The Catechol-O-methyltransferase Val(108/158)Met Genetic Polymorphism cannot be Recommended as a Biomarker for the Prediction of Venlafaxine Efficacy in Patients Treated in Psychiatric Settings

Abstract

The antidepressant venlafaxine is known to increase the turnover of cerebral monoamines, which are catabolized by the catechol-O-methyltransferase (COMT). The COMT (Val(108/158)Met, rs4680) genetic polymorphism affects the cerebral COMT activity. But whether this genetic polymorphism is associated with response to venlafaxine remains unclear. We assessed the impact of the COMT Val(108/158)Met, rs4680 genetic polymorphism on the efficacy of venlafaxine in depressed patients. This study was nested in the METADAP cohort, a real-world naturalistic treatment study in psychiatric settings. A total of 206 Caucasian patients with a unipolar major depressive episode (DSM-IVTR) treated with venlafaxine and evaluated with the Hamilton Depression Rating Scale (HDRS) were studied. One hundred and eighty patients were genotyped for the COMT Val(108/158)Met, rs4680 genetic polymorphism and classified into three genotype subgroups: Val/Val, Val/Met and Met/Met. The COMT genotype was the explanatory variable, and the variables to be explained were HDRS score, HDRS score improvement over time, response rate and remission rate. Venlafaxine had a trend to higher efficacy in the Val/Val patients as compared to Met/Met carriers, as shown by the HDRS score improvement after 3 months of treatment, but this result was not significant in mixed models [Val/Val: 59.78% (±22.4); Val/Met: 51.64% (±26.3); Met/Met: 39.52% (±27.6)]. The percentage of responders and remitters after 3 months of treatment was not significantly different in the three genotype groups, although coherent trends were shown. The COMT Val(108/158)Met, rs4680 genetic polymorphism cannot be recommended as a biomarker for the prediction of venlafaxine efficacy in patients treated in psychiatric settings.