REVIEW

LEARNING OBJECTIVE: Readers will prescribe antipsychotic drugs judiciously to manage delirium
in hospitalized patients
ROBYN PAULINE THOM, MD CLARE KELLEHER MOCK, MD POLINA TESLYAR, MD
Brigham and Women’s Hospital, Division of Hospital Medicine, Consult-Liaison Psychiatry,
Beth Israel Deaconess Medical Center; University of North Carolina Hospital; Beth Israel Deaconess Medical Center;
Harvard Longwood Psychiatry Resident, Assistant Professor, University of North Carolina Instructor, Harvard Medical School,
Harvard Medical School, Boston, MA School of Medicine, Chapel Hill Boston, MA

Delirium in hospitalized patients:

Risks and benefits of antipsychotics
ABSTRACT
Consensus panel guidelines advocate for the judicious
D elirium is common in hospitalized pa-
tients and contributes to healthcare costs
and poor patient outcomes, including death.
use of antipsychotic drugs to manage delirium in hospi- Its diagnosis and management remain clini-
talized patients when nonpharmacologic measures fail cally challenging. Although consensus panel
and the patient is in significant distress from symptoms, guidelines recommend antipsychotic medi-
poses a safety risk to self or others, or is impeding es- cations to treat delirium when conservative
sential aspects of his or her medical care. Here, we review measures fail, few head-to-head trials have
the use of haloperidol, olanzapine, quetiapine, risperi- been done to tell us which antipsychotic drug
done, and aripiprazole for this purpose. to select, and antipsychotic use poses risks in
the elderly.
KEY POINTS Here, we review the risks and benefits of
using antipsychotic drugs to manage delirium
Delirium is common in hospitalized patients and often and describe an approach to selecting and us-
leads to loss of independence and nursing-home place- ing 5 commonly used antipsychotics.
ment.
■ SCOPE OF THE PROBLEM
The first-line treatment is to identify and address pre- Delirium is common and serious, affecting
disposing factors, provide supportive care, and manage 11% to 42% of patients hospitalized on gen-
symptoms through behavioral strategies. eral medical wards.1 The burden to the pub-
lic and individual patient is extremely high.
Most antipsychotic medications can prolong the QT Delirium has been found to result in an ad-
interval and thus pose a risk for torsades de pointes. The ditional $16,303 to $64,421 per delirious pa-
effect is greatest with intravenous haloperidol and least tient per year, with a subsequent total 1-year
with aripiprazole. health-attributable cost between $38 billion
and $152 billion in the United States.2 Fur-
thermore, many patients who become deliri-
Lacking head-to-head trials of antipsychotics, we suggest ous in the hospital lose their independence
selecting the drug based on its pharmacologic properties and are placed in long-term care facilities.3
and the patient’s clinical context. Although delirium was originally thought
to be a time-limited neurocognitive disorder,
recent evidence shows that it persists much
longer4 and that some patients never return to
their previous level of function, suggesting that
a single episode of delirium can significantly
alter the course of an underlying dementia
with the dramatic initiation of cognitive de-
cline.3 Most alarmingly, delirium is associated
doi:10.3949/ccjm.84a.16077 with an increased rate of death.1
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 THOM AND COLLEAGUES

