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STAR*D研究中抗抑郁药的药物基因组学

Pharmacogenomics with antidepressants in the STAR*D study.

作者信息

Lin Eugene, Chen Po See

机构信息

Vita Genomics, Inc, 7 Fl., No. 6, Sec. 1, Jung-Shing Road, Wugu Shiang, Taipei, Taiwan.

出版信息

Pharmacogenomics. 2008 Jul;9(7):935-46. doi: 10.2217/14622416.9.7.935.

Abstract

Major depressive disorder is one of the most common psychiatric disorders worldwide. No single antidepressant has been shown to be more effective than any other in lifting depression, and the effectiveness of any particular antidepressant in an individual is difficult to predict; therefore, doctors must prescribe antidepressants based on educated guesses. SNPs can be used in clinical association studies to determine the contribution of genes to drug efficacy. Evidence is accumulating to suggest that the efficacy of antidepressants results from the combined effects of a number of genetic variants, such as SNPs. Although there are not enough data currently available to prove this hypothesis, an increasing number of genetic variants associated with antidepressant response are being discovered. In this article, we review the pharmacogenomics of the drug efficacy of antidepressants in major depressive disorder. First, we survey the SNPs and genes identified as genetic markers that are correlated and associated with the drug efficacy of antidepressants in the Sequenced Treatment Alternatives for Depression (STARD) study. Second, we investigate candidate genes that have been suggested as contributing to treatment-emergent suicidal ideation during the course of antidepressant treatment in the STARD study. Third, we briefly describe the pharmacokinetic genes examined in the STARD study, and finally, we summarize the limitations with respect to the pharmacogenomics studies in the STARD study. Future research with independent replication in large sample sizes is needed to confirm the role of the candidate genes identified in the STAR*D study in antidepressant treatment response.

摘要

重度抑郁症是全球最常见的精神疾病之一。尚无单一的抗抑郁药被证明在缓解抑郁方面比其他药物更有效,而且很难预测某一种抗抑郁药对个体的疗效;因此,医生必须凭经验猜测来开抗抑郁药。单核苷酸多态性(SNPs)可用于临床关联研究,以确定基因对药物疗效的影响。越来越多的证据表明,抗抑郁药的疗效是多种基因变异(如SNPs)共同作用的结果。尽管目前尚无足够数据证明这一假设,但与抗抑郁反应相关的基因变异正在不断被发现。在本文中,我们综述了重度抑郁症中抗抑郁药疗效的药物基因组学。首先,我们调查了在抑郁症序贯治疗(STARD)研究中被确定为与抗抑郁药疗效相关的基因标记的SNPs和基因。其次,我们研究了在STARD研究中被认为与抗抑郁治疗过程中出现的自杀意念有关的候选基因。第三,我们简要描述了STARD研究中检测的药代动力学基因,最后,我们总结了STARD研究中药物基因组学研究的局限性。需要在大样本中进行独立重复的未来研究,以证实STAR*D研究中确定的候选基因在抗抑郁治疗反应中的作用。

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