Applications of Precision Medicine in the Treatment of Psychiatric Disorders: A Literature Review

H. Hare, K. Sneed, Y. Pathak
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Abstract

Background: Scientific understanding of precision medicine is rapidly evolving as new associations are made between genetic variants and tolerance to pharmaceuticals [1]. Although pharmacogenetic testing and guidelines exist for many medications, there is limited clinical application of these technologies in part due to limitations of the evidence supporting its use in psychiatric treatment as well as lack of awareness by providers and patients [2]. This narrative literature review aims to assess and summarize the past decade of research in the field of psychiatric pharmacogenetics. Specifically, it will focus on the relationship between antidepressant/antipsychotic drug responses and polymorphisms in nine commonly studied genes: CYP1A2, CYP2B6, CYP2C19, CYP2D6, CYP3A4, CYP3A5, SLC6A4, HTR2A, and DRD2. Methods: Literature from PubMed and Embase that was published between the years 2010 and 2020 was found using strategic keywords and search phrases. Each study represented was a randomized controlled trial or clinical trial tested in adults over the age of eighteen. Results: Of the six CYP450 enzymes that were evaluated, all displayed impacts on the metabolism of psychiatric drugs except CYP3A4, although only one polymorphism (*1B) was included in analysis of that particular gene. Inconclusive results were discovered regarding SLC6A4 5-HTTLPR polymorphisms and further review should be done to determine its relationship with SSRI response. Additionally, review of literature pertaining to DRD2 showed unsubstantial evidence, as four out of seven articles found no connection between treatment or adverse drug reactions (ADR) associated with DRD2. In contrast, influential findings were documented by literature concerning HTR2A polymorphisms and therapeutic consequences and the evidence collected on benefits of pharmacogenomic testing supports the implementation of testing to guide psychiatric treatment with confidence that use may result in fewer failed trials prior to response or remission. Conclusion: Many polymorphic mutations have a significant impact on individual responses to psychiatric treatment and implementation of pharmacogenomic testing in a clinic setting may be beneficial to psychiatric patients. Further review of polymorphic relationships should be done, especially in the case of SLC6A4 and DRD2 variations.
精准医学在精神疾病治疗中的应用:文献综述
背景:随着基因变异与药物耐受性之间的新联系,对精准医学的科学理解正在迅速发展[1]。尽管存在许多药物的药物遗传学测试和指南,但这些技术的临床应用有限,部分原因是支持其用于精神治疗的证据有限,以及提供者和患者缺乏认识[2]。这篇叙述性的文献综述旨在评估和总结过去十年在精神病学药物遗传学领域的研究。具体而言,它将重点关注抗抑郁/抗精神病药物反应与九个常用基因多态性之间的关系:CYP1A2, CYP2B6, CYP2C19, CYP2D6, CYP3A4, CYP3A5, SLC6A4, HTR2A和DRD2。方法:利用战略关键词和搜索短语,从PubMed和Embase检索2010 - 2020年间发表的文献。每项研究都是在18岁以上的成年人中进行的随机对照试验或临床试验。结果:在被评估的6种CYP450酶中,除CYP3A4外,所有酶都显示出对精神药物代谢的影响,尽管在对该特定基因的分析中只包含了一种多态性(*1B)。SLC6A4 5-HTTLPR多态性尚无定论,有待进一步研究以确定其与SSRI反应的关系。此外,对有关DRD2的文献的回顾显示缺乏实质性证据,因为七篇文章中有四篇没有发现与DRD2相关的治疗或药物不良反应(ADR)之间的联系。相比之下,有关HTR2A多态性和治疗后果的文献记录了有影响力的发现,并且收集的关于药物基因组学测试益处的证据支持实施测试来指导精神病学治疗,并相信使用测试可能会减少在反应或缓解之前失败的试验。结论:许多多态性突变对个体对精神病治疗的反应有显著影响,在临床环境中实施药物基因组学检测可能对精神病患者有益。应该进一步研究多态性关系,特别是SLC6A4和DRD2变异。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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