262  Part IV  ◆  Learning and Developmental Disorders

behaviors (e.g., substance abuse), difficulty maintaining relationships,

Chapter 49  encounters with the law, death from suicide, and, if untreated, accidents
(Figs. 49.2 and 49.3).
Attention-Deficit/ ETIOLOGY
No single factor determines the expression of ADHD; ADHD may be
Hyperactivity Disorder a final common pathway for a variety of complex brain developmental
processes. Mothers of children with ADHD are more likely to experience
David K. Urion birth complications, such as toxemia, lengthy labor, and complicated
delivery. Maternal drug use has also been identified as a risk factor in
the development of ADHD. Maternal smoking, alcohol use during
Attention-deficit/hyperactivity disorder (ADHD) is the most common pregnancy, and prenatal or postnatal exposure to lead are frequently
neurobehavioral disorder of childhood, among the most prevalent chronic linked to the attentional difficulties associated with development of
health conditions affecting school-aged children, and one of the most ADHD, but less clearly to hyperactivity. Food coloring and preservatives
extensively studied neurodevelopmental disorders of childhood. ADHD have inconsistently been associated with increased hyperactivity in
is characterized by inattention, including increased distractibility and children with ADHD.
difficulty sustaining attention; poor impulse control and decreased There is a strong genetic component to ADHD. Genetic studies have
self-inhibitory capacity; and motor overactivity and motor restlessness primarily implicated 2 candidate genes, the dopamine transporter gene
(Table 49.1 and Fig. 49.1). Definitions vary in different countries (Table (DAT1) and a particular form of the dopamine 4 receptor gene (DRD4),
49.2). Affected children usually experience academic underachievement, in the development of ADHD. Additional genes that might contribute
problems with interpersonal relationships with family members and to ADHD include DOCK2, associated with a pericentric inversion 46N
peers, and low self-esteem. ADHD often co-occurs with other emotional, inv(3)(p14:q21) involved in cytokine regulation; a sodium-hydrogen
behavioral, language, and learning disorders (Table 49.3). Evidence also exchange gene; and DRD5, SLC6A3, DBH, SNAP25, SLC6A4, and HTR1B.
suggests that for many people, the disorder continues with varying Structural and functional abnormalities of the brain have been identi-
manifestations across the life cycle, leading to significant under- and fied in children with ADHD. These include dysregulation of the frontal
unemployment, social dysfunction and increased risk of antisocial subcortical circuits, small cortical volumes in this region, widespread

Table 49.1  DSM-5 Diagnostic Criteria for Attention-Deficit/Hyperactivity Disorder (ADHD)

A. A persistent pattern of inattention and/or hyperactivity/impulsivity f. Often talks excessively.
that interferes with functioning or development, as characterized Impulsivity.
by (1) and/or (2): g. Often blurts out answers before questions have been
1. Inattention: Six (or more) of the following symptoms of completed.
inattention have persisted for ≥6 mo to a degree that is h. Often has difficulty awaiting turn.
inconsistent with development level and that negatively i. Often interrupts or intrudes on others (e.g., butts into
impacts directly on social and academic/occupational activities: conversations or games).
a. Often fails to give close attention to details or makes B. Several inattentive or hyperactive/impulsive symptoms were
careless mistakes in schoolwork, at work, or during other present before 12 yr of age.
activities (e.g., overlooks or misses details, work is C. Several inattentive or hyperactive/impulsive symptoms are
inaccurate). present in 2 or more settings (e.g., at school [or work] or at home)
b. Often has difficulty sustaining attention in tasks or play and is documented independently.
activities. D. There is clear evidence of clinically significant impairment in
c. Often does not seem to listen when spoken to directly. social, academic, or occupational functioning.
d. Often does not follow through on instructions and fails to E. Symptoms do not occur exclusively during the course of
finish schoolwork, chores, or duties in the workplace (not schizophrenia, or another psychotic disorder, and are not better
due to oppositional behavior or failure to understand accounted for by another mental disorder (e.g., mood disorder,
instructions). anxiety disorder, dissociative disorder, personality disorder,
e. Often has difficulty organizing tasks and activities. substance intoxication or withdrawal).
f. Often avoids, dislikes, or is reluctant to engage in tasks
that require sustained mental effort (e.g., schoolwork, CODE BASED ON TYPE
homework). 314.01 Attention-deficit/hyperactivity disorder, combined
g. Often loses things necessary for tasks or activities (e.g., toys, presentation: if both Criteria A1 and A2 are met for the past 6 mo.
school assignments, pencils, books, tools). 314.00 Attention-deficit/hyperactivity disorder, predominantly
h. Is often easily distracted by extraneous stimuli. inattentive presentation: if Criterion A1 is met but Criterion A2 is
i. Is often forgetful in daily activities. not met for the past 6 mo.
2. Hyperactivity/impulsivity: Six (or more) of the following 314.01 Attention-deficit/hyperactivity disorder, predominantly
symptoms of inattention have persisted for ≥6 mo to a degree hyperactive-impulsive presentation: if Criterion A2 is met but
that is inconsistent with development level and that negatively Criterion A1 is not met for the past 6 mo.
impacts directly on social and academic/occupational activities. Specify if:
a. Often fidgets with hands or feet or squirms in seat. Mild: Few, if any, symptoms in excess of those required to make the
b. Often leaves seat in classroom or in other situations in which diagnosis are present, and if the symptoms result in no more than
remaining seated is expected. minor impairments in social and occupational functioning.
c. Often runs about or climbs excessively in situations in which Moderate: Symptoms or functional impairment between “mild” and
it is inappropriate (in adolescents or adults, may be limited “severe” are present.
to subjective feelings of restlessness). Severe: Many symptoms in excess of those required to make the
d. Often has difficulty playing or engaging in leisure activities diagnosis, or several symptoms that are particularly severe, are
quietly. present, or the symptoms result in marked impairment in social or
e. Is often “on the go” or often acts as if “driven by a motor.” occupational functioning.
From the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, Washington, DC, 2000, and Fifth Edition, (Copyright 2013). American
Psychiatric Association.

