Variation in the catechol-O-methyltransferase (COMT) gene and treatment response to venlafaxine XR in generalized anxiety disorder

Psychiatry Res. 2012 Jun 30;198(1):112-5. doi: 10.1016/j.psychres.2011.12.034. Epub 2012 Mar 13.

Abstract

Antidepressant drugs are the preferred choice for the treatment of generalized anxiety disorder (GAD). However, the choice of pharmacotherapy is determined on a trial-and-error basis, as the underlying mechanisms of treatment response are unknown. We examined whether the COMT gene, which has been known to play a role in antidepressant treatment response in major depressive disorder (MDD), has a pharmacogenetic effect in antidepressant treatment response in GAD. In our study, 156 patients diagnosed with GAD received venlafaxine XR treatment as part of an 18-month relapse prevention study. Genotypes were obtained for the COMT functional variant rs4680 (Val158Met) for all patients; however, pharmacogenetic analysis was only conducted for the European American population (n=112). We found no significant association between our primary Hamilton Anxiety Scale outcome measure and rs4680. However, we did find a nominally significant allelic association between this variant and a secondary treatment outcome measure (CGI-I) in our European American population (n=112). Furthermore, we show a slight dominant effect of the A-allele with the CGI-I measure in the European American population indicating a possible pharmacogenetic role of rs4680 in antidepressant treatment outcome in GAD. Further studies in a larger population are needed to confirm this effect.

Trial registration: ClinicalTrials.gov NCT00183274.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Anxiety / drug therapy*
  • Anxiety / genetics*
  • Catechol O-Methyltransferase / genetics*
  • Cyclohexanols / therapeutic use*
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Pharmacogenetics*
  • Venlafaxine Hydrochloride
  • Young Adult

Substances

  • Antidepressive Agents, Second-Generation
  • Cyclohexanols
  • Venlafaxine Hydrochloride
  • Catechol O-Methyltransferase

Associated data

  • ClinicalTrials.gov/NCT00183274