The Associations Between CYP2D6 Metabolizer Status and Pharmacokinetics and Clinical Outcomes of Venlafaxine: A Systematic Review and Meta-Analysis

Pharmacopsychiatry. 2019 Sep;52(5):222-231. doi: 10.1055/a-0792-1340. Epub 2018 Nov 28.

Abstract

Background: The association between CYP2D6 metabolizer status and clinical outcomes of venlafaxine was extensively investigated previously, but no widely accepted conclusion has been reached so far. To obtain a more precise estimation of the association, a systematic review by meta-analysis was conducted in the present study.

Methods: The PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Technology of Chongqing, and Wan Fang Database were searched for eligible studies up to August 2018.

Results: Fourteen related studies involving 1035 patients were finally included. Significant associations were found among 3 CYP2D6 phenotypes (NM, IM, and PM) and most pharmacokinetic parameters of venlafaxine. However, CYP2D6 phenotypes were not associated with Hamilton Depression Rating Scale response of venlafaxine. In addition, we also found no significant association between CYP2D6 phenotype and overall rate of adverse events.

Conclusions: CYP2D6 metabolizer status had significant influence on venlafaxine pharmacokinetics, but insufficient evidence demonstrated that CYP2D6 metabolizer status was associated with its therapeutic effects and overall rate of adverse events, which provided further evidence regarding the relationship between CYP2D6 metabolizer status and venlafaxine.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antidepressive Agents, Second-Generation / therapeutic use
  • Cytochrome P-450 CYP2D6 / genetics*
  • Depression / drug therapy*
  • Humans
  • Treatment Outcome
  • Venlafaxine Hydrochloride / adverse effects
  • Venlafaxine Hydrochloride / pharmacokinetics*
  • Venlafaxine Hydrochloride / therapeutic use*

Substances

  • Antidepressive Agents, Second-Generation
  • Venlafaxine Hydrochloride
  • Cytochrome P-450 CYP2D6