title: Influence of CYP2D6 and CYP2C19 gene variants on antidepressant response in obsessive-compulsive disorder.
abstract: Numerous studies have reported on pharmacogenetics of antidepressant response in depression. In contrast, little is known of response predictors in obsessive-compulsive disorder (OCD), a disorder with among the lowest proportion of responders to medication (40-60%). Our study is the largest investigation to date (N=184) of treatment response and side effects to antidepressants in OCD based on metabolizer status for CYP2D6 and CYP2C19. We observed significantly more failed medication trials in CYP2D6 non-extensive compared with extensive metabolizers (P=0.007). CYP2D6 metabolizer status was associated with side effects to venlafaxine (P=0.022). There were nonsignificant trends for association of CYP2D6 metabolizer status with response to fluoxetine (P=0.056) and of CYP2C19 metabolizer status with response to sertraline (P=0.064). Our study is the first to indicate that CYP genes may have a role in antidepressant response in OCD. More research is required for a future clinical application of genetic testing, which could lead to improved treatment outcomes.
authors.affiliation: 1] Department of Neuroscience, Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: E J
authors.initials: EJ
authors.lastname: Brandl
authors.affiliation: 1] Department of Neuroscience, Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: A K
authors.initials: AK
authors.lastname: Tiwari
authors.affiliation: 1] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada [2] Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.affiliation: 1] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada [2] Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Deluce
authors.affiliation: 1] Department of Neuroscience, Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: J L
authors.initials: JL
authors.lastname: Kennedy
authors.affiliation: 1] Department of Neuroscience, Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: D J
authors.initials: DJ
authors.lastname: Müller
authors.affiliation: 1] Department of Neuroscience, Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada [3] Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
authors.forename: M A
authors.initials: MA
authors.lastname: Richter
mesh_terms: D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
chemical_list: D000928:Antidepressive Agents; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6