanese woman. J. Psychosom. Obstet. Gynaecol. 15(1), 19–26.
43. Oga, M., Shono, H., Kohara, M., Ito, Y., Tanaka, T., and Sugimori, H. (1995) Chronological
changes in subjective symptoms during pregnancy in nulliparous and multiparous women. Acta
Obstet. Gynecol. Scand. 74(10), 784–787.
44. Hertz, G., Fast, A., Feinsilver, S. H,, Albertario, C. L., Schulman, H., and Fein, A. M. (1992)
Sleep in normal late pregnancy. Sleep 15(3), 246–251.
45. Hiscock, H. and Wake, M. (2001) Infant sleep problems and postnatal depression: a community-
based study. Pediatrics 107(6), 1317–1322.
46. Mirmiran, M., Brenner, E., van der Gugten, J., and Swaab, D. F. (1985) Neurochemical and
electrophysiological disturbances mediate developmental behavioral alterations produced by
medicines. Neurobehav. Toxicol. Teratol. 7(6), 677–683.
47. Mortola, J. F. (1989) The use of psychotropic agents in pregnancy and lactation. Psychiatr. Clin.
North Am. 12(1), 69–87.
124 Plotkin

48. Marchetti, F., Romero, M., Bonati, M., and Tognoni, G. (1993) Use of psychotropic drugs during
pregnancy. A report of the international co-operative drug use in pregnancy (DUP) study. Col-
laborative Group on Drug Use in Pregnancy. Eur. J. Clin. Pharmacol. 45(6), 495–501.
49. Ginsberg, M. L., Quirt, C., Ginsberg, A. D., and MacKillop, W. J. (1995) Psychiatric illness and
psychosocial concerns of patients with newly diagnosed lung cancer. CMAJ 152(12), 1961–1963.
50. Savard, J., Simard, S., Blanchet, J., Ivers, H., and Morin, C. M. (2001) Prevalence, clinical char-
acteristics, and risk factors for insomnia in the context of breast cancer. Sleep 24(5), 583–590.
51. Davidson, J. R., MacLean, A. W., Brundage, M. D., and Schulze, K. (2002) Sleep disturbance in
cancer patients. Soc. Sci. Med. 54(9), 1309–1321.
52. Stone, P., Richards, M., A’Hern, R., and Hardy, J. (2001) Fatigue in patients with cancers of the
breast or prostate undergoing radical radiotherapy. J. Pain Symptom. Manage. 22(6), 1007–1015.
53. Brooks, L. J., Koziol, S. M., Chiarucci, A. M., and Berman, B. W. (1996) Does sleep-disordered
breathing contribute to the clinical severity of sickle cell anemia? J. Pediatr. Hematol. Oncol. 18, 135.
54. Savard, J. and Morin, C. M. (2001) Insomnia in the context of cancer: a review of a neglected
problem. J. Clin. Oncol. 19(3), 895–908.
55. Davidson, J. R., Waisberg, J. L., Brundage, M. D., and MacLean, A. W. (2001) Nonpharmacologic
group treatment of insomnia: a preliminary study with cancer survivors. Psycho-Oncology 10(5),
389–397.
56. Mishima, K., Okawa, M., Satoh, K., Shimizu, T., Hozumi, S., and Hishikawa, Y. (1997) Differ-
ent manifestations of circadian rhythms in senile dementia of Alzheimer’s type and multi-infarct
dementia. Neurobiol. Aging 18, 105–109
57. Evans, L. K. (1987) Sundown Syndrome in the Institutionalized Elderly. J. Am. Geriatr. Soc.
35(2), 101–108.
58. Lipowski, Z. J. (1989) Delirium in the Elderly patient. N. Engl. J. Med. 320(9), 578–582.
58a. Boeve, B. F., Silber, M. H., Ferman, T. J., et al. (1998) REM sleep behavior disorder and degen-
erative dementia: an association likely reflecting Lewy body disease. Neurology 51(2), 363–370.
59. Montplaisir, J., Petit, D., Decary, A., et al. (1997) Sleep and quantitative EEG in patients with
progressive supranuclear palsy. Neurology 49(4), 999–1003.
60. Aldrich, M. S., Foster, N. L., White, R. F., Bluemlein, L., and Prokopowicz, G. (1989) Sleep
Abnormalities in progressive supranuclear palsy. Ann. Neurol. 25(6), 577–581.
61. Chokroverty, S. (1992) The assessment of sleep disturbance in autonomic failure. In: Autonomic
Failure: A textbook of Clinical Disorders of the Nervous System, 3rd ed. (Bannister, R. and
Mathias, C. J., eds.), Oxford University Press, London, pp. 442–461.
62. Montagna, P. (1999) Fatal familial insomnia: clinical, laboratory, and pathological features. Reve.
Neurol. 29(11), 1006–1009.
63. Taratuto, A. L., Piccardo, P., Reich, E. G., et al. (2002) Insomnia associated with thalamic in-
volvement in E200K Creutzfeldt-Jakob disease. Neurology 58(3), 362–367.
64. Terzano, M. G., Parrino, L., Pietrini, V., et al. (1995) Precocious loss of physiological sleep in a
case of Creutzfeldt-Jakob disease: a serial polygraphic study. Sleep 18(10), 849–858.
65. Chokroverty, S. (1996) Sleep and degenerative neurological disorders. Neurol. Clin. 14(4), 807–826.
66. Guilleminault, C., Quera-Salva, M. A., and Goldberg, M. P. (1993) Pseudo-hypersomnia and pre-
sleep behaviour with bilateral paramedian thalamic lesions. Brain 116, 1549–1563.
67. Autret, A., Lucas, B., Mondon, K., et al. (2001) Sleep and brain lesions: a critical review of the
literature and additional new cases. Neurophysiol. Clin. 31(6), 356–375.
68. Hosoda, S., Takimura, H., Shibayama, M., Kanamura, H., Ikeda, K., and Kumada, H. (2000)
Psychiatric symptoms related to interferon therapy for chronic hepatitis C: clinical features and
prognosis. Psychiatry Clin. Neurosci. 54(5), 565–572.
69. Tonomo, Y., Ono, Y., Matsumura, A., and Maki, Y. (1983) Insomnia in patients with pituitary
adenomas. Clin. Neurol. 23(8), 689–693.
70. Etzioni, A., Luboshitzky, R., Tiosano, D., Ben-Harush, M., Goldsher, D., and Lavie, P. (1996)
Melatonin replacement corrects sleep disturbances in a child with pineal tumor. Neurology 46(1),
261–263.
Medical and Neurological Causes 125

71. Zucconi, M. and Bruni, O. (2001) Sleep disorders in children with neurological diseases. Semin.
Pediatr. Neurol. 8(4), 258–275.
72. Sahota, P. K. and Dexter, J. D. (1993) Transient recurrent situational insomnia associated with
cluster headache. Sleep 16(3), 255–257.
73. Paiva, T., Batista, A., Martins, P., and Martins, A. (1995) The relationship between headaches
and sleep disturbances. Headache 35(10), 590–596.
74. Hering-Hanit, R., Yavetz, A., and Dagan, Y. (2000) Effect of withdrawal of misused medication on
sleep disturbances in migraine sufferers with chronic daily headache. Headache 40(10), 809–812.
75. Biondi, D. M. (2001) Headaches and their relationship to sleep. Dent. Clin. North Am. 45(4),
685–700.
76. Evans, R. W. (1992) The postconcussion syndrome and the sequelae of mild head injury. Neurol.
Clin. 10(4), 815–847.
77. Hodgson, A., Smith, T., Gagneux, S., et al. (2001) Survival and sequelae of meningococcal men-
ingitis in Ghana. Int. J. Epidemiol. 30(6), 1440–1446.
78. Deodhare, S., O’Connor, P., Ghazarian, D., and Bilbao, J. M. (1996) Paraneoplastic limbic en-
cephalitis in Hodgkin’s disease. Can. J. Neurol. Sci. 23(2), 138–140.
79. Greenberg, H. E., Ney, G., Scharf, S. M., Ravdin, L., and Hilton, E. (1995) Sleep quality in Lyme
disease. Sleep 18, 912.
80. Norman, S. E. and Chediak, A. D. (1992) Longitudinal analysis of sleep disturbances in HIV-
infected men. Sleep Res. 21, 304.
81. Hayman, M., Scheffer, I. E., Chinvarun, Y., Berlangieri, S. U., and Berkovic, S. F. (1997) Auto-
somal dominant frontal lobe epilepsy: demonstration of focal frontal onset and intrafamilial varia-
tion. Neurology 49(4), 969–975.
82. Sammaritano, M., Levtova, V., and Samson-Dollfus, D. (1994) Modification of sleep architec-
ture in patients with temporal lobe epilepsy. Epilepsia 35(8), 124
83. Wolf, P., Roder-Wanner, U. U., Brede, M., Noachtar, S., and Sengoku, A. (1985) Influences of
antiepileptic drugs on sleep. In: Biorhythms and Epilepsy (Martins da Silva, A., Binnie, C. D.,
and Meinardi, H., eds.), Raven Press, New York, pp. 137–148.
84. Johnson, L. C. (1982) Effects of anticonvulsant medication on sleep patterns. In: Sleep and Epi-
lepsy (Sterman, M. B., Shouse, M. N., and Passouant, P., eds.), Academic Press, New York, 381–
384.
126 Plotkin
Insomnia in Psychiatric Disorders 127

11
Insomnia in Psychiatric Disorders

Samy S. Karaz

The best bridge between despair and hope is a good night’s sleep
—E. Joseph Cossman

INTRODUCTION
Management of insomnia without a basic understanding of the possible underly-
ing psychiatric disorders might result in an inadequate, if not hazardous outcome.
Insomnia is listed in the fourth edition of the Diagnostic and Statistical Manual of
Mental Disorders (DSM-IV) as a symptom of several psychiatric disorders (see
Table 1) (1).
Insomnia related to other DSM-IV mental disorders was found to be as high as
77%. In more than 50% of the cases, the diagnosis was a depressive disorder (2).
In general, 57% of individuals reporting insomnia have a psychiatric disorder or
will develop one within a year (3). Second to depression, anxiety disorders are
strongly associated with insomnia.

SLEEP AND DEPRESSIVE DISORDERS

Patients with major depressive disorders present with depressed mood or loss of
interest or pleasure.
The full DSM-IV criteria of major depression are listed in Table 2 (4).
The most characteristic feature of insomnia seen in major depression is repeated
awakenings leading to early morning or “premature” insomnia. Waking up early
and not being able to return to sleep is a cardinal complaint (5). Younger depressed
patients might present with initial insomnia. The most characteristic sleep-tracing
(polysomnographic) features of major depression is earlier onset of the first rapid
eye movement (REM) period. Other abnormalities include reduced delta sleep and
increased REM sleep (5). The severity of insomnia correlates with the severity of
depression. Despite the overwhelming evidence of insomnia and sleep architecture
abnormalities, patients with major depression do not usually present with symp-
From: Current Clinical Neurology: Clinical Handbook of Insomnia
Edited by: H. P. Attarian © Humana Press Inc., Totowa, NJ

127
128 Karaz

Table 1
DSM–IV Diagnoses with Insomnia as a Symptom
Diagnosis DSM-IV Criteria
Separation anxiety disorder Reluctance or refusal to go to sleep without
being near a major attachment figure and
repeated nightmares involving the theme
of separation.
Alcohol withdrawal Insomnia
Stimulant withdrawal (including cocaine, Insomnia or hypersomnia
amphetamines, nicotine or caffeine)
Sedative withdrawal (including opiates, Insomnia
hypnotics, anxiolytics, and
antidepressants)
Major depression Insomnia or hypersomnia every day
Dysthymia Insomnia or hypersomnia
Posttraumatic stress disorder Recurrent distressing dreams of the
traumatic event leading to difficulty
falling or staying asleep.
Acute stress disorder Reexperiencing the trauma in recurrent
nightmares
Generalized anxiety disorder Insomnia
Primary insomnia The predominant complaint is difficulty
initiating or maintaining sleep or
nonrestorative sleep, for at least 1 month.
Nightmares Repeated awakening from any sleep period
due to frightening and vivid dreams
Sleep terrors Recurrent episodes of abrupt awakening
from sleep, usually occurring during the
first third of the major sleep episode.
Sleep disorder due to another psychiatric Insomnia due to the other psychiatric
disorder disorder
Sleep disorder due to another medical Insomnia due to other medical disorder
condition
Postconcussional disorder Insomnia or hypersomnia
Premenstrual dysphoric disorder Insomnia or hypersomnia
Adapted from ref. 1.

toms of excessive daytime sleepiness. Patients with major depression frequently

present with symptoms of tiredness and lack of energy. Accordingly, it is of clinical
importance to try to differentiate between tiredness with a lack of energy and
excessive daytime sleepiness in patients with insomnia. On the other hand, as a part
of bipolar disorder and seasonal affective disorder, depression is usually accompa-
nied by increased sleep efficiency, frequent napping, and daytime sleepiness (5).
In hypomanic or manic phase of bipolar disorder, patients usually sleep as little
as 2 to 4 hours each night, yet they wake up feeling subjectively refreshed. The
Insomnia in Psychiatric Disorders 129

Table 2
Diagnostic Criteria for a Major Depressive Episode
In the same 2 weeks, the patient has had five or more of the following symptoms, which
are a definite change from usual functioning. Either depressed mood or decreased
interest or pleasure must be one of the five.
• Depressed mood for almost all day nearly every day
• Markedly decreased interests for almost all day nearly every day.
• Appetite and or weight increased or decreased for almost all day nearly every day.
• Decreased or increased sleep for almost all day nearly every day.
• Patient agitated or retarded for almost all day nearly every day.
• Fatigue or loss of energy for almost all day nearly every day.
• Patient feels worthless or inappropriately guilty for almost all day nearly every
day.
• Trouble thinking or concentrating for almost all day nearly every day.
• Repeated thoughts about death (other than the fear of dying), suicide (with or
without a plan), or has made a suicide attempt.
These symptoms cause clinically important distress or impair work, social, or personal
functioning
This disorder is not directly caused by a general medical condition or the use of
substances, including prescription medications.
Unless the symptoms are severe (defined as severely impaired functioning, severe
preoccupation with worthlessness, ideas of suicide, delusions, or hallucinations, or
psychomotor retardation), the episode has not begun within 2 months of the loss of a
loved one.
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorder,
Fourth Edition, Text Revision. Copyright © 2000 American Psychiatric Association

absence of depression symptoms in the initial evaluation of insomnia should not

rule out the risk of major depression in future visits. Patients with insomnia and no
depression at intake were at approximately 40-fold higher risk of developing new
episodes of major depression in comparison to individuals with no insomnia (6).
There is another group of insomnia patients who have major depression, yet their
sole complaint is insomnia. The psychiatric literature described individuals with
“Alexithymia” (patients without words to express their feeling state). These indi-
viduals are more likely to have “masked depression.” They are particularly com-
monly seen in the primary care setting. Patients with masked depression substitute
somatic complaints such as insomnia for the traditional core symptoms of depressed
mood or loss of pleasure.
Therefore, it is important to focus on the objective component of the mental
status.
The general demeanor and posture of patients with depression may appear to be
slowed. They may walk slowly, holding their heads down and lacking spontaneity.
Patients with depression may respond to questions with long pauses and short
answers (7). Their facial expressions may be blunted and their eye contact may be
130 Karaz

poor. Focusing only on the contents of the patient’s complaints may result in over-
looking depression and in turn a poor treatment outcome. Severe insomnia is an
independent risk factor for suicide during the first 2 years of an episode of major
depression (8).

Treatment of Depression/Insomnia Symptoms

Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine, paroxetine,
sertraline, and fluvoxamine are commonly used for treatment of depression. SSRI
antidepressants decrease total sleep time (TST), increase number of arousals, sup-
press REM sleep, and increase the number of phasic REMs. Despite their arousing
effect on the sleep electroencephalogram (EEG), SSRI antidepressants improve
subjective sleep quality in subjects with major depression and primary insomnia
(9). On the other hand, insomnia is the most common residual symptom among
patients who have otherwise been successfully treated with fluoxetine for depres-
sion. This phenomenon may be unique to the newer antidepressant medications like
fluoxetine (8).
Tricyclic antidepressants play a role in treatment of depression/anxiety symp-
toms. Tricyclic antidepressants decrease REM sleep and increase REM latency.
EEG measures of sleep continuity may improve with tricyclic antidepressants (8).
The tertiary amine tricyclic antidepressants (e.g., Amitriptyline and Imipramine)
have a more sedating effect than the secondary amine tricyclics like Desipramine
and Nortriptyline. The secondary amines group has fewer adverse effects. Some
clinicians believe that depressed patients with marked insomnia and anxiety obtain
some immediate relief from the sedating antidepressants before the full antidepres-
sant effect takes place, which might increase the likelihood of compliance during
the acute phase of treatment (10).
One drawback of the tricyclic antidepressants is the risk of fatal effects if an
overdose is ingested. Patients were randomly assigned to an initial prescription of
the SSRI fluoxetine or the tricyclic Imipramine. The rate of improvement in insom-
nia was identical in both groups (11). Serotonin receptor modulators like Trazodone
and Nefazodone increase sleep continuity. However, Trazodone decreases REM
sleep and may cause daytime sedation, whereas Nefazodone increases REM and
has minimal daytime sedation (12).
Monoamine oxidase inhibitors (MAOIs), antidepressants like Tranylcypromine
(Parnate) and Phenelzine (Nardil), still have a role in the treatment of depression.
However, because of the necessity to regulate the diet and to continuously evaluate
the concomitant medications, MAOIs are not used as a first line of treatment (10).
Benzodiazepines like Lorazepam, Clonazepam, and Alprazolam are sedating,
induce sleep, and have anti-anxiety and muscle relaxant effects. Newer medica-
tions like Zolpidem act selectively on the ω1 benzodiazepine receptors and have a
sedative effect without anxiolytic, anticonvulsant, and muscle relaxant effects. They
do not cause rebound effects or withdrawal when discontinued (12). A double-
blind study by Smith and co-workers found that patients taking fluoxetine for
Insomnia in Psychiatric Disorders 131

depression showed greater improvement in their psychiatric symptoms when tak-

ing Clonazepam concomitantly (12). In a double-blind study by Rosenberg et al.,
Zolpidem was found to improve the quantity and quality of sleep without worsen-
ing depression when co-administered with antidepressants (12). Patient’s individual
susceptibility to certain side effects, personal and family history of previous response
to specific antidepressants, history of alcohol or drug abuse, patient’s age, and pos-
sible other concomitant underlying medical problems should all be factored in when
an antidepressant and/or benzodiazepine are to be selected.

Case 1
A 45-year-old married male was referred to the sleep center by his primary
care physician.
The patient presented with symptoms of frequent awakening and poor night’s
sleep.
He went to bed at 10:30 PM and was able to fall asleep within 15 to 20
minutes. Two to three hours later, he would wake up for a brief period of time
and would fall asleep again for several minutes. He would repeat the pattern
a few times before waking up between 3:30 and 4:00 AM, at which time he
would be unable to fall asleep for the rest of the night. He would stay in bed
tossing and turning and then get out of bed at 6 AM. He reported that his
symptoms started 3 months previously. He complained of feeling tired, yet
denied any symptoms of excessive daytime sleepiness.
He reported that his job as a banker started to become more stressful 6
months previously.
He did not drink alcohol and smoked 15 cigarettes a day. He has been a
smoker since age 18. He reported that he would smoke one or two cigarettes
at night when he could not sleep. He was unaware of any positive family
history of sleep disorders. He had a history of arthritic low back pain and high
cholesterol. He denied any past psychiatric history.
On physical exam, chest exam showed scattered rhonchi bilaterally and
the patient had some productive cough. Otherwise, physical exam was essen-
tially normal.
At the end of this visit, the patient was given educational material on sleep
hygiene and insomnia. Behavioral techniques like stimulus control therapy
and relaxation were discussed.
He was started on 1 mg of Lorazepam orally at bedtime. The patient did not
call between visits to report his progress although he was advised to do so.
On the second visit, 4 weeks later, the patient was apologetic. He admitted
to feeling guilty for not complying with the behavioral treatment recommen-
dations. He reported that he was not waking up as much during the night on
Lorazepam, yet he complained of ongoing difficulties waking up early in the
morning and feeling more tired during the day.
132 Karaz

He felt hopeless that his sleep would improve. His eye contact was poor,
and his affect appeared dysthymic. He admitted to loss of interest and to iso-
lating himself socially. He admitted to having brief death wishes, yet denied
any specific suicidal ideations or plans.
The patient was informed that he meets the diagnosis of major depression
and was started on 20 mg of fluoxetine orally in the morning. He was continued
on 1 mg of Lorazepam orally at bedtime.
On the third visit, 4 weeks later, the patient’s affect was brighter and he
reported that he was less tired and his sleep was improving. He also reported
improvement of his mood and level of interest. He denied any death wishes
or thoughts of suicide. He felt more hopeful. He was continued on the same
dose of fluoxetine and Lorazepam was switched to 1 mg at bedtime on an as
needed basis.
On the fourth visit, 6 weeks later, he was free of symptoms of depression
and insomnia. Lorazepam was infrequently used and accordingly, it was
gradually tapered and then discontinued. He continued on the same dose of
fluoxetine.

INSOMNIA AND ANXIETY DISORDERS

Sixteen million Americans suffer from anxiety disorders (13). The interrelation-
ship between anxiety disorders and insomnia is a very common finding in the clini-
cal setting. Anxiety and related conditions (tension, psychic distress) were found to
be quite prevalent among insomniacs in epidemiological studies of either the gen-
eral population or the elderly. The vast majority of insomniacs manifested the symp-
toms of apprehension, rumination, multiple fears, and excessive worrying (14).

