Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany.
Translational Department, Max Planck Institute for Psychiatry, München, Germany.
Expert Opin Drug Metab Toxicol. 2021 Nov;17(11):1249-1260. doi: 10.1080/17425255.2021.1991912. Epub 2021 Oct 15.
Anxiety disorders (AD) are among the most common mental disorders worldwide. Pharmacotherapy, including benzodiazepines, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants is currently based on 'trial-and-error,' and is effective in a subset of patients or produces partial response only. Recent research proposes that treatment response and tolerability of the drugs are associated with genetic factors.
In the present review, we provide information on pharmacogenetics (PGx) in AD, including pharmacokinetic and pharmacodynamic genes. Moreover, we discuss the future potential of PGx for personalized treatment.
In psychiatry, PGx testing is still in its infancy, especially in the treatment of AD. As of today, implementation in clinical routine is recommended only for CYP2D6 and CYP2C19, mainly in terms of safety of treatment and potentially of treatment outcome in general. However, the evidence for PGx testing addressing pharmacodynamics for specific AD is limited to date. Nevertheless, PGx may develop into a valuable and promising tool to improve therapy in AD, but there is a need for more research to fully exploit its possibilities. Future perspectives include research into single genes, polygenic risk scores, and pharmacoepigenetics to provide targeted therapy.
焦虑症（AD）是全球最常见的精神障碍之一。包括苯二氮䓬类、选择性 5-羟色胺再摄取抑制剂、5-羟色胺-去甲肾上腺素再摄取抑制剂和三环类抗抑郁药在内的药物治疗目前基于“试错法”，仅对一部分患者有效或仅产生部分反应。最近的研究表明，药物的治疗反应和耐受性与遗传因素有关。
在本综述中，我们提供了 AD 中药物遗传学（PGx）的信息，包括药代动力学和药效动力学基因。此外，我们还讨论了 PGx 对个性化治疗的未来潜力。
在精神病学中，PGx 测试仍处于起步阶段，特别是在 AD 的治疗中。截至今天，仅建议在治疗安全性和潜在的总体治疗效果方面，对 CYP2D6 和 CYP2C19 进行 PGx 测试，以实施临床常规。然而，迄今为止，针对 AD 特定药效动力学的 PGx 测试的证据有限。尽管如此，PGx 可能会发展成为改善 AD 治疗的有价值且有前途的工具，但仍需要进一步研究以充分挖掘其潜力。未来的研究方向包括对单基因、多基因风险评分和药物基因组学的研究，以提供靶向治疗。
