Behavioral Emergencies

Special Considerations in the Geriatric

Psychiatric Patient

a, b,c,d,e
Awais Aftab, MD *, Asim A. Shah, MD

KEYWORDS
 Geriatric psychiatry  Emergency psychiatry  Delirium  Dementia  Agitation
 Suicide

KEY POINTS
 As a result of multiple physiological and pharmacokinetic changes, the elderly are more
vulnerable to the side-effects of medications, and require lower doses of medications
and slower rates of titration.
 Geriatric population is a high-risk group for suicide, with more serious intent, fewer warn-
ing signs, and more lethality. Suicide risk assessment should be part of a standard emer-
gency psychiatric assessment.
 Prompt diagnosis and treatment of delirium in emergency settings is essential given the
association with worse outcomes such as prolonged hospital stay, risk of cognitive
decline, and increased mortality.
 Behavioral interventions for agitation in dementia are the first-line measure before phar-
macologic interventions. Pharmacologic options with demonstrable efficacy are mostly
limited to antipsychotics, the use of which is problematic, as all antipsychotics increase
the risk of mortality in dementia.

INTRODUCTION

It is estimated that by the year 2030 about 72 million US citizens will be age 65 or older,
making up about 20% of the US population.1 A total of 15.4% of visits to the

Disclosure: All authors have no relevant conflicts of interest or disclosures.

a
Department of Psychiatry, University Hospitals Cleveland Medical Center, Case Western
Reserve University, 10524 Euclid Avenue, 8th Floor, Cleveland, OH 44106, USA; b Psychiatric
Residency Education, Menninger Department of Psychiatry, Baylor College of Medicine, 1977
Butler Boulevard, Houston, TX 77030, USA; c Menninger Department of Family and Community
Medicine, Baylor College of Medicine, 3701 Kirby Drive Suite 600, Houston, TX 77098, USA;
d
Mood Disorder Research Program at BT, Neuropsychiatric Center, Ben Taub Hospital/HHS,
Room 2.125, 1502 Taub Loop, Houston, TX 77030, USA; e Community Behavioral Health Pro-
gram, Psychotherapy Services, Neuropsychiatric Center, Ben Taub Hospital/HHS, Room 2.125,
1502 Taub Loop, Houston, TX 77030, USA
* Corresponding author.
E-mail address: [email protected]

Psychiatr Clin N Am 40 (2017) 449–462

http://dx.doi.org/10.1016/j.psc.2017.05.010 psych.theclinics.com
0193-953X/17/ª 2017 Elsevier Inc. All rights reserved.
450 Aftab & Shah

emergency department are by the elderly,2 and the visit rates by older adults have had
the highest increase among all age groups in the last decades.2
Emergency psychiatric presentations in the elderly are often challenging, given the
lack of well-defined presenting complaints, multiple medical and neurologic comor-
bidities, and the complex nature of presentations. Psychiatric symptoms can often
be the result of a medical disorder in the elderly, and particularly new-onset psychiatric
symptoms should warrant a thorough medical and neurological work-up. Evaluation of
cognitive status and suicide risk assessment should be essential components of any
emergency psychiatric assessment of the elderly. Review of medications for polyphar-
macy and medication side effects are also important. Substance use is often over-
looked in the geriatric population and warrants careful history taking and urine
toxicology. Geriatric patients are sometimes unreliable historians, and collateral his-
tory taking in many cases is warranted. Common disorders like depression can also
have atypical presentations in the elderly compared with adults.
This report provides an overview of special psychiatric considerations in the geri-
atric population and common psychiatric emergencies of specific relevance in the
elderly that warrant prompt assessment and management.

