Comorbidities and the right dose: antipsychotics

Abstract

Introduction: The effects of antipsychotic drugs are dose-dependent, which is particularly true for their efficacy, each antipsychotic having a specific dose-response curve. This may justify individualizing doses for these agents.

Areas covered: We review the pharmacokinetic profiles of seven oral antipsychotics: haloperidol, risperidone, olanzapine, clozapine, quetiapine, ziprasidone, and aripiprazole. Their main indications are psychotic and affective disorders. They are prescribed in a very large population which may have comorbidities. Hence, we analyze the impact of the latter on the pharmacokinetic profiles of these antipsychotics, focusing on renal and hepatic impairment. Reviews and clinical trials were discussed based on a systematic literature search (PubMed) ranging from 1995 to 2022.

Expert opinion: Factors liable to impact antipsychotic dosage are numerous and their subsequent effects often hard to predict, due to multilevel interactions and compensatory phenomena. In clinical practice, physicians must be aware of these potential effects, but base their decisions on monitoring antipsychotic plasma levels.

Keywords: Antipsychotics; comorbidity; cytochrome P450; dosage individualization; pharmacokinetics.