Downloaded for Anonymous User (n/a) at GEORGE WASHINGTON UNIVERSITY from ClinicalKey.com by Elsevier on July
22, 2021. For personal use only. No other uses without permission. Copyright ©2021. Elsevier Inc. All rights reserved.
 Chapter 49  ◆  Attention-Deficit/Hyperactivity Disorder  262.e1

Keywords
ADHD
stimulant medication
hyperactivity
inattention
impulsivity
executive functions
behavior therapy

Downloaded for Anonymous User (n/a) at GEORGE WASHINGTON UNIVERSITY from ClinicalKey.com by Elsevier on July
22, 2021. For personal use only. No other uses without permission. Copyright ©2021. Elsevier Inc. All rights reserved.
 Chapter 49  ◆  Attention-Deficit/Hyperactivity Disorder  263

Poor concentration Hyperactivity Impulsivity

Difficulties with Struggle to Constrantly Less aware Strained family and

school work be organized on the go of danger peer relationships

Questions to ask

Is school attainment Do they: Do they: Do they: Difficulty maintaining

below what is peer relationships?
expected? Lose things? Run about excessively? Need high levels of
adult supervision? Strained parent-child
Do instructions often Forget what they Struggle to sit still relationships?
need to be repeated? were doing? during a favorite Have little road safety
movie or meal, or in awareness? Are they bullied or
Struggle to get ready the classroom? do they bully others?
for school? Experience many trivial
unintentional incidents? Easily led and
Struggle to complete influenced to engage
tasks? in thoughtless acts,
occasionally leading
to police involvement?

Fig. 49.1  How to assess children for attention-deficit/hyperactivity disorder. (From Verkuijl N, Perkins M, Fazel M: Childhood attention-deficit/
hyperactivity disorder, BMJ 350:h2168, 2015, Fig 2, p 146.)

Table 49.2  Differences Between U.S. and European Table 49.3  Differential Diagnosis of Attention-Deficit/
Criteria for ADHD or HKD Hyperactivity Disorder (ADHD)
DSM-5 ADHD ICD-10 HKD PSYCHOSOCIAL FACTORS
SYMPTOMS Response to physical or sexual abuse
Response to inappropriate parenting practices
Either or both of the following: All of the following:
Response to parental psychopathology
At least 6 of 9 inattentive At least 6 of 8 inattentive
Response to acculturation
symptoms symptoms
Response to inappropriate classroom setting
At least 6 of 9 hyperactive or At least 3 of 5 hyperactive
impulsive symptoms symptoms DIAGNOSES ASSOCIATED WITH ADHD BEHAVIORS
At least 1 of 4 impulsive symptoms
Fragile X syndrome
PERVASIVENESS Fetal alcohol syndrome
Some impairment from Criteria are met for >1 setting Pervasive developmental disorders
symptoms is present in >1 Obsessive-compulsive disorder
setting Gilles de la Tourette syndrome
Attachment disorder with mixed emotions and conduct
ADHD, Attention-deficit/hyperactivity disorder; HKD, hyperkinetic disorder;
DSM-5, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; MEDICAL AND NEUROLOGIC CONDITIONS
ICD-10, International Classification of Diseases, Tenth Edition. Thyroid disorders (including general resistance to thyroid hormone)
From Biederman J, Faraone S: Attention-deficit hyperactivity disorder, Lancet
366:237–248, 2005.
Heavy metal poisoning (including lead)
Adverse effects of medications
Effects of abused substances
small-volume reduction throughout the brain, and abnormalities of the Sensory deficits (hearing and vision)
cerebellum, particularly midline/vermian elements (see Pathogenesis). Auditory and visual processing disorders
Brain injury also increases the risk of ADHD. For example, 20% of Neurodegenerative disorder, especially leukodystrophies
Posttraumatic head injury
children with severe traumatic brain injury are reported to have sub-
Postencephalitic disorder
sequent onset of substantial symptoms of impulsivity and inattention.
However, ADHD may also increase the risk of traumatic brain injury. Note: Coexisting conditions with possible ADHD presentation include
Psychosocial family stressors can also contribute to or exacerbate the oppositional defiant disorder, anxiety disorders, conduct disorder, depressive
disorders, learning disorders, and language disorders. Presence of one or more
symptoms of ADHD, including poverty, exposure to violence, and of the symptoms of these disorders can fall within the spectrum of normal
undernutrition or malnutrition. behavior, whereas a range of these symptoms may be problematic but fall short
of meeting the full criteria for the disorder.
EPIDEMIOLOGY From Reiff MI, Stein MT: Attention-deficit/hyperactivity disorder evaluation
and diagnosis: a practical approach in office practice, Pediatr Clin North Am
Studies of the prevalence of ADHD worldwide have generally reported 50:1019–1048, 2003. Adapted from Reiff MI: Attention-deficit/hyperactivity
that 5–10% of school-age children are affected, although rates vary disorders. In Bergman AB, editor: 20 Common problems in pediatrics, New
considerably by country, perhaps in part because of differing sampling York, 2001, McGraw-Hill, p 273.