GENERAL PSYCHOPHARMACOLOGIC CONSIDERATIONS IN THE ELDERLY

Geriatric subjects are more vulnerable to the side effects of medications. This
increased susceptibility is a result of several physiologic changes associated with ag-
ing that lead to pharmacokinetic changes. For instance, decreased concentration of
plasma albumin can lead to increased plasma concentration of free drugs, decreased
glomerular filtration rate results in decreased renal clearance of medications and
active metabolites, reduction in hepatic blood flow can cause decreased hepatic
clearance, and increase in body fat can lead to increase in elimination half-life of lipid
soluble drugs.3,4 Furthermore, elderly patients are frequently subjected to polyphar-
macy, leading to an increased burden of side effects.3,4
Homeostatic mechanisms (eg, orthostatic circulation, postural control, and thermoreg-
ulation) are also less vigorous in the aged, which can lead to additional vulnerabilities, such
as increased risk of falls and hip fractures with psychotropics.4 The elderly are also more
vulnerable to the development of the syndrome of inappropriate antidiuretic hormone
secretion.4 Neurotransmitter changes such as reduction in dopamine and acetylcholine
function mean that elderly have increased sensitivity to extrapyramidal symptoms with an-
tipsychotics and cognitive impairment with anticholinergic medications4 (Table 1).
As a general rule, physicians should use lower doses of medications and slower
rates of titration in the elderly compared with the younger adult population.
As a result of reduced renal clearance and decreased total body water, the elderly
are more susceptible to lithium toxicity. This vulnerability is present even with thera-
peutic serum lithium levels, in particular to neurological adverse effects such as tremor
and ataxia.5 Elderly patients therefore generally are best maintained on serum levels
lower than those recommended in adults—in the range of 0.4 to 0.8 mEq/L.5
Benzodiazepines are best avoided in the geriatric population. Even short-term
use can lead to impairments in cognition and psychomotor functioning.3,5 These
drugs increase the risk of falls and hip fractures.3,5 These negative effects are in
addition to the general risk of abuse and dependence that exists with benzodiaze-
pine use. If benzodiazepines are clinically necessitated, lorazepam may be
preferred given that it does not undergo phase I hepatic metabolism, it has no
active metabolites, the half-life does not vary as much with age, and it is well
absorbed intramuscularly.5
 Considerations in Geriatric Population 451

Table 1
Physiologic and pharmacokinetic changes in the elderly and their consequences

Physiologic and Pharmacokinetic Changes Consequences

Decreased concentration of plasma albumin Increased plasma concentration of free drug
Decreased glomerular filtration rate Reduced renal clearance and accumulation of
medication in the body
Reduction in hepatic blood flow Reduced hepatic clearance and accumulation of
medication in the body
Increase in body fat Increase in half-life of lipid-soluble drugs
Reduced homeostatic integrity Increased risk of falls and hip fractures
Reduced dopamine function Increased sensitivity to extrapyramidal
symptoms
Reduced cholinergic function Increased sensitivity to anticholinergic
medications
Reduced total body water Vulnerability to medication toxicity

Data from Mulsant BH, Pollock BG. Psychopharmacology. In: Steffens DC, Blazer DG, Thakur ME,
editors. The American psychiatric publishing textbook of geriatric psychiatry. 5th edition. Arling-
ton (VA): American Psychiatric Publishing; 2015; and Roose SP, Pollock BG, Devanand DP. Treatment
during late life. In: Schatzberg AF, Nemeroff CB, editors. The American psychiatric publishing text-
book of psychopharmacology. 4th edition. Arlington (VA): American Psychiatric Publishing; 2009.

The increased risk of mortality with use of antipsychotics in individuals with demen-
tia is addressed later in this review.

GERIATRIC SUICIDALITY

Geriatric patients are among the highest-risk epidemiologic groups for suicide. World-
wide rates of completed suicide generally increase as a function of age for both men
and women.6 In elderly suicides, there is often more serious intent and fewer warning
signs, and suicides are more lethal when compared with the younger population.7,8
Additionally, depressed geriatric patients with suicidality are more difficult to treat
with higher relapse rates.9 The ratio between suicide attempts and completed suicides
progressively decreases with age: the ratio in United States is 36:1 in the youths, 8:1 in
the general population, and 4:1 in the elderly.10
A Swedish study that identified the characteristics of suicide attempters 70 years
and older compared with the general population comparison group reported that
elderly suicide attempters were more likely to be unmarried, to be living alone, have
low level of education, have a history of psychiatric treatment, and have prior suicide
attempts.11 Death of spouse is another risk factor for suicide in older subjects.12 In a
British survey of suicides in individuals 60 or older, hanging was the most common
method for men, with overdose most common method for women.13
Clinical risk factors include depression, alcohol use disorders, schizophrenia, per-
sonality disorders, and medical comorbidities.14 Psychiatric disorders are found on
psychological autopsies in 71% to 97% of elderly suicides subjects, with mood disor-
ders being the most widely reported.6 A study from Canada found that elderly patients
with 3 physical illnesses had an approximately 3-fold increase in estimated relative risk
for suicide compared with subjects who had no diagnosis, and the relative risk
increased to 9-fold when the number of physical illnesses was 7.15 Loss of indepen-
dence and financial problems are additional social risk factors.6,14
Elderly individuals may not be forthcoming about suicidal thoughts unless they are
directly queried about it. Assessing for suicidality should therefore be part of a
452 Aftab & Shah

