Dr. Purvis is a psychiatric pharmacy
resident and Dr. Hieber is a clinical
pharmacist at Western Missouri Mental
Health Center in Kansas City.
Fifty years ago, the terms "everyman's
psychosis" and "reversible
madness" referred to a mental
disorder to which everyone is susceptible—
delirium, an acute confused state
often overlooked by physicians.1
Up to 40% of hospitalized elderly patients
experience delirium, one of the
most preventable hospital-acquired
adverse events.2,3 Failure to uncover the
underlying etiology of delirium results
in extended stays, increased costs, and
increased morbidity and mortality.4,5
Delirium commences abruptly and encompasses
a broad range of disturbances.
These range from hyperactive to
hypoactive states, with fluctuations in
level of consciousness, attention, cognition
(memory impairment, disorientation,
language disturbance), and perception
Symptoms, including sleep pattern disturbance
and psychomotor behavior,
vary throughout the day and generally
resolve within 10 to 12 days.4,6
The primary goal in management is to
identify the underlying etiology and initiate
immediate interventions to ensure
patient safety. In elderly patients, delirium
is commonly a result of acute illness
or medication, the latter being the
most common reversible cause.7 Half
of all cases are missed by physicians;
thus, pharmacists play a major role
by recommending alternative treatment
strategies and minimizing the use of
high-risk medications (eg, anticholinergics,
analgesics).8 See Table 11,9,10 for
potential causes and treatment suggestions.
Table 2 provides tips the pharmacist
can implement to help prevent or
Delirium Causes and Treatment Recommendations
Treat underlying illness
Optimize environmental cues for day/night, nonpharmacotherapy options for insomnia
Provide familiar objects, moderate amount of stimuli, educate staff
Treat underlying illness(es)
Discontinue medication(s) or lower dose; recommend alternative with less deliriogenic risk
Discontinue medication(s) or lower dose; recommend alternative with less deliriogenic risk
Adapted from references 1,9,10.
Studies examining pharmacologic
prevention investigated low-dose antipsychotic
and an acetylcholinesterase
inhibitor (ACI), donepezil.11-13 No trial
was overwhelmingly significant; therefore,
using medication to prevent delirium
is not currently recommended.4
Acute agitation with delirium may
necessitate short-term pharmacologic
treatment; however, if the cause of
delirium is addressed, further intervention
may not be necessary. Standard
practice involves use of first-generation
antipsychotics (primarily haloperidol).4,14-19 Using lower doses of haloperidol,
between 0.5 and 4.5 mg/day,
keeps extrapyramidal side effects to
a minimum. The evidence for use of
second-generation antipsychotics (eg,
risperidone, olanzapine, quetiapine, ziprasidone)
A recent analysis of haloperidol versus
risperidone, olanzapine, and quetiapine
determined that all agents have
similar efficacy in treatment of agitation
in delirium.33 Second-generation anti-psychotics, especially olanzapine and quetiapine, are sedating,
which may be beneficial in some situations. Choosing an
agent should involve evaluating side effect profiles of each
Current controversy exists regarding evidence that mortality
is increased in elderly patients receiving antipsychotics.34-39
Clinical significance of these findings is under debate.
Recognize and prevent polypharmacy
Identify potential medication causes
If applicable, recommend alternative therapy
Obtain blood levels when appropriate (eg, lithium, phenytoin)
Adjust dosages in renal or hepatic impairment
Actively participate in medication reconciliation
Recognize potential substance withdrawal
Other medications evaluated in delirium treatment include
ACIs, benzodiazepines, and melatonin. Theoretically, ACIs
reverse anticholinergic-induced delirium, although the evidence
is limited to case reports.40 Benzodiazepines are to be
avoided, except in cases of alcohol withdrawal. A study using
alprazolam as treatment for delirium was terminated early
due to worsening of delirium.14 A case report uses melatonin
to treat delirium, although evidence supporting melatonin's
role in delirium is limited.41
- Beers M, ed. The Merck Manual of Diagnosis and Therapy. 18th ed. Rahway, NJ: Merck Publishing; 2006:1808-1811.
- Lipowski ZT. Delirium (acute confusional states). JAMA. 1987;258(13):1789-1792.
- Inouye SK, Bogardus ST Jr, Charpentier PA, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 1999;340(9):669-676.
- Trzepacz P, Breitbart W, Franklin J, et al. Practice guideline for the treatment of patients with delirium. American Psychiatric Association. Am J Psychiatry. 1999;156(5 Suppl):5-15.
- Inouye SK. Delirium in older persons. N Engl J Med. 2006;354(11):1157-1165.
- Sirois F. Delirium: 100 cases. Can J Psychiatry. 1988; 33(5):375-378.
- Demeure MJ, Fain MJ. The elderly surgical patient and postoperative delirium. J Am Coll Surg. 2006;203(5):752-757.
- Francis J. Delirium in older patients. J Am Geriatr Soc. 1992;40(8):829-838.
- Alagiakrishnan K, Wiens CA. An approach to drug induced delirium in the elderly. Postgrad Med J. 2004;80(945):388-393.
- Fick DM, Cooper JW, Wade WE, Waller JL, Maclean JR, Beers MH. Updating the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults: results of a U.S. Consensus Panel of Experts. Arch Intern Med. 2003;163(22):2716-2724.
- Kalisvaart KJ, de Jonghe JF, Bogaards MJ, et al. Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. J Am Geriatr Soc. 2005;53(10):1658-1666.
