Article

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

Department of Psychiatry, the Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
The Journal of Clinical Psychiatry (Impact Factor: 5.14). 05/2007; 68(5):747-53. DOI: 10.4088/JCP.v68n0512
Source: PubMed

ABSTRACT 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.
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.
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).
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.

Download full-text

Full-text

Available from: Damiaan Denys, Aug 11, 2015
0 Followers
 · 
125 Views
  • Source
    • "Finally, we did not examine interactions between the COMT gene and other genes, such as 5-HTTLPR and 5-HT2A, which have been associated with drug response in OCD (Denys et al., 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Catechol-O-methyltransferase (COMT) is an enzyme that participates in the metabolic inactivation of dopamine and norepinephrine, and the Met allele of the COMT Val158Met polymorphism is associated with lower enzymatic activity. The purpose of the present study was to investigate whether this functional variant is associated with obsessive-compulsive disorder (OCD) and the clinical responses in OCD. We first performed a case-control association study between the COMT Val158Met polymorphism and OCD (171 cases and 944 controls). Then, we examined the association between this polymorphism and the clinical responses in 91 of the OCD patients. Our study did not find a significant association between the Met allele and OCD risk or between the Met allele and clinical responses (p > 0.05). The present case-control/pharmacogenetic study did not provide clear evidence that the COMT Val158Met polymorphism is a predictor of OCD or of OCD patients' clinical responses. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    Human Psychopharmacology Clinical and Experimental 05/2015; DOI:10.1002/hup.2485 · 1.85 Impact Factor
  • Source
    • "Ninety-one outpatients gave written informed consent for participation in this study, which had been approved by the University of Utrecht Medical Ethical Review committee (Utrecht, The Netherlands ). The studied population is described in detail by Denys et al. [2]. Severity of obsessive-compulsive symptoms was rated with the YaleÁBrown Obsessive Compulsive Scale (YBOCS), depressive symptoms with the Hamilton Rating scale for Depression (HAM-D) and anxiety with the Hamilton Rating Scale for Anxiety (HAM-A). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The cornerstone of pharmacotherapy for OCD is serotonin reuptake inhibition, either with clomipramine or with selective serotonin reuptake inhibitors (SSRIs). In spite of the success of serotonin reuptake inhibiting drugs, nearly half of OCD patients do not respond to treatment. Treatment response may be affected by genetic polymorphisms of the P450 metabolic system. The four most common enzyme-activity reducing polymorphisms of the P450 CYP2D6 enzyme were determined in 91 outpatients with primary OCD according to DSM-IV criteria, receiving dosages titrated upward to 300 mg/day of venlafaxine or 60 mg/day of paroxetine, using a fixed dosing schedule. Our results show that the investigated CYP2D6 polymorphisms are not a decisive factor in the response to paroxetine and venlafaxine treatment in OCD in spite of their highly significant effect on the blood levels of these medicines.
    International Journal of Psychiatry in Clinical Practice 11/2009; 13(1):345-348. DOI:10.3109/13651500902903016 · 1.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Genetic discovery in obsessive-compulsive disorder and Tourette’s syndrome has made significant progress in the past decade. The two disorders are phenomenologically, epidemiologically, and probably pathophysiologically related; however, as with most neuropsychiatric disorders, gene discovery has been challenging. Genetic epidemiology studies support the existence of susceptibility genes in both disorders, and more extensive genome-wide studies are under way. Gene pathways involving neurotransmitter (serotonin, dopamine, glutamate) and neurodevelopment (synaptic, homeobox) domains have been examined, but more complex genetic mechanisms remain largely unexplored. This review addresses the current state of genetic research in obsessive-compulsive disorder and Tourette’s syndrome, emphasizing commonalities between the disorders. Questions on common genetic substrates, the use of endophenotypes, and the utility of genetic data to inform pharmacologic treatment are also addressed.
    Current Psychiatry Reports 04/2009; 11(2):162-166. DOI:10.1007/s11920-009-0025-x · 3.05 Impact Factor
Show more