standard emergency psychiatric assessment. An evaluation of a geriatric patient with

suicidality centers around the identification of the risk factors. Unfortunately, the pre-
dictive value of these risk factors at the individual level remains poor, making determi-
nation of suicide risk in a specific case a matter of clinician’s judgment. Patients
determined to be at high risk for suicide in the short term are best managed in the inpa-
tient psychiatric setting. If the risk is elevated, involuntary psychiatric admission may
be necessary, keeping in mind the applicable legal statues related to involuntary civil
commitment. If hospitalization against will is being pursued, it should be presented to
the patient as a means of helping them recover from a state of crisis by keeping them
in a supervised, safe setting. Patients with vague suicidal ideation with no intent or
plan, strong social support, and no ready access to means of suicide can generally
be managed closely on an outpatient basis.
It is crucial to investigate the presence of a suicide plan and availability of means to
carry out the plan, personal and family history of suicidal behavior, degree of available
social support, concurrent psychiatric and medical disorders, and presence of suicide
warning signs. Many behaviors in the elderly may be warning signs and precursors
leading to a suicide attempt. These behaviors include neglect of personal care; inten-
tional self-starvation; finalizing a will; distributing personal belongings to friends, family,
or charities; giving up positions of responsibility; and purchase of a gun.16–18 (Box 1).
Addressing the underlying factors related to suicidality remains the primary modality
of management. In most patients, suicidality would be present in the context of psy-
chiatric disorders, which is best addressed by the relevant pharmacotherapy (antide-
pressants, mood stabilizers, antipsychotics) and psychotherapy. For depressive
episodes with acute suicidality, electroconvulsive therapy remains an effective and
underutilized treatment in the geriatric patient population.

DELIRIUM AND AGITATION IN DELIRIUM

Delirium is a neurocognitive disorder characterized by disturbances in attention,

awareness (orientation to the surrounding environment), and various aspects of cogni-
tion (memory, language, visuospatial ability, perception), which develops over a rela-
tively short period and represents a significant change from baseline status. There is
commonly a waxing and waning fluctuation in the degree of confusion during the day.
Delirium can also be described as a neurobehavioral syndrome caused by dysregula-
tion of baseline neuronal activity secondary to systemic disturbances.19 It is an acute,
usually temporary, psychiatric disorder caused by an underlying medical condition,
substance intoxication/withdrawal, or medication adverse effect. Delirium is associ-
ated with several worse outcomes such as prolonged hospital stay, need for

Box 1
Suicide warning signs and precursors in the elderly

Neglect of personal care

Intentional self-starvation
Finalizing a will
Distribution of personal belongings
Giving up positions of responsibility
Purchase of a gun

Data from Refs.16–18

 Considerations in Geriatric Population 453

institutional postacute care, risk of cognitive decline, and increased cost of medical
care.20,21 Prompt diagnosis of delirium in the emergency room is also critical, as mor-
tality for undiagnosed delirious patients in the emergency department is significantly
higher than that of patients with a diagnosis of delirium.22

Epidemiology
Although the prevalence of delirium in the general population is low (1%–2%), the
prevalence increases steeply in the geriatric population—reported to be around
14% in subjects 85 or older.23 Delirium is highly prevalent in the hospital settings.
The overall occurrence rates (sum of incidence and prevalence) of delirium in the gen-
eral medical and geriatric wards are 29% to 64%.21 Delirium is present in 8% to 17%
of elderly patients and 40% of nursing home residents on presentation to the emer-
gency room.21 It is also very common postoperatively, in intensive care units, in
nursing homes, and in postacute care settings.

