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Influence of CYP2D6 and CYP2C19 gene variants on antidepressant response in obsessive-compulsive disorder

The Pharmacogenomics Journal volume 14, pages 176–181 (2014)Cite this article

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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.

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Acknowledgements

We thank Dr Andrea Gaedigk for her advice regarding the use of the activity score. AKT: NARSAD Young Investigator Award. DJM: Ministry of Research and Innovation of Ontario Early Researcher Award; CIHR operating grant, NARSAD Young Investigator Award, CIHR Michael Smith New Investigator Salary Prize for Research in Schizophrenia, OMHF New Investigator Fellowship. JLK: CIHR operating grant. MAR: Ontario Mental Health Foundation grant, and International OCD Foundation grant.

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  1. D J Müller and M A Richter: Co-senior authorship.

Authors and Affiliations

  1. Department of Neuroscience, Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

    E J Brandl, A K Tiwari, J L Kennedy, D J Müller & M A Richter

  2. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

    E J Brandl, A K Tiwari, X Zhou, J Deluce, J L Kennedy, D J Müller & M A Richter

  3. Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

    X Zhou, J Deluce & M A Richter

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JLK has been a consultant to GSK, Sanofi-Aventis and Dainippon-Sumitomo. All other authors declare no conflict of interest.

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Brandl, E., Tiwari, A., Zhou, X. et al. Influence of CYP2D6 and CYP2C19 gene variants on antidepressant response in obsessive-compulsive disorder. Pharmacogenomics J 14, 176–181 (2014). https://doi.org/10.1038/tpj.2013.12

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