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

CYP 2C19與CYP 2D6基因多型性之交互作用影響重度憂鬱症病人對Fluoxetine或Venlafaxine早期治療反應

張惠華(Hui-Hua Chang) ； 陳柏熹(Po-See Chen) ； 王璇璣(Hsuan-Chi Wang) ； 簡伯武(Po-Wu Gean) ； 楊延光(Yen-Kuang Yang) ； 陸汝斌(Ru-Band Lu)

《台灣精神醫學》 27卷3期 (2013/09) Pp. 216-227+III

摘要

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.

關鍵字

抗憂鬱劑 ； 基因多型性

並列摘要

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.

並列關鍵字

CYP 2C19 ； CYP 2D6 ； major depressive disorder ； polymorphism

參考文獻

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