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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
Author(s) -
Taranu Adela,
Asmar Khalil El,
Colle Romain,
Ferreri Florian,
Polosan Mircea,
David Denis,
Becquemont Laurent,
Corruble Emmanuelle,
Verstuyft Céline
Publication year - 2017
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12827
Subject(s) - rs4680 , catechol o methyl transferase , venlafaxine , medicine , genotype , cohort , cyp2d6 , psychology , psychiatry , oncology , antidepressant , genetics , biology , cytochrome p450 , metabolism , gene , hippocampus
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.