Generalized Anxiety Disorder

Patients with generalized anxiety disorders (GADs) experience chronic and per-
sistent anxiety and, not surprisingly, most report problems with insomnia (15). Fifty
to seventy percent of patients with GAD report trouble sleeping (16). Sleep distur-
bance is characterized by sleep-onset or maintenance insomnia due to excessive
anxiety and apprehensive expectations about one or more life circumstances. These
patients may express intense anxiety during the daytime about the inevitability of
each night’s poor sleep. Patients display chronic anxiety with features that include
trembling, muscle tension, restlessness, easy fatigability, shortness of breath, pal-
pitations, tremors, sweating, dry mouth, dizziness, keyed up feelings, and exagger-
ated startle response (5).
The DSM-IV criteria of GAD is listed in Table 3 (4).
The polysomnographic features of GAD reveal the nonspecific findings of
increased sleep latency (SL), decreased sleep efficiency, increased amount of stage
1 and stage 2 sleep and decreased slow wave sleep. These changes are often mild.
There is usually little to no physiologic sleepiness on the Multiple Sleep Latency
Insomnia in Psychiatric Disorders 133

Table 3
Diagnostic Criteria for Generalized Anxiety Disorder
Worries and anxieties over several events and activities for 50% of the time or more for at
least 6 months.
The person experiences difficulty or trouble trying to control these feelings.
In addition to the above there are at least three of the symptoms listed below for 50% of
the time or more for at least 6 months.
• Feels restless, edgy, keyed up
• Tires easily
• Trouble concentrating
• Irritability
• Increased muscle tension
• Trouble sleeping (initial insomnia or restless, unrefreshing sleep)
The cause of the anxiety and the worry is not an aspect of another psychiatric illness.
The anxiety is not the symptom of another medical condition.
The anxiety is not the symptom of another psychiatric condition.
The symptoms cause clinically important distress or impair work, social, or personal
functioning.
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorder,
Fourth Edition, Text Revision. Copyright © 2000 American Psychiatric Association

Test of patients with GAD (4). There are similarities between psychophysiologic
insomnia and GAD in both their clinical presentation and the polysomnographic
changes.
If anxiety permeates most aspects of functioning, a GAD is the usual diagnosis.
In contrast, if anxiety is focused almost exclusively on poor sleep and its conse-
quences on daytime functioning, psychophysiologic insomnia is the typical diag-
nosis (17).
On the other hand, patients with GAD experience pervasive anxiety during the
day, which interferes with their level of functioning well beyond the consequences
of poor sleep (10).
In contrast with GAD, sleep efficiency improves on the second night in patients
with psychophysiologic insomnia when their nighttime sleep polysomnogram
(PSG) is recorded in the sleep lab 2 nights in a row (4).
Treatment
Benzodiazepines like Alprazolam and Clonazepam continue to play a major role
in the management of GAD. SSRI antidepressant medications like fluoxetine,
paroxetine, sertraline, and a tricyclic antidepressant like Imipramine are found to
be valuable options in the treatment of GAD. Cognitive-behavioral therapy should
be strongly considered as an important tool in the treatment of GAD and the related
insomnia.
134 Karaz

Table 4
Diagnostic Criteria for Panic Disorder
The patient suddenly develops a severe fear or discomfort that peaks within 10 minutes.
During this discrete episode, four or more of the following symptoms occur:
• Choking sensation
• Chills or hot flashes
• Chest pain or other chest discomfort
• Fear of dying
• Dizzy, lightheaded, faint, or unsteady
• Derealization (feeling unreal) or depersonalization (feeling detached from self)
• Fears of loss of control or becoming insane
• Heart pounds, races, or skips beats
• Nausea or other abdominal discomfort
• Numbness or tingling
• Sweating
• Shortness of breath or smothering sensation
• Trembling
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorder,
Fourth Edition, Text Revision. Copyright © 2000 American Psychiatric Association

Panic Disorder
Sleep disturbances have been reported in 70% of patient’s with panic disorder
(18). The panic attack is characterized by a sudden, intense fear or terror of dying.
Symptoms include dizziness, choking, palpitation, trembling, chest pain, or dis-
comfort, and sweating (4).
Symptoms of panic attack as listed in the DSM-IV is shown in Table 4.
Panic disorder can be associated with sudden awakening from sleep. Nocturnal
panic attacks present with similar symptoms to daytime panic. Palpitation, dysp-
nea, and flushing are the most frequent symptoms of nocturnal panic attacks (18).
Polysomnographic monitoring of nocturnal panic demonstrates an abrupt awaken-
ing with a sensation of panic out of stage 2 or 3 sleep. It also presents with margin-
ally increased SL and decreased sleep efficiency.
Obstructive sleep apnea (OSA) may lead to awakening with panic-like symp-
toms. OSA usually presents with symptoms of snoring, sleepiness, and the absence
of daytime anxiety, which distinguishes OSA from panic disorder (4).
Night terrors, which also emerge from non-rapid eye movement (NREM) sleep
are usually followed by no recollection of the events and there is no daytime panic
symptoms. Nightmares differ from panic attacks as they usually cluster around the
early morning and contain much more mental content (4).
It is important to note that panic disorder is associated with major depression in
50 to 94% of patients (18). This comorbidity could result in alteration of the pre-
sentation of insomnia symptoms.
Insomnia in Psychiatric Disorders 135

Treatment
SSRI antidepressants like paroxetine, fluoxetine, sertraline, fluvoxamine, or
citalopram are the current consensus to start treating a patient with uncomplicated
panic. Many patients with panic disorder have what is described as supersensitivity
syndrome, which is an initial agitation and more frequent panic in the first 1 to 2
weeks of starting an SSRI medication. Further reduction of the dosage adding ben-
zodiazepine, or switching to a different compound from the same family usually
gets the patient through this relatively short period (10).
Benzodiazepines are powerful anti-panic drugs. The major advantage of benzo-
diazepines is their quick onset of action. Follow-up studies suggest that benzodiaz-
epine-responsive patients maintain their gain for several years and do not develop
tolerance. Maintenance doses are usually lower than the dosages used for acute
treatment (10).
MAOIs are potent anti-panic drugs, yet their use is limited by the necessity to
regulate the diet and continuously evaluate the concomitant medications.
Tricyclic antidepressants, particularly Imipramine and Clomipramine, are very
effective anti-panic medications.
Case 2
A 30-year-old single female was seen in the sleep center for symptoms of
difficulty initiating and maintaining sleep. She complained that her insomnia
symptoms started 1 year ago, yet it worsened in the previous 3 months. She
worked as a school teacher. The new school year started 2 months prior to her
visit. She admitted to lying in bed at night awake worrying about what might
go wrong at school. She went to bed at 10 PM. She stayed awake for a couple
of hours tossing, turning, and worrying. She woke up two to three times at
night and at least once she was up for about an hour. She glanced at the clock
and worried about not being able to fall asleep. She got up at 6 AM and usually
did not need an alarm.
She felt tired during the day, yet denied sleepiness behind the wheel or at
any time when physically inactive. She denied being able to take naps. The
patient did not smoke and seldom drank alcoholic beverages.
She denied any history of a psychiatric disorder. She reported a history of
a knee injury while jogging and denied any other medical problems. Physical
exam was essentially normal.
During the evaluation, the patient appeared tense and her voice was shaky.
In the latter part of the visit and while discussing the treatment plan, the pa-
tient appeared more anxious and was tremulous. She had increasing difficulty
focusing on the conversation.
When the patient’s anxiety signs were addressed, she reported that her
anxiety symptoms date back to at least 5 to 6 years ago if not longer. She
136 Karaz

complained of feeling anxious during the day and not only at night. She ad-
mitted to always worrying about what might end up going wrong. She com-
plained of feeling tired and not being able to control or stop these anxious
thoughts. She complained of always feeling keyed up. The patient appeared
to meet the criteria of GAD, as well as insomnia. She was educated regarding
the nature of her anxiety and the treatment plan was altered in order to treat
her anxiety disorder symptoms as well as insomnia. She was referred for cog-
nitive-behavioral therapy sessions with focus on relaxation training, and
worry reduction. She was started initially on .5 mg of Klonopin orally at bed-
time, which was increased to 1 mg at bedtime.
Six weeks later, during the second visit, the patient reported significant
improvement of both her anxiety and nighttime sleep. She was able to suc-
cessfully utilize the relaxation techniques. Klonopin was decreased down to
.5 mg at bedtime.
The patient reported later on that she was able to maintain solid sleep on
the lower dose of Klonopin in combination with utilizing the cognitive and
behavioral therapy techniques. The patient tried to stop Klonopin completely,
yet she experienced difficulties with some sleep fragmentation and resumed
the dose of .5 mg at bedtime.

Posttraumatic Stress Disorder

Insomnia and nightmares are common symptoms of posttraumatic stress disor-
der (PTSD). Of patients with PTSD or individuals exposed to major stress, 59–68%
report frequent nightmares (16). Insomnia is part of the hyperarousal complex of
symptoms and nightmares are characteristic in the symptoms cluster of reliving the
traumatic events (19). The anxiety arousals in PTSD may emerge from both REM-
related nightmares and may also arise from NREM sleep (16). Cognitive-behav-
ioral therapy for nightmares and insomnia was associated with improvement of the
symptoms of PTSD (20). SSRI antidepressants have also proven to be effective in
the treatment of PTSD and insomnia. Fluvoxamine was found to be effective, par-
ticularly in the treatment of traumatic-related nightmares and sleep maintenance
insomnia (9).
Trazodone was also found to be effective in the treatment of nightmares and
insomnia associated with PTSD (19). Benzodiazepines and tricyclic antidepres-
sants were also found to be effective in the treatment of PTSD.

OTHER DISORDERS
Other anxiety disorders (e.g., obsessive-compulsive disorder) and other psychi-
atric disorders (e.g., schizophrenia, eating disorders, dementia, and alcoholism) are
accompanied by problems with insomnia and sleep architecture changes. Details of
these changes are illustrated on Table 5 (15).
Insomnia in Psychiatric Disorders 137

Table 5
Sleep Abnormalities in Psychiatric Disorders
Disorder Symptoms Objective findings
Major depression Insomnia, vivid dreams, ↓total sleep ↑sleep latency
nightmares, and fatigue ↓sleep efficiency ↑wake
time ↑REM
Seasonal affective disorder/ Hypersomnia ↑total sleep time
bipolar depression
Mania Insomnia ↓total sleep ↑sleep latency
↓sleep efficiency ↑wake
time ↑REM
Anxiety disorders Insomnia ↓ sleep continuity
Posttraumatic stress Insomnia, flashback dreams Normal or ↑REM
disorder
Schizophrenia Insomnia, reversal of sleep ↓ sleep continuity, normal or
wake cycles ↓SWS, normal or ↓REM
sleep
Eating disorders Insomnia, sleep-related Normal or ↓ sleep continuity,
eating spells normal or ↓REM sleep
Alcoholism Insomnia ↓ sleep continuity, ↓SWS,
normal or ↓REM sleep,
normal or ↑REM %
Dementia Alzheimer’s Insomnia, reversal of sleep– ↓total sleep ↑sleep latency
type wake cycles ↑wake time, ↓SWS.
Adapted from ref. 15.
REM, rapid eye movement; SWS, slow-wave sleep

Insomnia and Substance Abuse

Alcoholism
Special attention needs to be given to alcoholism, as it is often associated with
anxiety disorders, depression, and insomnia. Acute alcohol use reduces the amount
of wakefulness for the first 3 to 4 hours of sleep. The amount of wakefulness in-
creases during the second half of the night and sometimes the number of dreams,
particularly anxiety dreams, increase.
Chronic, excessive alcohol use eventually results in fragmented and restless
sleep (5).
Sleep problems due to alcohol abuse could be confused with insomnia due to
psychiatric disorders or primary insomnia if the problem with alcoholism is over-
looked or not addressed.
It is advisable to avoid prescribing benzodiazepines if alcohol use is a problem.
Benzodiazepine-prescribing decisions vary widely among physicians. Although
some agreed with prescribing for patients with high probability of alcohol abuse,
138 Karaz

other physicians avoided benzodiazepines unnecessarily, depriving certain insom-

nia patients from a viable treatment option (21).
Caffeine
Caffeine is a stimulant that is consumed in coffee (85 mg–150 mg per cup), tea
(60–75 mg per cup), cocoa (50 mg per cup), chocolate, over-the-counter (OTC)
cold preparations (15 mg–60 mg per tablet), and OTC stimulants (100–200 mg).
Caffeine effects may last for 8 to 14 hours. Caffeine consumption might induce
or worsen insomnia, even if it is consumed as early as the late afternoon.
For most people, 1 g of caffeine may induce insomnia. Other more sensitive
individuals may become overstimulated on as little as 250 mg (16).
The polysomnography changes with caffeine shows increased SL, decreased
TST, increased wake after sleep onset (WASO), decreased REM sleep, and
decreased delta sleep (22).
Nicotine
Nicotine can be consumed by smoking, chewing tobacco, snuff, nicotine patches,
and nicotine gum. Nicotine is addictive. Withdrawal from nicotine starts 1 to 2
hours after the last smoke (16). Abrupt cessation or decrease of the nicotine con-
sumption can result in insomnia in the following 24 hours (4). Cigarette smoking
accelerates the metabolism of certain medications including Diazepam, Lorazepam,
Oxazepam, and Imipramine. This could result in a decrease of the sedative effect of
these medications among smokers. Nicotine polysomnography changes include in-
creased SL, decreased TST, and decreased REM sleep (22).
Stimulants
Amphetamines such as methamphetamine “speed” are taken intravenously, by
snorting, or by smoking “ice.” PSG changes on amphetamines are decreased TST,
increased WASO, increased movement during sleep, decreased REM sleep, and
decreased delta sleep (22).
Cocaine is also taken intravenously, by snorting, or smoking (as free base
“crack”).
PSG changes on cocaine are increased SL, decreased TST, and decreased REM
sleep (22).
Serious medical and psychiatric complications result from stimulant abuse and
among these complications are a disruption of the sleep–wake pattern and insom-
nia. Stimulants (e.g., amphetamines and methylphenidate) are used therapeutically
in the treatment of narcolepsy, attention deficit hyperactivity disorder, some causes
of depression, and other related disorders. The availability of objective diagnostic
tools and careful clinical monitoring helps decrease the risk of stimulant abuse
among these patients population.
Anxiolytics and Sedative Hypnotics
The present major anxiolytics and sedative hypnotics include benzodiazepine
and other miscellaneous drugs (Zolpidem, Chloral Hydrate, and Zalpelon) (16).
Insomnia in Psychiatric Disorders 139

The older sedative hypnotics like barbiturates are less frequently used due to the
higher risk of dependence and the more severe withdrawal symptoms like with-
drawal seizures.
The benzodiazepines polysomnographic changes include increased TST,
decreased WASO, decreased REM sleep, and increased sleep spindles in stage 2.
Most benzodiazepines decrease the SL and decrease delta sleep (22).
The sedative hypnotics abuse occurs predominantly in the context of
polysubstance abuse (16). Benzodiazepines with rapid onset of action (e.g.,
Alprazolam and Diazepam) are more likely to be abused than the longer onset of
action type of benzodiazepine (Oxazepam or Chlordiazepoxide). Withdrawal from
sedative hypnotics can result in a rebound insomnia or emergence of insomnia as a
new symptom (in prolonged high-dose use). Anxiety is a common withdrawal
symptom, which independently can initiate or worsen insomnia. In evaluating the
risks vs benefits of the sedative hypnotic therapy in patients including those who
have insomnia, it is helpful to distinguish between “drug-seeking behavior” from
“therapy-seeking behavior” (16).

REFERENCES
1. Harvey, A. G. (2001) Insomnia: symptom or diagnosis? Clin. Psychol. Rev. 21(7), 1037–1059.
2. Ohayon, M. M., Caulet, M., and Lemoine, P. (1998) Comorbidity of mental and insomnia disor-
ders in the general population. Compr. Psychiatry 39 (4), 185–197.
3. Bonnet, M. H. and Arand, D. L. (1999) Diagnosis and treatment of insomnia. Respir. Care Clin.
North Am. 5(3), 333–348.
4. American Psychiatric Association. (1994) Diagnostic and statistical manual of mental disorders
(4th ed.). American Psychiatric Association, Washington, DC.
5. American Sleep Disorders Association, Diagnostic Classification Steering Committee. (1997)
The international classification of sleep disorders, revised: diagnostic and coding manual. Ameri-
can Sleep Disorders Association, Rochester, MN.
6. Benca, R. M. (2001) Consequences of insomnia and its therapies. J. Clin. Psychiatry 62(10), 33–38.
7. Hales, S. C., Yudofsky, R. E., and Talbott, J. A., eds (1999) The American Psychiatric Press
Textbook of Psychiatry (3rd ed.). American Psychiatric Press, Inc., Washington, DC.
8. McCall, W.V. (2001) A psychiatric perspective on insomnia. J. Clin. Psychiatry 62(10), 27–32.
9. Naylan, T. C., Metzler, T. J., Schoenfeld, F. B., et al. (2001) Fluvoxamine and sleep disturbances
in posttraumatic stress disorders. J. Traum. Stress 14(3), 461–467.
10. Sadock, B. J. and Sadock V. A. eds. (1999) Kaplan and Sadock’s comprehensive textbook of psy-
chiatry (7th ed.). Lippincott Williams & Wilkins, Philadelphia, PA, pp. 1380–1384, pp. 1490–1503.
11. Simon, G. E., Heiligenstein, J. H., Grothaus, L., Katon, W., and Revicki, D. (1998) Should anxi-
ety and insomnia influence antidepressant selection: a randomized comparison of fluoxetine and
imipramine. J. Clin. Psychiatry 59(2), 49–55.
12. Kupfer, D. G. (1999) Pathophysiology and management of insomnia during depression. Ann.
Clin. Psychiatry 11(4), 267–276.
13. Bourdet, C. and Goldenberg, F. (1994) Insomnia and anxiety: Sleep EEG changes. J. Psychosom.
Res. 38(Suppl 1), 93–104.
14. Soldatos, C. R. (1994) Insomnia in relation to depression and anxiety: epidemiologic consider-
ations. J. Psychosom. Res. 38(Suppl 1) 3–8.
15. Martinez-Gonzalez, D., Obermeyer, W. H., and Benca, R. M. (2002) Comorbidity of insomnia
with medical and psychiatric disorders. Prim. Psychiatry 9(8), 37–49.
16. Kryger, M. H., Roth, T., and Dement, W. C., eds. (2000) Principles and practice of sleep medi-
cine (3rd ed.), WB Saunders, Philadelphia, PA, pp. 642, 1128, 1134–1135.
140 Karaz

17. Attarian, H. P. (2000) Helping patients who say they cannot sleep. Postgrad. Med. 107(3), 127–142.
18. Lepola, U., Koponen, H., and Leinonen, E. (1994) Sleep in panic disorders. J. Psychosom. Res.
38(1), 105–111.
19. Warner, M. D., Dorn, M. R., and Peabody, C. A. (2001) Survey on the usefulness of Trazodone in
patients with PTSD with insomnia or nightmares. Pharmacopsychiatry 34 (4), 128–131.
20. Krakow, B., Johnston, L., Melendrez, D., et al. (2001) An open trial of evidence-based cognitive
behavior therapy for nightmares and insomnia in crime victims with PTSD. Am. J. Psychiatry
158(12), 2043–2047.
21. Brown, R. L., Brown, R. L., Saunders, L. A., Castelaz, C. A., and Papasouliotis, O. (1997) Physi-
cians Decision to Prescribe Benzodiazepines for Nervousness and Insomnia. J. Gen. Intern. Med.
12, 44–52.
22. Chokroverty, S. ed. (1999) Sleep disorders medicine (2nd ed.). Butterworth-Heinemann Medical,
St Louis, 342–343.
Primary Sleep Disorders 141

12
Insomnia in Primary Sleep Disorders

Stephen Duntley

DEFINITION
Insomnia is defined in the International Classification of Sleep Disorders as
“difficulty in initiating and/or maintaining sleep” (1). In primary insomnia, the term
insomnia constitutes a diagnostic entity. In other disorders it is considered a symp-
tom and not a primary diagnosis. Insomnia is frequently a component of the symp-
tom complexes of other primary sleep disorders, and is listed among the diagnostic
criteria for the following dyssomnias: obstructive sleep apnea (OSA) syndrome,
central sleep apnea syndrome, central alveolar hypoventilation syndrome, periodic
limb movement disorder (PLMD), and restless legs syndrome (RLS). Disrupted
sleep is among the diagnostic criteria for narcolepsy. The complaint of insomnia
can also accompany parasomnias, and is listed among the diagnostic criteria for
sleep starts and nightmares (1). As in other forms of insomnia, in order to be con-
sidered a clinically significant problem, the complaint of sleep disturbance must be
associated with adverse daytime consequences such as fatigue, decreased concen-
tration, or irritability.

HISTORICAL PERSPECTIVES
In what is likely the first report of RLS in the medical literature, Thomas Willis,
an English physician, described a patient in the late 1600s for whom sleep was
impossible because of restlessness in the arms and legs, which were compared to a
person being tortured on the rack. There were subsequently sporadic reports of
patients with similar symptoms, but the syndrome was not described in detail until
the 1940s. A thorough description of the phenomenon of PLMs during sleep awaited
development and clinical application of polysomnography, with typical features
being described by Lugaresi and colleagues in 1966 (2). Insomnia associated with
OSA was first described by Guilleminault and colleagues in 1973 (3). Since these
initial reports, the common association between insomnia and these other sleep

From: Current Clinical Neurology: Clinical Handbook of Insomnia

Edited by: H. P. Attarian © Humana Press Inc., Totowa, NJ

141
142 Duntley

disorders has been confirmed, although the clinical significance of this relationship
continues to be defined.

EPIDEMIOLOGY
The epidemiology of insomnia in sleep disorders is dependent on the epidemiol-
ogy of the primary sleep disorder itself. One community-based population study
found about 2% of women and 4% of men have OSA syndrome (4). A recent uni-
versity-based study of patients with sleep-disordered breathing found that of 231
patients sampled, 116 complained of clinically significant insomnia (5). Among
postmenopausal women complaining of insomnia, 83% were noted to have upper
airway resistance syndrome (UARS) or OSA syndrome (6). Insomnia complaints
in patients with OSA syndrome, like insomnia complaints in general, may be more
frequent among women than men (7). Central sleep apnea syndrome is less com-
mon than OSA, but patients appear to be less likely to report daytime hypersomno-
lence and more likely to complain of insomnia (8). RLS is common, with a recent
population-based study revealing bedtime symptoms in 10–15% of individuals (9).
Difficulty falling asleep was reported by 84.7% of patients and 86% reported fre-
quent awakenings with difficulty falling back asleep because of symptoms (10).
PLMD increases with age, being uncommon before 30 years of age, seen in 5% of
individuals between 30 and 50 years of age, and in about 44% of individuals aged
65 and older (11). One multicenter study found PLMD to be the primary diagnosis
in 17% of patients complaining of insomnia (12). Narcolepsy has a prevalence of
about 0.05% (13). Fragmented sleep is found in up to 90% of patients with narco-
lepsy (14) and tends to be relatively mild initially, increasing in severity over time
(15). Nightmares with a frequency of once a week or greater are seen in 4% of the
adult population in Austria (16). One study in France found that 18.3% of insomnia
patients were diagnosed as having nightmares (17). Occasional sleep starts are a
nearly universal phenomenon. Sleep starts may rarely become repetitive at sleep
onset resulting in sleep-onset insomnia.

