Individualized medicine - implementation of pharmacogenetic diagnostics in antidepressant drug treatment of major depressive disorders

Abstract

Antidepressant drug therapy is characterized by a high rate of therapeutic failure. There is increasing evidence that genetic factors are contributing to the inter-individual variability in antidepressant drug response. Genetic variability is described in both the pharmacokinetic part of drug action as well as in pharmacodynamic structures mediating drug effects. Genetic polymorphisms in drug metabolizing enzymes are well characterized and have large effects on oral clearances or elimination half-lives of antidepressant drugs. These differences can be compensated by adapting the individual dose to genotype in addition to other factors such as gender, weight, age, liver and kidney function. On the part of drug action, genetic variability is described in molecular structures of antidepressant effects. Several studies on response of antidepressants have revealed influences of polymorphisms in neurotransmitter receptors and transporters changing sensitivity of patients to treatment with antidepressants; however, results were often contradictory. A pharmacogenomic approach to individualize antidepressant drug treatment is recommended to be based on several levels: 1) identifying and validating the candidate genes involved in drug-response; 2) providing therapeutic guidelines; and 3) developing a pharmacogenetic test-system for bedside-genotyping.