■ DSM-5 DEFINITION National Institute for Health and Care Ex-

According to the Diagnostic and Statistical Man- cellence,8 advocate for psychopharmacologic
ual of Mental Disorders, 5th edition (DSM-5),5 management of delirium symptoms in the fol-
delirium is a neurocognitive disorder character- lowing situations:
ized by the acute onset of disturbance in atten- • The patient is in significant distress from
tion, awareness, and cognition that fluctuates his or her symptoms
in severity throughout the day and is the direct • The patient poses a safety risk to self or
physiologic consequence of another medical others
condition. The cognitive impairment seen in • The patient is impeding essential aspects
delirium is typically global and can affect mem- of his or her medical care.
ory, orientation, language, visuospatial ability, Guidelines from these organizations rec-
and perception. Other prominent features in- ommend antipsychotic medications as the
clude psychomotor disturbance, sleep-cycle de- first-line drugs for managing delirium symp-
rangement, and emotional lability. toms not caused by substance withdrawal.
The pathogenesis of delirium is not clearly Nevertheless, the use of antipsychotics in the
delineated but may relate to cholinergic defi- management of delirium remains controver-
ciency and dopaminergic excess. sial. While a number of studies suggest these
drugs are beneficial,9–11 others do not.12 These
■ THE FIRST STEPS: consensus panels advocate for the judicious use
NONPHARMACOLOGIC MANAGEMENT of antipsychotics, limited to the specific situa-
tions outlined above.
Inouye3 outlined a general 3-part approach to
The use of antipsychotics in elderly and
managing delirium:
medically complex patients poses risks. One of
Identify and address predisposing factors.
the most significant safety concerns is increased
All patients found to have an acute change in
risk of death due to adverse cardiac events
mental status should be evaluated for the un-
caused by prolongation of the QT interval.
derlying cause, with special attention to the
most common causes, ie, infection, metabolic Antipsychotics, QT prolongation, The FDA
derangement, and substance intoxication and and torsades de pointes
withdrawal. A thorough medication reconcilia- Most antipsychotics have the potential to
recommends
tion should also be done to identify medications prolong the time of ventricular depolariza- cardiac
with psychoactive or anticholinergic effects. tion and repolarization and the QT interval
Provide supportive care, eg, addressing
monitoring
to some extent, which can lead to torsades de
volume and nutritional status, mobilizing the pointes.13 Other risk factors for prolonged QT for all patients
patient early, and giving prophylaxis against interval and torsades de pointes include: receiving
deep venous thrombosis. • Long QT syndrome (a genetic arrhythmia)
Manage symptoms. Behavioral strategies • Female sex
intravenous
should be instituted in every delirious patient • Old age haloperidol
and should include frequent reorientation, • Electrolyte abnormalities (hypokalemia,
use of observers, encouragement of family in- hypocalcemia, hypomagnesemia)
volvement, avoidance of physical restraints • Preexisting heart conditions such as brady-
and Foley catheters, use of vision and hearing cardia, left ventricular dysfunction, heart
aids, and normalizing the sleep-wake cycle. failure, mitral valve prolapse, and previous
myocardial infarction
■ ANTIPSYCHOTICS: • Medical conditions that cause electrolyte
ARE THEY SAFE AND EFFECTIVE? derangements
The US Food and Drug Administration • Medications, including antiarrhythmics,
(FDA) has not approved any medications antibiotics (macrolides, quinolones), anti-
for delirium. However, multiple consensus fungals, antimalarials, antiemetics, some opi-
statements, including those by the American oids (methadone), and most antipsychotics.
Psychiatric Association,6 the Canadian Coali- Haloperidol. Postmarketing analysis in
tion for Seniors’ Mental Health,7 and the UK 2007 found 73 cases of haloperidol-related
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 DELIRIUM IN HOSPITAL PATIENTS

