Use of CYP450 testing in psychiatric disease

Abstract

The metabolism of psychotropic drugs is mainly dependent on the CYP450 liver enzymes and the genetic polymorphisms encoding for these enzymes play an important role in their phenotypic expression. Inter-individual and inter-ethnic variations in drug metabolism and effects are largely determined by genes affecting these drug metabolising enzymes. Different rates of metabolism, particularly those involving CYP2D6 and CYP2C19 isoenzymes, give rise to several broad metabolic groups: ultrarapid, normal or extensive, intermediate and poor metabolisers, respectively. There are also ethnic variations in the prevalence of the respective isoenzyme alleles in different populations. Genotyping of pharmacogenetic alleles has the potential in predicting metabolic phenotypes, risks for side effects and likelihood of drug response for the individual patient. Applying a one size fits all approach in drug dosing may often result in less than optimal clinical response, and occasionally cause toxic adverse effects or in others loss of drug efficacy. Clinical implications of genotyping with respect to choice and dosing of psychotropics have been recommended to enable optimal response and to prevent excessive side effects. However, prediction of drug response in the complex clinical environment needs to also consider other clinical, cultural and environmental variables that impinge on drug response.