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Atypical antipsychotics in the management of delirium: A review of the empirical literature

  • SOENKE BOETTGER (a1) and WILLIAM BREITBART (a1)

Abstract

Objectives: To review the existing literature of atypical antipsychotics in the treatment of delirium and make recommendations regarding their use in the treatment of delirium.

Methods: I conducted a literature search in Pubmed, Psychlit, and Embase for studies using atypical antipsychotics in the treatment of delirium. In the absence of studies, case reports were used.

Results: Overall 13 studies examined the use of risperidone, olanzapine, and quetiapine, two cases were reported about ziprasidone, and no publication was found using aripiprazole in the treatment of delirium. Among the existing studies were retrospective and prospective, open label studies in addition to one with a double blind design using risperidone. Risperidone, olanzapine, and quetiapine may be all similarly effective in the treatment of delirium, whereas there may be limited efficacy in the use of olanzapine in the hypoactive subtype of delirium in elderly populations, which may generalize to the other atypical antipsychotics. The use of atypical antipsychotics in the treatment of delirium is safe and carries a low burden of side effects.

Significance of results: Although atypical antipsychotics are widely used in the treatment of delirium, well-designed studies do not exist. Among the existing studies, stronger data supports the use of risperidone and olanzapine, and also quetiapine may be considered in the treatment of delirium. Recommendations are made based on the existing data and literature. The need for well-designed studies to validate the use of atypical antipsychotics in the treatment of delirium continues.

Copyright

Corresponding author

Corresponding author: Soenke Boettger, M.D., Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 421, New York, NY 10021. E-mail: BoettgeS@mskcc.org