torsades de pointes. However, many of these atypical antipsychotics for a limited time in a
were confounded by other QT-prolonging closely monitored inpatient setting.
medications and medical conditions.14
The QT-prolonging effect of haloperidol Effectiveness of antipsychotics
administered orally or intramuscularly is ac- While several studies since the FDA black-
tually quite small. The equivalent oral dose box warning have shown that antipsychotics
of 15 mg of haloperidol (assuming 50% bio- are safe, the efficacy of these drugs in delirium
availability) given orally or intramuscularly management remains controversial.
increases the corrected QT interval (QTc) In a 2016 meta-analysis, Kishi et al18 found
by only 7 to 8 milliseconds. But intravenous that antipsychotics were superior to placebo
haloperidol can cause much more significant in terms of response rate (defined as improve-
QT prolongation: 8 of the 11 reported cases of ment of delirium severity rating scores), with
fatal torsades de pointes occurred when halo- a number needed to treat of 2.
peridol was given intravenously.14 Therefore, In contrast, a meta-analysis by Neufeld et
the FDA recommends cardiac monitoring for al12 found that antipsychotic use was not as-
all patients receiving intravenous haloperidol. sociated with a change in delirium duration,
Oral olanzapine, risperidone, and que- severity, or length of stay in the hospital or
tiapine prolong the QT interval approximate- intensive care unit. However, the studies in
ly as much as oral haloperidol. this meta-analysis varied widely in age range,
Aripiprazole has not been associated with study design, drug comparison, and treatment
significant QT prolongation.13 strategy (with drugs given as both prophylaxis
and treatment). Thus, the results are difficult
Atypical antipsychotics and stroke to interpret.
The FDA has issued multiple warnings for pre- Kishi et al18 found no difference in the in-
scribing antipsychotic medications in the elderly. cidence of death, extrapyramidal symptoms,
In 2003, it warned prescribers of increased cere- akathisia, or QT prolongation between patients
brovascular adverse events, including stroke, in treated with antipsychotic drugs vs placebo.
elderly patients with dementia who were treated In a prospective observational study, Hatta
Quetiapine with an atypical antipsychotic (risperidone, et al19 followed 2,453 inpatients who became
is the agent olanzapine, or aripiprazole) vs placebo.15 delirious. Only 22 (0.9%) experienced ad-
of choice verse events attributable to antipsychotic use,
Atypical antipsychotics and risk of death
the most common being aspiration pneumo-
in patients In 2005, the FDA issued a black-box warning
nia (0.7%), followed by cardiovascular events
about increased all-cause mortality risk in pa-
with Parkinson tients with dementia treated with atypical an-
(0.2%). Notably, no patient died of antipsy-
disease tipsychotics for behavioral disturbance (rela- chotic-related events. In this study, the anti-
tive risk 1.6–1.7).16 psychotic was stopped as soon as the delirium
This warning was likely based on a meta- symptoms resolved, in most cases in 3 to 7
analysis by Schneider et al17 of trials in which days.
patients with dementia were randomized to Taken together, these studies indicate that
receive either an atypical antipsychotic or despite the risk of QT prolongation with anti-
placebo. The death rate was 3.5% in patients psychotic use and increased rates of morbidity
treated with an atypical antipsychotic vs 2.3% with antipsychotic use in dementia, time-lim-
in patients treated with placebo, indicating ited management of delirium with antipsy-
a number needed to harm of 100. The most chotics is effective9–11 and safe.
common causes of death were cardiovascular
disease and pneumonia. However, the trials ■ SELECTING AND USING ANTIPSYCHOTICS
in this meta-analysis included only patients TO TREAT DELIRIUM
who were prescribed atypical antipsychotics Identifying a single preferred agent is difficult,
for ongoing management of behavioral dis- since we lack enough evidence from random-
turbances due to dementia in either the out- ized controlled trials that directly compared
patient or nursing home setting. None of the the various antipsychotics used in delirium
trials looked at patients who were prescribed management.
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 THOM AND COLLEAGUES

