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药物基因组学与情绪障碍的管理——综述

Pharmacogenomics and the Management of Mood Disorders-A Review.

作者信息

Kleine Schaars Kristian, van Westrhenen Roos

机构信息

Outpatient Clinic Pharmacogenetics, Parnassia Psychiatric Institute/PsyQ, Overschiestraat 57, 1062 HN Amsterdam, The Netherlands.

Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, De Crespigny Park, Denmark Hill, London SES 8AF, UK.

出版信息

J Pers Med. 2023 Jul 24;13(7):1183. doi: 10.3390/jpm13071183.

Abstract

Due to the chronic relapsing nature of mental disorders and increased life expectancy, the societal burden of these non-communicable diseases will increase even further. Treatments for mental disorders, such as depression, are available, but their effect is limited due to patients' (genetic) heterogeneity, low treatment compliance and frequent side effects. In general, only one-third of the patients respond to treatment. Today, medication selection in psychiatry relies on a trial-and-error approach based mainly on physicians' experience. Pharmacogenetic (PGx) testing can help in this process by determining the person-specific genetic factors that may predict clinical response and side effects associated with genetic variants that impact drug-metabolizing enzymes, drug transporters or drug targets. PGxis a discipline that investigates genetic factors that affect the absorption, metabolism, and transport of drugs, thereby affecting therapy outcome. These genetic factors can, among other things, lead to differences in the activity of enzymes that metabolize drugs. Studies in depressed patients show that genotyping of drug-metabolizing enzymes can increase the effectiveness of treatment, which could benefit millions of patients worldwide. This review highlights these studies, gives recommendations and provides future perspectives on how to proceed with PGx testing. Finally, it is recommended to consider genotyping for and , when there is an indication (side effects or inefficacy).

摘要

由于精神障碍的慢性复发性以及预期寿命的增加,这些非传染性疾病的社会负担将进一步加重。针对抑郁症等精神障碍的治疗方法虽有,但由于患者(基因)的异质性、低治疗依从性和频繁的副作用,其效果有限。一般来说,只有三分之一的患者对治疗有反应。如今,精神病学中的药物选择主要依靠基于医生经验的试错法。药物遗传学(PGx)检测可以通过确定个体特异性的遗传因素来帮助这一过程,这些遗传因素可能预测与影响药物代谢酶、药物转运体或药物靶点的基因变异相关的临床反应和副作用。PGx是一门研究影响药物吸收、代谢和转运的遗传因素从而影响治疗结果的学科。这些遗传因素尤其会导致药物代谢酶活性的差异。对抑郁症患者的研究表明,药物代谢酶的基因分型可以提高治疗效果,这可能使全球数百万患者受益。本综述重点介绍了这些研究,给出了建议,并就如何进行PGx检测提供了未来展望。最后,建议在有指征(副作用或无效)时考虑对[具体基因名称1]和[具体基因名称2]进行基因分型。

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本文引用的文献

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Pharmacogenetics at Scale: An Analysis of the UK Biobank.大规模药物遗传学分析:英国生物银行研究。
Clin Pharmacol Ther. 2021 Jun;109(6):1528-1537. doi: 10.1002/cpt.2122. Epub 2020 Dec 17.

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