Risk Factors
There are risk factors that increase the baseline vulnerability of delirium development,
and there are others that serve as precipitating factors.
The vulnerability factors include advanced age, sensory impairment, and neurologic
conditions such as dementia, stroke, and Parkinson disease. Delirium superimposed
on dementia is highly prevalent (ranging from approximately 20%–90%).24 In many
cases, it is the presence of delirium that brings attention to the underlying dementia
that had been hitherto undiagnosed. It is also important to note that in cases of
delirium without prior dementia, a significant percentage of these patients will go on
to have dementia over the next 5 years compared with controls (69% vs 20%).25
The list of precipitating factors is long and includes broad categories of medications
and toxins, substance intoxications and withdrawals, infections (systemic and central
nervous system), metabolic disturbances, systemic organ failures (eg, cardiac, hepat-
ic, pulmonary, renal), and extensive physical trauma such as burns.21,26 Conditions
such as seizures and psychiatric disorders (psychosis, mania, catatonia) can mimic
the clinical syndrome of delirium.21,26 Polypharmacy is a significant risk factor in the
elderly, and review of medications (both prescribed and over the counter) should be
an essential first step.

Clinical Features
A decrease in the level of awareness and deficit in attention are usually the earliest signs
of delirium. Initially, they may be subtle, picked up only by the family members, and may
be missed by clinicians who are not familiar with the patients (caregiver reports therefore
should not be summarily dismissed). Distractibility can progress to frank drowsiness
and lethargy, with further progression to a semicomatose condition in severe cases.
The sedation may be punctuated by episodes of psychomotor agitation. Perceptual dis-
turbances ranging from illusions to frank hallucinations are common. Unlike primary
psychotic disorders, visual hallucinations are more common than auditory, and halluci-
nations may range from simple to complex. Sleep disturbances, emotional lability, anx-
iety, and low mood are all commonly seen. Hypoactive delirium may be mistaken for
depression, and it is a common experience in consultation-liaison psychiatry to be con-
sulted for depression on patients with unrecognized delirium.
Delirium has a characteristic waxing and waning course, with interspersed periods
of lucidity. Once developed, delirium can linger on for days to months, even after the
underlying causes have been addressed.26 Delirium can be the first manifestation of
an acute medical illness in the elderly.26
454 Aftab & Shah

Diagnosis
Delirium remains a diagnosis based on clinical evaluation, although a medical workup
is essential. In cases where symptoms are subtle, cognitive screening measures are
helpful. Simple tests of attention such as serial subtraction, spelling a word (such as
world) backwards, repeating a sequence of random numbers, are highly useful in
bedside clinical practice and often suffice for clinical diagnosis. Confusion Assess-
ment Method has emerged as the standard clinical tool for screening of delirium.27
It is valid across different settings, has a sensitivity approaching 100% and specificity
of 90% to 95%, and has been found superior to Mini-Mental State Examination.28
Cognitive screening tools developed for dementia such as Mini-Mental State Exami-
nation and Montreal Cognitive Assessment are often cumbersome in the emergency
settings for use in delirium.

Evaluation
Because delirium is the consequence of an underlying medical disturbance, uncov-
ering the disease process is a priority. A comprehensive physical examination and
routine laboratory tests (complete blood count with differential, comprehensive
metabolic panel, urinalysis, urine toxicology, serum creatinine kinase if indicated)
should be undertaken. If the results show no obvious cause, neuroimaging and
electroencephalogram (EEG) should be conducted. Lumbar puncture may be indi-
cated if a neurologic process such as meningitis is suspected. Some authors
consider lumbar puncture to be mandatory when the cause of delirium is not
obvious,26 as meningitis in the elderly may present only with delirium and without
classic features. EEG can be helpful in ruling out seizures (EEG is the only definitive
method of diagnosing nonconvulsive status epilepticus) and finding the presence of
metabolic encephalopathy. EEG can also help differentiate delirium tremens from
other causes of encephalopathy. Metabolic encephalopathies will show diffuse
background slowing. Triphasic waves, classically associated with hepatic enceph-
alopathy, may be seen. In contrast, delirium tremens will show fast EEG activity
(Box 2).

Management
One aspect of the management of delirium directly springs from evaluation, and that
is to correct the underlying medical etiology of delirium. This correction should