TABLE 1
Antipsychotic agents
Agent Haloperidol Olanzapine Quetiapine Risperidone Aripiprazole
Dosage forms Oral tablets, Oral tablets, Oral tablets, Oral tablets, Oral tablets,
solution disintegrating solution disintegrating solution,
tablets tablets, solution distintegrating
Intramuscular tablets
and intravenous Intramuscular
solutions solution Intramuscular
solution
Starting dose 0.5–1 mg twice a day 2.5–5 mg twice a day 12.5–25 mg twice a day 0.5 mg twice a day 1 mg twice a day
Half-life (hours) 12–38 21–54 6 20 75
Clearance Hepatic Hepatic Hepatic Hepatic Hepatic
Common Akathisia Akathisia Agitation Parkinsonism Akathisia
adverse effects Dystonia Parkinsonism Agitation
Parkinsonism
Effects on Oral, intramuscular: Mild Mild Mild None
corrected Mild
QT interval
Intravenous:
Moderate
Orthostatic Mild Moderate Severe Severe Moderate
hypotension
Anticholinergic Mild Severe Moderate Mild Mild
effects a
Sedation Mild Moderate Severe Moderate Moderate
Drug-drug Substrate of: Substrate of: Substrate of: Substrate of: Substrate of:
interactions CYP1A2 (minor) CYP1A2 (major) CYP2D6 (minor) CYP2D6 (major) CYP2D6 (major)
(CYP450 CYP2D6 (major) CYP2D6 (minor) CYP3A4 (major) CYP3A4 (minor) CYP3A4 (major)
activity) CYP3A4 (major) 
Inhibits CYP2D6
(moderate)
Special Minimal effect Comes in Consider in Comes in May be useful
considerations on vital signs dissolvable form Parkinson disease dissolvable form for hypoactive
delirium
May worsen Helpful for cancer-
stiffness and motor related nausea No known effect
symptoms in on QTc
Do not combine
Parkinson disease
with parenteral
benzodiazepines
due to risk of
respiratory depression
May worsen control
of diabetes
a
Dry mouth, constipation, urinary retention.
Based on information from references 23–25.

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 DELIRIUM IN HOSPITAL PATIENTS

Both typical and atypical antipsychotics prospective study showed that low doses of
are used in clinical practice to manage de- haloperidol (< 3.5 mg/day) did not result in
lirium. The typical antipsychotic most often a greater frequency of extrapyramidal symp-
used is haloperidol, while the most commonly toms.22 Nevertheless, if a patient has a his-
used atypical antipsychotics for delirium in- tory of extrapyramidal symptoms, haloperidol
clude olanzapine, quetiapine, risperidone, and should likely be avoided in favor of an atypical
(more recently) aripiprazole. antipsychotic.
The American Psychiatric Association
guidelines6 suggest using haloperidol because Atypical antipsychotics
it is the antipsychotic that has been most Olanzapine, quetiapine, and risperidone are
studied for delirium,20 and we have decades of atypical antipsychotics that, like haloperi-
experience with its use. Despite this, recent dol, antagonize the dopamine D2 receptor,
prospective studies have suggested that the but also have antagonist action at serotonin,
atypical antipsychotics may be better because histamine, and alpha-2 receptors. This multi-
they have a faster onset of action and lower receptor antagonism reduces the risk of extra-
