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

• Published in: Human psychopharmacology Vol. 28; no. 5; pp. 516 - 522
• Main Authors: Ng, Chee, Sarris, Jerome, Singh, Ajeet, Bousman, Chad, Byron, Keith, Peh, Lai Huat, Smith, Deidre Joy, Tan, Chay Hoon, Schweitzer, Isaac
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.09.2013
• Subjects: Adult; Antidepressive Agents, Second-Generation - therapeutic use; Aryl Hydrocarbon Hydroxylases - genetics; Asian Continental Ancestry Group - ethnology; Asian Continental Ancestry Group - genetics; Citalopram - therapeutic use; Cyclohexanols - therapeutic use; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2D6 - genetics; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - ethnology; Depressive Disorder, Major - genetics; ethnopsychopharmacology; European Continental Ancestry Group - ethnology; European Continental Ancestry Group - genetics; Female; Humans; Male; Middle Aged; personalized medicine; Pharmacogenetics - methods; pharmacogenomic; Polymorphism, Genetic - genetics; Prospective Studies; Serotonin Plasma Membrane Transport Proteins - genetics; Single-Blind Method; Time Factors; Venlafaxine Hydrochloride; Young Adult; ethnopsychopharmacology; pharmacogenomic; personalized medicine
• DOI: 10.1002/hup.2340
• ISSN: 0885-6222; 1099-1077

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. Copyright © 2013 John Wiley & Sons, Ltd.