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[药物遗传学方法用于预测和个体化治疗重度抑郁症的可能性]

[Possibility of a pharmacogenetic approach for prediction and personalized medication in major depressive disorder treatment].

作者信息

Kato Masaki

机构信息

Department of Neuropsychiatry, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, 570-8506, Japan.

出版信息

Nihon Shinkei Seishin Yakurigaku Zasshi. 2010 Apr;30(2):83-92.

Abstract

The introduction of antidepressant drugs has revolutionized the treatment of mood disorders. However, even though sufficient doses of ADs have been used to treat depressive symptoms for sufficient periods, the treatment efficacy is considerably incomplete. The genetically determined investigation of pharmacological responses would be helpful to evaluate the best therapeutic tool for each depressed patient. However, the growing body of research in this field and heterogeneity across those studies could make it difficult for these candidates to be translated into treatment recommendations. Among other issues, the variety of ethnicity and therapeutic agents could play an important role as a confounder in pharmacogenetic results. To contribute to personalized medication for depression we should clarify the complicated, effect of these confounders. My colleagues and I reviewed the difference in genetic influence on antidepressant response between Asians and Caucasians based on a meta-analysis of pharmacogenetic studies. My colleagues and I also performed a randomized clinical trial (RCT) in Japanese subjects, "fluvoxamine vs paroxetine vs milnacipran," stratified by interesting genetic factors. The results showed that a pharmacogenetic approach could contribute, at least partially, to predict antidepressant response and personalized medication in depression with consideration of possible confounders.

摘要

抗抑郁药物的引入彻底改变了情绪障碍的治疗方法。然而,即使已使用足够剂量的抗抑郁药物来治疗抑郁症状足够长的时间,治疗效果仍相当不完全。对药物反应进行基因测定的研究将有助于为每位抑郁症患者评估最佳治疗手段。然而,该领域不断增加的研究以及这些研究之间的异质性可能使这些研究结果难以转化为治疗建议。在其他问题中,种族和治疗药物的多样性可能作为药物遗传学结果的一个混杂因素发挥重要作用。为了推动抑郁症的个性化用药,我们应该阐明这些混杂因素的复杂影响。我和我的同事基于对药物遗传学研究的荟萃分析,回顾了亚洲人和高加索人在抗抑郁反应上的基因影响差异。我和我的同事还在日本受试者中进行了一项随机临床试验(RCT),即“氟伏沙明vs帕罗西汀vs米那普明”,并按感兴趣的基因因素进行分层。结果表明,考虑到可能的混杂因素,药物遗传学方法至少可以部分地有助于预测抑郁症的抗抑郁反应和个性化用药。

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