Box 2
Common medical workup of delirium

 Comprehensive physical examination

 Complete blood count with differential
 Comprehensive metabolic panel
 Urinalysis
 Urine toxicology
 Serum creatinine kinase
 Neuroimaging
 EEG
 Lumbar puncture
 Considerations in Geriatric Population 455

accompany general medical supportive measures, such as ensuring the patient

remains hydrated, minimizing prolonged inactivity and immobilization, reducing
distracting stimuli in the environment, frequent reorientation, bedside sitters,
and addressing any comorbid pain. Physical restraints should be avoided, as they
may worsen delirium29 and should be used only when necessary as a last resort.
Severe agitation is often the most problematic behavioral manifestation of delirium
and usually the reason for psychiatric involvement as well. Evidence of efficacy is
limited, but among the available psychopharmacologic options, antipsychotic agents
are the medications of choice in addressing agitation in the context of delirium.20 Halo-
peridol has traditionally been used as the pharmacologic agent of choice. In recent
years, psychiatrists have relied more on atypical antipsychotic agents, which seem
to have similar efficacy to haloperidol in the management of agitation in delirium.
Lower doses of haloperidol (0.5 mg to 5 mg/d) are recommended, and it may be
used via oral or intramuscular routes. Intravenous administration remains commonly
used in intensive care unit settings. Although the intravenous route is not approved
by the US Food and Drug Administration (FDA), it can be a reasonable alternative if
the patient has electrocardiographic monitoring for QT prolongation and torsade, as
patients in an intensive care unit setting typically have.
General adult literature suggests that around 75% of delirious patients receiving
short-term treatment with low-dose antipsychotics experience clinical response,
with response rates consistent across different settings.30 However, robust and
generalizable evidence regarding the use of antipsychotics in delirium is sorely
lacking, even for haloperidol, the use of which is backed by decades of clinical
experience.31
With regard to controlled studies in the elderly population, studies have severe
methodologic limitations, and evidence of efficacy is further limited. Studies either
do not find an improvement in delirium or there is no impact on clinical outcomes
such as hospital length of stay or mortality. This has led some authors to state that
pharmacologic approaches to treatment of delirium are not currently recommen-
ded.21,32 Nonetheless, in cases of severe agitation, which either disrupts essential
medical therapy or poses a danger for the safety of patients, or involves severe, dis-
tressing psychotic symptoms, pharmacologic treatment with antipsychotics is often a
necessary clinical strategy.
Valproic acid may be a viable treatment of hyperactive or mixed delirium but re-
quires further investigation.33 Benzodiazepines can worsen confusion and have a
limited role in the treatment of delirium; unfortunately, they still are commonly pre-
scribed by many clinicians.34 Benzodiazepines remain preferred agents in delirium
treatment, and may be required in emergency situations where antipsychotics are
contraindicated and acute sedative effect is needed.
Many geriatric hospitalized individuals have evidence of thiamine deficiency, and
history of alcoholism is often missed in the elderly. As thiamine supplementation is
cheap and virtually without side effects, some authors recommend it as a consider-
ation in all cases of delirium.20
Patients with delirium typically lack decision-making capacity, and it is essential to
defer medical decision to next of kin/medical power of attorney/guardian in such sit-
uations. Nonetheless, the mere presence of delirium should not preclude a capacity
evaluation, as patients may have enough intact cognition to make some decisions.

Adverse Outcomes
Delirium is associated with an increased risk of subsequent mortality. A meta-analysis
looking at studies with follow-up ranging from 3 to 48 months found that the risk of
456 Aftab & Shah

death was elevated with a hazard ratio of 1.95.35 The mortality rate may be as high as
14% and 22% at 1 and 6 months, respectively.36
Delirium frequently leads to persistent cognitive dysfunction and increase in
the risk of subsequent dementia. In a meta-analysis, delirium was associated
with an increased rate of incident dementia over 3 to 5 years of follow-up with
an odds ratio of 12.52.35 In patients with pre-existing dementia, delirium increases
the rate of future cognitive decline. For instance, in a study of patients with Alz-
heimer disease, after an episode of delirium, subsequent cognitive deterioration
was at twice the rate, and this higher rate was noted even after 5 years from the
delirium.37

AGITATION AND NEUROPSYCHIATRIC SYMPTOMS IN DEMENTIA

Neuropsychiatric symptoms (NPS) are frequently reported and observed in

patients with neurocognitive disorders. These disorders include psychotic symp-
toms (delusions, hallucinations), agitation and aggression, depression, anxiety,
apathy, disinhibition, and wandering. Prevalence of these symptoms reported in
literature ranges from 60% to 90%, and generally greater prevalence is seen
with greater severity of dementia.38,39 Agitation and aggression in Alzheimer dis-
ease are reported to be prevalent with respective ranges of 20% to 80% and
11% to 46%.40
Psychotic symptoms have been reported with broad ranges in the literature, around
10% to 70% for delusions and 4% to 75% for hallucinations in Alzheimer disease.41,42
Dementia patients tend to be preoccupied with certain delusional themes, with delu-
sions of theft being the most common. Other delusions include phantom boarder syn-
drome, misidentification syndromes (such as Capgras delusion), persecutory
delusions, and delusions of infidelity. Psychotic symptoms increase with progression
of dementia; although they seem to plateau after 3 years,43 they are often persistent
and associated with poor prognosis.42

