Influence of ABCB1 polymorphisms and serum concentrations on venlafaxine response in patients with major depressive disorder
Sammanfattning
Background: The pharmacokinetics and the pharmacodynamics of antidepressants show large interindividual
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.