ETIOLOGY
The cause of insomnia varies according to the primary sleep disorder, and may
result from the sleep-onset and maintenance difficulties inherent in the disorder
itself or from secondary symptoms of the disorder. For instance, in OSA syndrome,
the termination of the apnea is associated with an arousal or awakening that may be
perceived and remembered by the patient. OSA syndrome is also associated with
other symptoms, such as nocturia and dry mouth, which can contribute to the devel-
opment of an insomnia complaint. In RLS, the dysesthesias and need to move the
legs prevents sleep onset, and may prevent returning to sleep after awakenings in
the middle of the night. In PLMD, limb movements are associated with arousals or
awakenings that may lead to the perception of difficulty initiating or maintaining
sleep. In narcolepsy, the neurochemical defect leads to dysregulation of sleep
Primary Sleep Disorders 143

architecture, with fragmented nocturnal sleep being a basic manifestation of this

dysregulation. Sleep paralysis and hypnogogic hallucinations can be unpleasant
enough to result in anxiety about sleeping. The stimulants and antidepressants used
to treat excessive daytime sleepiness and cataplexy can further contribute to diffi-
culty sleeping. The anxiety resulting from a nightmare may result in awakenings
and difficulty returning to sleep. With sleep starts, an awakening coincides with the
abnormal motor activity; when repetitive, this can result in difficulty falling asleep
or returning to sleep after awakening in the night.
In the primary sleep disorders, many patients do not develop a complaint of
insomnia despite demonstrable sleep fragmentation, suggesting individual differ-
ences in susceptibility. Psychophysiological insomnia has been shown to have a
familial tendency (18), and genetic predisposition likely plays a role in the devel-
opment of an insomnia complaint in the primary sleep disorders. Additionally, poor
sleep hygiene often develops, leading to further difficulty sleeping. For instance, in
RLS, patients often report that they get their best sleep late in the morning, leading
to a tendency to sleep in late when possible, leading to further difficulties initiating
sleep. In any of the disorders, the perception of difficulty sleeping can lead to anxi-
ety directed toward sleep and therefore a secondary component of psychophysi-
ological insomnia.

PATHOGENESIS AND PATHOPHYSIOLOGY

In OSA, repetitive complete or partial occlusions of the upper airway result in
repetitive arousals during sleep. Pharyngeal patency is maintained by a balance of
outward forces created by actively contracting pharyngeal muscles such as the
genioglossus that are phasically active during inspiration, and negative intralumi-
nal forces created during inspiration (19). In OSA, this patency is compromised
through a narrowing of the upper airway through either anatomical means such as
hypertrophied tonsils, or dynamic means such as reduction of the phasic inspiratory
contractions. This leads to an increased effort of breathing and hypoxemia, result-
ing in arousals or awakenings, associated with a surge in sympathetic nervous sys-
tem activity. Because most arousals and awakenings in OSA are brief, patients are
usually unaware of the frequency of awakenings. Some awakenings may be long
enough for the patient to recall, leading to an insomnia complaint. Apneas are some-
times associated with a sensation of choking, not breathing, dyspnea, or tachycar-
dia. This can lead to a fear of sleep that can sometimes reach phobic levels. The
total number of apneic and hypopneic episodes per hour of sleep is called either the
apnea-hypopnea index (AHI) or the respiratory disturbance index (RDI), although
many laboratories include events such as respiration effort-related arousals or snore
arousals in the RDI. An AHI score of 5 or higher is enough to establish the diagno-
sis of OSA syndrome.
The pathophysiology of RLS remains unclear. Most cases are idiopathic, but a
significant percentage are hereditary, with an autosomal-dominant pattern of inher-
144 Duntley

itance. A recent study established the presence of a susceptibility locus on chromo-

some 12q (20). RLS may also be associated with a variety of medical conditions,
including neuropathy (21), uremia (22), and iron deficiency (23). Medications such
as lithium or antidepressants may precipitate or worsen RLS symptoms (24–26), as
may withdrawal from medications such as benzodiazepines or anticonvulsants.
Sleep-onset insomnia is induced by the need to move the legs and the accompany-
ing paresthesias. Sleep maintenance difficulties may occur if symptoms are present
during nocturnal awakenings. Additionally, most patients with RLS have PLMs
while sleeping that may be associated with sleep maintenance difficulties. Although
many patients with PLMs during sleep complain of insomnia and daytime sleepi-
ness (11), the relationship between the leg movements and symptoms remains
unclear. Mendelson found no correlation between PLM arousal index and subjec-
tive complaint of disturbed sleep, subjective measurements of awakening refreshed
or Multiple Sleep Latency Test (MSLT) values (27). In a randomized, controlled
clinical trial, pramipexole normalized the PLM index in RLS patients without a
corresponding improvement in sleep architecture (28).
Although a dysregulation of rapid eye movement (REM) sleep is the most clini-
cally salient feature of narcolepsy, this disorder is also characterized by a
dysregulation of other aspects of sleep architecture including sleep continuity.
Recent evidence suggests this dysregulation is secondary to a deficiency in
hypocretin mechanisms. Narcolepsy in dogs was recently shown to be secondary to
mutations in the hypocretin-2 receptor gene (29) and hypocretin knockout mice
exhibit features characteristic of narcolepsy including episodes of atonia resem-
bling cataplexy and disrupted sleep (30). Most patients with narcolepsy have unde-
tectable cerebrospinal fluid hypocretin (31) and histology on six human narcolepsy
brains revealed a generalized absence of hypocretin (31). Systemic administration of
hypocretin-1 in narcoleptic dogs resulted in improvement in sleep architecture (33).
Nightmares may be triggered by emotionally charged experiences, and when
recurrent are felt to reflect unresolved daytime emotional conflicts (34). Night-
mares may also be caused by a variety of medications including β-blockers, dopam-
inergic agents, and some antidepressants (35–37). Nightmares are also a prominent
feature of other sleep disorders such as REM sleep behavior disorder. Ethanol with-
drawal can cause nightmares so unpleasant that some patients report a resumption
of drinking to prevent them (38). The end result is an awakening in which anxiety-
arousing dream content is recalled, resulting in prolongation of the awakening. It is
unclear if sleep starts are a primary motor disorder or if an abnormality in the sen-
sory system or abnormal central nervous system (CNS) imagery provokes the mo-
tor response as a secondary phenomenon.

CLINICAL MANIFESTATIONS
Patients usually have accompanying symptoms that distinguish their sleep dis-
order and the resulting insomnia from other etiologies of insomnia. Patients with
OSA typically have a combination of nocturnal and daytime symptoms that raise
Primary Sleep Disorders 145

suspicion of the disorder. Nocturnal symptoms include snoring, usually with a cre-
scendo pattern or interruption with snorting or choking noises, witnessed apneas or
pauses in snoring, arousals with choking or dyspnea, motor restlessness and limb
jerking, night sweats, nocturia, gastroesophageal reflux, and dry mouth and drool-
ing. Daytime symptoms include fatigue, excessive daytime sleepiness, morning
headaches, impaired concentration, decreased libido or impotence, and personality
changes such as irritability. Although patients present with varying combinations
of these symptoms, most of which are very nonspecific, most patients with insom-
nia secondary to sleep-disordered breathing will give enough symptoms in a care-
ful history to raise suspicion of apnea. Accompanying symptoms may be less
prominent in central sleep apnea, but evidence of respiratory failure or underlying
CNS or cardiopulmonary disease may be present.
RLS is characterized by four essential features: (1) a desire to move the limbs
that is usually associated with dysesthesias or paresthesias, (2) motor restlessness,
(3) symptoms that are exclusively present or worsened by rest and relieved at least
partially or temporarily by movement, and (4) a circadian rhythm with symptoms
that are worse in the evening or night, usually near the patient’s habitual bedtime
(39). Additionally, most patients have PLMs during sleep and may have involun-
tary limb movements while awake and at rest. Patients with PLMs without RLS
may be unaware of their limb movements. A disheveled bed may provide clues to
movements during sleep.
Narcolepsy is characterized by excessive daytime sleepiness accompanied by
manifestations of dysregulated REM sleep, including cataplexy, hypnogogic hallu-
cinations, and sleep paralysis (1). Cataplexy is the only symptom that is pathogno-
monic for narcolepsy but does not occur in all patients. Patients with nightmares
are aware of vivid dreaming with anxiety-provoking content. Patients with sleep

Case 1: Narcolepsy Presenting with Insomnia

A 25-year-old man presented with difficulty falling asleep for the past 4
months. Some nights he did not fall asleep until 4 or 5 AM, causing him to be
unable to get up in the morning, causing concentration problems during the
day, and leading him to frequently fall asleep unintentionally in sedentary
situations. The sleepiness affected his life significantly. He had to repeat his
second year of medical school because of frequent episodes of falling asleep
in class and a lack of concentration.
He did not have a regular bedtime. He reported that some nights he went to
bed around 10 PM, some nights 4 AM. Regardless, most nights it took him an
hour or more to fall asleep. Even when he got 8 hours of nighttime sleep, he
still felt tired in the morning. He was as likely to fall asleep during the day
when he got a few hours of sleep as when he got 8 hours of sleep. He did not
take naps routinely, but a couple of times per week he fell asleep studying on
the couch and usually napped for 1 to 3 hours.
146 Duntley

The patient’s primary care physician had tried several medications for in-
somnia including zolpidem, zaleplon, nortriptyline, and trazodone, but noth-
ing helped. The patient’s primary care doctor suspected that he was depressed;
however, he himself thought that his fatigue and depression were secondary
to the insomnia.
The patient denied uncomfortable lower extremity sensations. He denied
loud snoring or observed apneas, loss of muscle tone with any particular emo-
tion, sleep paralysis, or hallucinations. He had no past medical history. He
was not on any medications on initial presentation and had no family history
of insomnia. He did not drink coffee or consume any caffeine in the late after-
noon. He did not drink alcohol, did not use illicit drugs, and he quit smoking.
His physical exam was normal. His polysomnogram (PSG) was normal and his
MSLT showed a mean sleep latency of 3.9 minutes with sleep onset REM peri-
ods on three out of five naps.
He was started on modafenil and his nighttime sleep improved and insom-
nia resolved at a dose of 300 mg taken in the morning. His daytime sleepiness
improved significantly at a dose of 600 mg per day.

starts are typically aware of the sudden jerk. They may also experience a sensation
of falling, or brief sensory symptoms such as flashes.

DIFFERENTIAL DIAGNOSIS
The symptoms of primary sleep disorders are often nonspecific and the sleep
disorders must be differentiated from each other. For instance, periodic limb jerks
can occur with PLMD or in OSA syndrome. Sleep paralysis is a prominent mani-
festation of narcolepsy, but can also occur in any disorder causing sleep fragmenta-
tion or severe sleep restriction. It is sometimes difficult to distinguish insomnia
secondary to a primary sleep disorder from psychophysiological insomnia. Of 116
patients with sleep-disordered breathing and insomnia in one series, 20 presented
with a chief complaint of insomnia only (5). Many patients with insomnia initiated
by a primary sleep disorder will develop a component of conditioned insomnia as a
secondary phenenomenon. This emphasizes the need for careful evaluation so that
symptoms suggestive of a primary sleep disorder are not missed. Patients may
develop poor sleep habits such as irregular hours and excessive caffeine intake as
an attempt to compensate for symptoms of their sleep disorder, and these features
may be so prominent as to suggest that the insomnia is secondary to inadequate
sleep hygiene. In primary sleep disorders with longstanding symptoms from an
early age, idiopathic insomnia may be the differential diagnosis.

DIAGNOSTIC WORKUP
A thorough history to elicit symptoms of an underlying sleep disorder is essen-
tial. Because patients may be unaware of snoring, apneas, and other nocturnal signs,
Primary Sleep Disorders 147

bedpartners should be interviewed whenever possible. A thorough physical exami-

nation should be performed; symptoms elicited during the history may suggest par-
ticular systems that require particular emphasis. RLS is a clinical diagnosis based
on the four essential clinical features just noted. Polysomnography is not necessary
in straightforward cases unless further evaluation for PLMs during sleep is desired.
Medical causes should be excluded through careful physical examination and
appropriate laboratory evaluation. Nightmares do not require polysomnography un-
less the history or physical examination leads one to suspect the patient has another
contributing sleep disorder. Sleep starts rarely require evaluation beyond a careful
history and examination; if features of the history suggest possible seizures,
polysomnography with full montage electroencephalogram (EEG) monitoring may
be necessary. If OSA or PLMD is suspected, all-night polysomnography is recom-
mended for documentation and determination of severity. If narcolepsy is suspected,
then polysomnography followed by MSLT is required for definitive diagnosis. The
PSG is a polygraph of EEG findings, eye movements, electromyography readings,
oxygen saturation, limb movements, airflow, and chest and abdominal movements
taken during sleep, usually for the entire night. An MSLT is a series of four or five
opportunities, each separated by a 2-hour interval, to take a 15- to 20-minute nap.
The time to the onset of sleep (sleep latency [SL]) is calculated for each nap. The
presence or absence of REM sleep is also noted. The mean SL provides a measure
of the severity of sleepiness, and the occurrence of REM sleep during the naps is
helpful in the diagnosis of narcolepsy. Mean SLs of 5 minutes or less are indicative
of pathological sleepiness and SLs of 10 or more are normal. The presence of REM
sleep on two or more naps is abnormal and is found in many narcoleptic patients.
Nocturnal polysomnography should be performed on the night immediately pre-
ceding the MSLT to factor out the impact of sleep deprivation on the mean SL and
the patient should be free of any medication effects that may influence sleep.

Case 2: OSA Syndrome Presenting with Insomnia

A 42-year-old man presented with the complaint of approximately a 5-
year history of insomnia and severe nighttime snoring. Previously, he was a
relatively light, but good sleeper. About 5 years ago he started having prob-
lems with sleep maintenance insomnia. He also had snoring at night severe
enough for his wife to move out of the bedroom in order to be able to sleep.
She also had witnessed some pauses in his breathing. He denied falling asleep
in sedentary and unusual situations. He denied falling asleep while at work or
driving, but he stated that he feels very fatigued and tired. He denied taking
daytime naps. He denied uncomfortable sensations in his legs, morning heart-
burn, or waking up with a bitter taste in his mouth. He denied morning head-
aches, morning dry mouth, loss of muscle tone in response to emotions, sleep
paralysis, or hypnagogic hallucinations.
His bedtime was between 10 and 11 PM and it took him about 10–15 min-
utes to fall asleep, however, after 2 or 3 hours he was awake and could not
148 Duntley

return to sleep. He tossed and turned for the rest of the night, sleeping only
for 30- to 45-minute intervals at a time until his rise time at 6 or 7 AM. Al-
though he felt restored most of the time, he also had significant fatigue during
the day.
He had no allergies, was not presently on any medications except vita-
mins, and did not have a past medical history. There was a family history of
snoring and insomnia in one parent and one sibling. He consumed large
amounts of caffeine but did not smoke and used alcohol only in social settings.
A review of systems was significant for a 25-lb weight gain over the past year.
His physical exam was normal.
The patient underwent a PSG that revealed reduced sleep efficiency and
an RDI of 49.9 breathing events per hour. The lowest oxyhemoglobin satura-
tion was 70%. Following the diagnostic portion of the study, a nasal continu-
ous positive airway pressure (CPAP) trial was initiated. A pressure of 7 cm
H2O was found to be optimal.
The patient’s symptoms resolved completely after initiation of CPAP. At
the 3-month follow-up visit, he reported consolidated sleep at night and no
more daytime fatigue as well as resolution of snoring.

PREVENTION
Not enough is known about the etiology of narcolepsy, RLS, PLMD, or sleep
starts to allow effective prevention. OSA syndrome is amenable to some preventive
measures, such as maintenance of lean body weight, avoidance of ethanol and other
CNS depressants near bedtime, and avoidance of smoking. Many patients, how-
ever, will develop OSA even when known risk factors are not present. Although
there is little objective data on prevention of sleep disturbance from nightmares,
teaching patients effective methods to deal with emotional stresses and trauma may
help minimize sleep disturbance from nightmares. In all patients, teaching good
sleep hygiene and treating secondary conditioned insomnia may minimize insom-
nia symptoms resulting from the primary sleep disorder.
Case 3: RLS Presenting with Insomnia
A 50-year-old woman presented for a 4- to 5-year history of inability to
fall asleep. Over the past 4–5 years, she experienced significant trouble fall-
ing asleep, mainly due to uncomfortable, indescribable feelings in her legs
and sometimes in her arms when she was trying to fall asleep. This discom-
fort was usually relieved by moving or rubbing her feet. Occasionally, it woke
her up from sleep as well. She experienced this about two to three times a
week. She also complained of the same discomfort, although less frequently,
during the day when sedentary. For example, when she was sitting at her desk
at work or when she was riding in a car or an airplane, she often had to get up
Primary Sleep Disorders 149

and walk to relieve these symptoms. She was initially treated with
amytriptiline with only worsening of her symptoms and no relief.
She was tired during the day, but did not fall asleep inappropriately. Her
husband denied she had any kind of leg movements in her sleep. He denied
that she snored or gasped for air or that she had any pauses in her breathing
while asleep.
In the past, before this last 5 years, she had experienced these symptoms peri-
odically about five times in her life, mainly in the last trimester of each of her
pregnancies.
Her past medical history included hypertension, hysterectomy, carpal tun-
nel surgery, window placement in her sinuses, and appendectomy. She was
presently taking Maxzide and reported an allergy to codeine.
She did not smoke or drink alcohol. She did not abuse drugs. Her family
history was significant for RLS in her mother. This was never formally diag-
nosed, however. Her physical exam was normal.
The patient was diagnosed with RLS and started on 0.125 mg of
pramipexol at bedtime and an additional 0.125 mg dose as needed during the
day. Her symptoms completely resolved on this regimen.

PROGNOSIS AND COMPLICATIONS

The prognosis is good if the underlying sleep disorder can be effectively treated
and secondary causes of insomnia such as poor sleep hygiene and conditioned
insomnia can be addressed. If the underlying sleep disorder is not effectively treated
or the perpetuating factors are not recognized and treated, then insomnia can persist
or worsen. Complications include hypnotic dependence, ethanol abuse, and persis-
tent insomnia is a risk factor for depression (40,41).

MANAGEMENT
Effective management requires that the underlying sleep disorder be appropri-
ately diagnosed and treated. For OSA, general recommendations such as weight
loss if obesity is present and avoidance of CNS depressants at bedtime are made to
all patients. In some patients, apnea may be significant only in the supine position;
in these patients an irritating object such as a tennis ball in a stocking affixed to the
back of a nightgown to promote sleep in the lateral position may be sufficient
therapy. Nasal CPAP remains the gold standard treatment and breathing may be
normalized in most patients, although compliance can be problematic. Patients with
a significant insomnia complaint may find CPAP uncomfortable and it may be dif-
ficult to obtain compliance with therapy. In these patients, time-intensive desensiti-
zation techniques may be helpful. In carefully selected patients, hypnotic
administration to promote CPAP compliance may be appropriate. Surgery on the
upper airway and therapy with an oral prosthesis are other alternative treatments.
150 Duntley

Treatment of RLS should begin with treating any precipitating or aggravating

conditions such as iron deficiency anemia, and the elimination of aggravating medi-
cations if possible. Caffeine and other methylxanthines may aggravate symptoms
and reduction or elimination of these should be attempted. Nonpharmacological
treatments such as massage and stretching or hot baths are beneficial for some
patients. Effective pharmacological therapies include dopamine agonists such as
ropinerole or pramipexole, benzodiazepines, or opiates. Several anticonvulsants,
most notably neurontin, have been reported to be beneficial. Most patients obtain at
least partial relief of their symptoms. PLMs are treated by the same pharmacologi-
cal agents as RLS. Although reduction in leg movements can usually be achieved,
symptom reduction is less reliable (42).
Treatment of the sleep disturbance in narcolepsy can be problematic as agents
used to promote daytime alertness can aggravate insomnia, and medications used
to promote sleep can worsen daytime sleepiness. Treatment options include the use
of a short-acting benzodiazepine agonist or a sedating tricyclic antidepressant.
Xyrem was recently approved to treat cataplexy in narcolepsy patients. Xyrem has
hypnotic properties and improves daytime alertness, making it a promising medica-
tion for many narcolepsy patients with insomnia (43).
Treatment modalities for nightmares include psychotherapy, systematic desen-
sitization and relaxation techniques, imagery rehersal, eye movement desensitiza-
tion, and hypnosis (44–48). Hypnotic medications benefit patients with repetitive
sleep starts.
All patients with insomnia secondary to these sleep disorders may develop per-
petuating factors such as poor sleep hygiene and conditioned insomnia and may
require training in sleep hygiene and behavioral therapy for the conditioned insom-
nia. Judicious use of hypnotic medications may be indicated, although the clinician
should remain aware of the potential for some medications to worsen OSA syn-
drome.

