Impact of CYP2D6 on venlafaxine metabolism in Trinidadian patients with major depressive disorder

Pharmacogenomics. 2018 Feb;19(3):197-212. doi: 10.2217/pgs-2017-0142. Epub 2018 Jan 12.

Abstract

Aim: This study aimed to assess the impact of CYP2D6 and CYP2C19 variation on venlafaxine (VEN) at steady state in patients from Trinidad and Tobago of Indian and African descent with major depressive disorder.

Patients & methods: Patients were phenotyped with dextromethorphan, genotyped for CYP2D6 and CYP2C19, and metabolic ratios for VEN obtained at 2-week intervals.

Results: Of 61 patients, 55 were genotyped and phenotyped and 47 completed 8 weeks of VEN treatment. The majority of patients had metabolic ratios for VEN that were consistent with those for dextromethorphan and genotype-predicted phenotype using activity scores. One subject presented with a novel no-function allele, CYP2D6*99. No correlations were observed with CYP2C19 genotype.

Conclusion: CYP2D6 genotype analysis provides valuable information to individualize drug therapy with VEN.

Keywords: CYP2C19; CYP2D6; MDD; venlafaxine.

MeSH terms

  • Adult
  • Black People / genetics
  • Cytochrome P-450 CYP2D6 / genetics*
  • Depressive Disorder, Major / blood
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / enzymology
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Indians, South American / genetics
  • Male
  • Polymorphism, Single Nucleotide*
  • Serotonin and Noradrenaline Reuptake Inhibitors / blood
  • Serotonin and Noradrenaline Reuptake Inhibitors / metabolism*
  • Serotonin and Noradrenaline Reuptake Inhibitors / therapeutic use
  • Trinidad and Tobago
  • Venlafaxine Hydrochloride / blood
  • Venlafaxine Hydrochloride / metabolism*
  • Venlafaxine Hydrochloride / therapeutic use

Substances

  • Serotonin and Noradrenaline Reuptake Inhibitors
  • Venlafaxine Hydrochloride
  • Cytochrome P-450 CYP2D6