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


METHODS
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.
Denys
Damiaan
D
Department of Psychiatry, the Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands. d.a.j.p.denys@umcutrecht.nl
Van Nieuwerburgh
Filip
F
Deforce
Dieter
D
Westenberg
Herman G M
HG
D000328:Adult; D003511:Cyclohexanols / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000235:genetics*; D017374:Paroxetine / Q000494:pharmacology / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics* / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics* / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
D003511:Cyclohexanols; D017374:Paroxetine; D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride