Fast Fact and Concept #060: Pharmacologic Management of Delirium; Update on Newer Agents

Author(s): Earl Quijada, M.D. and J. Andrew Billings, M.D.

Delirium is a common psychiatric disorder in the terminally ill (See Fast Fact #1). Delirium can deeply disturb the patient and family; treatment is generally indicated in either a hyperactive or hypoactive delirium. Management options include identifying and treating the underlying cause, as well as symptomatic treatment through non-pharmacological and pharmacological interventions. Common reversible etiologies in advanced terminal illness include drug toxicity, infection, hypotension, hypoxia, hypoglycemia, hyponatremia, hypercalcemia, elevated ammonia, alcohol-sedative drug withdrawal, and sleep deprivation.

With the exception of treating delirium due to drug withdrawal or anticholinergic excess, neuroleptics are the first-line pharmacological agents for symptomatic management. Benzodiazepines should be avoided unless the source of delirium is alcohol-sedative drug withdrawal or when severe agitation is not controlled by the neuroleptic; these agents can cause "paradoxical" worsening of confusional states. The best studied neuroleptic, and the agent of choice for most patients, is haloperidol (Haldol), which has a favorable side effect profile and can be administered safely through oral and parenteral routes. Starting doses are 0.5 - 1.0 mg PO or IM/IV; titration can occur by 2.0 - 5.0 mg every 1 hour until a total daily requirement is established, which is then administered in 2-3 divided doses per day. Intravenous haloperidol may cause less extrapyramidal symptoms than oral haloperidol.

Other neuroleptics are probably comparable to haloperidol in controlling delirium (and many are also good anti-emetics), but may have a higher incidence of side effects: extrapyramidal reactions, sedation, and hypotension. Chlorpromazine (Thorazine) has been advocated for dying patients in whom sedation is desired, especially for terminal delirium.

Newer atypical neuroleptics, olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal) may be helpful in the management of confusional states. Evidence supporting usage of atypical neuroleptics in delirium is scant, so they should not be considered a first-line treatment. However, these agents are associated with fewer drug- induced movement disorders than haloperidol, and may be agents of choice in patients with Parkinson's disease and related neuromuscular disorders, as well as patients with a history of extrapyramidal reactions from neuroleptics.

The starting dose for olanzapine is 5 mg PO every day; after one week, the dose can be raised to 10 mg a day and titrated to 20 mg a day. Quetiapine is initially given 25 mg PO twice a day which can be raised by 25 - 50 mg per dose every 2 - 3 days up to a target of 300 - 400 mg a day, divided into 2 - 3 doses. Risperidone is given 1 - 2 mg PO at night and is gradually raised 1 mg every 2 - 3 days until an effective dose (usually 4 - 6 mg PO hs) is reached. These agents are not available in either intramuscular or intravenous routes.

The switch to an atypical neuroleptic may be made abruptly but it is probably wiser to taper off the typical agent slowly while titrating up the atypical agent. Atypical antipsychotics may not work as fast as conventional antipsychotics for acutely aggressive and agitated patients requiring onset of action within minutes. Quetiapine is the most sedating of the newer agents and has potential applicability in treating agitated delirium, especially at the end of life.

References

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2. Breitbart W, Marotta R, Platt MM, Weisman H, Derevenco M, Grau C, Corbera K, Raymond S, Lund S, Jacobson P. A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients. Am J.Psych1996 ;153:231-7.
3. Inouye SK, Bogardus ST Jr, Charpentier PA, Leo-Summers L, Acampora D, Holford TR, Cooney LM Jr. A multicomponent intervention to prevent delirium in hospitalized older patients N Engl J Med 1999; 4: 340:669-76.
4. Lawlor PG, Gagnon B, Mancini IL, Pereira JL, Hanson J. Suarez-Almazor ME, Bruera ED. Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study Arch Intern Med 2000; 160:786-94.
5. McIver B, Walsh D, Nelson K. The use of chlorpromazine for symptom control in dying cancer patients J Pain Symptom Manage 1994; 9:341-5.
6. Menza MA, Murray GB, Holmes VF, Rafuls WADecreased extrapyramidal symptoms with intravenous haloperidol J Clin Psych 1987; 48:278-280.
7. Sadock B, Sadock V. Kaplan and Sadock's Pocket handbook of Psychiatric Drug Treatment 3rd ed. Philadelphia PA: Lippincott Williams and Williams 2001.
8. Stahl, S. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications 2nd ed. Cambridge University Press 2000.

Fast Facts were edited by David Weissman MD, Palliative Care Center, Medical College of Wisconsin until January 2007.  For comments/questions write to the current editor, Drew Rosielle MD: drosiell@mcw.edu. The complete set of Fast Facts is available at EPERC: www.eperc.mcw.edu

Copyright and Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Citation for referencing. Fast Facts and Concepts #60 Pharmacologic Management of Delirium; update on newer agents. Earl Quijada, M.D. and J. Andrew Billings, M.D.. January, 2002. End-of-Life Physician Education Resource Center www.eperc.mcw.edu.

Disclaimer: Fast Facts provide educational information, this information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

Creation Date: 1/2002

Purpose: Instructional Aid, Self-Study Guide, Teaching

Audience(s)

ACGME Competencies: Medical Knowledge, Patient Care

Keyword(s): Non pain symptoms & syndromes; psychiatric disorders

Specific Disease and Organ System Category(s): Psychiatric Disorders