Cytochrome P450 polymorphisms and response to antipsychotic therapy
- 1 March 2002
- journal article
- review article
- Published by Future Medicine Ltd in Pharmacogenomics
- Vol. 3 (2), 201-218
- https://doi.org/10.1517/14622416.3.2.201
Abstract
Antipsychotic drugs are used for the treatment of schizophrenia and other related psychotic disorders. The antipsychotics currently available include older or classical compounds and newer or atypical agents. Most antipsychotic drugs are highly lipophilic compounds and undergo extensive metabolism by cytochrome P450 (CYP) enzymes in order to be excreted. There is a wide interindividual variability in the biotransformation of antipsychotic drugs, resulting in pronounced differences in steady-state plasma concentrations and, possibly, in therapeutic and toxic effects, during treatment with fixed doses. Many classical and some newer antipsychotics are metabolized to a significant extent by the polymorphic CYP2D6, which shows large interindividual variation in activity. Other CYPs, especially CYP1A2 and CYP3A4, also contribute to the interindividual variability in the kinetics of antipsychotics and occurrence of drug interactions. No relationship between CYP2D6 genotype or activity and therapeutic effects of classical antipsychotic drugs has been found in the few studies performed. On the other hand, some investigations suggest that poor metabolizers (PMs) of CYP2D6 would be more prone to oversedation and, possibly, Parkinsonism during treatment with classical antipsychotics, while other studies, mostly retrospective, have been negative or inconclusive. For the newer antipsychotics, such data are lacking. To date, CYP2D6 phenotyping and genotyping appear, therefore, to be clinically useful for dose predicting only in special cases and for a limited number of antipsychotics, while their usefulness in predicting clinical effects must be further explored.Keywords
This publication has 97 references indexed in Scilit:
- Identification of the human cytochrome P450 isoforms mediating in vitro N‐dealkylation of perphenazineBritish Journal of Clinical Pharmacology, 2000
- The effects of ketoconazole on ziprasidone pharmacokinetics —a placebo‐controlled crossover study in healthy volunteersBritish Journal of Clinical Pharmacology, 2000
- The effect of carbamazepine on the steady‐state pharmacokinetics of ziprasidone in healthy volunteersBritish Journal of Clinical Pharmacology, 2000
- Failure to respond to treatment with typical antipsychotics is not associated with CYP2D6 ultrarapid hydroxylationBritish Journal of Clinical Pharmacology, 1999
- The effect of nefazodone on clozapine plasma concentrationsInternational Clinical Psychopharmacology, 1999
- Study of the association between cytochromes P450 2D6 and 2E1 genotypes and the risk of drug and chemical induced idiosyncratic aplastic anaemiaBritish Journal of Haematology, 1999
- Identification of cytochrome P450 enzymes involved in the metabolism of zotepine, an antipsychotic drug, in human liver microsomesXenobiotica, 1999
- The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapineBritish Journal of Clinical Pharmacology, 1997
- P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclaturePharmacogenetics, 1996
- Coadministration of Fluvoxamine Increases SerumJournal of Clinical Psychopharmacology, 1994