Nonpharmacologic Management
Authors and guidelines universally recommend nonpharmacologic interventions for
agitation in major neurocognitive disorder as the first-line measure before pharmaco-
logic interventions. Randomized, controlled trials (RCTs) are limited currently, but
research is accumulating over time. Person-centered care, communication skills
training, and adapted dementia care mapping were behavioral interventions shown
to reduce agitation immediately and in the long term (up to 6 months) in a systematic
review of RCTs.44 Group activities and music therapy decreased agitation immediately
but had no long-term effect. Aroma therapy and light therapy were ineffective in
controlled trials.
It is also crucial to assess and exclude sources of distress, for instance pain, hunger,
thirst, and constipation. Educating the caregivers is also important. A behavioral plan
that identifies the environmental triggers and calming influences for the patient is vital.
Other helpful measures include redirecting the patient, adjusting the routine to the pa-
tient’s schedule, regular toileting, and avoiding stimulants such as coffee in the
evening.45

Approved Pharmacologic Agents and Off-Label Prescribing

No pharmacologic agent has approval from the FDA for the treatment of NPS in de-
mentia in the United States; therefore, all treatment with medications is off label.
Although off-label prescribing increases risk of liability, this should not hinder judicious
 Considerations in Geriatric Population 457

use when risks and benefits have been carefully weighed and consent has been
obtained.

USE OF ANTIPSYCHOTIC DRUGS IN DEMENTIA

Efficacy
More than a dozen RCTs investigating typical antipsychotics (haloperidol, thiorida-
zine, thiothixene, chlorpromazine, trifluoperazine, acetophenazine, perphenazine)
show that their efficacy in the management of NPS is small at best.46 A Cochran re-
view found haloperidol to be effective for the treatment of aggression but not
agitation.47
RCTs of olanzapine and risperidone examined in 2 systematic reviews generally
show modest efficacy for treatment of NPS, with the trials mostly being conducted
in nursing home residents with moderate-to-severe dementia.46,48 A meta-analysis49
looking at aripiprazole, olanzapine, quetiapine, and risperidone found aripiprazole and
olanzapine to be efficacious with small effect sizes. Two CATIE-AD studies have been
conducted50,51 investigating olanzapine, quetiapine, and risperidone. In the first
CATIE-AD study, time to discontinuation owing to lack of efficacy favored olanzapine
and risperidone, but on other outcomes there was no difference from placebo.50 In the
second CATIE-AD study, olanzapine and risperidone again showed efficacy on
various neuropsychiatric rating scales compared with placebo, but quetiapine was
not significantly different from placebo.51

Risk of Mortality
In 2003, the FDA updated the prescribing information for risperidone with a warning for
increased cerebrovascular adverse events, including stroke, in elderly patients with
dementia.52 In 2005, the FDA issued a black box warning for the entire class of atypical
antipsychotics, with a reported 1.6- to 1.7-fold increase in mortality in placebo-
controlled trials performed with olanzapine, aripiprazole, risperidone, and quetia-
pine.52 Most of the causes of death were heart-related events (eg, heart failure, sud-
den death) or infections events (mostly pneumonia).24 In 2008, the black box warning
was also applied to typical antipsychotic drugs.52
The increased risk of mortality with the use of both typical and atypical antipsy-
chotics has consistently been reproduced in subsequent studies. A meta-analysis
of RCTs by Schneider and colleagues53 found that there was increased mortality in de-
mentia patients treated with atypical antipsychotics with an odds ratio of 1.54 (95%
confidence interval, 1.06–2.23). The mortality risk increases with the duration of treat-
ment and has been studied up to 36 months.54
Typical antipsychotics seem to have a significantly higher adjusted risk of death
compared with atypical antipsychotics with relative risk of 1.37 (95% confidence
interval, 1.27–1.49).55 Studies56–58 reported a higher risk of mortality with haloperidol
(hazard ratio, w1.5) and a lower risk of mortality with quetiapine (hazard ratio, w0.8)
compared with risperidone. Aripiprazole and olanzapine seem to have similar risk.
Higher doses of antipsychotics are associated with a higher mortality risk. A study
published in 2015 indicated that the mortality risk may be even higher than what
had been reported in the prior studies.59

