Cytochrome P450 2D6 genotyping: potential role in improving treatment outcomes in psychiatric disorders

Abstract

The specific reaction toward a given drug varies a lot between individuals and, for many drugs, pharmacogenetic polymorphisms are known to affect biotransformation and clinical outcome. Estimation of the individual's drug-metabolizing capacity can be undertaken by genotyping drug-metabolizing enzymes involved in the respective drug metabolism. Consequences that arise from genotyping may be the adjustment of dose according to genotype, choice of therapeutic strategy, or even choice of drug. One of the first fields where the clinical application of pharmacogenetics may be used is in that of antipsychotic and antidepressant drug treatment because there is a special need for individualized therapy in psychiatry. The pharmacokinetics of many TCAs, some SSRIs and other antidepressant drugs is significantly altered by polymorphisms; however, some controversy still exists as to whether therapeutic efficacy may be improved and/or adverse events can be prevented by genetically driven adjustment of drug dosage. Pharmacogenetic diagnostics may be an important factor in individualizing drug treatment according to the genetic make-up of the patients. However, routine application of pharmacogenetic dose adjustment in clinical practice requires prospective validation.