title: Influence of ABCB1 polymorphisms and serum concentrations on venlafaxine response in patients with major depressive disorder.
abstract: BACKGROUND
  The pharmacokinetics and the pharmacodynamics of antidepressants show large inter-individual variations which result in unpredictable clinical responses.
  
  
  OBJECTIVE
  The aim of the study was to examine the effect of ABCB1 polymorphisms and the serum concentrations on the efficacy and tolerability of venlafaxine in patients with major depressive disorder (MDD).
  
  
  METHODS
  Fifty-two outpatients who met the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for MDD were recruited for the study. The severity of depression was assessed using the 17-item Hamilton Rating Scale for Depression scale (HDRS17) and tolerability was assessed based on a query regarding side-effects for 6 weeks. The ABCB1 C3435T/A and G2677T/A polymorphisms were genotyped by PCR/RFLP and steady-state serum venlafaxine concentrations were measured by high-performance liquid chromatography.
  
  
  RESULTS
  Patients with the TT genotype for the C3435T and the TT/TA genotype for the G2677T/A polymorphism showed significantly higher frequencies in venlafaxine-induced akathisia. This relationship was not observed for efficacy. As regards serum venlafaxine concentrations, patient groups showed no significant differences in efficacy and tolerability.
  
  
  CONCLUSIONS
  The results suggest that individuals with the TT-TT/TA genotypes for the C3435T-G2677T/A polymorphisms of ABCB1 may be pre-disposed to a risk of akathisia.
authors.affiliation: a Department of Pharmacology , Akdeniz University Medical Faculty , Antalya , Turkey.
authors.forename: Gul
authors.initials: G
authors.lastname: Ozbey
authors.affiliation: b Department of Psychology , Isık University , Istanbul , Turkey.
authors.forename: Feryal Cam
authors.initials: FC
authors.lastname: Celikel
authors.affiliation: c Department of Psychiatry , Inonu University Medical Faculty , Malataya , Turkey.
authors.forename: Birgul Elbozan
authors.initials: BE
authors.lastname: Cumurcu
authors.affiliation: d Department of Genetics , Gazi University Medical Faculty , Ankara , Turkey.
authors.forename: Derya
authors.initials: D
authors.lastname: Kan
authors.affiliation: e Izmir State Authority , Izmir , Turkey.
authors.forename: Berna
authors.initials: B
authors.lastname: Yucel
authors.affiliation: f Department of Psychiatry , Sivas State Hospital , Sivas , Turkey.
authors.forename: Ekrem
authors.initials: E
authors.lastname: Hasbek
authors.affiliation: g Department of Genetics , Gazi University Medical Faculty , Ankara , Turkey.
authors.forename: Ferda
authors.initials: F
authors.lastname: Percin
authors.affiliation: h Department of Research and Development, Division of Psychiatry , St Olavs University Hospital , Trondheim , Norway.|i Department of Neuroscience, Faculty of Medicine , Norwegian University of Science and Technology , Trondheim , Norway.
authors.forename: Ismail Cüneyt
authors.initials: IC
authors.lastname: Guzey
authors.affiliation: j Department of Pharmacology , Gazi University Medical Faculty , Ankara , Turkey.
authors.forename: Canan
authors.initials: C
authors.lastname: Uluoglu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000368:Aged; D017109:Akathisia, Drug-Induced / Q000235:genetics*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D000069470:Venlafaxine Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride
keywords: ABCB1 polymorphism; akathisia; response; serum concentration; venlafaxine