- Leung JM, Sands LP, Rico M, et al. Pilot clinical trial of gabapentin to decrease postoperative delirium in older patients. Neurology. 2006;67(7):1251-1253.
- Sampson E, Raven PR, Ndhlovu PN, et al. A randomized, double-blind, placebo-controlled trial of donepezil hydrochloride (Aricept) for reducing the incidence of postoperative delirium after elective total hip replacement. Int J Geriatr Psychiatry. 2007;22(4):343-349.
- Breitbart W, Marotta RD, Platt MM, et al. A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients. Am J Psychiatry. 1996;153(2):231-237.
- Smith GR, Taylor CW, Linkous P. Haloperidol versus thioridazine for the treatment of psychogeriatric patients: A double-blind clinical trial. Psychosomatics. 1974;15:134-138.
- Gelfand SB, Indelicato J, Benjamin J. Using intravenous haloperidol to control delirium. Hosp Community Psychiatry. 1992;43(3):215.
- Frye MA, Coudreaut MF, Hakeman SM, et al. Continous droperidol infusion for management of agitated delirium in an intensive care unit. Psychosomatics. 1995;36(3):301-305.
- Riker RR, Fraser GL, Cox PM. Continuous infusion of haloperidol controls agitation in critically ill patients. Crit Care Med. 1994;22(3):433-440.
- Levenson JL. High-dose intravenous haloperidol for agitated delirium following lung transplantation. Psychosomatics. 1995;36(1):66-68.
- Schwartz TL, Masand PS. The role of atypical antipsychotics in the treatment of delirium. Psychosomatics. 2002;43(3):171-174.
- Horikawa N, Yamazaki T, Miyamoto K, et al. Treatment for delirium with risperidone: results of a prospective open trial with 10 patients. Gen Hosp Psychiatry. 2003;25(4):289-292.
- Ravona-Springer Ramit, Dolberg OT, Hirschmann S, Grunhaus L. Delirium in elderly patients treated with risperidone: A report of three cases. J Clin Psychopharmacol. 1998;18(2):171-172.
- Sipahimalani A, Masand PS. Use of risperidone in delirium: case reports. Ann Clin Psychiatry. 1997;9(2):105-107.
- Sasaki Y, Matsuyama T. A prospective, open-label, flexible-dose study of quetiapine in the treatment of delirium. J Clin Psychiatry. 2003;64(11):1316-1321.
- Torres R, Mittal D, Kennedy R. Use of quetiapine in delirium. Psychosomatics. 2001;42:347-349.
- Al-Samarrai S, Dunn J, Newmark T, Gupta S. Quetiapine for treatment-resistant delirium. Psychosomatics. 2003;44(4):350-351.
- Schwartz TL, Masand PS. Treatment of delirium with quetiapine. Prim Care Companion J Clin Psychiatry. 2000;2(1):10-12.
- Kim KY, Bader GM, Kotlyar V, Gropper D. Treatment of delirium in older adults with quetiapine. J Geriatr Psychiatry Neurol. 2003;16(1):29-31.
- Passik SD, Cooper M. Complicated delirium in a cancer patient successfully treated with olanzapine. J Pain Symptom Manage. 1999;17(3):219-223.
- Kim KS, Pae CU, Chae JH, Bahk WM, Jun T. An open pilot trial of olanzapine for delirium in the Korean population. Psychiatry Clin Neurosci. 2001;55(5):515-519.
- Breitbart W, Tremblay A, Gibson C. An open trial of olanzapine for the treatment of delirium in hospitalized cancer patients. Psychosomatics. 2002;43(3):175-182.
- Leso L, Schwartz TL. Ziprasidone treatment of delirium. Psychosomatics. 2002;43(1):61-62.
- Rea RS, Battistone S, Fong JJ, Devlin JW. Atypical antipsychotics versus haloperidol for treatment of delirium in acutely ill patients. Pharmacotherapy. 2007;27(4):588-594.
- Food and Drug Administration. FDA Public Health Advisory: Deaths with Antipsychotics in Elderly Patients with Behavioral Disturbances. www.fda.gov/cder/drug/advisory/antipsychotics.htm. Accessed October 17, 2008.
- Nasrallah HA, White T, Nasrallah AT. Lower mortality in geriatric patients receiving risperidone and olanzapine versus haloperidol: preliminary analysis of retrospective data. Am J Geriatr Psychiatry. 2004;12(4):437-439.
- Herrmann N, Mamdani M, Lanctot DL. Atypical antipsychotics and risk of cerebrovascular accidents. Am J Psychiatry. 2004;161(6):1113-1115.
- Wang PS, Schneeweiss S, Avorn J, et al. Risk of Death in Elderly Users of Conventional vs. Atypical Antipsychotic Medications. N Engl JMed. 2005;353(22):2335-2341.
- Ray WA, Meredith S, Thapa PB, Meador KG, Hall K, Murray KT. Antipsychotics and the risk of sudden cardiac death. Arch Gen Psychiatry. 2001;58(12):1161-1167.
- Trifiro G, Verhamme KMC, Ziere G, Caputi AP, Ch Stricker BH, Sturkenboom MC. All-cause mortality associated with atypical and typical antipsychotics in demented outpatients. Pharmacoepidemiol Drug Saf. 2007;16(5):538-544.
- Gleason OC. Donepezil for postoperative delirium. Psychosomatics. 2003;44(5):437-438.
- Hanania M, Kitain E. Melatonin for treatment and prevention of postoperative delirium. Anesth Analg. 2002;94(2):338?339.