incidence of extrapyramidal symptoms.18,21 pyramidal symptoms but increases the risk of
Because we lack enough head-to-head tri- orthostatic hypotension.
als comparing the efficacy of the 5 most com- Quetiapine, in particular, imposes an unac-
monly used antipsychotics for the manage- ceptably high risk of orthostatic hypotension
ment of delirium, and because the prospective and so is not recommended for use in delirium
trials that do exist show equal efficacy across in the emergency department.27 Additionally,
the antipsychotics studied,22 we suggest con- quetiapine is anticholinergic, raising concerns
sidering the unique pharmacologic properties about constipation and urinary retention.
of each drug within the patient’s clinical con- Although the association between fall
text when selecting which antipsychotic to risk and antipsychotic use remains contro-
use. versial,28,29 a study found that olanzapine con-
Table 123–25 summarizes some key charac- ferred a lower fall risk than quetiapine and
Upon discharge, teristics of the 5 most commonly used antipsy- risperidone.30
chotics. Of these drugs, only olanzapine is avail-
reconcile the able in an intramuscular dosage form. Both
medications Haloperidol risperidone and olanzapine are available in
and discontinue Haloperidol, a typical antipsychotic, is a po- dissolvable tablets; however, they are not sub-
tent antagonist of the dopamine D2 receptor. lingually absorbed.
antipsychotics Haloperidol has the advantage of having Randomized controlled trials have shown
once delirium the strongest evidence base for use in deliri- that olanzapine is effective in managing can-
um. In addition, it is available in oral, intra- cer-related nausea, and therefore it may be
has resolved venous, and intramuscular dosage forms, and useful in managing delirium in oncology pa-
it has minimal effects on vital signs, negligible tients.31,32
anticholinergic activity, and minimal interac- Patients with Parkinson disease are ex-
tions with other medications.21 quisitely sensitive to the antidopaminergic
Intravenous haloperidol poses a significant effects of antipsychotics but are also vulner-
risk of QT prolongation and so should be used able to delirium, so they present a unique
judiciously in patients with preexisting cardi- treatment challenge. The agent of choice in
ac conditions or other risk factors for QT pro- patients with Parkinson disease is quetiapine,
longation as outlined above, and with careful as multiple trials have shown it has no effect
cardiac monitoring. Parenteral haloperidol is on the motor symptoms of Parkinson disease
approximately twice as potent as oral halo- (reviewed by Desmarais et al in a systematic
peridol. meta-analysis33).
Some evidence suggests a higher risk of Aripiprazole is increasingly used to man-
acute dystonia and other extrapyramidal age delirium. Its mechanism of action differs
symptoms with haloperidol than with the from that of the other atypical antipsychotics,
atypical antipsychotics.21,26 In contrast, a 2013 as it is a partial dopamine agonist. It is avail-
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 THOM AND COLLEAGUES

