The Dosing of Atypical Antipsychotics

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