Downloaded for Anonymous User (n/a) at GEORGE WASHINGTON UNIVERSITY from ClinicalKey.com by Elsevier on July
22, 2021. For personal use only. No other uses without permission. Copyright ©2021. Elsevier Inc. All rights reserved.
264  Part IV  ◆  Learning and Developmental Disorders

Adulthood
Mood
College age instability
Academic Low self-esteem
Adolescence failure
Relationship
Not fulfilling Not coping
School age problems
academic with routine
potential tasks
Behavioral Increased
Preschool disturbance, road and
Reduced tolerance Occupational
including aggressive occupational
Behavioral by peers difficulties
tendencies incidents
disturbance
Low self-esteem Low self-esteem
Academic Difficulty planning and
Unintentional impairment completing tasks
injuries Smoking/alcohol/ Alcohol and
drug experimentation substance misuse
Difficulties in social Alcohol and
Feelings of parental interaction often substance misuse
incompetence Antisocial behavior Injuries/
tolerated by peers
unintentional Inconsistent parenting
incidents style

Fig. 49.2  Possible developmental impacts of attention-deficit/hyperactivity disorder. (From Verkuijl N, Perkins M, Fazel M: Childhood attention-
deficit/hyperactivity disorder, BMJ 350:h2168, 2015, Fig 1, p 145.)

present with comorbid neuropsychiatric diagnoses, including oppositional

Violence defiant disorder, conduct disorder, learning disabilities, and anxiety
Antisocial disorders disorders. The incidence of ADHD appears increased in children with
Crime neurologic disorders such as the epilepsies, neurofibromatosis, and
tuberous sclerosis (see Table 49.3).

PATHOGENESIS
Accidents
Brain MRI studies in children with ADHD indicate a reduction or even
Substance use loss of the normal hemispheric asymmetry in the brain, as well as
Fighting
smaller brain volumes of specific structures, such as the prefrontal cortex
and basal ganglia. Children with ADHD have approximately a 5–10%
ADHD reduction in the volume of these brain structures. MRI findings suggest
low blood flow to the striatum. Functional MRI data suggest deficits
Accidents in dispersed functional networks for selective and sustained attention
Inattention and Impulsivity in ADHD that include the striatum, prefrontal regions, parietal lobe,
Poor health habits
and temporal lobe. The prefrontal cortex and basal ganglia are rich in
dopamine receptors. This knowledge, plus data about the dopaminergic
mechanisms of action of medication treatment for ADHD, has led to
the dopamine hypothesis, which postulates that disturbances in the
Health risks dopamine system may be related to the onset of ADHD. Fluorodopa
Risky behaviors positron emission tomography (PET) scans also support the dopamine
Accidents
hypothesis through the identification of low levels of dopamine activity
in adults with ADHD.

Mood disorders Suicide CLINICAL MANIFESTATIONS

Development of the Diagnostic and Statistical Manual of Mental Disorders,
Fig. 49.3  Pathways to premature death in persons with attention-deficit/ Fifth Edition (DSM-5) criteria leading to the diagnosis of ADHD has
hyperactivity disorder (ADHD). (From Faraone SV: Attention deficit occurred mainly in field trials with children 5-12 yr of age (see Table
hyperactivity disorder and premature death, Lancet 385:2132–2133, 49.1 and Fig. 49.1). The DSM-5 notably expanded the accepted age of
2015.) onset for symptoms of ADHD, and studies utilizing these broader criteria
demonstrate a good correlation with data from DSM-IV criteria–based
and testing techniques. Rates may be higher if symptoms (inattention, studies. The current DSM-5 criteria state that the behavior must be
impulsivity, hyperactivity) are considered in the absence of functional developmentally inappropriate (substantially different from that of
impairment. The prevalence rate in adolescent samples is 2–6%. other children of the same age and developmental level), must begin
Approximately 2% of adults meet criteria for ADHD. ADHD is often before age 12 yr, must be present for at least 6 mo, must be present
underdiagnosed in children and adolescents. Youth with ADHD are in 2 or more settings and reported as such by independent observers,
often undertreated with respect to what is known about the needed and must not be secondary to another disorder. DSM-5 identifies three
and appropriate doses of medications. Many children with ADHD also presentations of ADHD. The inattentive presentation is more common