able in oral, orally dissolvable, and intramus- of extrapyramidal symptoms, other comorbidi-
cular forms. It appears to be slightly less effec- ties such as Parkinson disease and cancer, and
tive than the other atypical antipsychotics,34 the desired route of administration.
but it may be useful for hypoactive delirium At the time the patient is discharged, we
as it is less sedating than the other agents.35 recommend a careful medication reconcilia-
Because its effect on the QT interval is neg- tion and discontinuation of the antipsychotic
ligible, it may also be favored in patients who drug once delirium has resolved. Studies
have a high baseline QTc or other predispos- show that at least 26% of antipsychotics ini-
ing factors for torsades de pointes. tiated in the hospital are continued after dis-
charge.36,37
■ BALANCING THE RISKS Current delirium consensus statements
Antipsychotic drugs have been shown to be recommend limiting the use of antipsychot-
effective and generally safe. Antipsychotics do ics to target patient distress, impediment of
prolong the QT interval. However, other than care, or safety, because of the putative risks
with intravenous administration of haloperi- of antipsychotic use in the elderly. However,
dol, the absolute effect is minimal. Although a growing body of evidence shows that low-
large meta-analyses have shown a higher rate dose, time-limited antipsychotic use is safe
of all-cause mortality in elderly outpatients and effective in the treatment of delirium. In
with dementia who are prescribed atypical an- fact, González et al found that delirium is an
tipsychotics, an increase in death rates has not independent risk factor for death, and each
been borne out by prospective studies focusing 48-hour increase in delirium is associated with
on hospitalized patients who receive low doses an increased mortality risk of 11%, suggesting
of antipsychotics for a limited time. that delay in treating delirium may actually
There are no head-to-head randomized increase the risk of death.38
controlled trials comparing the efficacy of all Therefore, we must balance the risks of
of the 5 most commonly used antipsychotics. prescribing antipsychotics in medically vul-
Therefore, we suggest considering the unique nerable patients against the increasing bur-
psychopharmacologic properties of each agent den of evidence supporting the serious risks of
within the patient’s clinical setting, specifical- morbidity and mortality of delirium, as well as
ly taking into account the risk of cardiac ar- the costs. Much remains to be studied to opti-
rhythmia, risk of orthostasis and falls, history mize antipsychotic use in delirium. ■
■ REFERENCES 8. National Institute for Health and Care Excellence (NICE). Delirium:
prevention, diagnosis and management. www.nice.org.uk/guidance/
1. Siddiqi N, House AO, Holmes JD. Occurrence and outcome of cg103. Accessed July 13, 2017.
delirium in medical in-patients: a systematic literature review. Age 9. Bourne RS, Tahir TA, Borthwick M, Sampson EL. Drug treatment of
Ageing 2006; 35:350–364. delirium: past, present and future. J Psychosom Res 2008; 65:273–
2. Leslie DL, Marcantonio ER, Zhang Y, Leo-Summers L, Inouye SK. 282.
One-year health care costs associated with delirium in the elderly 10. Campbell N, Boustani MA, Ayub A, et al. Pharmacological manage-
population. Arch Intern Med 2008; 168:27–32. ment of delirium in hospitalized adults—a systematic evidence
3. Inouye SK. Delirium in older persons. N Engl J Med 2006; 354:1157– review. J Gen Intern Med 2009; 24:848–853.
1165. 11. Devlin JW, Skrobik Y. Antipsychotics for the prevention and treat-
4. Levkoff SE, Evans DA, Liptzin B, et al. Delirium: the occurrence and ment of delirium in the intensive care unit: what is their role? Harv
persistence of symptoms among elderly hospitalized patients. Arch Rev Psychiatry 2011; 19:59–67.
Intern Med 1992; 152:334–340. 12. Neufeld KJ, Yue J, Robinson TN, Inouye SK, Needham DM. Anti-
5. American Psychiatric Association. Diagnostic and statistical manual psychotic medication for prevention and treatment of delirium in
of mental disorders. 5th ed. Arlington, VA: American Psychiatric hospitalized adults: a systematic review and meta-analysis. J Am
Publishing; 2013. Geriatr Soc 2016; 64:705–714.
6. Trzepacz P, Breitbart W, Franklin J, Levenson J, Martini DR, Wang P; 13. Beach SR, Celano MC, Noseworthy PA, Januzzi JL, Huffman JC. QTc
American Psychiatric Association (APA). Practice guideline for the prolongation, torsades de pointes, and psychotropic medications.
treatment of patients with delirium. http://psychiatryonline.org/pb/ Psychosomatics 2013; 54:1–13.
assets/raw/sitewide/practice_guidelines/guidelines/delirium.pdf. Ac- 14. US Food and Drug Administration (FDA). Information for healthcare
cessed July 13, 2017. professionals: haloperidol (marketed as Haldol, Haldol decanoate
7. Canadian Coalition for Seniors’ Mental Health. National guide- and Haldol lactate). www.fda.gov/Drugs/DrugSafety/ucm085203.
lines for seniors’ mental health: the assessment and treatment of htm. Accessed July 13, 2017.
delirium. http://ccsmh.ca/wp-content/uploads/2016/03/NatlGuide- 15. US Food and Drug Administration Center for Drug Evaluation and
line_Delirium.pdf. Accessed July 13, 2017. Research. Approval package for: Application Number: NDA 20-

