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Basic Clin Pharmacol Toxicol. 2017 Nov;121(5):435-441. doi: 10.1111/bcpt.12827. Epub 2017 Aug 6.

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 information

1
INSERM UMR1178, Team 'Depression and Antidepressants', University of Medicine of Paris-Sud, University Paris-Sud, Le Kremlin Bicetre, France.
2
Service of Psychiatry, Group of Hospitals of Paris Sud, AP-HP, Hospital Bicetre, Le Kremlin Bicetre, France.
3
Service of Psychiatry, Group of Hospitals of Paris Est, AP-HP, Hospital Saint-Antoine, Paris, France.
4
Grenoble Institute of Neurosciences, Inserm U1216 GIN, University of Grenoble Alpes, Grenoble, France.
5
Hospital of Grenoble, Grenoble, France.
6
Clinical Research Center (CRC), Group of Hospitals of Paris Sud, AP-HP, Hospital Bicetre, Le Kremlin Bicetre, France.
7
Service of Molecular Genetics, Pharmacogenetics and Hormonology, Group of Hospitals of Paris Sud, AP-HP, Hospital Bicetre, Le Kremlin Bicetre, France.
8
Center of Biological Ressources of Paris-Sud, Group of Hospitals of Paris Sud, AP-HP, Hospital Bicetre, Le Kremlin Bicetre, France.

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.

PMID:
28627776
DOI:
10.1111/bcpt.12827
[Indexed for MEDLINE]

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