Yoshida Keizo, Higuchi Hisashi, Takahashi Hitoshi, Kamata Mitsuhiro, Sato Kazuhiro, Inoue Kazuyuki, Suzuki Toshio, Itoh Kunihiko, Ozaki Norio
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hum Psychopharmacol. 2008 Mar;23(2):121-8. doi: 10.1002/hup.907.
Genetic polymorphisms of the noradrenergic pathway can be factors to predict the effect of antidepressants when their pharmacological mechanisms of action include the noradrenergic system. The purpose of the present study was to determine whether the tyrosine hydroxylase (TH) val81met and catechol-O-methyltransferase (COMT) val158met polymorphisms are associated with the antidepressant effect of milnacipran, a serotonin/noradrenaline reuptake inhibitor.
Eighty-one Japanese patients with major depressive disorder were treated with milnacipran for 6 weeks. Severity of depression was assessed with the Montgomery and Asberg Depression Rating Scale (MADRS). Assessments were carried out at baseline and at 1, 2, 4 and 6 weeks of treatment. The method of polymerase chain reaction was used to determine allelic variants.
The met/met genotype of the COMT val158met polymorphism was associated with a significantly faster therapeutic effect of milnacipran in the MADRS score during this study. No influence of the TH val81met polymorphism on the antidepressant effect of milnacipran was detected.
These results suggest that the COMT val158met polymorphism in part determines the antidepressant effect of milnacipran.
当抗抑郁药的药理作用机制涉及去甲肾上腺素能系统时，去甲肾上腺素能途径的基因多态性可能是预测其疗效的因素。本研究的目的是确定酪氨酸羟化酶（TH）val81met和儿茶酚-O-甲基转移酶（COMT）val158met基因多态性是否与5-羟色胺/去甲肾上腺素再摄取抑制剂米那普明的抗抑郁作用相关。
81例日本重度抑郁症患者接受米那普明治疗6周。采用蒙哥马利-艾斯伯格抑郁量表（MADRS）评估抑郁严重程度。在基线以及治疗第1、2、4和6周时进行评估。采用聚合酶链反应方法确定等位基因变异。
在本研究中，COMT val158met基因多态性的met/met基因型与米那普明治疗MADRS评分时显著更快的疗效相关。未检测到TH val81met基因多态性对米那普明抗抑郁作用的影响。
这些结果表明，COMT val158met基因多态性部分决定了米那普明的抗抑郁作用。
