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

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.