REFERENCES
1. American Sleep Disorders Association. (1997) International classification of sleep disorders:
diagnostic and coding manual. American Sleep Disorders Association, Rochester, MN.
2. Lugaresi, E., Coccagna, G., Gambi, D., Ceroni, G. B., and Poppi, M. (1966) Apropos of some
nocturnal myoclonic manifestations. Revue Neurologique 115(3), 547–555.
3. Young, T., Palta, M., Dempsey, J., et al. (1993) The occurrence of sleep disordered breathing
among middle-aged adults. N. Engl. J. Med. 328, 1230–1235.
4. Guilleminault,C., Eldridge, F. L., and Dement, W. C. (1973) Insomnia with sleep apnea: a new
syndrome. Science 181(8), 856–858.
5. Krakow, B., Melendrez, D., Ferreira, E., et al. (2001) Prevalence of insomnia symptoms in pa-
tients with sleep-disordered breathing. Chest 120, 1923–1929.
6. Guilleminault, C., Palombini, L., Poyares, D., and Chowdhuri, S. (2001) Chronic insomnia, post-
menopausal women, and sleep disordered breathing Part 1. Frequency of sleep disordered breath-
ing in a cohort. J. Psychosom. Res. 53, 611–615.
7. Roehrs, T., Conway, W., Wittig, R., et al. (1985) Sleep-wake complaints in patients with sleep-
related respiratory disturbances. Am. Rev. Respir. Dis. 132, 520–523.
Primary Sleep Disorders 151

8. Bradley, T. D., McNicholas, W., Rutherford, R., et al. (1986) Clinical and physiological hetero-
geneity of the central sleep apnea syndrome. Am. Rev. Respir. Dis. 134, 217–221.
9. Lavigne, G. and Montplaisir, J. (1994) Restless legs syndrome and sleep bruxism: prevalence and
association among Canadians. Sleep 17, 739–743.
10. Montplaisir, J.,Boucher, S., Poirer, G., Lavigne, G., Lapierre, O., and Lesperance, P. (1996) Clini-
cal polysomnographic and genetic characteristics of restless legs syndrome: a study of 133 patients
diagnosed with new standard criteria. Mov. Disord. 12, 61–65.
11. Coleman, R., Bliwise, D., Sajben, N., et al. (1988) Epidemiology of periodic movements during
sleep. In: Sleep/Wake Disorders, Natural History, Epidemiology and Long Term Evolution
(Guilleminault, C. and Lugaresi. E., eds.), Raven Press, New York, NY, 217–229.
12. Coleman, R., Pollak, C., and Weitzman, E. (1980) Periodic movements in sleep (nocturnal myo-
clonus): relation to sleep disorders. Ann. Neurol. 8, 416–421.
13. Dement, W., Zarcone, V., Varner, V., et al. (1972) The prevalence of narcolepsy. Sleep Res. 1, 148.
14. Bassetti, C. and Aldrich, M. (1996) Narcolepsy. Neurol. Clin. 14, 545–571.
15. Billard, M., Besset, A., and Cadilhac, J. (1983) The clinical and polygraphic development of
narcolepsy. In: Sleep/Wake Disorders: Natural History, Epidemiology and Long Term Evolution
(Builleminault, C. and Lugaresi, E., eds.), Raven Press, New York, NY, 187–199.
16. Stepansky, R., Holzinger, B., Schmeiser-Rieder, A., et al. (1998) Austrian dream behavior: re-
sults of a representative population survey. Dreaming 8, 23–30.
17. Ohayon, M., Morselli, P., and Guilleminault, C. (1997) Prevalence of nightmares and their rela-
tionship to psychopathology and daytime functioning in insomnia subjects. Sleep 20, 340–348.
18. Bastien, C. H. and Morin, C. M. (2000) Familial incidence of insomnia. J. Sleep Res. 9, 49–54.
19. Remmers, J., deGroot, W., Sauerland, E., et al. (1978) Pathogenesis of upper airway occlusion
during sleep. J. Appl. Physiol. 44, 931–938.
20. Kock, N., Culjkovic, B., Maniak, S., et al. (2002) Mode of inheritance and susceptibility locus for
restless legs syndrome, on chromosome 12q. Am. J. Hum. Genet. 71, 205–208.
21. Ondo, W. and Jankovic, J. (1996) Restless legs syndrome: clincoetiologic correlates. Neurology
47, 1435–1441.
22. Sandyk, R., Bernick, C., Lee, S., et al. (1987) L-dopa in uremic patients with the restless legs
syndrome. Int. J. Neurosci. 35, 233–235.
23. Matthews, W. (1986) Iron deficiency and restless legs. Br. Med. J. 1, 898.
24. Heimen, E. and Christie, M. (1986) Lithium-aggravated nocturnal myoclonus and restless legs
syndrome. Am. J. Psychiatry 143, 1191–1192.
25. Ware, J., Brown, F., Moorad, P., et al. (1984) Nocturnal myoclonus and tricyclic antidepressants.
Sleep Res. 13, 72.
26. Bakshi, R. (1996) Fluoxetine and restless legs syndrome. J. Neurol. Sci. 142, 151–152.
27. Mendelson, W. (1996) Are periodic leg movements associated with clinical sleep disturbance.
Sleep 19, 219–223.
28. Montplaisir, J., Nicolas, A., Denesle, R., and Gomez-Mancilla, B. (1999) Restless legs syndrome
imiproved by pramipexole: a double-blind randomized trial. Neurology 52, 938–943.
29. Lin, L., Faraco, J., Li, R., et al. (1999) The sleep disorder canine narcolepsy is caused by a muta-
tion in the hypocretin (orexin) receptor 2 gene. Cell 98, 409–412.
30. Chemelli, R., Willie, J., Sinton, C., et al. (1999) Narcolepsy in orexin knockout mice: molecular
genetics of sleep regulation. Cell 98, 409–412.
31. Ripley, B., Overeem, S., Fujiki, N., et al. (2001) CSF hypocretin/orexin levels in narcolepsy and
other neurological conditions. Neurology 57, 2253–2258.
32. Peyron, C., Faraco, J., Rogers, W., et al. (2000) A mutation in a case of early onset narcolepsy and
a generalized absence of hypocretin peptides in human narcoleptic brains. Nat. Med. 6, 991–997.
33. John, J., Wu, M., and Siegel, J. (2000) Systemic administration of hypocretin-1 reduces cata-
plexy and normalizes sleep and waking durations in narcoleptic dogs. Sleep Research Online 3,
23–28.
152 Duntley

34. Cartwright, R. (1979) The nature and function of repetitive dreams: a survey and speculation.
Psychiatry 42, 131–137.
35. Cove-Smith, J. and Kirk, C. (1985) CNS-related side-effects with metropolol and atenolol. Eur.
J. Pharmacol. 28, 69–72.
36. Sharf, B., Moskovitz, C., Lupton, M., et al. (1978) Dream phenomena induced by chronic
levodopa therapy. J. Neural. Trams. 43, 143–151.
37. Lepkifker, W., Dannon, P., Iancu, I., et al. (1995) Nightmares related to fluoxetine treatment.
Clin. Neuropharmacol. 18, 90–94.
38. Hershon, H. (1977) Alcohol withdrawal symptoms and drinking behavior. J. Stud. Alcohol. 38,
953–971.
39. The International Restless Legs Syndrome Study Group. (1995) Towards a better definition of
the restless legs syndrome from the international restless legs syndrome study group. Mov. Disord.
10, 634–642.
40. Roehrs, T., Papineau, K., Rosenthal, L., and Roth, T. (1999) Ethanol as a hypnotic in insomniacs:
self-administration and effects on sleep and mood. Neuropsychopharmacology 20(3), 279–286.
41. Ford, D. E. and Kamerow, D. B. (1989) Epidemiologic study of sleep disturbances and psychiat-
ric disorders. An opportunity for prevention? JAMA 226(11), 1479–1484.
42. Chesson, A., Hartse, K., Anderson, W. M., et al. (1999) Practice parameters for the treatment of
restless legs syndrome and periodic limb movement disorder. An American Academy of Sleep
Medicine Report. Standards of Practice Committee of the American Academy of Sleep Medicine.
Sleep 22(7), 961–968.
43. US Xyrem Multicenter Study Group. (2002) A randomized, double blind, placebo-controlled
multicenter trial comparing the effects of three doses of orally administered sodium oxybate with
placebo for the treatment of narcolepsy. Sleep 25, 42–49.
44. Coalson, B. (1995) Nightmare help: treatment of of trauma survivors with PTSD. Psychotherapy
32, 381–388.
45. Miller, W. and DiPilato, M. (1983) Treatment of nightmares via relaxation and desensitization: a
controlled evalustion. J. Consult. Clin. Psychol. 51, 870–877.
46. Keller, R., et al. (1992) Changes in chronic nightmares after one session of desensitization or
rehersal instructions. Am. J. Psychiatry 149, 659–663.
47. Marquis J. (1991) A report on seventy-eight cases treated by eye movement desensitization. J.
Behav. Ther. Exp. Psychiatry 22, 187–192.
48. Kingsbury, S. J. (1993) Brief hypnotic treatment of repetitive nightmares. Am. J. Clin. Hypn. 35,
161–169.
Cognitive-Behavioral Therapy 153

IV Treatment of Insomnia
154 Perlis et al.
Cognitive-Behavioral Therapy 155

13
Cognitive-Behavioral Therapy for Insomnia

Michael L. Perlis, Michael T. Smith, Carla R. Jungquist,

Sara Nowakowski, Henry Orff, and James Soeffing

INTRODUCTION
This chapter provides an overview of how primary insomnia is assessed and
treated using cognitive-behavioral therapy (CBT). Additionally, we provide some
upfront information that reviews the CBTs regarding the etiology of chronic
insomnia and some follow-up information of the efficacy of CBT for insomnia.
The former is provided so that the reader may appreciate the principles on which
CBT is founded. The latter is provided so that the reader may appreciate the extent
to which CBT for insomnia has been empirically validated.

THEORETICAL PERPSECTIVES ON INSOMNIA

Behavioral Perspective
Since the late 1980s, insomnia has largely been conceptualized from within a
behavioral framework. The original model was proposed by Spielman and col-
leagues and it continues to be the leading theory for both sleep medicine and the
subspecialty area of behavioral sleep medicine (1). As illustrated in Fig. 1, the
behavioral model posits that insomnia occurs acutely in relation to both predispos-
ing (trait) and precipitating (state) factors and occurs chronically in relation to per-
petuating or maintaining factors. Thus, an individual may be prone to insomnia due
to trait characteristics, experience acute episodes because of precipitating events,
and have chronic insomnia owing to a variety of perpetuating factors.
With respect to trait factors, personality characteristics (2,3), physiological
arousal (2,3), and genetic predisposition (4) are each thought to contribute to pre-
dispose the individual to acute episodes of insomnia. Typical precipitating events
(which represent stressors within the larger stress diathesis model of disease)
include situational stress (5), acute injury or pain, bereavement, and so on. Perpetu-
ating factors, as the term implies, maintain the chronic form of the disorder even

From: Curent Clinical Neurology: Clinical Handbook of Insomnia

Edited by: H. P. Attarian © Humana Press Inc., Totowa, NJ

155
156 Perlis et al.

Fig. 1. A schematic of the differential diagnosis process for the diagnosis of primary
insomnia.

after the precipitating events have either been stabilized or resolved. Perpetuating
factors are any of a variety of compensatory strategies in which the patient engages
in an attempt to cope with insomnia symptoms. Typical examples of such factors
include excessive daytime napping, extending sleep opportunity, keeping variable
sleep–wake schedules, use of alcohol as a hypnotic, spending excessive time awake
in bed, diminishing daily activity level due to fatigue, and so on.
Central to the behavioral model of chronic insomnia is the role of classical condi-
tioning as the primary maintaining factor. It is hypothesized that, over time, insomnia
becomes a conditioned response to the bed and bedroom environment. This process
presumably occurs via traditional principles of classical conditioning, resulting from
repeated pairings of the bed and bedroom (conditioned stimuli) with states of psycho-
physiologic hyperarousal (unconditioned stimuli) that are thought to interfere with
the normal biological processes of sleep initiation and maintenance.

Cognitive Perspective
A number of authors have stressed the importance of cognitive factors in pri-
mary insomnia (6–8). Given their emphasis on the role of cognition, they and oth-
ers have developed interventions, which provide for the cognitive component of
the more broad-based cognitive-behavioral approach. Within this perspective, two
related types of cognitions are thought to be operational: one set is related to the
patient’s beliefs about his or her disorder; the other is related to cognitive processes
like intrusive thoughts and worry.
Cognitive-Behavioral Therapy 157

Morin et al., for example, found that patients with primary insomnia have a num-
ber of maladaptive beliefs about sleep, including unrealistic views about what con-
stitutes adequate sleep and catastrophic beliefs about the consequences of insomnia.
Such beliefs presumably contribute to insomnia by increasing sleep-related perfor-
mance anxiety and by prompting and promoting maladaptive compensatory
behaviors. Support for the role of such factors derives from data showing that suc-
cessful CBT of insomnia is associated with a reduction in negative beliefs and atti-
tudes about sleep (9,10). Although this is suggestive, more work is needed to
demonstrate the “insomnogenic” potential of such cognitions. This is so because
one can easily imagine that successful therapy may change one’s thoughts and
beliefs, but also that such changes may not be responsible for the treatment gains.
Hall et al. and Harvey and colleagues focused more on cognitive process (vs
content) issues (5,8). Central to this area is that patients with insomnia often com-
plain that they are unable to sleep because of intrusive thoughts or excessive worry.
These thoughts and images are characterized as being “intrusive” and may occur in
isolation or as unwanted perseverative-type problem solving (worry). The content
of the “thoughts and worry” may be centered on the kind of dysfunctional attitudes
and beliefs described previously, but they are often more general in content. The
ideation and imagery that occurs as intrusive thoughts is often related to mundane
daily activities and/or work or relationship issues. As with dysfunctional attitudes
and beliefs, intrusive thoughts and perseverative thinking (from within the radical
cognitive perspective) are thought to be responsible for the occurrence and severity
of insomnia. The more moderate view is that these phenomena are, along with be-
havioral and conditioning factors, contributory.
Support for the cognitive perspective comes from a variety of studies that have
found that patients with primary insomnia complain of higher levels of pre-sleep
rumination compared to normal controls (11,12). Investigations of pre-sleep thought
content have found that the pre-sleep cognitions of patients with primary insomnia
tend to be more negatively toned, and that patients report increased general prob-
lem solving and thoughts pertaining to environmental stimuli at or around sleep
onset (13–15).

Neurocognitive Perspective
In sharp contrast to the cognitive model, the neurocognitive perspective all but
suggests that dysfunctional beliefs and worry are epiphenomena. It is posited that
cognitive factors are likely to mediate the occurrence and severity of insomnia when
the disorder is acute. When, however, the disorder is chronic, cognition occurs sec-
ondary to conditioned arousal. Put differently, patients with chronic insomnia are
not awake because they are given to rumination and worry, but rather ruminate
because they are awake.
The neurocognitive perspective (3) is an extension of the traditional behavioral
model. As laid out by Spielman and colleagues (1), the behavioral model allows for
a compelling conceptualization regarding how maladaptive behaviors lead to con-
158 Perlis et al.

ditioned arousal and chronic insomnia. The Spielman model does not, however,
spell out what the conditioned arousal is, or why and how “arousal” interferes with
sleep initiation and/or maintenance and/or the perception of sleep. These latter
issues are precisely the province of the neurocognitive model that defines “arousal”
as conditioned cortical arousal. This form of arousal may be observed in patients
with primary insomnia as high frequency electroencephalogram (EEG) activity (14–
45 Hz) at or around sleep onset and during non-rapid eye movement (NREM) sleep
(15,16). High-frequency EEG activity, it is hypothesized, allows for abnormal lev-
els of sensory and information processing and long-term memory formation.
Increased sensory processing is thought to interfere with the ability to initiate sleep
(as measured by traditional polysomnographic measures). Increased information pro-
cessing during polysomnographic-defined sleep is thought to interfere with the
subject’s ability to perceive polysomnographic sleep as “sleep.” Increased long-term
memory formation (attenuation of the normal mesograde amnesia of sleep) is thought
to interfere with the patient’s morning judgments about sleep quality and quantity.
Support for the neurocognitive perspective (17) comes from a variety of studies
that have found β EEG (14–45 Hz) (1) to be elevated in patients with insomnia
(16,18–21), (2) to be positively associated with patient perceptions of sleep quality
(22,23), (3) to be positively associated with sleep state misperception (SSM; the
degree of discrepancy between subjective and objective measures of sleep) (16,24),
and (4) to vary with successful CBT treatment for insomnia (25). There is also
preliminary evidence that the occurrence of elevated NREM β activity is sensitive
and specific to primary insomnia (vs insomnia secondary to major depressive dis-
order) (16) and data that suggest the long-term memory function at peri-sleep onset
intervals is altered in patients with chronic insomnia (26).

ASSESSMENT AND MEASUREMENT

Self-Report Assessment
Behavioral sleep medicine specialists often utilize a number of retrospective
assessment tools to gather more precise diagnostic information. Additionally,
behavioral sleep medicine specialists utilize daily sleep diaries (27) to prospec-
tively monitor sleep complaints. Prospective assessment is important for evaluat-
ing the severity of insomnia complaints on a day-to-day basis, identifying the
behaviors that maintain the insomnia, determining the extent to which circadian
dysrhythmia is present, and gathering the data needed to measure and guide treat-
ment response.
The sleep component of sleep–wake diaries are typically completed after wak-
ing and obtain information on time to bed, wake time, sleep latency (SL), frequency
of nightly awakenings (FNA), wake time after sleep onset (WASO), total sleep
time (TST), early morning awakenings (EMA), medication/ substances taken before
bed, and subjective assessments of sleep quality. The daytime measures, which are
completed prior to going to bed, include nap frequency and duration, fatigue rat-
ings, stimulant consumption, and medication usage.
Cognitive-Behavioral Therapy 159

Objective Assessment
In current clinical practice, the diagnosis of primary insomnia does not require
an in-laboratory, polysomnographic study to substantiate the diagnosis. This is true
for three reasons. First, there is enough of a general correspondence between the
subjective complaint and objective measures so that polysomnographic assessment
is not required to verify the sleep continuity disturbance. Second, traditional
polysomnography does not reveal, or allow for the quantification of, the underlying
sleep pathophysiologies that presumably give rise to the patient’s complaints. Third,
and most pragmatically, third-party payers will not reimburse for sleep studies on
patients with likely primary insomnia. However, sleep studies are indicated if the
patient demonstrates symptoms consistent with other intrinsic sleep disorders and/
or fails to respond to treatment.
When assessed with polysomnography, patients with primary insomnia reliably
exhibit increased SL, increased FNAs, increased WASO time, and decreased TST
relative to good sleeper controls. Polysomnographic findings, however, do not
correspond in a one-to-one fashion to patient perceptions of sleep continuity.
Patients with insomnia routinely report more severe sleep disturbance than is evi-
dent on traditional polysomnographic measures (28–30). Some have argued that
this discrepancy might be explained by the findings that patients with primary in-
somnia show a greater degree of psychopathology, including tendencies to somatize
internal conflicts and exaggerate symptoms (31–33). Others have argued that the
subjective–objective discrepancy findings reflect a cardinal feature of the disorder,
that is, the persistence of sensory and information processing into NREM sleep. The
continuance of such processes into polysomnographic-defined sleep are thought to be
the basis for patient difficulties distinguishing between wakefulness and sleep (3).
The extent to which one or both of these factors contributes to the discrepancies
between subjective and objective measures of sleep in insomnia continues to be a
matter of ongoing debate. (For additional information on these issues, please see the
following section on the cognitive-behavioral perspective on insomnia.)
When polysomnography is not feasible, the use of alternative, less costly objec-
tive devices can be particularly helpful when the clinician suspects a high degree of
SSM. SSM is a term (as well as disorder) used to describe the common finding
among patients with insomnia that there is a discrepancy between a patient’s sub-
jective impression of sleep parameters and what is measured via objective record-
ing methods. At the level of self-report, extreme values (gathered retrospectively or
prospectively) may suggest that this is a component of the disorder (e.g., SLs >2
hours, WASO >2 hours, or a TST of ≤4 hours). In the absence of a
polysomnographic study, actigraphs may be used to obtain corroborating prospec-
tive data. Actigraphs are wristwatch-like devices that utilize sophisticated move-
ment detectors to estimate the traditional sleep continuity parameters (e.g., SL,
WASO, FNA, and TST). This information may, in turn, be compared to the self-
report data to assess the degree to which SSM is occurring. The extent to which
subjective–objective discrepancies can be resolved using actigraphy has not been
160 Perlis et al.

subjected to empirical validation. In our clinical practice, however, we have found

that actigraphy can be used to assess for SSM.

COGNITIVE-BEHAVIORAL TREATMENT
The most common CBTs for primary insomnia are sleep hygiene education,
stimulus control therapy (SCT), sleep restriction therapy (SRT), relaxation train-
ing, and cognitive therapy. (For a detailed explanation of each of these therapies
see ref. 6.)
Of all the available psychological treatments, SCT is the most well-validated
and is considered the “gold standard” for the behavioral treatment of insomnia. In
practice, most behavioral sleep medicine clinicians adopt a multicomponent
approach that usually contains SCT, SRT, and sleep hygiene therapy.

Therapeutic Regimen
The CBT of insomnia generally requires 4 to 8 weeks time with once-a-week,
face-to-face meetings with the clinical provider. Sessions range from 30 to 90 min-
utes depending on the stage of treatment and the degree of patient compliance.
Intake sessions are usually 60 to 90 minutes in duration. During this session, the
clinical history is obtained and the patient is instructed in the use of sleep diaries.
No intervention is provided during the first week. This time frame is used to collect
the baseline sleep–wake data that will guide treatment for the balance of therapy.
The primary interventions (SCT and SRT) are deployed over the course of the next
one to two 60-minute sessions. Once these treatments are delivered, the patient
enters into a phase of treatment where TST is upwardly titrated over the course of
the next two to five visits. These follow-up sessions require about 30 minutes, unless
additional interventions are being integrated into the treatment program or extra
effort is required to gain patient compliance. Adjunctive treatments include cogni-
tive therapy, relaxation training, and relapse prevention.

