Gul Ozbey1, Feryal Cam Celikel2, Birgul Elbozan Cumurcu3, Derya Kan4, Berna Yucel5, Ekrem Hasbek6, Ferda Percin7, Ismail Cüneyt Guzey8,9, Canan Uluoglu10. 1. a Department of Pharmacology , Akdeniz University Medical Faculty , Antalya , Turkey. 2. b Department of Psychology , Isık University , Istanbul , Turkey. 3. c Department of Psychiatry , Inonu University Medical Faculty , Malataya , Turkey. 4. d Department of Genetics , Gazi University Medical Faculty , Ankara , Turkey. 5. e Izmir State Authority , Izmir , Turkey. 6. f Department of Psychiatry , Sivas State Hospital , Sivas , Turkey. 7. g Department of Genetics , Gazi University Medical Faculty , Ankara , Turkey. 8. h Department of Research and Development, Division of Psychiatry , St Olavs University Hospital , Trondheim , Norway. 9. i Department of Neuroscience, Faculty of Medicine , Norwegian University of Science and Technology , Trondheim , Norway. 10. j Department of Pharmacology , Gazi University Medical Faculty , Ankara , Turkey.
Abstract
BACKGROUND: The pharmacokinetics and the pharmacodynamics of antidepressants show large inter-individual variations which result in unpredictable clinical responses. AIM: 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. CONCLUSION: 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.
BACKGROUND: The pharmacokinetics and the pharmacodynamics of antidepressants show large inter-individual variations which result in unpredictable clinical responses. AIM: 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 ABCB1C3435T/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. CONCLUSION: 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.