Downloaded for Anonymous User (n/a) at GEORGE WASHINGTON UNIVERSITY from ClinicalKey.com by Elsevier on July
22, 2021. For personal use only. No other uses without permission. Copyright ©2021. Elsevier Inc. All rights reserved.
 Chapter 49  ◆  Attention-Deficit/Hyperactivity Disorder  265

in females and is associated with relatively high rates of internalizing to highway with deposition of lead in topsoil from automobile exhaust
symptoms (anxiety and low mood). The other two presentations, years ago). Behavior in the structured laboratory setting might not
hyperactive-impulsive and combined, are more often diagnosed in males reflect the child’s typical behavior in the home or school environment.
(see Fig. 49.1). Thus, computerized attentional tasks and electroencephalographic
Clinical manifestations of ADHD may change with age (see Fig. assessments are not needed to make the diagnosis, and compared to
49.2). The symptoms may vary from motor restlessness and aggressive the clinical gold standard, these are subject to false-positive and false-
and disruptive behavior, which are common in preschool children, to negative errors. Similarly, observed behavior in a physician’s office is
disorganized, distractible, and inattentive symptoms, which are more not sufficient to confirm or rule-out the diagnosis of ADHD.
typical in older adolescents and adults. ADHD is often difficult to
diagnose in preschoolers because distractibility and inattention are often Differential Diagnosis
considered developmental norms during this period. Chronic illnesses, such as migraine headaches, absence seizures, asthma/
allergies, hematologic disorders, diabetes, and childhood cancer, affect
DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS up to 20% of U.S. children and can impair children’s attention and
A diagnosis of ADHD is made primarily in clinical settings after a school performance, because of either the disease itself or the medications
thorough evaluation, including a careful history and clinical interview used to treat or control the underlying illness (medications for asthma,
to rule in or to identify other causes or contributing factors; completion corticosteroids, anticonvulsants, antihistamines) (see Table 49.3). In
of behavior rating scales by different observers from at least 2 settings older children and adolescents, substance abuse can result in declining
(e.g., teacher and parent); a physical examination; and any necessary or school performance and inattentive behavior (see Chapter 140).
indicated laboratory tests that arise from conditions suspected based on Sleep disorders, including those secondary to chronic upper airway
history and/or physical examination. It is important to systematically obstruction from enlarged tonsils and adenoids, often result in behavioral
gather and evaluate information from a variety of sources, including and emotional symptoms that can resemble or exacerbate ADHD (see
the child, parents, teachers, physicians, and when appropriate, other Chapter 31). Periodic leg movements of sleep/restless leg syndrome has
caretakers, over the course of both diagnosis and subsequent management. been associated with attentional symptoms, and inquiry regarding this
should be made during the history. Behavioral and emotional disorders
Clinical Interview and History can cause disrupted sleep patterns as well.
The clinical interview allows a comprehensive understanding of whether Depression and anxiety disorders can cause many of the same
the symptoms meet the diagnostic criteria for ADHD. During the inter- symptoms as ADHD (inattention, restlessness, inability to focus and
view, the clinician should gather information pertaining to the history concentrate on work, poor organization, forgetfulness) but can also be
of the presenting problems, the child’s overall health and development, comorbid conditions (see Chapters 38 and 39). Obsessive-compulsive
and the social and family history. The interview should emphasize factors disorder can mimic ADHD, particularly when recurrent and persistent
that might affect the development or integrity of the central nervous thoughts, impulses, or images are intrusive and interfere with normal
system or reveal chronic illness, sensory impairments, sleep disorders, daily activities. Adjustment disorders secondary to major life stresses
or medication use that might affect the child’s functioning. Disruptive (death of a close family member, parents’ divorce, family violence, parents’
social factors, such as family discord, situational stress, and abuse or substance abuse, a move, shared social trauma such as bombings or
neglect, can result in hyperactive or anxious behaviors. A family history other attacks) or parent–child relationship disorders involving conflicts
of first-degree relatives with ADHD, mood or anxiety disorders, learning over discipline, overt child abuse and/or neglect, or overprotection can
disability, antisocial disorder, or alcohol or substance abuse might indicate result in symptoms similar to those of ADHD.
an increased risk of ADHD and comorbid conditions. Although ADHD is believed to result from primary impairment of
attention, impulse control, and motor activity, there is a high prevalence
Behavior Rating Scales of comorbidity with other neuropsychiatric disorders (see Table 49.3).
Behavior rating scales are useful in establishing the magnitude and Of children with ADHD, 15–25% have learning disabilities, 30–35%
pervasiveness of the symptoms, but are not sufficient alone to make a have developmental language disorders, 15–20% have diagnosed mood
diagnosis of ADHD. A variety of well-established behavior rating scales disorders, and 20–25% have coexisting anxiety disorders. Children with
have obtained good results in discriminating between children with ADHD can also have concurrent diagnoses of sleep disorders, memory
ADHD and controls. These measures include, but are not limited to, impairment, and decreased motor skills.
the Vanderbilt ADHD Diagnostic Rating Scale, the Conner Rating Scales
(parent and teacher), ADHD Rating Scale 5, the Swanson, Nolan, and TREATMENT
Pelham Checklist (SNAP), and the ADD-H: Comprehensive Teacher Rating Psychosocial Treatments
Scale (ACTeRS). Other broad-band checklists, such as the Achenbach Once the diagnosis of ADHD has been established, the parents and
Child Behavior Checklist (CBCL) or Behavioral Assessment Scale for child should be educated with regard to the ways ADHD can affect
Children (BASC), are useful, particularly when the child may be learning, behavior, self-esteem, social skills, and family function. The
experiencing coexisting problems in other areas (anxiety, depression, clinician should set goals for the family to improve the child’s interper-
conduct problems). Some, such as the BASC, include a validation scale sonal relationships, develop study skills, and decrease disruptive
to help determine the reliability of a given observer’s assessment of behaviors. Parent support groups with appropriate professional consulta-
the child. tion to such groups can be very helpful.