First-Line Interventions
Stimulus Control Therapy
SCT is recommended for both sleep initiation and sleep maintenance problems.
SCT is generally considered the first-line behavioral treatment for chronic primary
insomnia because it has the most research support (34). SCT instructions limit the
amount of time patients spend awake in the bed/bedroom, and are designed to
decondition pre-sleep arousal and re-associate the bed/bedroom environment with
rapid, well-consolidated sleep. Typical instructions include (1) maintaining a fixed
wake time 7 days a week, irrespective of how much sleep one gets during the night;
(2) avoiding any behavior in the bed or bedroom other than sleep or sexual activity;
(3) sleeping only in the bedroom; (4) leaving the bedroom when awake for approxi-
mately 15 to 20 minutes; (5) returning to the bedroom only when sleepy. Some
clinicians, in an effort to prevent “clock-watching” behavior, encourage patients to
leave the bedroom as soon as they feel “clearly awake” or experience annoyance
Cognitive-Behavioral Therapy 161

and irritation over the fact that they are awake. The combination of these instruc-
tions re-establishes the bed and bedroom as strong cues for sleep, and entrains the
circadian sleep–wake cycle to the desired phase.
Sleep Restriction
SRT is recommended for both sleep initiation and sleep maintenance problems.
SRT requires patients to limit the amount of time in bed (TIB) to an amount equal
to their average TST. In order to accomplish this, the clinician works with the pa-
tient to establish a fixed wake time and decrease sleep opportunity by limiting the
subject’s TIB to an amount that equals his or her average TST as ascertained by
baseline sleep diary measures. Once a target amount of TIB is set, the patient’s bed-
time is delayed to later in the night so that the TIB and average TST are the same.
Initially, this intervention results in a reduction in TST, such that the patient gets less
total sleep than he or she is accustomed to. This controlled form of sleep loss usually
corresponds to a decrease in SL and WASO time. Thus, during the acute phase of
treatment, the patient gets less sleep, but sleeps in a more consolidated fashion (i.e.,
he or she fall asleeps more quickly and stays asleep for longer periods of time). The
increase in consolidated sleep is formally represented as sleep efficiency (TST/TIB).
The patient’s sleep efficiency is monitored on a weekly basis. If the patient’s
average weekly sleep efficiency reaches 85–90% (depending on age), then sleep
opportunity is incrementally increased by 15 minutes. The increase in sleep oppor-
tunity is accomplished by having the patient retire 15 minutes earlier for the next
week of treatment. The upward titration process is usually continued for about
4 weeks, thus allowing for an increase of about 1 hour in sleep opportunity.
When the patient does not reach the 85–90% benchmark, some clinicians reduce
the total sleep opportunity to the previous “set point,” others maintain the subject’s
total sleep opportunity until adequate sleep efficiency is observed, whereas still
others combine these approaches. With respect to the last possibility, the clinician
may maintain the subject’s total sleep opportunity for 2–3 weeks and then down-
wardly titrate the TIB when there is clear evidence that the patient cannot sustain
his or her clinical gains.
SRT is thought to be effective for two reasons. First, it prevents the patient from
coping with his or her insomnia by extending sleep opportunity. This strategy,
although increasing the opportunity to get more sleep, produces a form of sleep that
is shallow and fragmented. Second, the initial sleep loss that occurs with SRT is
thought to increase the “pressure for sleep,” which in turn produces quicker SLs,
less WASO, and more efficient sleep.
Three points merit further comment. First, total TIB is manipulated by phase
delaying the patient’s sleep period. This, along with keeping a fixed wake time,
results in sleep restriction. It is plausible, however, that total TIB could be altered
by having the subject wake up at an earlier time. This approach is not adopted
because fixing “wake up time” at an early hour (1) does not capitalize on the fact
that extending wakefulness is easier to tolerate than curtailing sleep, (2) delays the
initial increase in time awake before sleep for 24 hours (and thus delays the clinical
162 Perlis et al.

effect), (3) may reinforce the tendency for EMAs, and (4) undermines the opportu-
nity to pair “sleep” with the bed/bedroom.
Second, it should be noted that SRT has some paradoxical aspects. One paradox
is that patients who report being unable to sleep are in essence being told to sleep
less. The other paradox occurs over the course of treatment. With therapy, patients
find that it is difficult to stay awake until the prescribed hour. This, if not paradoxi-
cal, is at least ironic for the patient who initially presents with sleep-onset difficul-
ties. Finally, it should be noted that SRT may be contraindicated in patients with
histories of mania or seizure disorder because it may aggravate these conditions.
Adjunctive Interventions
Sleep Hygiene Education
Sleep hygiene education is recommended, along with SRT and SCT, for both sleep
initiation and maintenance problems. It may also have some value as a means toward
increasing TST. Sleep hygiene education addresses a variety of behaviors that may
influence sleep quality and quantity. The intervention most often involves providing
the patient with a handout and then reviewing the items and the rationales for them.
Table 1 contains a set of sleep hygiene instructions. It should be noted that in this
formulation, several aspects of other therapies are adopted. For example, items 1, 2,
12, 13, and 15 are traditionally considered part of SCT and/or SRT.
Sleep hygiene education is most helpful when tailored to a behavioral analysis
of the patient’s sleep–wake behaviors. The tailoring process allows the clinician
the opportunity to (1) demonstrate the extent to which he or she comprehends the
patient’s individual circumstances (by knowing which items do and do not apply),
(2) suggest modifications, and (3) show the patient the rules, which are in many
ways too “absolutistic.” Consider the following two examples:
• The admonishment to avoid caffeinated products may be, in general, too simply con-
strued. Caffeinated beverages may be used to combat daytime fatigue (especially dur-
ing acute therapy) and, if the withdrawal is timed correctly, may actually enhance the
subject’s ability to fall asleep.
• The prohibition against napping may not be practical. Elderly subjects or subjects with
extreme work performance demands may indeed need to compensate for sleep loss. A
more considerate approach to napping may entail taking into account the time of the
nap, the duration of the nap, and how nocturnal sleep is handled on days when subjects
nap. Napping earlier in the day will allow for more homeostatic pressure for nocturnal
sleep. Limiting the duration of the nap will allow for less of a discharge of the
homeostat and enhance the subjects sensation of feeling rested from the nap (by avoid-
ing awakening from slow wave sleep). Going to bed later, when one naps during the
day, may minimize the effects of the nap on nocturnal sleep.
Finally, it can be argued that the most important aspect of sleep hygiene educa-
tion derives not so much from the “tips” provided, but from allowing the clinician
the opportunity to demonstrate his or her knowledge. A thoughtful and elaborate
review may enhance the patient’s confidence in the therapist and in the treatment
regimen. Such enhanced confidence may lead to greater adherence or compliance
with the more difficult aspects of therapy.
Cognitive-Behavioral Therapy 163

Table 1
Sleep Hygiene Instructions
1. Sleep only as much as you need to feel refreshed during the following day. Restrict-
ing your time in bed helps to consolidate and deepen your sleep. Excessively long
times in bed lead to fragmented and shallow sleep. Get up at your regular time the
next day, no matter how little you slept.
2. Get up at the same time each day, 7 days a week. A regular wake time in the morning
leads to regular times of sleep onset, and helps to set your “biological clock.”
3. Exercise regularly. Schedule exercise times so that they do not occur within 3 hours
of when you intend to go to bed. Exercise makes it easier to initiate sleep and deepen
sleep.
4. Make sure your bedroom is comfortable and free from light and noise. A comfortable,
noise-free sleep environment will reduce the likelihood that you will wake up during
the night. Noise that does not awaken you may also disturb the quality of your sleep.
Carpeting, insulated curtains, and closing the door may help.
5. Make sure that your bedroom is at a comfortable temperature during the night. Exces-
sively warm or cold sleep environments may disturb sleep.
6. Eat regular meals and do not go to bed hungry. Hunger may disturb sleep. A light
snack at bedtime (especially carbohydrates) may help sleep, but avoid greasy or
“heavy” foods.
7. Avoid excessive liquids in the evening. Reducing liquid intake will minimize the need
for nighttime trips to the bathroom.
8. Cut down on all caffeine products. Caffeinated beverages and foods (coffee, tea, cola,
chocolate) can cause difficulty falling asleep, awakenings during the night, and shal-
low sleep. Even caffeine early in the day can disrupt nighttime sleep.
9. Avoid alcohol, especially in the evening. Although alcohol helps tense people fall
asleep more easily, it causes awakenings later in the night.
10. Smoking may disturb sleep. Nicotine is a stimulant. Try not to smoke during the night
when you have trouble sleeping.
11. Don’t take your problems to bed. Plan some time earlier in the evening for working
on your problems or planning the next day’s activities. Worrying may interfere with
initiating sleep and produce shallow sleep.
12. Train yourself to use the bedroom only for sleeping and sexual activity. This will help
condition your brain to see bed as the place for sleeping. Do not read, watch TV, or
eat in bed.
13. Do not try to fall asleep. This only makes the problem worse. Instead, turn on the
light, leave the bedroom, and do something different like reading a book. Don’t en-
gage in stimulating activity. Return to bed only when you are sleepy.
14. Put the clock under the bed or turn it so that you can’t see it. Clock watching may
lead to frustration, anger, and worry, which interfere with sleep.
15. Avoid naps. Staying awake during the day helps you to fall asleep at night.
Note. The list includes the usual practices described as “good sleep hygiene,” but it also in-
cludes some principles subsumed under stimulus control therapy (principles 2,12,13), sleep restric-
tion therapy (principles 1,2,15), and relaxation (principles 11,13).

163
164 Perlis et al.

Cognitive Therapy
Several forms of cognitive therapy for insomnia have been developed. Some
have a didactic focus (6), some use paradoxical intention (35), others employ “dis-
traction and imagery” (36), and still others use a form of cognitive restructuring
(37). Although the approaches differ in procedure, all are based on the observation
that patients with insomnia have negative thoughts and beliefs about their condi-
tion and its consequences. Helping patients challenge the veracity of these beliefs
is thought to decrease the anxiety and arousal associated with insomnia. The cogni-
tive restructuring approach, adapted from for the procedure used for panic disorder
(38-40), is illustrated below.
Cognitive restructuring focuses on catastrophic thinking and the belief that poor
sleep is likely to have devastating consequences. Although psychoeducation may
also address these kinds of issues, the more important ingredient of cognitive
restructuring lies not in disabusing the patient of erroneous information, but rather
in having the patient discover that his or her estimates are ridiculously inaccurate (a
testament to the tendency to think in less than clear terms in the middle of the
night). When undertaking this exercise with a patient, it needs to be introduced in a
considerate way, one that avoids any hint that the therapist is being pedantic,
patronizing, or condescending.
The following are examples of the catastrophic thinking that occurs when the
patient is lying in bed trying to sleep...
“If I don’t get a good night’s sleep,

I’ll be in a bad mood tomorrow. If my mood is poor tomorrow, I will—yet again—

be short with my wife. If I’m irritable with my wife (again), she may start think-
ing about not putting up with this anymore. If she thinks about not putting up
with this anymore, she’ll consider leaving me...” [get divorced].

I won’t be able to stay awake or concentrate when I’m driving to work. If I don’t
stay awake or concentrate when I’m driving, I may get into an accident...” [wreck
the car].

I won’t be able to function tomorrow at work. If I am not able to function at work,

I may get a reprimand. If I get reprimanded... ” [get fired].
The first step in the cognitive restructuring process is to have patients discuss
and list the kinds of negative things they think can happen when their sleep is poor.
Usually, the list is constructed with the patient and placed, as a chart, on the cogni-
tive therapist’s ever present in-office chalkboard. The first column in the chart lists
catastrophic events. Note that the patient may need to be prompted to identify the
underlying and most catastrophic thought. For example, the patient may say “I
worry about not being able to fall sleep” when what he or she is primarily worried
about is the extreme version of this proposition: spending the entire night awake.
Once the list is compiled (5 to 10 things constitutes a reasonable list), patients
are then asked how likely they think each of the events are, given a night of poor
Cognitive-Behavioral Therapy 165

sleep. For instance, the therapist may ask, “When you are lying in bed imagining
being so tired tomorrow that you might perform badly at work, at that moment how
certain are you that your work will be ‘substandard’, how certain are you that you’ll
be ‘reprimanded,’” and so on. These data are represented in column 2. Next, the
patient is asked how frequently his or her sleep is poor, and for how many years he
or she has been suffering from insomnia. This number is coded as the “number of
days with insomnia” and is set to the side of the table (to be coded later in column
3). The final data needed from the patient is an estimate of how frequently each of
the catastrophic events have occurred. These are coded into column 4. The combi-
nation of these four sources of data are then used to show the patient that there is a
substantial mismatch between his or her degree of certainty and the number of times
the negative events have actually transpired.
For example, the clinician might observe, “You have suffered from insomnia for
5 nights a week for the last 3 years. This means that you have had about 800 really
bad nights. You also said that when you’re thinking about what might happen if you
don’t fall asleep, you are 90% certain that on the next day you are going to perform so
badly that you’ll be reprimanded. If it happened 90% of the time and you’ve had 800
bad nights, then you should have been reprimanded about 700—lets say 500—times.”
These data are represented in column 5. The last column of data is then compared to
the list in column 4, so that the patient can see the mismatch between the number of
instances that should have occurred and the number of instances that actually
occurred. For an example of the chart just described, see Table 2.
Relaxation Training
Different relaxation techniques target different physiological systems. Progres-
sive muscle relaxation is used to diminish skeletal muscle tension (41–45). Dia-
phragmatic breathing is used to make respiration slower, deeper, and mechanically
driven from the abdomen as opposed to the thorax. (It is interesting to note that this
form of respiration resembles what occurs naturally at sleep onset.) Autogenic train-
ing focuses on increasing peripheral blood flow by having subjects imagine, in a
systematic way, that each of their extremities feel warm.
Most practitioners select the optimal relaxation method based on which technique
is easiest for the patient to learn and which is most consistent with how the patient
manifests arousal. Like cognitive techniques, learning to effectively use relaxation
training often requires substantial practice. Many clinicians recommend the patient
rehearse the skill during the day in addition to practicing prior to sleep. If relaxation
training causes some initial “performance anxiety” when integrating it into SCT in-
structions, it may be best to have the patient practice in a room other than the bed-
room. It also should be kept in mind that some patients, especially those with a history
of panic disorder, may experience a paradoxical response to relaxation techniques.

Phototherapy
Although many clinicians may not consider phototherapy a behavioral interven-
tion, it is often important to integrate the use of bright light into the treatment regi-
166 Perlis et al.

Table 2
Cognitive Restructuring
1 2 3 4 5
Certainty No. of event
when lying occurences
Catastrophic awake and No. days with No. of event given
events unable to sleep insomnia occurrences certainty
Get reprimanded 90% 800 5 620 (500)
Get fired
Get divorced
Wreck the car
Be awake all night

men. This is especially true when circadian factors appear to substantially contrib-
ute to the insomnia complaint. There is substantial empirical evidence that bright
light has sleep-promoting effects.
In the case where the patient’s insomnia has a phase-delay component (i.e., the
patient prefers to go to bed late and wake up late), bright light exposure in the
morning for a period of 30 minutes or more may enable the patient to “feel sleepy”
at an earlier time in the evening. In the case where the patient’s insomnia has a
phase-advance component (i.e., the patient prefers to go to bed early and wake up
early), bright light exposure in the late evening/early night may enable him or her to
stay awake until a later hour. Phototherapy is often accomplished via a light box
that typically generates white light, or more selectively, blue spectrum light at
5000–10,000 lux. The dose is adjusted by altering the distance and duration of light
exposure. It is generally assumed that phototherapy has no significant side effects,
but this is not always the case. Mania may be triggered by bright light, but rarely, if
ever, in patients not previously diagnosed with bipolar mood disorder. Other side
effects are insomnia, hypomania, agitation, visual blurring, eye strain, and head-
aches. Light boxes may not be recommended for individuals with certain eye con-
ditions, including retinopathy secondary to diabetes. In some cases, equivalent or
better phase-shifting properties may be accomplished by scheduling time outdoors
(e.g., taking early morning walks).
The sleep-promoting effects of bright light may occur via several mechanisms,
including shifting the circadian system, enhancement of the amplitude of the circa-
dian pacemaker, promoting wakefulness during the day and sleep at night, or indi-
rectly, via its antidepressant effects.

Complicating Factors
There are a number of potential complicating factors that require continuous
monitoring and evaluation throughout the course of treatment, particularly if the
patient fails to show expected clinical gains after two to four sessions of active
treatment. The most common complicating factors are poor treatment compliance,
Cognitive-Behavioral Therapy 167

issues related to comorbid psychiatric and medical disorders, and the simultaneous
use of sedative hypnotics.
Treatment Compliance
The single most important complicating factor is poor treatment compliance. At
the beginning of treatment, the clinician should proactively address the fact that the
prescriptions may seem counterintuitive and that adhering to the treatment will be
difficult. Providing the patient with a complete and thoughtful rationale for each
aspect of the treatment, managing the patient’s expectations, and encouraging an
active self-management approach are essential. Providing the rationale for treat-
ment is likely to gain patient compliance in at least two ways. First, the effort to
explain therapy is less imperative, thereby making the patient an active partner in
the treatment process and making him or her less resistant or reactive to the pre-
scriptions. Second, a fluid, interesting, and compelling explanation will support
and enhance the patient’s perception of the clinician as a competent authority.
With respect to expectation, the patient should not anticipate that the results will
be immediate. In fact, the patient should be cautioned that his or her sleep problem
is likely to briefly “get worse before it gets better.” Sometimes an appeal to the
research literature, demonstrating that treatment gains are maintained and often
continue to improve in the long-term, may help maintain the patient’s motivation
despite the short-term difficulty adjusting to the procedures.
With respect to “active self-management,” it is important to remember that the
treatment alternative is medication and that this requires very little in the way of
lifestyle change. Thus, the clinician must spend a considerable amount of time
working with the patient to “make and stay with the investment.”
Comorbity of Mental and Medical Disorders
Many patients with chronic insomnia report mild or subthreshold levels of
depressive symptoms. When depressive symptoms become severe, they may inter-
fere with the patient’s ability and motivation to successfully follow the recom-
mended protocol. If medical factors become exacerbated, expectations for clinical
gains need to be tempered until stabilization occurs. Throughout the course of treat-
ment, both medical and psychiatric factors should be monitored and consideration
should be given for further evaluation and intervention.
CBT and Sedative Hypnotics
Not yet addressed is the possibility of using sedative hypnotics acutely, along with
CBT for insomnia (i.e., dual or combined therapy). This is a promising and
underinvestigated area of inquiry. Initial studies were mixed (46–48), but promising
work continues (49). The benefit of combined therapy is a more rapid reduction of
symptoms. The risk of combining pharmacotherapy with behavioral treatment, how-
ever, is that once patients start using medications, they may be less inclined to adopt
or tolerate behavioral interventions. Work is ongoing to determine the most effective
way to combine these two strategies to capitalize on the immediate reduction in symp-
toms afforded by sedative hypnotics and the long-term efficacy of CBT (50).
168 Perlis et al.

Perhaps more important than the issue of combined therapy to the practice of
CBT for insomnia is that many of the patients referred for CBT have been taking
sedative hypnotics for years and are very apprehensive about discontinuing treat-
ment. Often, the initial phases of treatment involve collaboration with the referring
physician to assist the patient in the weaning process. Use of sleep diaries to pro-
vide feedback about sleep continuity during the withdrawal process and education
about rebound insomnia and the medication itself are important for this kind of
intervention. It should be noted that the chronic use of sedative hypnotics often
leaves the patient with as poor a sleep continuity profile as if no medications at all
were being used. This is difficult for the patient to appreciate because of the rebound
insomnia that occurs during the withdrawal period. As noted previously in this chap-
ter, the natural assumption during the withdrawal from medication is, “This is how
I will sleep without medications from now on.” In combination with a careful wean-
ing process, sleep diaries may serve as the “hard data” to demonstrate to the patient
that this assumption is not true.

THE EFFICACY OF CBT

There are a variety of studies that attest to the efficacy of behavioral treatments
for primary insomnia. These studies have been reviewed in two meta-analyses
(51,52). Results from the two quantitative reviews are as follows: 32–41% global
improvement in sleep following behavioral treatment where SL was reduced by
39.5–43% (effect sizes: 0.87–0.88), number of intermittent awakenings was reduced
by 30–73% (effect sizes: 0.53–0.63), duration of intermittent awakenings was re-
duced by 46% (effect size: 0.65) and TST increased by 8–9.4% (effect size: 0.42).
In actual minutes, pre–post measures revealed that patients fell asleep 24–28 min-
utes sooner, had 0.5–1.2 fewer awakenings and obtained about 30–32 more min-
utes of sleep a night. Comparative data showed that SRT or SCT yielded the greatest
improvement, followed by multicomponent therapies. Treatment gains were main-
tained or enhanced over follow-up periods ranging from 3 weeks to 3 years. In
addition to these data, there is a study by Morin and colleagues that suggests that
behavior therapy yields, during acute treatment, comparable results to pharmaco-
therapy for insomnia and that behavior therapy has better long-term efficacy (51).
A recent study by our group (53) confirms this finding in a comparative meta-
analytic study and extends it by demonstrating that during acute treatment behav-
ior, therapy yields results comparable to those of pharmacotherapy and may provide
superior results for sleep-onset problems.

REFERENCES
1. Spielman, A., Caruso, L., and Glovinsky, P. (1987) A behavioral perspective on insomnia treat-
ment. Psychiatr. Clin. North Am. 10, 541–553.
2. Stepanski, E. J. (2000) Behavioral therapy for insomnia. In: Principles and Practice of Sleep
Medicine (Kryger, M. H., Roth, T. G., and Dement, W. C., eds.), W. B. Saunders Company,
Philadelphia, PA, pp. 647–656.
Cognitive-Behavioral Therapy 169

3. Perlis, M. L., Giles, D. E., Mendelson, W. B., Bootzin, R. R., and Wyatt, J. K. (1997) Psychophysi-
ological insomnia: the behavioural model and a neurocognitive perspective. J. Sleep Res. 6, 179–188.
4. Bastien, C. H. and Morin, C. M. (2000) Familial incidence of insomnia. J. Sleep Res. 9, 49–54.
5. Hall, M., Buysse, D. J., Reynolds, C. F., Kupfer, D. J., and Baum, A. (1996) Stress-related intru-
sive thoughts disrupt sleep onset and contiguity. Sleep Res. 25, 163.
6. Morin, C. M. (1993) Insomnia: Psychological assessment and management. Guilford Press, New
York, NY.
7. Espie, C. A. (1991) The psycological treatment of insomnia. John Wiley and Sons, New York, NY.
8. Harvey, A. G. (2002) A cognitive model of insomnia. Behav. Res. Therapy 40, 869–893.
9. Edinger, J. D., Wohlgemuth, W. K., Radtke, R. A., Marsh, G. R., and Quillian, R. E. (2001)
Cognitive behavioral therapy for treatment of chronic primary insomnia: a randomized controlled
trial. JAMA 285, 1856–1864.
10. Morin, C. M., Blais, F., and Savard, J. (2002) Are changes in beliefs and attitudes about sleep
related to sleep improvements in the treatment of insomnia? Behav. Res. Ther. 40, 741–752.
11. Lichstein, K. and Rosenthal, T. (1980) Insomniacs’ perceptions of cognitive versus somatic de-
terminants of sleep disturbance. J. Abnorm. Psychol. 89, 105–107.
12. Nicassio, P. M., Mendlowitz, D. R., Fussell, J. J., and Petras, L. (1985) The phenomenology of the
pre-sleep state: the development of the pre- sleep arousal scale. Behav. Res. Ther. 23, 263–271.
13. Van Egeren, L., Haynes, S. N., Franzen, M., and Hamilton, J. (1983) Presleep cognitions and attri-
butions in sleep-onset insomnia. J. Behav. Med. 6, 217–232.
14. Kuisk, L. A., Bertelson, A. D., and Walsh, J. K. (1989) Presleep cognitive hyperarousal and affect
as factors in objective and subjective insomnia. Perceptual and Motor Skills 69, 1219–1225.
15. Watts, F. N., Coyle, K., and East, M. P. (1994) The contribution of worry to insomnia. Br. J. Clin.
Psychol. 33, 211–220.
16. Perlis, M. L., Smith, M. T., Orff, H. J., Andrews, P. J., and Giles, D. E. (2001) Beta/gamma EEG activity
in patients with primary and secondary insomnia and good sleeper controls. Sleep 24, 110–117.
17. Perlis, M. L., Merica, H., Smith, M. T., and Giles, D. E. (2001) Beta EEG in insomnia. Sleep Med.
Rev.in press.
18. Merica, H., Blois, R., and Gaillard, J. M. (1998) Spectral characteristics of sleep EEG in chronic
insomnia. Eur. J. Neurosci. 10, 1826–1834.
19. Merica, H. and Gaillard, J. M. (1992) The EEG of the sleep onset period in insomnia: a discrimi-
nant analysis. Physiol. Behav. 52, 199–204.
20. Freedman, R. (1986) EEG power in sleep onset insomnia. Electroencephalogr. Clin.
Neurophysiol. 63, 408–413.
21. Lamarche, C. H. and Ogilvie, R. D. (1997) Electrophysiological changes during the sleep onset period
of psychophysiological insomniacs, psychiatric insomniacs, and normal sleepers. Sleep 20, 724–733.
22. Hall, M., Buysse, D. J., Nowell, P. D., et al. (2000) Symptoms of stress and depression as corre-
lates of sleep in primary insomnia. Psychosom. Med. 62, 227–230.
23. Perlis, M. L., Giles, D. E., Mendelson, W. B., Bootzin, R. R., and Wyatt, J. K. (1997) Subjective
- objective discrepancies in psychophysiologic insomnia: A neurocognitive perspective. J. Sleep.
Res. 6, 179–188.
24. Krystal, A. D., Edinger, J. D., Wohlgemuth, W. K., and Michaels, C. (2002) A within-subject
study of the relationship of non-REM EEG spectral amplitude and the agreement between subjec-
tive and objective assessments of sleep time. Sleep 25(Abstract Suppl.), A33–A34.
25. Krystal, A. D., Edinger, J. D., Wohlgemuth, W. K., and Marsh, G. R. (2001) A pilot study of the
sleep EEG power spectral effects of behavioral therapy in primary insomniacs. Sleep 24(Ab-
stract Suppl.), A62.
26. Perlis, M. L., Smith, M. T., Orff, H. J., Andrews, P. J., and Giles, D. E. (2001) The mesograde
amnesia of sleep may be attenuated in subjects with primary insomnia. Physiol. Behav. 74, 71–76.
27. Monk, T. H., Reynolds, C. F., and Kupfer, D. J. (1994) The Pittsburgh Sleep Diary (PghSD). J.
Sleep. Res. 3, 111–120.
170 Perlis et al.

