The usefulness of genotyping cytochrome P450 enzymes in the treatment of depression

Expert Opin Drug Metab Toxicol. 2015 Mar;11(3):369-79. doi: 10.1517/17425255.2015.998996. Epub 2015 Jan 2.

Abstract

Introduction: Pharmacogenomics, which is derived from genome-wide association studies (GWAS), and pharmacogenetics, which involves candidate gene association studies (CGASs), are proving increasingly useful in personalized cancer care. Research in psychiatric applications has primarily involved genetic polymorphisms of P450 CYP enzymes, which mediate oxidative metabolism, particularly CYP2D6, which is involved in the metabolism of at least 30 psychotropic medications. This work has been supplemented by genotyping of proteins for the drug efflux pump P-glycoprotein (P-gp), serotonin receptors, and the serotonin reuptake pump.

Areas covered: This review covers principles of pharmacogenetics and pharmacogenomics, previous analyses of pharmacokinetic and pharmacodynamics studies, newer studies of the predictive value of genetic testing in the treatment of depression, obstacles to implementation of genetic testing in predicting treatment response and side effects, and suggestions for future research.

Expert opinion: Studies of multiple genes have produced some positive results in groups of patients, but genetic testing does not yet seem to be applicable to choosing medications for a specific patient.

Keywords: CYP P450; depression; genetic; metabolism; pharmacokinetics.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents / metabolism
  • Antidepressive Agents / therapeutic use*
  • Cytochrome P-450 CYP2D6 / genetics
  • Cytochrome P-450 Enzyme System / genetics
  • Depression / drug therapy*
  • Depression / genetics
  • Genetic Testing / methods
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Pharmacogenetics*
  • Polymorphism, Genetic
  • Precision Medicine

Substances

  • Antidepressive Agents
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP2D6