Dr. Purvis is a psychiatric pharmacyresident and Dr. Hieber is a clinicalpharmacist at Western Missouri MentalHealth Center in Kansas City.
Fifty years ago, the terms "everyman'spsychosis" and "reversiblemadness" referred to a mentaldisorder to which everyone is susceptible—delirium, an acute confused stateoften overlooked by physicians.1
Up to 40% of hospitalized elderly patientsexperience delirium, one of themost preventable hospital-acquiredadverse events.2,3 Failure to uncover theunderlying etiology of delirium resultsin extended stays, increased costs, andincreased morbidity and mortality.4,5
Delirium commences abruptly and encompassesa broad range of disturbances.These range from hyperactive tohypoactive states, with fluctuations inlevel of consciousness, attention, cognition(memory impairment, disorientation,language disturbance), and perception(visual/tactile hallucinations).Symptoms, including sleep pattern disturbanceand psychomotor behavior,vary throughout the day and generallyresolve within 10 to 12 days.4,6
The primary goal in management is toidentify the underlying etiology and initiateimmediate interventions to ensurepatient safety. In elderly patients, deliriumis commonly a result of acute illnessor medication, the latter being themost common reversible cause.7 Halfof all cases are missed by physicians;thus, pharmacists play a major roleby recommending alternative treatmentstrategies and minimizing the use ofhigh-risk medications (eg, anticholinergics,analgesics).8 See Table 11,9,10 forpotential causes and treatment suggestions.Table 2 provides tips the pharmacistcan implement to help prevent ortreat delirium.
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 pharmacologicprevention investigated low-dose antipsychotichaloperidol, anticonvulsantgabapentin,and an acetylcholinesteraseinhibitor (ACI), donepezil.11-13 No trialwas overwhelmingly significant; therefore,using medication to prevent deliriumis not currently recommended.4
Acute agitation with delirium maynecessitate short-term pharmacologictreatment; however, if the cause ofdelirium is addressed, further interventionmay not be necessary. Standardpractice involves use of first-generationantipsychotics (primarily haloperidol).4,14-19 Using lower doses of haloperidol,between 0.5 and 4.5 mg/day,keeps extrapyramidal side effects toa minimum. The evidence for use ofsecond-generation antipsychotics (eg,risperidone, olanzapine, quetiapine, ziprasidone)is expanding.4,20-32
A recent analysis of haloperidol versusrisperidone, olanzapine, and quetiapinedetermined that all agents havesimilar efficacy in treatment of agitationin delirium.33 Second-generation anti-psychotics, especially olanzapine and quetiapine, are sedating,which may be beneficial in some situations. Choosing anagent should involve evaluating side effect profiles of eachpotential medication.
Current controversy exists regarding evidence that mortalityis increased in elderly patients receiving antipsychotics.34-39Clinical 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 includeACIs, benzodiazepines, and melatonin. Theoretically, ACIsreverse anticholinergic-induced delirium, although the evidenceis limited to case reports.40 Benzodiazepines are to beavoided, except in cases of alcohol withdrawal. A study usingalprazolam as treatment for delirium was terminated earlydue to worsening of delirium.14 A case report uses melatoninto treat delirium, although evidence supporting melatonin'srole 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.