28. Carskadon, M., Dement, W., Mitler, M., Guilleminault, C., Zarcone, V. P., and Spiegel, R. (1976)
Self-reports versus sleep laboratory findings in 122 drug-free subjects with complaints of chronic
insomnia. Am. J. Psychiatry 133, 1382–1388.
29. Frankel, B. L., Coursey, R., Buchbinder, R., and Snyder, F. (1976) Recorded and reported sleep
in primary chronic insomnia. Arch. Gen. Psuchiatry 33, 615–623.
30. Coates, T. J., Killen, J., George, J., Marchini, E., Hamilton, S., and Thoresen, C. (1982) Estimat-
ing sleep parameters: A multitrait-multimethod analysis. J. Consult. Clin. Psychol. 50, 345–352.
31. Kales, A., Caldwell, A., and Preston, T. (1976) Personality patterns in insomnia. Arch. Gen.
Psychiatry 33, 1128–1134.
32. Kales, A., Bixler, E., Vela-Bueno, A., Cadieux, R., Soldatos, C., and Kales, J. (1984)
Biopsychobehavioral correlates of insomnia: III. Polygraphic findings of sleep difficulty and their
relationship to psychopathology. Int. J. Neurosci. 23, 43–56.
33. Bonnet, M. H. and Arand, D. L. (1997) Physiological activation in patients with sleep state
misperception. Psychosom. Med. 59, 533–540.
34. Chesson, A. L., Jr., Anderson, W. M., Littner, M., et al. (1999) Practice parameters for the
nonpharmacologic treatment of chronic insomnia. An American Academy of Sleep Medicine
report. Standards of Practice Committee of the American Academy of Sleep Medicine. Sleep 22,
1128–1133.
35. Shoham-Salomon, V. and Rosenthal, R. (1987) Paradoxical interventions: A meta-analysis. J.
Consult. Clin. Psychol. 55, 22–28.
36. Harvey, A. G. and Payne, S. (2002) The management of unwanted pre-sleep thoughts in insom-
nia: distraction with imagery versus general distraction. Behav. Res. Ther. 40, 267–277.
37. Buysse, D. J. and Perlis, M. L. (1996, March) The evaluation and treatment of insomnia. J. Prac.
Psych. Behav. Health 80–93.
38. Barlow, D. H., J. A. Cerny, and K. J. S. (1989) Behavioral treatment of panic disorder. Behav.
Ther. 20.
39. Barlow, D. H. (1992) Cognitive-behavioral approaches to panic disorder and social phobia. Bul-
letin of the Menninger Clinic 56.
40. Barlow, D. H. (1997) Cognitive-behavioral therapy for panic disorder: Current status. J. Clin.
Psychiatry 58.
41. Lichstein, K. L., Riedel, B. W., Wilson, N. M., Lester, K. W., and Aguillard, R. N. (2001) Relax-
ation and sleep compression for late-life insomnia: a placebo- controlled trial. J. Consult Clin.
Psychol. 69, 227–239.
42. Haynes, S. N., Woodward, S., Moran, R., and Alexander, D. (1974) Relaxation treatment of in-
somnia. Behav. Ther. 5, 555–558.
43. Freedman, R. and Papsdorf, J. D. (1976) Biofeedback and progressive relaxation treatment of
sleep-onset insomnia: a controlled, all-night investigation. Biofeedback Self Regul. 1, 253–271.
44. Bootzin, R. R. (1984) Evaluation of stimulus control instructions, progressive relaxation, and
sleep hygiene as treatments for insomnia. In: Sleep (Koella, W. P., Ruther, E., and Schulz, H.,
eds.), Gustav Fischer Verlag., Stuttgart, Germany, pp. 142–144.
45. Borkovec, T. D. and Fowles, D. C. (1973) Controlled investigation of the effects of progressive
and hypnotic relaxation on insomnia. J. Abnorm. Psychol. 82, 153–158.
46. Hauri, P. J. (1997) Can we mix behavioral therapy with hypnotics when treating insomniacs?
Sleep 20, 1111–1118.
47. Milby, J. B., Williams, V., Hall, J. N., Khuder, S., McGill, T., and Wooten, V. (1993) Effective-
ness of combined triazolam-behavioral therapy for primary insomnia. Am. J. Psychiatry 150,
1259–1260.
48. Morin, C. M., Colecchi, C., Stone, J., Sood, R., and Brink, D. (1999) Behavioral and pharmaco-
logical therapies for late-life insomnia: a randomized controlled trial. JAMA 281, 991–999.
49. Morin, C. M., Colecchi, C. A., Ling, W. D., Sood, R. K., and Williams, H. (1994) Cognitive-
behavioral therapy for benzodiazepine-dependent insomniacs. Sleep Res. 23, 295.
Cognitive-Behavioral Therapy 171

50. Vallieres, A., LeBlanc, M., Guay, B., and Morin, C. M. (2002) Sequntial use of medication and
behavioural therapies for chronic insomnia. Sleep 25(Abstract Suppl.), A69–A70.
51. Morin, C. M., Culbert, J. P., and Schwartz, S. M. (1994) Nonpharmacological interventions for
insomnia: a meta-analysis of treatment efficacy. Am. J. Psychiatry 151, 1172–1180.
52. Murtagh, D. R. and Greenwood, K. M. (1995) Identifying effective psychological treatments for
insomnia: a meta-analysis. J. Consult. Clin. Psychol. 63, 79–89.
53. Smith, M. T., Perlis, M. L., Park, A., et al. Comparative meta-analysis of pharmacotherapy and
behavior therapy for persistent insomnia. Am. J. Psychiatry 159, 5–11.
172 Perlis et al.
Pharmacological Treatment 173

14
Pharmacological Treatment of Insomnia

Hrayr P. Attarian

INTRODUCTION
Insomnia is the most common sleep-related complaint and the second most com-
mon overall complaint (after pain) reported in primary care settings. It affects 35%
of the general population, according to the 1984 report of the National Institutes of
Mental Health (1). Insomnia is not defined by total sleep time but by the inability to
obtain sleep of sufficient length or quality to produce refreshment the following
morning. For example, a person who needs only 4 hours of sleep does not have
insomnia if he or she is refreshed in the morning after having 4 hours of sleep,
whereas someone who needs 10 hours of sleep may have insomnia if he or she does
not feel refreshed even after 8 hours of sleep. Contrary to popular lore, psychiatric
or psychological factors are not the most frequent causes of insomnia. Insomnias
can be divided into two major categories: the primary insomnias and the secondary
insomnias. As discussed elsewhere in this volume, primary insomnias are condi-
tions in which the insomnia is the main pathophysiological process, whereas sec-
ondary insomnias are conditions where the insomnia is a symptom of another
disorder.

Primary Insomnias
Briefly, the primary insomnias are as follows:
1. Psychophysiological insomnia: a disorder of somatized tension and learned sleep-pre-
venting associations that results in a complaint of insomnia and associated decreased
functioning during wakefulness.
2. Idiopathic, or childhood-onset, insomnia: a lifelong inability to obtain adequate sleep
that is presumably due to an abnormality in the neurological control of the sleep–wake
system.
3. Sleep state misperception insomnia: complaints of insomnia occur without any objec-
tive evidence.
The treatment of most primary insomnias is a combination of behavioral and
pharmacological therapies.

From: Current Clinical Neurology: Clinical Handbook of Insomnia

Edited by: H. P. Attarian © Humana Press Inc., Totowa, NJ

173
174 Attarian

Secondary Insomnias
Restless legs syndrome (RLS) is a common condition found in varying degrees
in up to 10% of the population. The four cardinal symptoms are as follow:
1. A desire to move the legs.
2. Accompanying paresthesias that are characterized as uncomfortable or indescribable.
3. Motor restlessness.
4. Worsening of symptoms at night and at rest.
Symptoms of RLS may worsen with administration of tricyclic antidepressants
or selective serotonin reuptake inhibitors and during pregnancy.
Menopause-related insomnia is a high level of sleep disturbance occurring in
about 42% of middle-aged women. Other secondary insomnias include insomnia
due to other sleep disorders, insomnia due to poor sleep hygiene, neurological, psy-
chiatric, other sleep disoders or other medical conditions, and medication-induced
insomnia. Secondary insomnias most often respond to the treatment of the underly-
ing cause. In this chapter, only the pharmacological treatments of primary
insomnias, menopause-related insomnia, and RLS are discussed.

HISTORICAL PERSPECTIVES
In the late 1800s, two compounds similar to alcohol were used to treat insomnia:
paraldehyde and chloral hydrate. Synthesized by Justin Liebig in 1832, chloral hy-
drate is the oldest synthetic hypnotic agent. It has been used since 1869 as a hyp-
notic. It is still used for this purpose, but only rarely (2). These two medications fell
out of favor because of adverse effect profiles and problems with withdrawal after
the advent of barbiturates in the early 20th century. Barbiturates were widely used
as treatments of choice for insomnia for about half a century. In the 1950s, prob-
lems with tolerance, addiction, withdrawal, and overdose became apparent. Mep-
robamate was introduced to solve these issues, but it and its congeners turned out to
have the same problems of addiction, tolerance, and withdrawal as the barbiturates.
In 1960, chlordiazepoxide was introduced as the first benzodiazepine. Since then,
the safety and efficacy of this class has made the former methods of pharmacologi-
cal treatment of insomnia obsolete. There is much controversy regarding the inci-
dence of addiction, tolerance, and dependence with benzodiazepine use. Because
of this, many natural products have been studied as insomnia drugs. In 1970 L-
tryptophan, an amino acid precursor of serotonin, was found to be effective in the
treatment of insomnia (3). In 1989, cases of eosinophilia-myalgia syndrome from
all over the world were being reported in association with manufactured L-tryp-
tophan (4–6). In November 1989, the substance was recalled. By July 1990, only in
the United States, 1531 cases were reported, with 27 resulting in death despite treat-
ment and discontinuation of the drug (5). By the early 1990s, L-tryptophan became
obsolete as a hypnotic.
Pharmacological Treatment 175

Current Pharmacological Therapies for Insomnia

A large proportion of people with persistent insomnia are not treated medically
for their insomnia. Of patients suffering from insomnia, 25–30% self-medicate with
either alcohol, over-the-counter (OTC) hypnotics, or a combination of the two (7).
Among people with insomnia, alcohol is the most commonly used substance for
self-medicating.

Antihistamine OTC Hypnotic Drugs

Among the pharmaceutical substances, the OTC antihistamine hypnotics are the
most used by insomnia sufferers and the most recommended and prescribed by
physicians despite absence of data supporting their efficacy and the presence of
several studies showing significant adverse effects. In 2000, Weiler and colleagues
(8) looked at the effects of fexofenadine (an antihistamine), diphenhydramine, and
alcohol on a person’s ability to drive. They enrolled 40 licensed drivers with sea-
sonal allergic rhinitis who were 25 to 44 years of age. The drivers were randomized
to receive either placebo, fexofenadine (60 mg), diphenhydramine (50 mg), or al-
cohol (approximately 0.1% blood alcohol concentration). Their driving abilities
were tested on the Iowa Driving Simulator. Participants had similar performance
when treated with fexofenadine or placebo. After alcohol use, overall driving per-
formance was poorer. After participants took diphenhydramine, driving perfor-
mance was poorest, indicating that diphenhydramine had a greater impact on driving
than did alcohol (8). In 2003, Basu et al. published their data examining hypnotic
use in a group of 1627 individuals age 65 and older over a period of 12 years. They
found that prescription sedative/hypnotic use remained relatively stable, whereas
OTC sedative use, principally diphenhydramine, increased substantially. They also
found a positive association of this drug with cognitive impairment in older adults
without dementia (9).
Other researchers also have published reports discouraging the use of antihista-
mines as sedative/hypnotics because of their poor side-effect profile, propensity for
drug–drug interactions, and lack of proven efficacy (10,11).
In conclusion, OTC hypnotics containing antihistamines should be avoided in
the treatment of insomnia because of their lack of clinically proven efficacy and
significant adverse effect profile.

Herbal and Dietary Supplements Used as Hypnotics

Also available over the counter are herbal and dietary supplements. Two of
these—melatonin and valerian root—are marketed as sleep aids.
Several studies have shown efficacy of melatonin in the treatment of circadian
rhythm problems. As far as its use in primary insomnia, there is some evidence that
melatonin may be helpful in the treatment of age-related insomnia. Zhadonova et
al. conducted a double-blind, placebo-controlled study comparing 15 subjects over
176 Attarian

50 years of age who slept normally to another group of subjects who exhibited
actigraphically confirmed decreases in sleep efficiency (12). All 30 received, in
randomized order, a placebo and three melatonin doses (0.1, 0.3, and 3 mg) orally
30 minutes before bedtime for 1 week. Treatments were separated by 1-week wash-
out periods. Sleep data were obtained by polysomnography on the last 3 nights of
each treatment period. The data demonstrated that the physiological melatonin dose
of 0.3 mg restored sleep efficiency, acting principally in the mid third of the night;
it also elevated plasma melatonin levels to normal. The pharmacologic dose (3 mg),
like the lowest dose (0.1 mg), also improved sleep; however, it induced hypother-
mia and caused plasma melatonin to remain elevated into the daylight hours. Al-
though control subjects, like insomniacs, had low melatonin levels, their sleep was
unaffected by any melatonin dose (12). Melatonin has also been shown to help
aleviate chronic sleep-onset insomnia in children. Smits et al., in the Netherlands,
studied 40 elementary school children, 6 to 12 years of age, who suffered from
chronic sleep-onset insomnia for more than 1 year (13). The study was double-
blind and placebo-controlled. The children were randomly assigned to receive ei-
ther 5 mg of melatonin or placebo. The study consisted of a 1-week baseline,
followed by a 4-week treatment period. The study demonstrated that 5 mg of mela-
tonin taken at 6 PM was relatively safe in the short term and significantly more
effective than placebo in advancing sleep onset and increasing sleep duration in
school children with chronic sleep-onset insomnia (13). Another group in whom
melatonin seems to help alleviate insomnia are people with schizophrenia. Shamir
et al. enrolled 19 subjects who met the DSM–IV criteria for schizophrenia, in a
double-blind, randomized, cross-over, clinically based trial. They were given ei-
ther 2 mg of controlled release melatonin or placebo for two treatment periods of 3
weeks each with 1-week washouts between treatment periods. Those patients who
had poor sleep at baseline had significant improvement in sleep efficiency with the
melatonin (80%) compared to when they were on placebo (67%). They also had a
significant increase in sleep duration (on average by 45 minutes) and also a signifi-
cant reduction in sleep latency (SL) on the average (by 40 minutes) (14). The data
available, however, do not support its use as a wide-spectrum hypnotic. Addition-
ally, there is little information on its long-term safety (15,16). The reason it seems
to improve sleep in the above mentioned distinct population groups is most likely
based on the fact that they all had low endogenous melatonin, which most primary
insomniacs do not (12,14,17). This is the same theory by which melatonin is thought
to work in circadian rhythm problems. In fact, Stone et al. studied its effects in
healthy volunteers. They compared melatonin given at 11:30 PM and at 8 PM to
temazepam given at similar times. They measured both sleep parameters and core
body temperature. They concluded that melatonin given at 11:30 had no significant
clinical effect on nocturnal sleep in healthy individuals. Hypnotic activity of mela-
tonin, when given in the early evening (presumably in the absence of endogenous
melatonin), was similar to 20 mg of temazepam (18).
Pharmacological Treatment 177

Over the past few years, multiple small trials, both open-label and double-blind
(placebo-controlled and using oxazepam as an active control) have shown clini-
cally significant polygraphic and subjective improvement in the sleep of patients
with primary insomnia who were given different valerian products at doses ranging
from 460 to 600 mg. Dominguez et al. gave 470 mg of valerian root to 23 volun-
teers with complaints of persistent insomnia for 2 weeks. Twenty subjects followed
through with the study. Of the 20 volunteers, 16 rated their sleep as moderate at the
end of the first week. Fifteen of those rated their sleep as extremely improved at the
end of the second week. No significant side effects were reported (19). The same
year (2000), Donath et al. enrolled 16 adult patients with psychophysiological in-
somnia in a double-blind, placebo-controlled trial of valerian extract. They used
both objective (polysomnographic) measures and subjective questionnaires. Their
study duration was also 2 weeks. They showed statistically significant improve-
ment in both subjective and objective sleep parameters such as reduced SL, in-
creased sleep efficiency, and increased slow wave sleep with valerian root that was
more pronounced with continued use. Again, no serious adverse effects were re-
ported (20). Fussell et al. reported similar results in an open label trial of 250 mg of
valerian with 60 mg of hop extract (21). Dorn, comparing valerian to oxazepam as
an active control, randomized 75 subjects with primary insomnia to either 10 mg of
oxazepam or 600 mg of valerian. The outcome measures were standardized ques-
tionnaires assessing subjective improvement of sleep. In both groups, sleep quality
improved significantly but no statistically significant difference could be found
between groups. Again, no serious adverse effects were reported (22). In 2002,
Ziegler et al. replicated the results of Dorn in a larger group of subjects (202) with
primary insomnia showing again comparable efficacy of 600 mg of valerian to 10
mg of oxazepam during a 6-week treatment phase (23). Valerian has also been
shown to improve sleep after benzodiazepine withdrawal. Poyares and colleagues
studied 19 insomniacs who had been on nightly benzodiazepines for an average
duration of 7.1 years. The subjects were withdrawn from benzodiazepines and were
randomized to either placebo or valerian. The valerian group showed significant
subjective improvement in sleep and decreased wake after sleep onset time (WASO)
vs the placebo group (23). There are other preliminary studies looking at other
herbal supplements such as essential oil of Citrus aurantium L. (sour orange) (24)
and other concoctions that have varying ingredients of herbal products (25). These
studies, however, did not produce any conclusive evidence of clinically significant
efficacy of these substances.
In conclusion, among the herbal supplements, valerian shows promise as an ef-
fective hypnotic with little adverse effects. Melatonin seems effective only in cer-
tain special circumstances discussed above. No other herbal supplement has been
studied well enough to suggest its efficacy as a hypnotic. Additionally, all herbal
supplements discussed previously lack long-term safety data and there are no Food
and Drug Adminstraiton-regulated standard formulations of valerian, melatonin, or
any other herbal supplements.
178 Attarian

Antidepressants
Because of concerns of benzodiazepine tolerance, addiction, and dependence,
antidepressants (specifically amitriptyline and trazodone) have been used more fre-
quently in the treatment of insomnia. There has been an upward trend in the number
of antidepressants that were prescribed for insomnia since 1987, despite the paucity
of reliable data regarding their efficacy as hypnotics and the presence of lingering
daytime sedation after nighttime administration and other adverse effects that are
discussed here (26). Drs. Walsh and Schweitzer obtained data from the National
Disease and Therapeutic Index , which samples office-based physicians in 24 spe-
cialties. They looked at total drug mentions for the treatment of insomnia from
1987 to 1996. Total drug use for the treatment of insomnia fell 24.4%. Hypnotic
use decreased 53.7%, and antidepressants increased 146%. This demonstrates a
dramatic shift to use of antidepressants in lieu of hypnotics for the symptomatic
treatment of insomnia (26). In fact, trimipramine and trazodone are the only two
antidepressants with some clinical data regarding efficacy in insomnia. Scharf and
Sachais administered 150–400 mg of trazodone to six depressed patients with sig-
nificant sleep disturbances in an 8-week single-blind study design. Patients were
evaluated by psychological questionnaires and polysomnography. Five of the six
subjects completed treatment. There was statistically significant improvement in
SL (by 44%), total sleep time (14%), stage 4 sleep (an increase of 153%), and sleep
efficiency (by 80.6%) after 5 weeks of treatment (27). There have been other re-
ports of its efficacy as a hypnotic in the literature (28–30).
Of note, all these trials were small and the subjects enrolled in them did not have
primary insomnia but insomnia and comorbid depression. Trazodone has signifi-
cant lingering daytime sedation even at low doses (31) and can cause significant
rebound insomnia (32). Incidentally, when Montgomery et al. tried trazodone in a
small group of insomniacs, in addition to rebound insomnia they reported a dis-
crepancy between subjective and objective improvement of sleep. These subjects
all reported subjective improvement but had absolutely no change in their SL and
duration polysomnographically (32). Unlike other antidepressants, trazodone does
not tend to aggravate RLS and periodic limb movements (PLMs). Recently, Ri-
emann et al. studied trimipramine in primary insomnia. They enrolled 55 subjects
in a double-blind, placebo- and benzodiazepine-controlled study. Trimipramine was
used at an average dose of 100 mg over a period of 4 weeks. Trimipramine im-
proves subjective sleep and objective sleep efficiency but not sleep duration. There
was no evidence of any rebound effect from trimipramine. Side effects from
trimipramine were only marginal (33). In conclusion, antidepressants have the ad-
verse effects of lingering daytime sedation after nighttime administration and other
adverse effects (with tricyclics aggravation of RLS and anticholinergic effects)
makes them poor choices for the treatment of insomnia.