Physical Examination and Laboratory Findings Behaviorally Oriented Treatments

No laboratory tests are available to identify ADHD in children. The Treatments geared toward behavioral management often occur in the
presence of hypertension, ataxia, or symptoms of a sleep or thyroid time frame of 8-12 sessions. The goal of such treatment is for the clinician
disorder should prompt further neurologic or endocrine diagnostic to identify targeted behaviors that cause impairment in the child’s life
evaluation. Impaired fine motor movement and poor coordination and (disruptive behavior, difficulty in completing homework, failure to obey
other subtle neurologic motor signs (difficulties with finger tapping, home or school rules) and for the child to work on progressively
alternating movements, finger-to-nose, skipping, tracing a maze, cutting improving his or her skill in these areas. The clinician should guide the
paper) are common but not sufficiently specific to contribute to a parents and teachers in setting appropriate expectations, consistently
diagnosis of ADHD. The clinician should also identify any possible implementing rewards to encourage desired behaviors and consequences
vision or hearing problems. The clinician should consider testing for to discourage undesired behaviors. In short-term comparison trials,
elevated lead levels in children who present with some or all of the stimulants have been more effective than behavioral treatments used
diagnostic criteria, if these children are exposed to environmental factors alone in improving core ADHD symptoms for most children. Behavioral
that might put them at risk (substandard housing, old paint, proximity interventions are modestly successful at improving core ADHD symptoms

Downloaded for Anonymous User (n/a) at GEORGE WASHINGTON UNIVERSITY from ClinicalKey.com by Elsevier on July
22, 2021. For personal use only. No other uses without permission. Copyright ©2021. Elsevier Inc. All rights reserved.
266  Part IV  ◆  Learning and Developmental Disorders

and are considered the first-line treatment in preschool-age children Pediatric patient under consideration
with ADHD. In addition, behavioral treatment may be particularly for or currently being treated with
useful for children with comorbid anxiety, complex comorbidities, family stimulant medication
stressors, and when combined with medication.