CL E V E L AND CL I NI C J O URNAL O F M E DI CI NE V O L UM E 84 • NUM BE R 8 AUG US T 2 0 1 7 621

 DELIRIUM IN HOSPITAL PATIENTS

272/S-033, 20-588/S-021 & 21-444/S-004. www.accessdata.fda.gov/ open-label study of quetiapine for treatment of moderate psy-
drugsatfda_docs/nda/2003/020588_S021_RISPERDAL_TABLETS.pdf. chotic agitation in the emergency setting. J Psychiatr Pract 2006;
Accessed July 13, 2017. 12:223–228.
16. US Food and Drug Administration. Public health advisory: deaths 28. Chatterjee S, Chen H, Johnson ML, Aparasu RR. Risk of falls and
with antipsychotics in elderly patients with behavioral disturbances. fractures in older adults using atypical antipsychotic agents: a
www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformation- propensity score-adjusted, retrospective cohort study. Am J Geriatr
forpatientsandproviders/ucm053171. Accessed July 13, 2017. Pharmacother 2012; 10:84–94.
17. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical anti- 29. Rigler SK, Shireman TI, Cook-Wiens GJ, et al. Fracture risk in nursing
psychotic drug treatment for dementia: meta-analysis of random- home residents initiating antipsychotic medications. J Am Geriatr
ized placebo-controlled trials. JAMA 2005; 294:1934–1943. Soc 2013; 61: 715–722.
18. Kishi T, Hirota T, Matsunaga S, Iwata N. Antipsychotic medications 30. Bozat-Emre S, Doupe M, Kozyrskyj AL, Grymonpre R, Mahmud
for the treatment of delirium: a systematic review and meta-analysis SM. Atypical antipsychotic drug use and falls among nursing
of randomised controlled trials. J Neurol Neurosurg Psychiatry 2016; home residents in Winnipeg, Canada. Int J Geriatr Psychiatry 2015;
87:767–774. 30:842–850.
19. Hatta K, Kishi Y, Wada K, et al. Antipsychotics for delirium in the 31. Navari RM, Gray SE, Kerr AC. Olanzapine versus aprepitant for
general hospital setting in consecutive 2453 inpatients: a prospec- the prevention of chemotherapy-induced nausea and vomiting: a
tive observational study. Int J Geriatr Psychiatry 2014; 29;253–262. randomized phase III trial. J Support Oncol 2011; 9:188–195.
20. Breitbart W, Marotta R, Platt MM, et al. A double-blind trial of 32. Navari RM. Olanzapine for the prevention and treatment of chronic
haloperidol, chlorpromazine, and lorazepam in the treatment nausea and chemotherapy-induced nausea and vomiting. Eur J
of delirium in hospitalized AIDS patients. Am J Psychiatry 1996; Pharmacol 2014; 722:180–186.
153:231–237. 33. Desmarais P, Massoud F, Filion J, Nguyen QD, Bajsarowicz P. Que-
21. Wilson MP, Pepper D, Currier GW, Holloman GH Jr, Feifel D. The tiapine for psychosis in Parkinson disease and neurodegenerative
psychopharmacology of agitation: consensus statement of the Parkinsonian disorders: a systematic review. J Geriatr Psychiatry
American Association For Emergency Psychiatry Project Beta Psycho- Neurol 2016; 29:227–236.
pharmacology Workgroup. West J Emerg Med 2012; 13:26–34. 34. Citrome L. Comparison of intramuscular ziprasidone, olanzapine,
22. Yoon HJ, Park KM, Choi WJ, et al. Efficacy and safety of haloperi- or aripiprazole for agitation: a quantitative review of efficacy and
dol versus atypical antipsychotic medications in the treatment of safety. J Clin Psychiatry 2007; 68:1876–1885.
delirium. BMC Psychiatry 2013; 13:240. 35. Marder SR, McQuade RD, Stock E, et al. Aripiprazole in the
23. American Psychiatric Association. Manual of Clinical Psychopharma- treatment of schizophrenia: safety and tolerability in short-term,
cology. 8th ed. Arlington, VA: American Psychiatric Publishing; 2015. placebo-controlled trials. Schizophr Res 2003; 61:123–136.
24. Conley RR, Kelly DL. Pharmacologic Treatment of Schizophrenia. 3rd 36. Loh KP, Ramdass S, Garb JL, et al. Long-term outcomes of elders
ed. West Islip, NY: Professional Communications; 2007. discharged on antipsychotics. J Hosp Med 2016; 11:550–555.
25. American Psychiatric Association (APA). The American Psychiatric 37. Herzig SJ, Rothberg MB, Guess JR, et al. Antipsychotic use in hos-
Publishing Textbook of Psychosomatic Medicine. Psychiatric Care pitalized adults: rates, indications, and predictors. J Am Geriatr Soc
of the Medically Ill, 2nd ed. Arlington, VA: American Psychiatric 2016; 64:299–305.
Publishing; 2011. 38. González M, Martínez G, Calderón J, et al. Impact of delirium on
26. Boettger S, Jenewein J, Breitbart W. Haloperidol, risperidone, short-term mortality in elderly inpatients: a prospective cohort
olanzapine and aripiprazole in the management of delirium: a study. Psychosomatics 2009; 50:234–238.
comparison of efficacy, safety, and side effects. Palliat Support Care
2015; 13:1079–1085. ADDRESS: Robyn Pauline Thom, MD, Beth Israel Deaconess Medical Cen-
27. Currier GW, Trenton AJ, Walsh PG, van Wijngaarden E. A pilot, ter, 330 Brookline Ave, Boston MA 02215; [email protected]

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