Benzodiazepines
The benzodiazepines are γ-aminobutyric acid (GABA) agonists. They potentiate
the action of GABA by displacing an endogenous inhibitor of GABA receptor bind-
Pharmacological Treatment 179

Table 1
Benzodiazepines Approved in the United States for the Treatment of
Insomnia
Peak plasma Active
Drug T 1/2 half life level metabolites Type
Quazepam 39 hours 2 hours Yes Long half-life
Estazolam 10–15 hours 0.5–2 hours No Medium half-life
Flurazepam 48–120 hours 2 hours Yes Long half-life
Temazepam 8–15 hours 30–60 min No Medium half-life
Triazolam 1.5–5.5 hours 15–30 min No Short half-life

ing. They have potent hypnotic, muscle relaxant, anticonvulsant, and anti-anxiety
properties.
Benzodiazepines act nonselectively at two central receptor sites, named
omega(1) and omega(2), which are located in different areas of the central nervous
system. The sedative action of benzodiazepines is related to omega(1) receptors,
whereas omega(2) receptors are responsible for their effects on memory and cogni-
tive functioning (34). According to their pharmacokinetic profile, benzodiazepines
can be classified into three groups: short half-life (<3 hours), medium half-life (8–
24 hours), and long half-life (>24 hours). Table 1 lists those benzodiazepines
approved for the treatment of insomnia.
Benzodiazepines are proven to be efficacious in the treatment of insomnia. In
2000, in Canada, Holbrook et al. (35) published a meta-analysis of benzodiazepine
trials in primary insomnia. They identified 89 randomized controlled trials but
excluded 44 from the meta-analysis for various reasons. The remaining 45 random-
ized controlled trials represented 2672 patients. Twenty-seven studies compared a
benzodiazepine with a placebo, 13 compared a benzodiazepine with an alternate ac-
tive treatment, and 5 studies involved a combination of both. The duration of the
studies ranged from 1 day to 6 weeks. There was a statistically significant difference
of SL and sleep duration both subjectively and objectively between a benzodiazepine
and placebo. The question of whether tolerance to any sleep-promoting effect of ben-
zodiazepines occurs could not be answered because all of the trials eligible for the
meta-analyses were of short duration. Although more adverse effects were experi-
enced by patients taking a benzodiazepine for the treatment of insomnia, dropout
rates in the benzodiazepine and placebo groups were similar (35).
Most benzodiazepine adverse reactions are viewed as extensions of the thera-
peutic effect beyond the desired time. Mendelson et al. looked at the reported rate
of adverse effects in a 1000-bed hospital over a period of 3 years and discovered
that the median frequency of reported adverse reactions was 0.01%, or 1 in 10,000
doses. The vast majority of reactions was considered mild, and without sequelae.
All adverse reactions occurred in patients over 55 years old except for four patients
under age 50 who received lorazepam (36). Temazepam, the most commonly used
benzodiazepine as a hypnotic, has been shown to be safe even in the elderly (37).
180 Attarian

The use of benzodiazepines has been generally restricted in the treatment of

insomnia because of concerns of addiction, dependence, and tolerance. The risk of
habituation and abuse, however, is lower than previously thought in patients who
are properly diagnosed and use these medications for medicinal purposes (38). In a
double-blind fashion, Roehrs et al. gave 18 subjects with insomnia 1 week of
triazolam and 1 week of placebo. The number of triazolam capsules taken nightly
was stable and the number of placebo capsules variable. It was concluded that in-
somniacs showed no short-term escalation of triazolam dose, but did choose an
increased and variable number of placebos, a pattern that was interpreted as being
insomnia relief-seeking behavior (39). Schenck and Mahowald followed 170 pa-
tients for 12 years who were receiving nightly benzodiazepines for the treatment of
a variety of sleep disorders including injurious sleepwalking and sleep terrors (n =
69); rapid eye movement sleep behavior disorder (n = 52); chronic, severe insom-
nia (n = 25); and RLS/periodic limb movement disorder (n = 24). Only 2% had
relapses of alcohol or chemical abuse requiring hospitalization and another 2% at
times misused their medications (40).
In conclusion, benzodiazepines are effective and safe in treating primary insom-
nia. There some strong data to suggest that in the absence of prior history of alcohol
or substance abuse, when used judiciously, that the risk of tolerance, abuse, depen-
dence and addiction is low. More studies are needed to fully answer that question,
however.

Imidazopyridines
The newer non-benzodiazepine agents (see Table 2) zopiclone, zolpidem, and
zaleplon, have a hypnotic action comparable with that of benzodiazepines, but they
display specific pharmacokinetic and pharmacodynamic properties. They are struc-
turally unrelated to benzodiazepines and belong to a new chemical class, the
imidazopyridines. These three agents all share a short plasma half-life and limited
duration of action. Additionally, these agents are selective compounds that interact
preferentially with omega(1) receptors (sedative effect), whereas benzodiazepines
also interact with omega(2) receptors (adverse effects on cognitive performance
and memory). Zaleplon is characterized by an ultrashort half-life, zolpidem and
zopiclone have longer half-lives. These properties, together with the low risk of
residual effect, may explain the limited negative influences of these agents on day-
time performance. Cognitive functions are better preserved by non-benzodiazepine
agents than by benzodiazepines (34). When present, cognitive deficits almost al-
ways coincide with the peak plasma concentration, especially in the first hours af-
ter drug administration, whereas cognitive testing administered 7–8 hours later (i.e.,
in the morning) generally shows no impairment (34).
Zolpidem is an effective and safe hypnotic with minimal adverse effects and no
dependence, withdrawal, tolerance, or rebound insomnia over long-term use.
Zolpidem’s elimination half-life is 2.2 hours, and peak plasma levels are reached in
90 minutes. The dose needs to be adjusted in the setting of hepatic impairment but
Pharmacological Treatment 181

Table 2
Nonbenzodiazepine Hypnotics
Drug T 1/2 half life Onset of action Peak plasma conc Active metabolites
Zolpidem 1.5–2.4 hours 30 minutes 1.5 hours No
Zaleplon 1 hours 30 minutes 1 hour No
Zopiclone 5–6 hours 30 minutes 2 hours No

not with altered renal function. Schlich et al. as early as 1991, studied 107 patients
with insomnia, about 60% of whom were over 60 years of age. The subjects were
given 10 mg of zolpidem on a nightly basis for 6 months. An improvement in all
efficacy parameters—time taken to fall asleep, total amount of nocturnal sleep, and
number of nocturnal awakenings—was reported by the investigator and the pa-
tients; the improvement was evident from the first evaluation day and was main-
tained throughout the trial. Improvement was also maintained during the washout
period with a lack of rebound insomnia. There was no sign of withdrawal symp-
toms and tolerance to zolpidem did not develop over the 6-month treatment period.
Adverse events were mild and infrequent, and tended to resolve with a dose reduc-
tion (41). The following year, Maarek and colleagues reported the results of their
open-label zolpidem trial. They enrolled 96 subjects who received 10–20 mg of
zolpidem a night for 6 to 12 months. Again, improvement in all sleep parameters
was noted in 90% of subjects with no rebound and withdrawal effects on discon-
tinuation (42). Saletu-Zyhlarz et al., in a single-blind, placebo-controlled cross-
over study, compared 10 mg of zolpidem to placebo. Fifteen adult patients
diagnosed with nonorganic insomnia were enrolled. Objective and subjective sleep
and awakening quality measures were investigated in 3 subsequent nights in the
sleep laboratory. There was a significant lengthening of the total sleep period and
total sleep time, an improvement in sleep efficiency and a shortening of SLs after
zolpidem as compared with placebo. Zolpidem also increased the length of stage 4
and stage 3 + 4 non-REM sleep as compared with placebo (43).These are some of
the important studies looking at zolpidem; there are others in the medical literature
that have produced results, concordant with the above.
Zaleplon also is an effective and safe hypnotic (44). The onset of action is
approximately 30 minutes, and the duration of action is about 4 hours. Peak zaleplon
serum concentrations occur in about 1 hour, and its elimination half-life is also
about 1 hour. Similar to zolpidem, its dose needs to be adjusted with altered hepatic
function but not with renal impairment. The Zaleplon Clinical Study Group looked
at the efficacy and safety of three doses of zaleplon, a novel compared with those of
placebo in outpatients with insomnia in this 4-week study, using 10 mg of zolpidem
as active control. Post-sleep questionnaires were used to determine treatment ef-
fects on the patient’s perception of sleep, development of tolerance during therapy,
or rebound insomnia or withdrawal on discontinuation of therapy. SL was signifi-
cantly shorter throughout the 4 weeks of study with any dose of zaleplon compared
182 Attarian

to placebo. Zaleplon also had significant effects on sleep duration, number of awak-
enings, and sleep quality compared to placebo. No pharmacological tolerance
developed with zaleplon and there were no indications of rebound insomnia or with-
drawal symptoms after treatment discontinuation. There was no significant differ-
ence in the frequency of adverse events with active treatment compared to placebo.
These results show that zaleplon provides effective treatment of insomnia with a
favorable safety profile (45). A similar study was done to look at its efficacy and
safety in the elderly (>65 years) population. Again, zaleplon proved to be a safe and
effective treatment for insomnia in the elderly with no significant adverse effects of
rebound insomnia (46). Because of its short half-life, there is no residual sedation
when zaleplon is administered in the middle of the night; hence, it is the ideal medi-
cation for sleep maintenance insomnia. Walsh et al. assessed residual sedation after
10 mg of zaleplon in a randomized, double-blind, placebo- and active drug-con-
trolled cross-over study with 30 mg of flurazepam (as an active control). The drug
(zaleplon, flurazepam, or placebo) was taken during a nocturnal awakening in pa-
tients with sleep maintenance insomnia. Twenty-two healthy sleep maintenance
insomniacs were enrolled and received zaleplon, flurazepam, or placebo after an
experimental awakening 3.5 hours after bedtime on 2 consecutive nights. Residual
sedation was measured with SL testing (5 and 6.5 hour postdrug), and other psy-
chometric tests. Zaleplon did not differ from placebo on any measure of residual
sedation; flurazepam showed significant sedation on all measures (47).
A related medication, zopiclone (not available in the United States), has also
been shown in several studies to be as effective as benzodiazepines in relieving
symptoms of insomnia and as safe as the other “Z” medications (35). It can also be
helpful in shift-work insomnia. In a recent study, 29 shift workers suffering from
insomnia were included and treated with zopiclone (7.5 mg/day) or placebo accord-
ing to a random, double-blind protocol. Patients completed a sleep diary and a wrist
actigraph was used to evaluate episodes of rest and activity. A self-administered
subjective sleep questionnaire was filled out just after awakening. Zopicone was
found to increase the duration of sleep significantly over the baseline duration after
the first and second night on duty. Subjective estimation of sleep was better in
patients taking zopiclone who exhibited a smaller number of shorter awakening
episodes (48).
Another method of use of hypnotics have come into favor in recent years that
maximizes benefits for chronic insomniacs and minimizes tolerance or dependence.
Several studies, mainly with zolpidem, have shown that non-nightly, discontinuous
use with stimulus control therapy (SCT) has shown to be both effective and safe in
chronic use (49). In 2002, Hajak et al. published their data on discontinuous, non-
nightly hypnotic therapy in the treatment of chronic insomnia. In a prospective,
observational open study in 550 primary care settings throughout Germany, 2690
patients with chronic insomnia were treated with zolpidem according to an “as-
needed” administration treatment schedule (up to five tablets per week chosen by
the patient), in addition to the optional use of SCT, during drug-free nights. After
Pharmacological Treatment 183

the 3 weeks of treatment, in 63% of patients the weekly number of tablets used was
reduced in contrast to baseline without any significant impact on the treatment effi-
cacy. Efficacy of treatment was rated as very good or good in 93% by the investiga-
tors. Adverse events were observed only in 1.2% of patients and were generally of
mild nature. No serious adverse event occurred (49).
In conclusion, the non-benzodiazepine hypnotics (zolpidem, zoplicone, and
zaleplon) are safe and effective hypnotics with minimal adverse effects and no de-
pendence, withdrawal, tolerance, or rebound insomnia over long-term use
(43,45,46,50) Of course given the relatively small number of studies further re-
search is warranted to assess both the efficacy and the safety of long-term use.

SECONDARY INSOMNIAS REQUIRING SPECIFIC

PHARMACOLOGICAL TREATMENTS
Restless Legs Syndrome
RLS and the resulting insomnia respond only to medication. Behavioral thera-
pies have no role in the treatment of RLS. Sometimes, antidepressants and other
medications aggravate RLS. Cessation of these medications helps alleviate the
symptoms. In those patients who have low serum ferritin, iron replacement, may be
helpful. Most patients, however, require medication. The most effective medica-
tions for treating RLS symptoms belong to three distinct classes: (1) the
dopaminergics agents, e.g., pramipexole (51,52), ropinirole hydrochloride (53,54),
pergolide mesylate (55) bromocriptine mesylate (55), and levodopa (56); (2) the
opiates (57); and (3) the benzodiazepines, especially clonazepam (58). Studies have
shown that the newer anticonvulsants gabapentin (59,60) and clonidine (especially
in patients who do not have a large amount of PLMs) (61) are also effective in
controlling RLS. The doses of the above medication used in the treatment of RLS
are usually much lower than the doses utilized in the treatment of other conditions
such as Parkinson’s disease, pain, anxiety, seizures, and other medical conditions
for which the above medications are effective. In rare instances, higher doses are
reached by titrating to the patients’ symptoms.

Menopause-Related Insomnia
In menopause-related insomnia, estrogen replacement therapy (ERT) may con-
trol insomnia along with other menopause-related symptoms (62,63). The recent
medical problems reported with ERT have led to a search for other alternatives.
One herbal alternative, Black Cohosh, has been studied but there is no conclusive
evidence as to its efficacy in menopausal insomnia (64).

REFERENCES
1. NIH Consensus Development Conference Summary. (1984) Drugs and insomnia: the use of medi-
cation to promote sleep. JAMA 251(18), 2410–2414.
2. Gauillard, J. Cheref, S., Vacherontrystram, M. N., and Martin, J. C. (2002) [Chloral hydrate: a
hypnotic best forgotten?]. Encephale 28(3 Pt 1), 200–204.
184 Attarian

3. Wyatt, R. J., Engelman, K., Kupfer, O. J., Fram, D. H., Sjverdsma, A., Snyder, F. (1970) Effects
of L-tryptophan (a natural sedative) on human sleep. Lancet 2(7678), 842–846.
4. Glickstein, S. L., Gertner, E., Smith, S. A., et al. (1990) Eosinophilia-myalgia syndrome associ-
ated with L-tryptophan use. J. Rheumatol. 17(11), 1534–1543.
5. Marks, D. R. (1990) A case of L-tryptophan-induced eosinophilia-myalgia resulting in death.
Conn. Med. 54(10), 552–554.
6. Zollner, N., Sorg, M., and Kruger, K. (1990) [Eosinophilia myalgia syndrome in administration
of L-tryptophan]. Klin. Wochenschr. 68(14), 739–742.
7. Roehrs, T., Hollebeek, E., Drake, C., and Roth, T. (2002) Substance use for insomnia in Metro-
politan Detroit. J. Psychosom. Res. 53(1), 571–576.
8. Weiler, J. M., Bloomfield, J. R., Woodsworth, G. G., et al. (2000) Effects of fexofenadine, diphen-
hydramine, and alcohol on driving performance. A randomized, placebo-controlled trial in the
Iowa driving simulator. Ann. Intern. Med. 132(5), 354–363.
9. Basu, R., Dodge, H., Stoehr, G. P., Ganguli, M. (2003) Sedative-hypnotic use of diphenhydramine
in a rural, older adult, community-based cohort: effects on cognition. Am. J. Geriatr. Psychiatry
11(2), 205–213.
10. Gilhooly, T. C., Webster, M. G., Poole, N. W., Ross, S. (1998) What happens when doctors stop
prescribing temazepam? Use of alternative therapies. Br. J. Gen. Pract. 48(434), 1601–1602.
11. Sproule, B. A., Busto, U. E., Buckle, C., Herrmann, N., and Bowles, S. (1999) The use of non-
prescription sleep products in the elderly. Int. J. Geriatr. Psychiatry 14(10), 851–857.
12. Zhdanova, I. V., Wurtman, R. J., Regan, M. M., Taylor, J. A., Shi, J. P., Leclair, O. U. (2001)
Melatonin treatment for age-related insomnia. J. Clin. Endocrinol. Metab. 86(10), 4727–4730.
13. Smits, M. G., Nagtegaal, E. E., van der heijden, j., Coenen, A. M. and Kerkhof, G. A. (2001)
Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial. J.
Child. Neurol. 16(2), 86–92.
14. Shamir, E., Landon, M., Barak, Y., et al. (2000) Melatonin improves sleep quality of patients
with chronic schizophrenia. J. Clin. Psychiatry 61(5), 373–377.
15. Sack, R. L., Lewy, A. J. and Hughes, R. J. (1998) Use of melatonin for sleep and circadian rhythm
disorders. Ann. Med. 30(1), 115–121.
16. Arendt, J. (1998) Complex effects of melatonin. Therapie 53(5), 479–488.
17. Olde Rikkert, M. G. and Rigaud, A. S. (2001) Melatonin in elderly patients with insomnia. A
systematic review. Z. Gerontol. Geriatr. 34(6), 491–497.
18. Stone, B. M., Turner, C., Mills, S. L, and Nicholson, A. N. (2000) Hypnotic activity of melatonin.
Sleep 23(5), 663–669.
19. Dominguez, R. A., Bravo-Valverde, R. L., Kaplowitz, B. C., and Cott, J. M. (2000) Valerian as a
hypnotic for Hispanic patients. Cultur. Divers. Ethnic Minor. Psychol. 6(1), 84–92.
20. Donath, F., Quispe, S., Diefenbach, K., Maurer, A., Fietze, I., and Roots, I. (2000) Critical evalu-
ation of the effect of valerian extract on sleep structure and sleep quality. Pharmacopsychiatry
33(2), 47–53.
21. Fussel, A., Wolf, A., and Brattstrom, A. (2000) Effect of a fixed valerian-Hop extract combina-
tion (Ze 91019) on sleep polygraphy in patients with non-organic insomnia: a pilot study. Eur. J.
Med. Res. 5(9), 385–390.
22. Dorn, M. (2000) [Efficacy and tolerability of Baldrian versus oxazepam in non-organic and non-
psychiatric insomniacs: a randomised, double-blind, clinical, comparative study]. Forsch.
Komplementarmed. Klass. Naturheilkd. 7(2), 79–84.
23. Ziegler, G., Ploch, M., Miettinern-Baumann, A., Collet, W. (2002) Efficacy and tolerability of
valerian extract LI 156 compared with oxazepam in the treatment of non-organic insomnia: a
randomized, double-blind, comparative clinical study. Eur. J. Med. Res. 7(11), 480–486.
24. Carvalho-Freitas, M. I. and Costa, M. (2002) Anxiolytic and Sedative Effects of Extracts and
Essential Oil from Citrus aurantium L. Biol. Pharm. Bull. 25(12), 1629–1633.
25. Chung, K. F. and Lee, C. K. (2002) Over-the-counter sleeping pills: a survey of use in Hong
Kong and a review of their constituents. Gen. Hosp. Psychiatry 24(6), 430–435.
Pharmacological Treatment 185

26. Walsh, J. K. and Schweitzer, P. K. (1999) Ten-year trends in the pharmacological treatment of
insomnia. Sleep 22(3), 371–375.
27. Scharf, M. B. and Sachais, B. A. (1990) Sleep laboratory evaluation of the effects and efficacy of
trazodone in depressed insomniac patients. J. Clin. Psychiatry 51(Suppl), 13–17.
28. Mashiko, H., Niwa, S., Kumashiro, H., et al. (1999) Effect of trazodone in a single dose before
bedtime for sleep disorders accompanied by a depressive state: dose-finding study with no con-
comitant use of hypnotic agent. Psychiatry Clin. Neurosci. 53(2), 193–194.
29. Parrino, L., Spaggiari, M. C., Boselli, M., DiGiovanni, G., and Terzano, M. G. (1994) Clinical
and polysomnographic effects of trazodone CR in chronic insomnia associated with dysthymia.
Psychopharmacology (Berl.) 116(4), 389–395.
30. Kallepalli, B. R., Bhatara, V. S., Fogas, B. S., Tervo, R. C., and Misra, L. K. (1997) Trazodone is
only slightly faster than fluoxetine in relieving insomnia in adolescents with depressive disor-
ders. J. Child. Adolesc. Psychopharmacol. 7(2), 97–107.
31. Metz, A. and Shader, R. I. (1990) Adverse interactions encountered when using trazodone to treat
insomnia associated with fluoxetine. Int. Clin. Psychopharmacol. 5(3), 191–194.
32. Montgomery, I., Oswald, I., Morgan, K., and Adam, K. (1983) Trazodone enhances sleep in
subjective quality but not in objective duration. Br. J. Clin. Pharmacol. 16(2), 139–144.
33. Riemann, D., Voderholzer, U., Cohrs, S., et al. (2002) Trimipramine in primary insomnia: results
of a polysomnographic double-blind controlled study. Pharmacopsychiatry 35(5), 165–174.
34. Terzano, M. G., Rossi, M., Palomba, V., Smerieri, A., and Parrino, L. (2003) New drugs for insom-
nia: comparative tolerability of zopiclone, zolpidem and zaleplon. Drug Saf. 26(4), 261–282.
35. Holbrook, A. M., Crowther, R., Lotter, A., Chang, K., and King, D. (2000) Meta-analysis of
benzodiazepine use in the treatment of insomnia. Cmaj 162(2), 225–233.
36. Mendelson, W. B., Thompson, C., and Franko, T. (1996) Adverse reactions to sedative/hypnotics:
three years’ experience. Sleep 19(9), 702–706.
37. Morin, C. M., Bastien, C. H., Brink, D., and Brown, T. R. (2003) Adverse effects of temazepam
in older adults with chronic insomnia. Hum. Psychopharmacol. 18(1), 75–82.
38. Taylor, F. K. (1989) The damnation of benzodiazepines. Br. J. Psychiatry 154, 697–704.
39. Roehrs, T., Pedrosi, B., Rosenthal, L., and Roth, T. (1996) Hypnotic self administration and dose
escalation. Psychopharmacology (Berl.) 127(2), 150–154.
40. Schenck, C. H. and Mahowald, M. W. (1996) Long-term, nightly benzodiazepine treatment of
injurious parasomnias and other disorders of disrupted nocturnal sleep in 170 adults. Am. J. Med.
100(3), 333–337.
41. Schlich, D., L’Heritier, C., Coquelin, J. P., Attali, P., and Kryrein, H. J. (1991) Long-term treat-
ment of insomnia with zolpidem: a multicentre general practitioner study of 107 patients. J. Int.
Med. Res. 19(3), 271–279.
42. Maarek, L., Cramer, P., Attali, P., Coquelin, J. P., and Morselli, P. L. (1992) The safety and
efficacy of zolpidem in insomniac patients: a long-term open study in general practice. J. Int.
Med. Res. 20(2), 162–170.
43. Saletu-Zyhlarz, G., Anderer, P., Brandstatter, N., et al. (2000) Placebo-controlled sleep labora-
tory studies on the acute effects of zolpidem on objective and subjective sleep and awakening
quality in nonorganic insomnia related to neurotic and stress-related disorder.
Neuropsychobiology 41(3), 139–148.
44. Israel, A. G. and Kramer, J. A. (2002) Safety of zaleplon in the treatment of insomnia. Ann.
Pharmacother. 36(5), 852–859.
45. Fry, J., Scharf, M., Mangano, R., and Fujimori, M. (2000) Zaleplon improves sleep without pro-
ducing rebound effects in outpatients with insomnia. Zaleplon Clinical Study Group. Int. Clin.
Psychopharmacol. 15(3), 141–152.
46. Hedner, J., Yaechi, R., Emilien, G., Farr, I. and Salinas, E. (2000) Zaleplon shortens subjective
sleep latency and improves subjective sleep quality in elderly patients with insomnia. The
Zaleplon Clinical Investigator Study Group. Int. J. Geriatr. Psychiatry 15(8), 704–712.
47. Walsh, J. K., Pollak, C. P., Scharf, M. B., Schweitzer, P. K., and Vogel, G. W. (2000) Lack of
186 Attarian

