title: Pharmacogenetic polymorphisms and response to escitalopram and venlafaxine over 8 weeks in major depression.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Chee
authors.initials: C
authors.lastname: Ng
authors.forename: Jerome
authors.initials: J
authors.lastname: Sarris
authors.forename: Ajeet
authors.initials: A
authors.lastname: Singh
authors.forename: Chad
authors.initials: C
authors.lastname: Bousman
authors.forename: Keith
authors.initials: K
authors.lastname: Byron
authors.forename: Lai Huat
authors.initials: LH
authors.lastname: Peh
authors.forename: Deidre Joy
authors.initials: DJ
authors.lastname: Smith
authors.forename: Chay Hoon
authors.initials: CH
authors.lastname: Tan
authors.forename: Isaac
authors.initials: I
authors.lastname: Schweitzer
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D015283:Citalopram / Q000627:therapeutic use*; D003511:Cyclohexanols / Q000627:therapeutic use*; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D016037:Single-Blind Method; D013997:Time Factors; D000069470:Venlafaxine Hydrochloride; D044465:White People / Q000208:ethnology / Q000235:genetics*; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D015283:Citalopram; D000069470:Venlafaxine Hydrochloride; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6
keywords: ethnopsychopharmacology; personalized medicine; pharmacogenomic