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

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

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 investig...

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Published in:The pharmacogenomics journal Vol. 14; no. 2; pp. 176 - 181
Main Authors: Brandl, E J, Tiwari, A K, Zhou, X, Deluce, J, Kennedy, J L, Müller, D J, Richter, M A
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01-04-2014
Nature Publishing Group
Subjects:
631/154/436/434
692/699/476
Adolescent
Adult
Antidepressants
Antidepressive Agents - administration & dosage
Antidepressive Agents - adverse effects
Biomedical and Life Sciences
Biomedicine
Child
Clinical trials
CYP2D6 protein
Cytochrome P-450 CYP2C19 - genetics
Cytochrome P-450 CYP2D6 - genetics
Cytochrome P450
Drug metabolism
Drug therapy
Female
Fluoxetine
Gene Expression
Genetic aspects
Genetic screening
Genetic Variation
Human Genetics
Humans
Identification and classification
Male
Mental depression
Middle Aged
Neuroses
Obsessive compulsive disorder
Obsessive-Compulsive Disorder - drug therapy
Obsessive-Compulsive Disorder - genetics
Obsessive-Compulsive Disorder - pathology
Oncology
original-article
Patient outcomes
Pharmacogenetics
Pharmacotherapy
Psychopharmacology
Sertraline
Side effects
Venlafaxine
obsessive-compulsive disorder (OCD)
CYP2C19
CYP2D6
treatment response
pharmacogenetics
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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.
AbstractList 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.
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.
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. The Pharmacogenomics Journal (2014) 14, 176-181; doi: 10.1038/tpj.2013.12; published online 2 April 2013 Keywords: obsessive-compulsive disorder (OCD); pharmacogenetics; CYP2D6; CYP2C19; treatment response
Audience Academic
Author Müller, D J
Deluce, J
Tiwari, A K
Brandl, E J
Zhou, X
Kennedy, J L
Richter, M A
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  fullname: Tiwari, A K
  organization: Department of Neuroscience, Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto
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  surname: Zhou
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  organization: Department of Psychiatry, University of Toronto, Department of Psychiatry, Sunnybrook Health Sciences Centre
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  fullname: Richter, M A
  email: peggy.richter@sunnybrook.ca
  organization: Department of Neuroscience, Neurogenetics Section, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Department of Psychiatry, Sunnybrook Health Sciences Centre
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Keywords obsessive-compulsive disorder (OCD)
CYP2C19
CYP2D6
treatment response
pharmacogenetics
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Snippet Numerous studies have reported on pharmacogenetics of antidepressant response in depression. In contrast, little is known of response predictors in...
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SubjectTerms 631/154/436/434
692/699/476
Adolescent
Adult
Antidepressants
Antidepressive Agents - administration & dosage
Antidepressive Agents - adverse effects
Biomedical and Life Sciences
Biomedicine
Child
Clinical trials
CYP2D6 protein
Cytochrome P-450 CYP2C19 - genetics
Cytochrome P-450 CYP2D6 - genetics
Cytochrome P450
Drug metabolism
Drug therapy
Female
Fluoxetine
Gene Expression
Genetic aspects
Genetic screening
Genetic Variation
Human Genetics
Humans
Identification and classification
Male
Mental depression
Middle Aged
Neuroses
Obsessive compulsive disorder
Obsessive-Compulsive Disorder - drug therapy
Obsessive-Compulsive Disorder - genetics
Obsessive-Compulsive Disorder - pathology
Oncology
original-article
Patient outcomes
Pharmacogenetics
Pharmacotherapy
Psychopharmacology
Sertraline
Side effects
Venlafaxine
Title Influence of CYP2D6 and CYP2C19 gene variants on antidepressant response in obsessive-compulsive disorder
URI https://link.springer.com/article/10.1038/tpj.2013.12
https://www.ncbi.nlm.nih.gov/pubmed/23545896
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Volume 14
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