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The Dosing of Atypical Antipsychotics

Dr. de Leon is the Medical Director of the University of Kentucky Mental Health Research Center, Eastern State Hospital, Lexington; and Associate Professor of Psychiatry, College of Medicine, University of Kentucky, Lexington. Dr. Armstrong is the Medical Director, Center for Geriatric Psychiatry, Tuality Forest Grove Hospital, Forest Grove, Ore., and Associate Clinical Professor of Psychiatry, Oregon Health Sciences University, Portland, Ore. Dr. Cozza is a staff psychiatrist for the Infectious Disease Service, Department of Medicine, Walter Reed Army Medical Center, Washington, D.C., and Assistant Professor of Psychiatry, Uniformed Services University of Health Sciences, Bethesda, Md. Drs. Armstrong and Cozza are co-authors, along with Dr. Jessica R. Oesterheld, of the Concise Guide to Drug Interaction Principles for Medical Practice: Cytochrome P450s, UGTs, P-glycoproteins, 2nd edition (American Psychiatric Publishing, Inc., 2003). Address correspondence and reprint requests to Dr. de Leon, Mental Health Research Center at Eastern State Hospital, 627 West Fourth St., Lexington, KY 40508; jdeleon{at}uky.edu (e-mail).
The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.

Drug-drug interactions or genetic variability may require using doses different from those recommended for atypical antipsychotics. Dosage alterations of olanzapine and clozapine, dependent on cytochrome P450 1A2 (CYP1A2) for clearance, and quetiapine, dependent on cytochrome P450 3A (CYP3A), may be necessary when used with other drugs that inhibit or induce their metabolic enzymes. Smoking cessation can significantly increase clozapine, and perhaps olanzapine, levels. Ziprasidone pharmacokinetic drug-drug interactions are not likely to be important. Genetic variations of cytochrome P450 2D6 (CYP2D6) and drug-drug interactions causing inhibition (CYP2D6 and/or CYP3A) or induction (CYP3A) may be important for risperidone, and perhaps for aripiprazole, dosing. Adding inhibitors may cause side effects more easily in drugs with a narrow therapeutic window, such as clozapine or risperidone, than in those with a wide therapeutic window, such as olanzapine or aripiprazole. Adding inducers may be associated with a gradual development of lost efficacy.

This article has been cited by other articles:

				J. de Leon, N. B. Sandson, and K. L. Cozza A Preliminary Attempt to Personalize Risperidone Dosing Using Drug-Drug Interactions and Genetics: Part II Psychosomatics, July 1, 2008; 49(4): 347 - 361. [Full Text] [PDF]

				J. de Leon, S. C. Armstrong, and K. L. Cozza Clinical guidelines for psychiatrists for the use of pharmacogenetic testing for CYP450 2D6 and CYP450 2C19. Psychosomatics, January 1, 2006; 47(1): 75 - 85. [Abstract] [Full Text] [PDF]

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