The influence of cytochrome p450 pharmacogenetics on disposition of common antidepressant and antipsychotic medications

Review Article

The Influence of Cytochrome P450 Pharmacogenetics on Disposition of Common Antidepressant and Antipsychotic Medications
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Department of Clinical Chemistry, St Jansdal Hospital, Harderwijk, The Netherlands, Psychiatric Hospital Meerkanten, Ermelo, The Netherlands * For correspondence: Dr Jan van der Weide e-mail: [e-mail]

Jan van der Weide and John WJ Hinrichs

Abstract Since the identification of all the major drug-metabolising cytochrome P450 (CYP) enzymes and their major gene variants, pharmacogenetics has had a major impact on psychotherapeutic drug therapy. CYP enzymes are responsible for the metabolism of most clinically used drugs. Individual variability in CYP activity is an important reason for drug therapy failure. Variability in CYP activity may be caused by various factors, including endogenous factors such as age, gender and morbidity as well as exogenous factors such as co-medication, food components and smoking habit. However, polymorphisms, present in most CYP genes, are responsible for a substantial part of this variability. Although CYP genotyping has been shown to predict the majority of aberrant phenotypes, it is currently rarely performed in clinical practice.

Introduction Psychiatric drug treatment is characterised by large interindividual differences in drug response and dosage requirement. The final clinical effect of a psychotropic drug depends on different factors influencing the pharmacogenetics and pharmacodynamics of the drug. The majority of these factors can be explained by individual variability. Since all antipsychotics and antidepressives are highly lipophilic compounds, they are subject to extensive metabolism in the body before they are excreted. Additionally, many drugs have active metabolites contributing to the pharmacological effects of the drug. The metabolic capacity varies highly between individuals, with variable drug serum concentrations as a result. Especially when a drug has