Pharmacogenetic polymorphisms and response to escitalopram and venlafaxine over 8 weeks in major depression

Ng, Chee, Sarris, Jerome, Singh, Ajeet, Bousman, Chad, Byron, Keith, Peh, Lai Huat, Smith, Deirdre Joy, Tan, Chay Hoon and Schweitzer, Isaac 2013, Pharmacogenetic polymorphisms and response to escitalopram and venlafaxine over 8 weeks in major depression, Human psychopharmacology: clinical and experimental, vol. 28, no. 5, pp. 516-522, doi: 10.1002/hup.2340.

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Title Pharmacogenetic polymorphisms and response to escitalopram and venlafaxine over 8 weeks in major depression
Author(s) Ng, Chee
Sarris, Jerome
Singh, Ajeet
Bousman, Chad
Byron, Keith
Peh, Lai Huat
Smith, Deirdre Joy
Tan, Chay Hoon
Schweitzer, Isaac
Journal name Human psychopharmacology: clinical and experimental
Volume number 28
Issue number 5
Start page 516
End page 522
Total pages 7
Publisher Wiley
Place of publication Chichester, Eng.
Publication date 2013-09
ISSN 0885-6222
Keyword(s) pharmacogenomic
personalized medicine
Antidepressive Agents, Second-Generation
Aryl Hydrocarbon Hydroxylases
Asian Continental Ancestry Group
Cytochrome P-450 CYP2C19
Cytochrome P-450 CYP2D6
Depressive Disorder, Major
European Continental Ancestry Group
Middle Aged
Polymorphism, Genetic
Prospective Studies
Serotonin Plasma Membrane Transport Proteins
Single-Blind Method
Time Factors
Venlafaxine Hydrochloride
Young Adult
Science & Technology
Social Sciences
Life Sciences & Biomedicine
Clinical Neurology
Pharmacology & Pharmacy
Neurosciences & Neurology
Summary OBJECTIVE: The objective of this study is to investigate the influence of the 5-HTTLPR (serotonin transporter-linked promoter region), cytochrome P450 2C19, and cytochrome P450 2D6 polymorphisms on escitalopram (ESC) and venlafaxine (VEN) responses in major depressive disorder.

METHOD: A prospective multi-site study of 106 patients (Caucasian and Han Chinese ethnicities) with major depressive disorder treated with either ESC or VEN was conducted. The 17-item Hamilton Depression scale (HDRS), Clinical Global Impression Scale, and an adverse events scale (UKU) were assessed over 8 weeks, blind to genotype.

RESULTS: At the 8-week end point, a significant HDRS reduction for both ESC and VEN occurred (p < 0.0001). The 5-HTTLPR l/l genotype was associated with significantly greater score reductions on the HDRS compared with s/s carriers (p = 0.016) among Caucasian subjects receiving ESC (n = 47). Response rates were significantly higher for l/l (92%) compared with l/s (61%) and s/s (46%) variants (p = 0.042). For every l allele a participant carried, there was a 3.33 (95% confidence interval 1.25, 8.84; p = 0.02) times greater odds of ESC response. No significant associations between any of the genotypes and adverse effects were found.

CONCLUSION: Ethnicity may have differential effects on the 5-HTTLPR genotype-efficacy relationship. Results suggest that l/l allele for 5-HTTLPR is associated with a robust treatment response to ESC in Caucasian subjects only.
Language eng
DOI 10.1002/hup.2340
Field of Research 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
1115 Pharmacology And Pharmaceutical Sciences
1701 Psychology
1702 Cognitive Science
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2013, Wiley
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Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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