Prediction of response to paroxetine and venlafaxine by serotonin-related genes in obsessive-compulsive disorder in a randomized, double-blind trial

被引:46
作者
Denys, Damiaan
Van Niewuwerburgh, Filip
Deforce, Dieter
Westenberg, Herman G. M.
机构
[1] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Psychiat, NL-3508 GA Utrecht, Netherlands
[2] Univ Ghent, Pharmaceut Biotech Lab, Ghent, Belgium
关键词
D O I
10.4088/JCP.v68n0512
中图分类号
B849 [应用心理学];
学科分类号
040203 ;
摘要
Objective: Serotonin reuptake inhibitors (SRIs) are the most effective pharmacologic treatment currently available for patients with obsessive-compulsive disorder (OCD). Still, up to 40% to 60% of OCD patients do not respond to SRI treatment. The purpose of the present study was to determine whether polymorphisms of the serotonin transporter (5-HTT), 5-HT(1B), and 5-HT(2A) receptor genes affect the efficacy of SRI treatment in OCD. Method: 91 outpatients with OCD according to DSM-IV criteria consented to the study and were randomly assigned in a 12-week, double-blind trial to receive dosages titrated upward to 300 mg/day of venlafaxine or 60 mg/day of paroxetine. Primary efficacy was assessed by the change from baseline on the Yale-Brown Obsessive Compulsive Scale (YBOCS), and response was defined as a >= 25% reduction on the YBOCS. Responders and nonresponders were stratified according to 5-HTT, 5-HT(1B), and 5-HT(2A) genotypes and differentiated in paroxetine- or venlafaxine-treated groups. The study was conducted from August 1998 to July 2002. Results: In the whole group, 64% of responders carried the S/L genotype of the 5-HTTLPR polymorphism (chi(2) = 7.17, df = 2, p = .028). In the paroxetine-treated patients, the majority of responders carried the G/G genotype of the 5-HT(2A) polymorphism (chi(2) = 8.66, df = 2, p = .013), whereas in the venlafaxine-treated patients, the majority of responders carried the S/L genotype of the 5-HTTLPR polymorphism (chi(2) = 9.72, df = 2, p = .008). Conclusions: The results of this study suggest that response in venlafaxine-treated OCD patients is associated with the S/L genotype of the 5-HTTLPR polymorphism and in paroxetine-treated OCD patients with the G/G genotype of the 5-HT(2A) polymorphism.
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页码:747 / 753
页数:7
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