Risk of Cerebrovascular Events and Stroke

Studies also indicate that antipsychotics carry an increased risk of cerebrovascular
events such as stroke. One study reported that odds of stroke were 1.8 times higher
when exposed to antipsychotics than when unexposed.60 In a systematic review of
458 Aftab & Shah

RCTs and observational studies, a 2- to 3-fold increased risk of all cerebrovascular

events was reported with atypical antipsychotics compared with placebo, but no as-
sociation with serious stroke that required hospitalization was discovered.61 These
studies, however, have methodologic limitations, and some studies have reported
no associations.62

American Psychiatric Association Guidelines

The American Psychiatric Association (APA) has recently issued practice guidelines
on the use of antipsychotics in the treatment of agitation or psychosis in patients
with dementia.63 The guidelines mostly reflect existing recommendations such as us-
ing nonpharmacologic interventions before nonemergency use of antipsychotics,
assessing for modifiable contributing factors such as pain, using the lowest effective
dose, and attempting to taper after stabilization of symptoms. Some points, however,
stand out. The APA recommends that response to treatment be determined with a
quantitative measure in patients with dementia with agitation or psychosis, some-
thing that is not commonly used currently in clinical settings. The APA also recom-
mends that in the absence of delirium and in nonemergency situations, haloperidol
should not be used as a first-line agent. The APA also recommends against using a
long-acting injectable antipsychotic medication (unless it is indicated for a comorbid
chronic psychotic disorder). Readers are referred to the guidelines for additional
information.

Other Pharmacologic Agents

Evidence regarding the use of cholinesterase inhibitors for treatments of NPS is
limited. A systematic review reported that only 3 of 14 studies had statistically signif-
icant but modest differentiation from placebo.64 The authors, however, recommended
that given the absence of alternative safe and effective options, the use of cholines-
terase inhibitors is an appropriate pharmacologic strategy. A systematic review and
meta-analysis by Wang and colleagues65 showed no efficacy of memantine for treat-
ment of NPS in Alzheimer disease.
Anticonvulsants have no proven efficacy in NPS of dementia. A Cochrane review
looking at the use of valproate for agitation in dementia concluded that it is
ineffective for treatment of agitation in dementia and that it is associated with
unacceptable rates of adverse effects.66 There is some small and limited evidence
for use of carbamazepine.67 Other newer anticonvulsants require further investigation.
There are limited and mixed results regarding efficacy of antidepressants. In a
Cochrane review, 2 small studies found some benefit with citalopram and sertraline
in treatment of NPS compared with placebo, whereas multiple other studies with an-
tidepressants found none.68 In a 12-week RCT in nondepressed patients with demen-
tia comparing citalopram and risperidone, no statistical difference was found in the
efficacy of citalopram and risperidone for the treatment of either agitation or psychotic
symptoms.69 Use of citalopram should be cautious because of concerns for QTc pro-
longation and arrhythmias at higher doses over 40 mg. The maximum recommended
dose in the geriatric population is 20 mg/d.
Benzodiazepines are associated with cognitive decline and contribute to increased
falls and hip fractures, and should be avoided.41 Multiple studies found negative ef-
fects of benzodiazepines of cognitive function in dementia, and despite recommenda-
tions against their use, the use of benzodiazepines in dementia remains prevalent.70
Studies on the use of benzodiazepines for NPS show inconsistent results and gener-
ally suggest a positive effect in less than half of agitated patients in the short term70
(Table 2).
 Considerations in Geriatric Population 459

Table 2
Pharmacologic treatment of agitation and neuropsychiatric symptoms in dementia

Treatment Efficacy
Typical antipsychotics Modest efficacy at best; possibly higher risk of mortality compared
with atypical antipsychotics
Atypical antipsychotics Modest efficacy at best; risperidone, olanzapine and aripiprazole
have some support from evidence; quetiapine seems to have
minimal efficacy; increased risk of mortality
Valproic acid No demonstrable efficacy
Carbamazepine Very limited evidence of efficacy
Cholinesterase inhibitors Minimal efficacy at best
Memantine No proven efficacy
Antidepressants Limited evidence of benefit with citalopram and sertraline
Benzodiazepines Possible short-term benefit; not recommended because of
demonstrated negative effects on cognition

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