Interaction between CYP 2C19 and CYP 2D6 Genetic Polymorphisms Influences the Early Response of Fluoxetine/Venlafaxine Treatment among Patients with Major Depressive Disorder

Objective: The relationship between CYP 2C19*2 G681A, CYP 2C19*3 G636A and CYP 2D6*10 C100T polymorphisms and the treatment response to fluoxetine or venlafaxine in patients with major depressive disorder (MDD) remains unclear. In this study, we intended to clarify this issue. Methods: One hundred and forty outpatients diagnosed with MDD were randomized into either the fluoxetine or venlafaxine treatment group and genotyped. The 21-item Hamilton Rating Scale for Depression (HAM-D) was administered to evaluate depressive symptoms at baseline and biweekly over 6 weeks of treatment. Results: Neither polymorphisms of CYP 2C19*2 G681A, CYP 2C19*3 G636A nor that of CYP 2D6*10 C100T genotype were associated with treatment response in either the fluoxetine or venlafaxine groups. When the effects of the SNP*SNP interaction on treatment response was examined, CYP 2C19*2 G681A and CYP 2D6*10 C100T had significant interactions effects on the treatment response at weeks 2, 4, and 6 (p ＜ 0.05, p ＜ 0.01 and p ＜ 0.01, respectively) in the venlafaxine group, while CYP 2C19*3 G636A and CYP 2D6*10 C100T had significant interactions effects at weeks 2, and 4 (p = 0.001 and p ＜ 0.05, respectively) in the fluoxetine group. Conclusion: The study results indicated that two major variants of CYP 2C19 had significant interactions with CYP 2D6 in the early response of fluoxetine/venlafaxine treatment.