residual sedation following middle-of-the-night zaleplon administration in sleep maintenance

insomnia. Clin. Neuropharmacol. 23(1), 17–21.
48. Quera-Salva, M. A., Philip, P., Taillard, J., et al. (2002) [Study of the real situation of improve-
ment by Zopiclone in treatment of insomnia among persons working during night shifts]. Rev.
Neurol. (Paris) 158(11), 1102–1106.
49. Hajak, G., Bardelow, B., Zulley, J., and Pittrow, D. (2002) “As needed” pharmacotherapy com-
bined with stimulus control treatment in chronic insomnia—assessment of a novel intervention
strategy in a primary care setting. Ann. Clin. Psychiatry 14(1), 1–7.
50. Hajak, G., Cluydts, R., Dederck, A., et al. (2002) Continuous versus non-nightly use of zolpidem
in chronic insomnia: results of a large-scale, double-blind, randomized, outpatient study. Int.
Clin. Psychopharmacol. 17(1), 9–17.
51. Becker, P. M., Ondo, W., and Sharon, D. (1998) Encouraging initial response of restless legs
syndrome to pramipexole. Neurology 51(4), 1221–1223.
52. Lin, S. C., kaplan, J., Burger, C., D., and Fredrickson, P. A. (1998) Effect of pramipexole in
treatment of resistant restless legs syndrome. Mayo Clin. Proc. 73(6), 497–500.
53. Saletu, B., Gruber, G., Saletu, B., et al. (2000) Sleep laboratory studies in restless legs syndrome
patients as compared with normals and acute effects of ropinirole. 1. Findings on objective and
subjective sleep and awakening quality. Neuropsychobiology 41(4), 181–189.
54. Saletu, M., Anderer, P., Saletu, B., et al. (2000) Sleep laboratory studies in restless legs syndrome
patients as compared with normals and acute effects of ropinirole. 2. Findings on periodic leg
movements, arousals and respiratory variables. Neuropsychobiology 41(4), 190–199.
55. Wetter, T. C., Stjasny, K., Winkelmann, J., et al. (1999) A randomized controlled study of
pergolide in patients with restless legs syndrome. Neurology 52(5), 944–950.
56. Brodeur, C., Montplaisir, J., Godbout, R., and Mariner, R. (1998) Treatment of restless legs syn-
drome and periodic movements during sleep with L-dopa: a double-blind, controlled study. Neu-
rology 38(12), 1845–1848.
57. Walters, A. S., Wagner, M. L., Hening, W, A,, et al. (1993) Successful treatment of the idiopathic
restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo. Sleep
16(4), 327–332.
58. Peled, R. and Lavie, P. (1987) Double-blind evaluation of clonazepam on periodic leg move-
ments in sleep. J. Neurol. Neurosurg. Psychiatry 50(12), 1679–1681.
59. Happe, S., Klosch, G., Saletu, B., and Zeitlhofer, J. (2000) Treatment of idiopathic restless legs
syndrome (RLS) with gabapentin. Neurology 57(9), 1717–1719.
60. Garcia-Borreguero, D., Larrosa, O., de la Llave, Y., Verger, K., Masramon, X., and Hernandez G.
(2002) Treatment of restless legs syndrome with gabapentin: a double-blind, cross-over study.
Neurology 59(10), 1573–1579.
61. Wagner, M. L., Walters, A. S., Coleman, R. G., Hening, W. A., Grasing, K., and Chokroverty, S.
(1996) Randomized, double-blind, placebo-controlled study of clonidine in restless legs syn-
drome. Sleep 19(1), 52–58.
62. Moe, K. E. (1999) Reproductive hormones, aging, and sleep. Semin. Reprod. Endocrinol. 17(4),
339–348.
63. Polo-Kantola, P., Erkkola, R., Irjala, K., Pullinen, S., Virtanen, I., and Polo, O. (1999) Effect of
short-term transdermal estrogen replacement therapy on sleep: a randomized, double-blind cross-
over trial in postmenopausal women. Fertil. Steril. 71(5), 873–880.
64. Mahady, G. B., Fabricant, D., Chadurch, L. R., and Diets, B. (2002) Black cohosh: an alternative
therapy for menopause? Nutr. Clin. Care 5(6), 283–289.
Index 187

Index

A B
Actigraphy, 45, 46, 47, 48, 60, 73, 85, 86, Barbiturates, 85, 114, 121, 139, 174
92, 94, 95, 159, 160, 176, 182 Benzodiazepines, 17, 33, 58, 61, 74, 85,
Acute stress disorder, 128 86, 114, 116, 121, 130, 131, 133,
Addiction, 74, 85, 178, 180 135, 137, 138, 139, 144, 150, 174,
Adjustment sleep disorder, 57, 84, 103, 128 177, 178, 179, 180, 181, 182, 183
Adrenal, adrenaline, 23, 24, 69, 109, 115, Biofeedback, 105, 117
119 Biological clock, 53, 57, 58, 59, 105, 163
Affective disorder, 43, 47, 72, 73, 92, 128, Biphasic Positive Airway Pressure
137 (BiPAP), 113
Albuterol, 112 Bipolar depression, 58, 137
Alcohol, 16, 17, 25, 43, 71, 72, 73, 85, Black Cohosh, 183
100, 102, 103, 104, 128, 131, 135, Bladder, 114, 115, 119, 120
136, 137, 144, 148, 149, 156, 163, Bromocriptine, 183
174, 175, 180 Bruxism, 57, 112
Allergy, 42, 85, 110, 111, 112, 114, 118, Burn, 110 118
119, 148, 175
C
Alprazolam, 83, 130, 133, 139
Altitude insomnia, 103 Caffeine, 25, 26, 28, 29, 30, 33, 34, 35, 71,
Alzheimer’s Dementia, 72, 117, 119 74, 86, 100, 103, 104, 112, 114, 128,
Amitriptyline, 110, 112, 130, 178 138, 146, 148, 150, 163
Amphetamines, 128, 138 Cancer, 114, 116, 117
Amyotrophic lateral sclerosis (ALS), 120 Carbamazepine, 117
Angelman syndrome, 61 Cataplexy, 42, 71, 92, 101,103, 143, 144,
Angina, 113 145, 150
Anticonvulsant medications, 72, 130, 144, Central nervous system, 35, 81, 109, 110,
150 112, 116, 145, 148, 149, 179
Antidepressants, 17, 41, 74, 128, 130, 131, Central sleep apnea, 113, 142
133, 135, 136, 143, 144, 174, 178, 183 Cerebral mass lesions, 120
Antihistamine, 74, 112, 114, 175 Cerebral palsy, 61, 120
Antiparkinsonian medications, 117 Cheyne-Stokes, 113
Anxiety, 4, 15, 23, 29, 30, 31, 33, 40, 43, 47, Chloral hydrate, 138, 174
57, 67, 70, 71, 73, 83, 116, 127, 128, Chlordiazepoxide, 139, 174
130, 132, 133, 134, 135, 136, 137, Cholinergic agonists, 117, 120
143, 145, 157, 164, 165, 179, 183 Chronic obstructive pulmonary disease
Anxiolytics, 113, 128, 130, 138 (COPD), 112, 118
Apnea Hypopnea Index (AHI), 25, 143 Chronotherapy, 47, 58, 61
Arthritis, 115 Circadian rhythm, 41, 42, 47, 53, 55, 57,
Asthma, 55, 57, 101, 112, 113 58, 62, 71, 92, 175, 176
Attention deficit hyperactivity disorder Citalopram, 135
(ADHD), 57, 103 Citrus aurantium, 177
Autism, 61, 62 Clonazepam, 112, 130, 131, 133, 183
187
188 Index

Clonidine, 183 Electromyogram (EMG), 23, 24, 69, 112,

CNS arousal, 35, 40, 70, 90, 91, 121, 157, 147
158, 160, 164, 165 Encephalitis, 120, 121
Cocaine, 128, 138 Epilepsy, 120, 121
Cognitive therapy, 117, 155, 156, 157, 160, Estazolam, 86, 111, 179
164, 165, 166 Estrogen replacement therapy (ERT), 183
Cognitive-behavioral therapy (CBT), 8, 96, Extrinsic sleep disorders, 40
105, 133, 136, 155, 157, 158, 159,
F
160, 167, 168
Conditioned stimuli, 40, 69, 156, 157 Fatal Familial Insomnia, 40, 41, 72, 117
Congestive heart failure (CHF), 15, 113, 119 Fatigue, 3, 5, 9, 23, 24, 28, 29, 30, 31, 70,
Continuous positive airway pressure 74, 77, 84, 91, 116, 119, 141, 145,
(CPAP), 111, 148, 149 146, 147, 148
Corticosteroids or steroids, 23, 24, 112 Felbatol, 43, 72, 121, 156, 158, 162
Creutzfeldt-Jakob disease, 72, 117, 120 Ferritin, 47, 183
Fexofenadine, 175
D
Fluoxetine, 91, 130, 132, 133, 135
Delayed sleep phase, 42, 47, 57, 58, 59, 71 Flurazepam, 179
Dementia, 117, 119, 120 Fluvoxamine, 130, 135, 136
Dependence, 74, 85, 96, 121, 139, 149, Food allergies, 103, 114, 119
178, 180, 182, 183
G
Depression, 4, 15, 16, 23, 25, 39, 43, 47,
57, 58, 72, 73, 101, 102, 103, 116, Gabapentin, 121, 183
127, 128, 129, 130, 131, 132, 137, Gastroesophageal reflux disease (GERD),
138, 146, 149, 178 42, 54, 55, 114, 119, 145
Depressive disorders, 15, 72, 127 Generalized anxiety disorder, 43, 47, 71,
Dermatitis, 118 92, 101, 128, 132, 133
Desipramine, 130
Diabetes, 119 H
Diazepam, 33, 112, 138, 139 H2 receptor blockers, 114
Digoxin, 113 Head injury, 120
Diphenhydramine, 175 Headache, 68, 70, 92, 113, 115, 120, 121,
Diuretics, 113 145
Dopaminergic, 117, 144, 150, 183 Herpes zoster, 110, 118
DSM-IV (Diagnostic and Statistical Human immunodeficiency virus (HIV), 72,
Manual on Mental Disorders, 4th 120, 121
ed), 4, 11, 12, 43, 67, 72, 81, 89, 95, Huntington’s disease, 117, 120
127, 128, 132, 134 Hypnogogic hallucinations, 42, 71, 92,
Dysthymia, 72, 128 101,103, 143, 147
E Hypocretin, 144
Hypoxia, 112, 113, 143
Eating disorders, 136, 137
Eczema, 111 I
Electroencephalogram (EEG), 6, 23, 24, Idiopathic Insomnia, 5, 6, 41, 71, 81, 82,
25, 26, 28, 31, 33, 35, 41, 43, 69, 82, 83, 84, 85, 86, 101, 146
83, 90, 91, 115, 117, 121, 130, 147, Imidazopyridines, 180
158 Imipramine, 130, 133, 135, 138, 178
Index 189

Inflammatory bowel disease, 114, 119 Neuropathy, 117, 120

Insufficient sleep syndrome, 103 Nicotine, 100, 128, 138, 163
Interferon therapy, 120 Nightmares, 117, 128, 134, 136, 137, 142,
International Classification of Sleep Disor- 144, 148
ders (ICSD), 4, 5, 10, 67, 70, 81, 89, Nocturnal eating or drinking syndrome,
99, 141 103
Nortriptyline, 112, 130
L
NREM sleep, 8, 115, 158, 159, 181
Laceration, 118
O
Lamotrigine, 43, 72, 117, 121
Laryngospasm, 112 Obstructive sleep apnea, 25, 42, 70, 95, 99,
Levodopa, 117, 183 101, 111, 141, 142, 143, 144, 146,
Limit-setting sleep disorder, 55, 84, 103 147, 148, 149, 150
Lorazepam, 130, 131, 132, 138, 179 Opiates, 86, 128, 150, 183
L-tryptophan, 174 Orthopnea, 113, 118
M Over-the-counter (OTC) sleep aids, 17, 74,
102, 138, 175
Mania, 58, 137 Oxazepam, 74, 138, 139, 177
Melatonin, 47, 58, 59, 61, 62, 86, 175, 176, Oxcarbazepine, 121
177
Menopause, 40, 42, 72, 119, 174, 183 P
Menses, 119 Pain, 4, 8, 11, 39, 42, 68, 72, 85, 110, 112,
Metabolic rate, 26, 28, 29, 30, 31, 34, 69, 114, 119, 173, 183
91 Panic disorder, 16, 134, 135, 164, 165
Methylxanthines, 112, 150 Parkinson’s disease, 72, 117, 119
Milk allergy, 114, 119 Paroxetine, 91, 113, 130, 133, 135
Milk-protein intolerance, 55 Peptic ulcer disease (PUD), 114, 119
Monoamine oxidase inhibitors (MAOIs), Pergolide, 117, 183
130, 135 Periodic limb movement disorder (PLMD),
Mood, 6, 24, 28, 29, 30, 34, 35, 40, 43, 61, 25, 41, 42, 95, 101, 115, 116, 117,
70, 72, 73, 127, 129, 132 141, 142, 144, 145, 146, 147, 148,
Morphine, 113 150, 178, 183
Multiple sclerosis, 120 Pharmacotherapy, 58, 105, 116
Multiple Sleep Latency Test (MSLT), 24, Pharynx, 118, 143
26, 28, 29, 30, 31, 32, 34, 43, 48, 68, Phenelzine, 130
89, 91, 95, 144, 146, 147 Phenytoin, 121
Muscular dystrophy, 117, 120 Phototherapy, 47, 58, 59, 61, 113, 165
Musculoskeletal, 119 Polysomnogram (PSG), 47, 48, 67, 69, 70,
Myelopathy, 117, 120 73, 82, 83, 85, 89, 90, 91, 92, 95,
Myocardial infarction, 113, 119 104, 109, 111, 114, 115, 133, 138,
Myopathy, 120 146, 147, 148
N Posttraumatic stress disorder, 57, 136
Prader-Willi syndrome, 61
Narcolepsy, 42, 43, 99, 101, 142, 143, 144, Pramipexole, 144, 150, 183
145, 146, 147, 150 Pregnancy, 41, 70, 116, 119, 174
Neck, 118 Premenstrual dysphoric disorder, 128
Nefazodone, 91, 130 Prostate, 15, 114, 119
190 Index

Proton pump inhibitors, 114 Sleep hygiene, 34, 40, 41, 47, 48, 67, 70,
Psychophysiologic hyperarousal, 24, 28, 71, 73, 74, 85, 86, 92, 99, 100, 101,
30, 35, 82, 100, 155, 156 102, 104, 105, 131, 143, 148, 150,
Psychophysiological insomnia, 5, 6, 25, 26, 160, 162, 163, 174
27, 29, 30, 31, 32, 35, 40, 43, 67, 68, Sleep latency, 5, 6, 9, 24, 29, 40, 43, 69,
69, 70, 71, 72, 73, 81, 84, 90, 91, 95, 83, 86, 90, 132, 137, 147, 158, 159,
96, 99, 101, 104, 173, 177 176, 177, 178, 181
Sleep log, 42, 43, 47, 55, 58, 61, 73, 77,
R
92, 93
Radiculopathy, 117, 120 Sleep paralysis, 42, 77, 92, 103, 143, 146,
Rebound, 31, 74, 130, 139, 168, 178, 180, 147
181, 182, 183 Sleep restriction, 74, 77, 105, 113, 146,
Relaxation therapy, 35, 74, 105, 117, 150, 160, 161, 162, 168
160, 165 Sleep state misperception (SSM), 5, 7, 25,
REM sleep, 8, 27, 83, 116, 117, 121, 127, 26, 27, 28, 40, 41, 71, 81, 89, 90, 91,
130, 132, 134, 135, 136, 137, 138, 92, 95, 158, 159, 160, 173
139, 144, 145, 147 Sleep terrors, 128, 180
Renal disease, 115, 119 Sleep-onset association disorder, 54, 61,
Respiratory disturbance index (RDI), 42, 84, 103
143, 148 Sleep–wake center, 58, 59, 61, 62, 82, 84
Restless legs syndrome (RLS), 41, 42, 47, Slow-wave sleep, 26, 31, 137, 173
101,103, 141, 142, 143, 144, 145, Smith-Magenis syndrome, 61
147, 148, 149, 150, 174, 178, 180, Stage 1 sleep, 69, 90
183 Stage 2 sleep, 83, 90
Rett syndrome, 61, 62 Stage 3 sleep, 26, 90, 181
Reverse first night effect, 83, 85 Stage 4 sleep, 26, 90, 178, 181
Rheumatoid disorders, 115, 119 Stimulant, 43, 57, 72, 73, 85, 95, 100, 128,
Rhinitis, 112, 118, 175 138, 143
Ropinerole, 150, 183 Stimulus control therapy, 74, 105, 160,
162, 165, 168, 182
S Stroke, 54, 120
Sanfilippo syndrome, 61 Substance abuse, 5, 8, 15, 73, 137, 139,
Schizophrenia, 15, 136, 137, 176 180
Seasonal affective disorder, 128, 137 Suprachiasmatic nucleus, 100
Sedative hypnotics, 11, 16, 17, 43, 48, 72, T
73, 74, 85, 86, 92, 95, 103, 112, 113,
114, 115, 149, 150, 167, 168, 175 Temazepam, 74, 77, 112, 176, 179
Seizures, 120 121, 128, 139, 147 Theophylline, 43, 72, 112
Separation anxiety disorder, 128 Thyroid, 85, 109, 115, 119
Serotonin reuptake inhibitors (SSRI), 43, 72, Tiagabine, 121
113, 114, 130, 133, 135, 136, 174 Time in bed (TIB), 25, 26, 27, 32, 77, 161
Sertraline, 130, 133, 135 Tolerance, 74, 85, 174, 178, 180, 181, 182,
Shift work, 25, 42, 70, 100, 182 183
Sinusitis, 112 Total sleep time (TST), 4, 8, 9, 26, 27, 31,
Sleep efficiency, 6, 25, 29, 34, 61, 77, 83, 32, 33, 74, 90, 158, 159, 160, 161,
86, 91, 128, 132, 133, 134, 137, 176, 162, 168
177, 178, 181 Toxin-induced sleep disorder, 72, 103
Index 191

Tranylcypromine, 130 W
Trazodone, 74, 83, 111, 112, 113, 130,
Wake after sleep onset (WASO), 90, 116,
136, 146, 178
121, 138, 139, 158, 159, 161, 177
Triazolam, 33, 179, 180 Withdrawal, 29, 30, 43, 72, 121, 128, 130,
Tricyclic antidepressants, 74, 86, 112, 113, 138, 139, 178, 180, 181, 182, 183
114, 130, 133, 135, 136, 150, 174,
178 X
Trimipramine, 112, 178 Xyrem, 150
U Z
Unconditioned stimuli, 156 Zaleplon, 17, 74, 86, 111, 146, 180, 181,
Urine, 114, 116, 119, 145 182, 183
V Zeitgebber, 53
Zolpidem, 17, 58, 74, 83, 85, 101, 103,
Valerian, 74, 175, 177 111, 130. 131, 138, 146, 180, 181,
Valproic acid, 121 182, 183
Vigabatrin, 121 Zopiclone, 17, 74, 180, 181, 182
 CURRENT CLINICAL NEUROLOGY ™
Series Editor: DANIEL TARSY, MD

Clinical Handbook of Insomnia

Edited by
Hrayr P. Attarian, MD
Sleep Program in Neurology and Sleep Laboratory of the Clinical Neurophysiology Laboratories,
University of Vermont College of Medicine, Burlington, VT
Foreword by
Mark W. Mahowald, MD
Minnesota Regional Sleep Disorder Center, Hennepin County Medical Center
and University of Minnesota Medical School, Minneapolis, MN

Although insomnia is the second most common complaint, after pain, in the primary care setting,
medical texts and reference books often fail to give full treatment to the subject. In Clinical Handbook of
Insomnia, expert clinicians and researchers provide practicing primary health care providers the first clinically
oriented, comprehensive textbook devoted to the evaluation and treatment of insomnia. Summarizing the
latest findings published in a wide variety of medical journals, these experts concisely review the primary
insomnias (those in children and adults, psychophysiological and idiopathic insomnia, and sleep state misper-
ception), as well as those caused by medical, neurological, and psychiatric problems. They then fully discuss
the latest pharmacological and nonpharmacological treatments for insomnia, illustrating each topic with
detailed case studies, algorithms, charts, and graphs to better demonstrate the points presented. Also
included is a simple algorithm for the differential diagnosis of insomnia.
Comprehensive, easy to read, and up-to-date, Clinical Handbook of Insomnia considers the dis-
order in all its multiple forms, helping the practicing health care provider to identify the problem early
on, to recognize its underlying cause, and to prescribe the most efficacious treatment.

Features
䊏 Comprehensive review of insomnia in all 䊏 An easily readable format designed to rapidly
its multiple forms and its treatment help the practicing health care provider
䊏 Discussion of both pharmacological 䊏 Numerous case studies, algorithms, charts,
and nonpharmacological therapies and graphs
䊏 Detailed differential diagnosis of insomnia
in adults and children

Contents
Part I: Overview. Defining Insomnia. Epidemiology of Insomnia. Physiological Basis of Insomnia. Differential
Diagnosis of Insomnia. Part II: The Primary Insomnias. Insomnia in Children and Adolescents. Psychophys-
iological Insomnia. Idiopathic Insomnia. Sleep State Misperception. Sleep Hygiene. Part III: The Secondary
Insomnias. Insomnia Caused by Medical and Neurological Disorders. Insomnia in Psychiatric Disorders.
Insomnia in Primary Sleep Disorders. Part IV: Treatment of Insomnia. Cognitive-Behavioral Therapy for
Insomnia. Pharmacological Treatment of Insomnia. Index.

90000

Current Clinical Neurology™

CLINICAL HANDBOOK OF INSOMNIA
ISBN: 1-58829-272-X E-ISBN: 1-59259-662-2
humanapress.com 9 781588 292728