References

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REFERENCES

American Psychiatric Association. (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Association.
Ananth, J., Parameswaran, S., & Gunatilake, S. (2004). Side effects of atypical antipsychotic drugs. Current Pharmaceutical Design, 10, 22192229.
Borison, R.L. & Diamond, B.I. (1983). Regional selectivity of neuroleptic drugs: An argument for site specificity. Brain Research Bulletin, 11, 215218.
Breitbart, W., Marotta, R., Platt, M.M., et al. (1996). A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients. American Journal of Psychiatry, 153, 231237.
Breitbart, W., Rosenfeld, B., Roth, A., et al. (1997). The Memorial Delirium Assessment Scale. Journal of Pain and Symptom Management, 13, 128137.
Breitbart, W. & Strout, D. (2000). Delirium in the terminally ill. Clinics in Geriatric Medicine, 16, 357372.
Breitbart, W., Tremblay, A., & Gibson, C. (2002). An open trial of olanzapine for the treatment of delirium in hospitalized cancer patients. Psychosomatics, 43, 175182.
Bucht, G., Gustafson, Y., & Sandberg, O. (1999). Epidemiology of delirium. Dementia and Geriatric Cognitive Disorders, 10, 315318.
Cole, M., McCusker, J., Dendukuri, N., et al. (2003). The prognostic significance of subsyndromal delirium in elderly medical inpatients. Journal of the American Geriatric Society, 51, 754760.
Conn, D.K. & Lieff, S. (2001). Diagnosing and managing delirium in the elderly. Canadian Family Physician, 47, 101108.
Doyle, M. & Warden, D. (1996). Use of SPECT to evaluate postcardiotomy delirium. American Journal of Psychiatry, 153, 838839.
Ereshefsky, L. & Lacombe, S. (1993). Pharmacological profile of risperidone. Canadian Journal of Psychiatry, 38(Suppl. 3), S80S88.
Factor, S.A. (2002). Pharmacology of atypical antipsychotics. Clinical Neuropharmacology, 25, 153157.
Fischer, P. (2001). Successful treatment of nonanticholinergic delirium with a cholinesterase inhibitor. Journal of Clinical Psychopharmacology, 21, 118.
Fulton, B. & Goa, K.L. (1997). Olanzapine. A review of its pharmacological properties and therapeutic efficacy in the management of schizophrenia and related psychoses. Drugs, 53, 281298.
Goren, J.L. & Levin, G.M. (1998). Quetiapine, an atypical antipsychotic. Pharmacotherapy, 18, 11831194.
Grant, S. & Fitton, A. (1994). Risperidone. A review of its pharmacology and therapeutic potential in the treatment of schizophrenia. Drugs, 48, 253273.
Han, C.H. & Kim, Y.K. (2004). A double-blind trial of risperidone and haloperidol for the treatment of delirium. Psychosomatics, 45, 297301.
Harrigan, E.P., Miceli, J.J., Anziano, R., et al. (2004). A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition. Journal of Clinical Psychopharmacology, 24, 6269.
Herrmann, N., Mamdani, M., & Lanctot, K.L. (2004). Atypical antipsychotics and risk of cerebrovascular accidents. American Journal of Psychiatry, 161, 11131115.
Horikawa, N., Yamazaki, T., Miyamoto, K., et al. (2003). Treatment for delirium with risperidone: Results of a prospective open trial with 10 patients. General Hospital Psychiatry, 25, 289292.
Ichikawa, J., Dai, J., O'Laughlin, I.A., et al. (2002a). Atypical, but not typical, antipsychotic drugs increase cortical acetylcholine release without an effect in the nucleus accumbens or striatum. Neuropsychopharmacology, 26, 325339.
Ichikawa, J., Li, Z., Dai, J., et al. (2002b). Atypical antipsychotic drugs, quetiapine, iloperidone, and melperone, preferentially increase dopamine and acetylcholine release in rat medial prefrontal cortex: Role of 5-HT1A receptor agonism. Brain Research, 956, 349357.
Inouye, S.K. (1998). Delirium in hospitalized older patients. Clinics in Geriatric Medicine, 14, 745764.
Kapur, S. & Seeman, P. (2001). Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics? A new hypothesis. American Journal of Psychiatry, 158, 360369.
Kennedy, J.S., Zagar, A., Bymaster, F., et al. (2001). The central cholinergic system profile of olanzapine compared with placebo in Alzheimer's disease. International Journal of Geriatric Psychiatry, 16(Suppl. 1), S24S32.
Kim, J.Y., Jung, I.K., Han, C., et al. (2005). Antipsychotics and dopamine transporter gene polymorphisms in delirium patients. Psychiatry and Clinical Neurosciences, 59, 183188.
Kim, K.S., Pae, C.U., Chae, J.H., et al. (2001). An open pilot trial of olanzapine for delirium in the Korean population. Psychiatry and Clinical Neurosciences, 55, 515519.
Kim, K.Y., Bader, G.M., Kotlyar, V., et al. (2003). Treatment of delirium in older adults with quetiapine. Journal of Geriatric Psychiatry and Neurology, 16, 2931.
Koponen, H.J. (1999). Neurochemistry and delirium. Dementia and Geriatric Cognitive Disorders, 10, 339341.
Leso, L. & Schwartz, T.L. (2002). Ziprasidone treatment of delirium. Psychosomatics, 43, 6162.
Lieberman, J.A., Mailman, R.B., Duncan, G., et al. (1998). Serotonergic basis of antipsychotic drug effects in schizophrenia. Biological Psychiatry, 44, 10991117.
Lipowski, Z.J. (1987). Delirium (acute confusional states). Journal of the American Medical Association, 258, 17891792.
Liu, C.Y., Juang, Y.Y., Liang, H.Y., et al. (2004). Efficacy of risperidone in treating the hyperactive symptoms of delirium. International Clinical Psychopharmacology, 19, 165168.
