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[抗抑郁药疗效和安全性的药物基因组学和药物代谢组学生物标志物:聚焦于选择性5-羟色胺再摄取抑制剂]

[Pharmacogenomic and pharmacometabolomic biomarkers of the efficacy and safety of antidepressants: focus on selective serotonin reuptake inhibitors].

作者信息

Gareeva A E, Borodina L S, Pozdnyakov S A, Timerbulatov I F

机构信息

Institute of Biochemistry and Genetics of the Ufa Federal Research Center of the Russian Academy of Sciences, Ufa, Russia.

Kemerovo State University, Kemerovo, Russia.

出版信息

Zh Nevrol Psikhiatr Im S S Korsakova. 2024;124(6):26-35. doi: 10.17116/jnevro202412406126.

Abstract

The efficacy and safety of psychopharmacotherapy with antidepressants is of great medical importance. The search for clinical and biological predictors for choosing the optimal psychopharmacotherapy with antidepressants is actively underway all over the world. Research is mainly devoted to searching for associations of polymorphic gene variants with the efficacy and safety of therapy. However, information about a patient's genetic polymorphism is often insufficient to predict the efficacy and safety of a drug. Modern research on the personalization of pharmacotherapy should include, in addition to genetic, phenotypic biomarkers. This is important because genotyping, for example, cannot accurately predict the actual metabolic activity of an isoenzyme. To personalize therapy, a combination of methods is required to obtain the most complete profile of the efficacy and safety of the drug. Successful treatment of depression remains a challenge, and inter-individual differences in response to antidepressants are common. About half of patients with depressive disorders do not respond to the first attempt at antidepressant therapy. Serious side-effects of antidepressant pharmacotherapy and discontinuation of treatment due to their intolerance are associated with ineffective therapy. This review presents the results of the latest studies of «omics» biomarkers of the efficacy and safety of antidepressants.

摘要

抗抑郁药心理药物治疗的疗效和安全性具有重大医学意义。世界各地都在积极寻找临床和生物学预测指标,以选择最佳的抗抑郁药心理药物治疗方案。研究主要致力于寻找多态性基因变异与治疗疗效和安全性之间的关联。然而,关于患者基因多态性的信息往往不足以预测药物的疗效和安全性。现代药物治疗个性化研究除了基因生物标志物外,还应包括表型生物标志物。这很重要,因为例如基因分型无法准确预测同工酶的实际代谢活性。为了实现治疗的个性化,需要结合多种方法来获得药物疗效和安全性的最完整概况。抑郁症的成功治疗仍然是一项挑战,个体对抗抑郁药的反应差异很常见。约一半的抑郁症患者对首次抗抑郁药治疗无反应。抗抑郁药药物治疗的严重副作用以及因不耐受而停药与治疗无效有关。本综述介绍了抗抑郁药疗效和安全性的 “组学” 生物标志物的最新研究结果。

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