The Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
Department of Psychiatry, University of Calgary, AB, Canada.
Psychol Med. 2023 Dec;53(16):7983-7993. doi: 10.1017/S0033291723002817. Epub 2023 Sep 29.
Psychotropic medication efficacy and tolerability are critical treatment issues faced by individuals with psychiatric disorders and their healthcare providers. For some people, it can take months to years of a trial-and-error process to identify a medication with the ideal efficacy and tolerability profile. Current strategies (e.g. clinical practice guidelines, treatment algorithms) for addressing this issue can be useful at the population level, but often fall short at the individual level. This is, in part, attributed to interindividual variation in genes that are involved in pharmacokinetic (i.e. absorption, distribution, metabolism, elimination) and pharmacodynamic (e.g. receptors, signaling pathways) processes that in large part, determine whether a medication will be efficacious or tolerable. A precision prescribing strategy know as pharmacogenomics (PGx) assesses these genomic variations, and uses it to inform selection and dosing of certain psychotropic medications. In this review, we describe the path that led to the emergence of PGx in psychiatry, the current evidence base and implementation status of PGx in the psychiatric clinic, and finally, the future growth potential of precision psychiatry via the convergence of the PGx-guided strategy with emerging technologies and approaches (i.e. pharmacoepigenomics, pharmacomicrobiomics, pharmacotranscriptomics, pharmacoproteomics, pharmacometabolomics) to personalize treatment of psychiatric disorders.
精神药物的疗效和耐受性是精神障碍患者及其医疗保健提供者面临的关键治疗问题。对于一些人来说，可能需要数月甚至数年的反复试验才能确定一种具有理想疗效和耐受性的药物。目前解决这一问题的策略（如临床实践指南、治疗算法）在人群层面上可能是有用的，但在个体层面上往往不够。部分原因是参与药物代谢动力学（即吸收、分布、代谢、消除）和药效学（如受体、信号通路）过程的基因存在个体差异，这些差异在很大程度上决定了一种药物是否有效或耐受。一种称为药物基因组学（PGx）的精准处方策略评估这些基因组变异，并利用其来为某些精神药物的选择和剂量调整提供信息。在这篇综述中，我们描述了精神药理学中 PGx 出现的途径，PGx 在精神科临床中的当前证据基础和实施状况，最后，通过将 PGx 指导策略与新兴技术和方法（即药物基因组学、药物微生物组学、药物转录组学、药物蛋白质组学、药物代谢组学）相结合，来个性化治疗精神障碍，探讨精准精神病学的未来增长潜力。