Medications
The most widely used medications for the treatment of ADHD are the Known cardiac disease?
No Yes
presynaptic dopaminergic agonists, commonly called psychostimulant
medications, including methylphenidate, dexmethylphenidate, amphet-
amine, and various amphetamine and dextroamphetamine preparations. Patient history, family Further evaluation – if
Longer-acting, once-daily forms of each of the major types of stimulant history, or physical Yes indicated, obtain input from
medications are available and facilitate compliance with treatment exam suggestive of a pediatric cardiologist.
and coverage over a longer period (see Table 49.3). When starting a cardiac disease?
stimulant, the clinician can select either a methylphenidate-based or Yes
an amphetamine-based compound. If a full range of methylphenidate No
After initiating treatment,
dosages is used, approximately 25% of patients have an optimal response Treatment with stimulants does history or exam
on a low dose (<0.5 mg/kg/day for methylphenidate, <0.25 mg/kg/day does not require additional change to suggest possible
for amphetamines), 25% on a medium dose (0.5-1.0 mg/kg/day for cardiac testing. cardiac disease?
methylphenidate, 0.25-0.5 mg/kg/day for amphetamines), and 25% on
a high dose (1.0-1.5 mg/day for methylphenidate, 0.5-0.75 mg/kg/day No
for amphetamine); another 25% will be unresponsive or will have side
effects, making that drug particularly unpalatable for the family (See Fig. 49.4  Cardiac evaluation of children and adolescents with ADHD
Table 33.2 for more information on dosing). receiving or being considered for stimulant medications. (From Perrin
JM, Friedman RA, Knilans TK: Cardiovascular monitoring and stimulant
Over the first 4 wk of treatment, the physician should increase the
drugs for attention-deficit/hyperactivity disorder, Pediatrics 122:451–453,
medication dose as tolerated (keeping side effects minimal to absent) 2008.)
to achieve maximum benefit. If this strategy does not yield satisfactory
results, or if side effects prevent further dose adjustment in the presence
of persisting symptoms, the clinician should use an alternative class of
stimulants that was not used previously. If a methylphenidate compound children. In some of the reported cases, the patient had an underlying
is unsuccessful, the clinician should switch to an amphetamine product. disorder, such as hypertrophic obstructive cardiomyopathy, which is
If satisfactory treatment results are not obtained with the 2nd stimulant, made worse by sympathomimetic agents. These events are rare but
clinicians may choose to prescribe atomoxetine, a noradrenergic reuptake nonetheless warrant consideration before initiating treatment and during
inhibitor that has been approved by the U.S. Food and Drug Administra- monitoring of therapy with stimulants. Children with a positive personal
tion (FDA) for the treatment of ADHD in children, adolescents, and or family history of cardiomyopathy, arrhythmias, or syncope require
adults. Atomoxetine should be initiated at a dose of 0.3 mg/kg/day and an electrocardiogram and possible cardiology consultation before a
titrated over 1-3 wk to a maximum total daily dosage of 1.2-1.4 mg/ stimulant is prescribed (Fig. 49.4).
kg/day. The dose should be divided into twice-daily portions. Once-daily
dosing appears to be associated with a high incidence of treatment PROGNOSIS
failure. Long-acting guanfacine and clonidine are also FDA approved A childhood diagnosis of ADHD often leads to persistent ADHD
for the treatment of ADHD (see Chapter 33). These medications can throughout the life span. From 60–80% of children with ADHD continue
also treat motor and vocal tics and so may be a reasonable choice in a to experience symptoms in adolescence, and up to 40–60% of adolescents
child with a comorbid tic disorder. Drugs to treat ADHD do not increase exhibit ADHD symptoms into adulthood. In children with ADHD, a
the incidence of tics in children predisposed to a tic disorder. In the reduction in hyperactive behavior often occurs with age. Other symptoms
past, tricyclic antidepressants have been used to treat ADHD, but TCAs associated with ADHD can become more prominent with age, such as
are rarely used now because of the risk of sudden death, particularly if inattention, impulsivity, and disorganization, and these exact a heavy
an overdose is taken. toll on young adult functioning. Risk factors in children with untreated
The clinician should consider careful monitoring of medication a ADHD as they become adults include engaging in risk-taking behaviors
necessary component of treatment in children with ADHD. When (sexual activity, delinquent behaviors, substance use), educational
physicians prescribe medications for the treatment of ADHD, they tend underachievement or employment difficulties, and relationship difficulties.
to use lower-than-optimal doses. Optimal treatment usually requires With proper treatment, the risks associated with ADHD, including
somewhat higher doses than tend to be found in routine practice settings. injuries, can be significantly reduced. Consistent treatment with medica-
All-day preparations are also useful to maximize positive effects and tion and adjuvant therapies appears to lower the risk of adverse outcomes,
minimize side effects, and regular medication follow-up visits should such as substance abuse.
be offered (≥4 times/yr) as opposed to the twice-yearly medication
visits often used in standard community care settings. PREVENTION
Medication alone may not be sufficient to treat ADHD in children, par- Parent training can lead to significant improvements in preschool
ticularly when children have multiple psychiatric disorders or a stressed children with ADHD symptoms, and parent training for preschool
home environment. When children do not respond to medication, it youth with ADHD can reduce oppositional behavior. To the extent that
may be appropriate to refer them to a mental health specialist. Consulta- parents, teachers, physicians, and policymakers support efforts for earlier
tion with a child psychiatrist, developmental-behavioral pediatrician, detection, diagnosis, and treatment, prevention of long-term adverse
or psychologist can also be beneficial to determine the next steps for effects of ADHD on affected children’s lives should be reconsidered
treatment, including adding other components and supports to the within the lens of prevention. Given the effective treatments for ADHD
overall treatment program. Evidence suggests that children who receive now available, and the well-documented evidence about the long-term
careful medication management, accompanied by frequent treatment effects of untreated or ineffectively treated ADHD on children and
follow-up, all within the context of an educative, supportive relationship youth, prevention of these consequences should be within the grasp
with the primary care provider, are likely to experience behavioral gains. of physicians and the children and families with ADHD for whom we
Stimulant drugs used to treat ADHD may be associated with an are responsible.
increased risk of adverse cardiovascular events, including sudden cardiac
death, myocardial infarction, and stroke, in young adults and rarely in Bibliography is available at Expert Consult.

Downloaded for Anonymous User (n/a) at GEORGE WASHINGTON UNIVERSITY from ClinicalKey.com by Elsevier on July
22, 2021. For personal use only. No other uses without permission. Copyright ©2021. Elsevier Inc. All rights reserved.
 Chapter 49  ◆  Attention-Deficit/Hyperactivity Disorder  266.e1

Bibliography Knight M: Stimulant-drug therapy for attention-deficit disorder (with or without

