Effect of Cytochrome P450 polymorphism on the action and metabolism of selective serotonin reuptake inhibitors.

INTRODUCTION: The aim of this article is to review the field of clinically relevant pharmacogenetic effects of cytochrome P450 polymorphisms on metabolism, kinetics, and action of selective serotonin reuptake inhibitors (SSRIs). AREAS COVERED: The relevant literature in humans on the implications of genetic variation on SSRI drug exposure, drug safety, and efficacy was systematically evaluated. There is a large amount of evidence on the influences of CYP polymorphisms on the pharmacokinetics of SSRIs. Regulatory agencies have issued warnings or advice considering dose adjustments in the presence of affected metabolic phenotypes for several SSRIs. Evidence-based dose adjustments for drugs dependent on CYP genotype are available to clinicians. However, few data on the relationship between genetically determined elevated plasma concentrations of SSRIs and specific side effects or therapeutic failure are currently available. EXPERT OPINION: Genetic polymorphisms in CYP2D6 and CYP2C19 exert large influences on the individual exposure to SSRIs, leading to the aim to achieve similar concentration time courses in different metabolizer phenotypes. The implementation of a stratified approach to medication with SSRIs in different metabolic phenotypes on a rational basis will require new studies assessing the association between clinical outcomes (such as adverse reactions) and genetically determined elevated plasma concentrations.