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-HT1B, and 5-HT2A 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 > or = 25% reduction on the YBOCS. Responders and nonresponders were stratified according to 5-HTT, 5-HT1B, and 5-HT2A 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 (chi2 = 7.17, df = 2, p = .028). In the paroxetine-treated patients, the majority of responders carried the G/G genotype of the 5-HT2A polymorphism (chi2 = 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 (chi2 = 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-HT2A polymorphism.
RCT Entities:
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 OCDpatients do not respond to SRI treatment. The purpose of the present study was to determine whether polymorphisms of the serotonin transporter (5-HTT), 5-HT1B, and 5-HT2A 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 > or = 25% reduction on the YBOCS. Responders and nonresponders were stratified according to 5-HTT, 5-HT1B, and 5-HT2A 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 (chi2 = 7.17, df = 2, p = .028). In the paroxetine-treated patients, the majority of responders carried the G/G genotype of the 5-HT2A polymorphism (chi2 = 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 (chi2 = 9.72, df = 2, p = .008). CONCLUSIONS: The results of this study suggest that response in venlafaxine-treated OCDpatients is associated with the S/L genotype of the 5-HTTLPR polymorphism and in paroxetine-treated OCDpatients with the G/G genotype of the 5-HT2A polymorphism.
Authors: Todd L Edwards; Digna R Velez Edwards; Raquel Villegas; Sarah S Cohen; Maciej S Buchowski; Jay H Fowke; David Schlundt; Jirong Long; Ji Rong Long; Qiuyin Cai; Wei Zheng; Xiao-Ou Shu; Margaret K Hargreaves; Jeffrey Smith; Smith Jeffrey; Scott M Williams; Lisa B Signorello; William J Blot; Charles E Matthews Journal: Am J Epidemiol Date: 2011-11-20 Impact factor: 4.897
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Authors: Filip C W Van Nieuwerburgh; Damiaan A J P Denys; Herman G M Westenberg; Dieter L D Deforce Journal: Int J Psychiatry Clin Pract Date: 2009-06-01 Impact factor: 1.812