American Academy of Pediatrics/American Heart Association: AAP/AHA clarifica- hyperactivity) and sudden cardiac death, Pediatrics 119:154–155, 2007.
tion of statement on cardiovascular evaluation and monitoring of children and Kollins S, Greenhill L, Swanson J, et al: Rationale, design, and methods of the Preschool
adolescents with heart disease receiving medications for ADHD: 2008, J Dev Behav ADHA Treatment Study (PATS), J Am Acad Child Adolesc Psychiatry 45:1275–1283,
Pediatr 29(4):335, 2008. 2006.
Atkinson M, Hollis C: NICE guideline: attention deficit hyperactivity disorder, Arch Langberg JM, Brinkman WB, Lichtenstein PK, et al: Interventions to promote the
Dis Child Educ Pract Ed 95:24–27, 2010. evidence-based care of children with ADHD in primary-care settings, Expert Rev
Babcock T, Ornstein CS: Comorbidity and its impact in adult patients with attention- Neurother 9:477–487, 2009.
deficit/hyperactivity disorder: a primary care perspective, Postgrad Med 121:73–82, Man KKC, Chan EW, Ip P, et al: Prenatal antidepressant use and risk of attention-
2009. deficit/hyperactivity disorder in offspring: population based cohort study, BMJ
Barbaresi W, et al: Mortality, ADHD, and psychosocial adversity in adults with childhood 357:j2350, 2017.
ADHD: a prospective study, Pediatrics 131(4):637–644, 2013. McCann D, Barrett A, Cooper A, et al: Food additives and hyperactive behaviour in
Barkley RA, Fischer M, Smallish L, et al: Young adult outcome of hyperactive children: 3-year-old and 8/9-year-old children in the community: a randomized, double-blind,
adaptive functioning in major life activities, J Am Acad Child Adolesc Psychiatry placebo-controlled trial, Lancet 370:1560–1567, 2007.
45:192–202, 2006. The Medical Letter: Guanfacine extended-release (Intuniv) for ADHD, Med Lett Drugs
Bouchard MF, Bellinger DC, Wright RO, et al: Attention-deficit hyperactivity disorder Ther 52:82, 2010.
and urinary metabolites of organophosphate pesticides, Pediatrics 125:e1270–e1277, The Medical Letter: Drugs for ADHD, Med Lett Drugs Ther 57:37–40, 2015.
2010. The Medical Letter: Two new amphetamines for ADHD, Med Lett Drugs Ther
Brookes KJ, Mill J, Guindalini C, et al: A common haplotype of the dopamine transporter 58(1497):80–81, 2016.
gene associated with attention-deficit/hyperactivity disorder and interacting with Mosholder AD, Gelperin K, Hammad TA, et al: Hallucinations and other psychotic
maternal use of alcohol during pregnancy, Arch Gen Psychiatry 63:74–81, 2006. symptoms associated with the use of attention-deficit/hyperactivity disorder drugs
Caspi A, Langley K, Milne B, et al: A replicated molecular genetic basis for subtyping in children, Pediatrics 123:611–616, 2009.
antisocial behavior in children with attention-deficit/ hyperactivity disorder, Arch Newcorn JH: Managing ADHD and comorbidities in adults, J Clin Psychiatry 70(2):e40,
Gen Psychiatry 65:203–210, 2008. 2009.
Centers for Disease Control and Prevention: Percentage of children and teens aged Newcorn JH, Kratochvil CJ, Allen AJ, et al: Atomoxetine and osmotically released
4-17 years ever diagnosed with attention-deficit/hyperactivity disorder (ADHD) methylphenidate for the treatment of attention deficit hyperactivity disorder: acute
by sex and urbanization of county residence—National Health Interview Survey, comparison and differential response, Am J Psychiatry 165:721–730, 2008.
2013–2015, MMWR Morb Mortal Wkly Rep 66(23):625, 2016. Newcorn JH, Sutton VK, Weiss MD, et al: Clinical responses to atomoxetine in
Chan E, Fogler JA, Hammerness PG: Treatment of attention-deficit/hyperactivity attention-deficit/hyperactivity disorder: the integrated Data Exploratory Analysis
disorder in adolescents: a systematic review, JAMA 315(18):1997–2008, 2016. (IDEA) study, J Am Acad Child Adolesc Psychiatry 48:511–518, 2009.
Chang Z, Quinn PD, Hur K, et al: Association between medication use for attention- Nutt DJ, Fone K, Asherson P, et al: Evidence-based guidelines for management of
deficit/hyperactivity disorder and risk of motor vehicle crashes, JAMA Psychiatry attention-deficit/hyperactivity disorder in adolescents in transition to adult services
74(6):597–603, 2017. and in adults: recommendations from the British Association for Psychopharmacol-
Cohen SC, Mulqueen JM, Ferracioli-Oda E, et al: Meta-analysis: risk of tics associated ogy, J Psychopharmacol 21:10–41, 2007.
with psychostimulant use in randomized, placebo-controlled trials, J Am Acad Okie S: ADHD in adults, N Engl J Med 354:2637–2641, 2006.
Child Adolesc Psychiatry 54(9):728–736, 2015. Pelsser LM, Frankena K, Toorman J, et al: Effects of restricted elimination diet on the
