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

(2007) JOURNAL OF CLINICAL PSYCHIATRY. 68(5). p.747-753
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Abstract
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 >= 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 (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-HT2A 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-HT2A polymorphism.
Keywords
5-HT2A RECEPTOR GENE, MAJOR DEPRESSIVE DISORDER, REUPTAKE INHIBITORS, TRANSPORTER GENE, PROMOTER POLYMORPHISM, NO ASSOCIATION, GENOTYPE, BRAIN, SCHIZOPHRENIA, AVAILABILITY

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Citation

Please use this url to cite or link to this publication:

Chicago
Denys, Damiaan, Filip Van Nieuwerburgh, Dieter Deforce, and Herman GM Westenberg. 2007. “Prediction of Response to Paroxetine and Venlafaxine by Serotonin-related Genes in Obsessive-compulsive Disorder in a Randomized, Double-blind Trial.” Journal of Clinical Psychiatry 68 (5): 747–753.
APA
Denys, D., Van Nieuwerburgh, F., Deforce, D., & Westenberg, H. G. (2007). Prediction of response to paroxetine and venlafaxine by serotonin-related genes in obsessive-compulsive disorder in a randomized, double-blind trial. JOURNAL OF CLINICAL PSYCHIATRY, 68(5), 747–753.
Vancouver
1.
Denys D, Van Nieuwerburgh F, Deforce D, Westenberg HG. Prediction of response to paroxetine and venlafaxine by serotonin-related genes in obsessive-compulsive disorder in a randomized, double-blind trial. JOURNAL OF CLINICAL PSYCHIATRY. 2007;68(5):747–53.
MLA
Denys, Damiaan, Filip Van Nieuwerburgh, Dieter Deforce, et al. “Prediction of Response to Paroxetine and Venlafaxine by Serotonin-related Genes in Obsessive-compulsive Disorder in a Randomized, Double-blind Trial.” JOURNAL OF CLINICAL PSYCHIATRY 68.5 (2007): 747–753. Print.
@article{411808,
  abstract     = {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 {\textrangle}= 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 (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-HT2A 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-HT2A polymorphism.},
  author       = {Denys, Damiaan and Van Nieuwerburgh, Filip and Deforce, Dieter and Westenberg, Herman GM},
  issn         = {0742-1915},
  journal      = {JOURNAL OF CLINICAL PSYCHIATRY},
  language     = {eng},
  number       = {5},
  pages        = {747--753},
  title        = {Prediction of response to paroxetine and venlafaxine by serotonin-related genes in obsessive-compulsive disorder in a randomized, double-blind trial},
  url          = {http://www.psychiatrist.com/abstracts/abstracts.asp?abstract=200705/050711.htm},
  volume       = {68},
  year         = {2007},
}

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