Lockwood, A.H., Yap, E.W., Rhoades, H.M., et al. (1991). Altered cerebral blood flow and glucose metabolism in patients with liver disease and minimal encephalopathy. Journal of Cerebral Blood Flow and Metabolism, 11, 331336.
Manos, P.J. & Wu, R. (1997). The duration of delirium in medical and postoperative patients referred for psychiatric consultation. Annals of Clinical Psychiatry, 9, 219226.
Massie, M.J., Holland, J., & Glass, E. (1983). Delirium in terminally ill cancer patients. American Journal of Psychiatry, 140, 10481050.
Melkersson, K. & Dahl, M.L. (2004). Adverse metabolic effects associated with atypical antipsychotics: Literature review and clinical implications. Drugs, 64, 701723.
Mittal, D., Jimerson, N.A., Neely, E.P., et al. (2004). Risperidone in the treatment of delirium: Results from a prospective open-label trial. Journal of Clinical Psychiatry, 65, 662667.
Miyamoto, S., Duncan, G.E., Marx, C.E., et al. (2005). Treatments for schizophrenia: A critical review of pharmacology and mechanisms of action of antipsychotic drugs. Molecular Psychiatry, 10, 79104.
Nasrallah, H.J. & Newcomer, J.W. (2004). Atypical antipsychotics and metabolic dysregulation: Evaluating the risk/benefit equation and improving the standard of care. Journal of Clinical Psychopharmacology, 24, S7S14.
Pae, C.U., Lee, S.J., Lee, C.U., et al. (2004). A pilot trial of quetiapine for the treatment of patients with delirium. Human Psychopharmacology, 19, 125127.
Parellada, E., Baeza, I., de Pablo, J., et al. (2004). Risperidone in the treatment of patients with delirium. Journal of Clinical Psychiatry, 65, 348353.
Platt, M.M., Breitbart, W., Smith, M., et al. (1994). Efficacy of neuroleptics for hypoactive delirium. Journal of Neuropsychiatry and Clinical Neurosciences, 6, 6667.
Raedler, T.J., Knable, M.B., Jones, D.W., et al. (2000). In vivo olanzapine occupancy of muscarinic acetylcholine receptors in patients with schizophrenia. Neuropsychopharmacology, 23, 5668.
Robertsson, B. (1999). Assessment scales in delirium. Dementia and Geriatric Cognitive Disorders, 10, 368379.
Rockwood, K. (1993). The occurrence and duration of symptoms in elderly patients with delirium. Journal of Gerontology, 48, M162M166.
Sasaki, Y., Matsuyama, T., Inoue, S., et al. (2003). A prospective, open-label, flexible-dose study of quetiapine in the treatment of delirium. Journal of Clinical Psychiatry, 64, 13161321.
Schwartz, T.L. & Masand, P.S. (2000). Treatment of delirium with quetiapine. Primary Care Companion to the Journal of Clinical Psychiatry, 2, 1012.
Schwartz, T.L. & Masand, P.S. (2002). The role of atypical antipsychotics in the treatment of delirium. Psychosomatics, 43, 171174.
Sipahimalani, A. & Masand, P.S. (1998). Olanzapine in the treatment of delirium. Psychosomatics, 39, 422430.
Skrobik, Y.K., Bergeron, N., Dumont, M., et al. (2004). Olanzapine vs. haloperidol: Treating delirium in a critical care setting. Intensive Care Medicine, 30, 444449.
Someya, T., Endo, T., Hara, T., et al. (2001). A survey on the drug therapy for delirium. Psychiatry and Clinical Neurosciences, 55, 397401.
Tejera, C.A., Saravay, S.M., Goldman, E., et al. (1994). Diphenhydramine-induced delirium in elderly hospitalized patients with mild dementia. Psychosomatics, 35, 399402.
Trzepacz, P.T. (1999). Update on the neuropathogenesis of delirium. Dementia and Geriatric Cognitive Disorders, 10, 330334.
Trzepacz, P.T. (2000). Is there a final common neural pathway in delirium? Focus on acetylcholine and dopamine. Seminars in Clinical Neuropsychiatry, 5, 132148.
Trzepacz, P.T., Baker, R.W., & Greenhouse, J. (1988). A symptom rating scale for delirium. Psychiatry Research, 23, 8997.
Trzepacz, P.T., Breitbart, W., Franklin, J., et al. (1999). Practice guideline for the treatment of patients with delirium. American Psychiatric Association. American Journal of Psychiatry, 156, 120.
Trzepacz, P.T., Mittal, D., Torres, R., et al. (2001). Validation of the Delirium Rating Scale-revised-98: Comparison with the delirium rating scale and the cognitive test for delirium. Journal of Neuropsychiatry and Clinical Neurosciences, 13, 229242.
Trzepacz, P.T., Sclabassi, R.J., & Van Thiel, D.H. (1989). Delirium: A subcortical phenomenon? Journal of Neuropsychiatry and Clinical Neurosciences, 1, 283290.
Tuomisto, L., Lozeva, V., Valjakka, A., et al. (2001). Modifying effects of histamine on circadian rhythms and neuronal excitability. Behavioural Brain Research, 124, 129135.
Wengel, S.P., Roccaforte, W.H., & Burke, W.J. (1998). Donepezil improves symptoms of delirium in dementia: Implications for future research. Journal of Geriatric Psychiatry and Neurology, 11, 159161.
Wooltorton, E. (2002). Risperidone (Risperdal): Increased rate of cerebrovascular events in dementia trials. Canadian Medical Association Journal, 167, 12691270.
Yokota, H., Ogawa, S., Kurokawa, A., et al. (2003). Regional cerebral blood flow in delirium patients. Psychiatry and Clinical Neurosciences, 57, 337339.
Young, C.C. & Lujan, E. (2004). Intravenous ziprasidone for treatment of delirium in the intensive care unit. Anesthesiology, 101, 794795.

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