Brandl E J, Tiwari A K, Zhou X, Deluce J, Kennedy J L, Müller D J, Richter M A
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.
1] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada [2] Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
Pharmacogenomics J. 2014 Apr;14(2):176-81. doi: 10.1038/tpj.2013.12. Epub 2013 Apr 2.
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.
许多研究报告了抑郁症中抗抑郁反应的药物遗传学。相比之下，对于强迫症（OCD）的反应预测因素知之甚少，强迫症是一种药物反应者比例最低（40%-60%）的疾病。我们的研究是迄今为止基于CYP2D6和CYP2C19代谢状态对强迫症患者抗抑郁治疗反应和副作用进行的最大规模调查（N=184）。我们观察到，与广泛代谢者相比，CYP2D6非广泛代谢者的药物试验失败显著更多（P=0.007）。CYP2D6代谢状态与文拉法辛的副作用相关（P=0.022）。CYP2D6代谢状态与氟西汀反应之间以及CYP2C19代谢状态与舍曲林反应之间存在无统计学意义的关联趋势（P=0.056和P=0.064）。我们的研究首次表明CYP基因可能在强迫症的抗抑郁反应中起作用。基因检测在未来临床应用中还需要更多研究，这可能会改善治疗效果。