Dalsgaard S, Leckman JF, Mortensen PB, et al: Effect of drugs on the risk of injuries behaviour of children with attention-deficit hyperactivity disorder (INCA study):
in children with attention deficit hyperactivity disorder: a prospective cohort study, a randomised controlled trial, Lancet 377:494–503, 2011.
Lancet Psychiatry 2:702–709, 2015. Perrin JM, Friedman RA, Knilans TK: Cardiovascular monitoring and stimulant
Eigenmann PA, Haenggeli CA: Food colourings, preservatives, and hyperactivity, drugs for attention-deficit/hyperactivity disorder, Pediatrics 122:451–453, 2008.
Lancet 370:1524–1525, 2007. Safren SA, Sprich S, Mimiaga MJ, et al: Cognitive behavioral therapy vs relaxation with
Faraone SV: Attention deficit hyperactivity disorder and premature death, Lancet educational support for medication—adults with ADHD and persistent symptoms,
385:2132–2133, 2015. JAMA 304:875–880, 2010.
Franke AG, Gransmark P, Agricola A, et al: Methylphenidate, modafinil, and caffeine Shaw P: Quantifying the benefits and risks of methylphenidate as treatment for
for cognitive enhancement in chess: a double-blind, randomized controlled trial, childhood attention-deficit/hyperactivity disorder, JAMA 315(18):1953–1954, 2016.
Eur Neuropsychopharmacol 27:248–260, 2017. Shin JY, Roughhead EE, Park BJ, Pratt NL: Cardiovascular safety of methylphenidate
Friedland S, Walkup JT: Meta-assurance: no tic exacerbation caused by stimulants, J among children and young people with attention-deficit/hyperactivity disorder
Am Acad Child Adolesc Psychiatry 54(9):706–708, 2015. (ADHD): nationwide self- controlled case series study, BMJ 353:i2550, 2016.
Gloss D, Varma JK, Pringsheim T, Nuwer MR: Practice advisory: the utility of EEG Shum SBM, Pang MYC: Children with attention deficit hyperactivity disorder have
theta/beta power ratio in ADHD diagnosis, Neurology 97:1–5, 2016. impaired balance function: involvement of somatosensory, visual, and vestibular
Gould MS, Walsh BT, Munfakh JL, et al: Sudden death and use of stimulant medications systems, J Pediatr 155:245–249, 2009.
in youths, Am J Psychiatry 166:992–1101, 2009. Silk TJ, Vance A, Rinehart N, et al: Dysfunction in the fronto-parietal network in
Greenhill L, Kollins S, Abikoff H, et al: Efficacy and safety of immediate-release attention deficit hyperactivity disorder (ADHD): an fMRI study, Brain Imaging
methylphenidate treatment for preschoolers with ADHD, J Am Acad Child Adolesc Behav 2:2008, 1931.
Psychiatry 45:1284–1293, 2006. Smith AK, Mick E, Faraone SV: Advances in genetic studies of attention-deficit/
Hammerness P, Wilens T, Mick E, et al: Cardiovascular effects of longer-term, high-dose hyperactivity disorder, Curr Psychiatry Rep 11:143–148, 2009.
OROS methylphenidate in adolescents with attention deficit hyperactivity disorder, Sowell ER, Thompson PM, Welcome SE, et al: Cortical abnormalities in children and
J Pediatr 155:84–89, 2009. adolescents with attention-deficit disorder, Lancet 362:1699–1707, 2008.
Harpin VA: Medication options when treating children and adolescents with ADHA: Spencer TJ: ADHD and comorbidity in childhood, J Clin Psychiatry 67(Suppl 8):27–31,
interpreting the NICE guidance 2006, Arch Dis Child Educ Pract Ed 93:58–66, 2008. 2006.
Hartanto TA, Krafft CE, Iosif AM, Schweitzer JB: A trial-by-trial analysis reveals more Thapar A, Cooper M: Attention deficit hyperactivity disorder, Lancet 387:1240–1248,
intense physical activity is associated with better cognitive control performance in 2016.
attention-deficit/hyperactivity disorder, Child Neuropsychol 22(5):618–626, 2016. Thomas PE, Carlo WE, Decker JA, et al: Impact of the American Heart Association
Jones K, Daley D, Hutchings J, et al: Efficacy of the Incredible Years Programme as scientific statement on screening electrocardiograms and stimulant medications,
an early intervention for children with conduct problems and ADHD: long-term Arch Pediatr Adolesc Med 165(2):166–170, 2011.
follow-up, Child Care Health Dev 34:380–390, 2008. Verkuijl N, Perkins M, Fazel M: Childhood attention-deficit/hyperactivity disorder,
Kendall T, Taylor E, Perez A, et al: Diagnosis and management of attention-deficit/ BMJ 350:h2168, 2015.
hyperactivity disorder in children, young people, and adults: summary of NICE Wilens TE, Prince JB, Spencer TJ, et al: Stimulants and sudden death: What is a
guidance, BMJ 337:751–754, 2008. physician to do? Pediatrics 118:1215–1219, 2006.

Downloaded for Anonymous User (n/a) at GEORGE WASHINGTON UNIVERSITY from ClinicalKey.com by Elsevier on July
22, 2021. For personal use only. No other uses without permission. Copyright ©2021. Elsevier Inc. All rights reserved.