The effect of prolonged treatment with antipsychotic drugs on cytochrome P450 - drug metabolizing enzymes. Mechanisms of action and significance for pharmacotherapy.

Abstract

Introduction: The treatment of schizophrenia and other psychosis-related mental disorders requires long-term therapy with selected drugs possessing adequate pharmacological receptor spectra, relevant to the patient's clinical state. Antipsychotics can interact with cytochrome P450 (CYP) reciprocally affecting each other in different ways. The enzyme plays an important role in the metabolism of antipsychotics, whereas antipsychotics can affect CYP enzymes in the liver and brain.

Areas covered: The effects of short and prolonged administration of antipsychotic drugs belonging to different groups (first-, second- and third-generation) on the expression and activity of CYP enzymes in the liver and brain are presented (based on PubMed 3 December 2024). Possible relations between pharmacological receptor spectra of antipsychotics and their influence on the regulation of cytochrome P450 in the liver and brain are considered. The results are discussed in the light of pharmacological and therapeutic significance.

Expert opinion: During continuous treatment in vivo, the direct mechanisms (drug/metabolite binding to the CYP enzyme) overlap with the effect of antipsychotics on CYP regulation (enzyme induction or inhibition). Clinicians using the information on particular drug-CYP interaction in combination with pharmacogenetic data can make informed decisions about drug selection and dosage, ultimately advancing more effective and safer pharmacotherapy.