Clinical efficacy and safety of Zuranolone (SAGE-217) in individuals with major depressive disorder.
Clinical efficacy and safety of Zuranolone (SAGE-217) in individuals with major depressive disorder.
复制标题
Zuranolone (SAGE-217) 对重度抑郁症患者的临床疗效和安全性。
DOI：
10.1016/j.jad.2023.08.027
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发表时间：
2023
影响因子：
6.6
通讯作者：
McIntyre,RogerS
中科院分区：
文献类型：
--
作者：
Meshkat,Shakila;Teopiz,KaylaM;DiVincenzo,JoshuaD;Bailey,JuliaB;Rosenblat,JoshuaD;Ho,RogerC;Rhee,TaehoGreg;Ceban,Felicia;Kwan,AngelaTH;Cao,Bing;McIntyre,RogerS
重度抑郁症（MDD）是一种常见的精神障碍，发病率和死亡率很高。 MDD 病因学的一些研究表明，γ-氨基丁酸 (GABA) 信号功能失调。 Zuranolone (SAGE-217) 是一种新型口服神经活性类固醇，也是一种正在研究的突触和突触外 GABAA 受体的正变构调节剂。在此，我们的目的是评估 Zuranolone 对 MDD 患者的疗效和安全性。我们回顾了七项研究，包括 1662 名患有重度抑郁症的参与者。 Zuranolone 作为口服、每日一次、为期 14 天的疗程进行了研究。我们的合成结果表明，Zuranolone 的抗抑郁作用是快速的、具有临床意义的，并且在多个随机临床试验中得到了复制。除了可重复的疗效外，Zuranolone 还与可接受的治疗中出现的不良事件水平以及在没有严重不良事件的情况下停药有关。据信，Zuranolone 的抗抑郁作用源自其通过增加突触和突触外 GABAA 活性以及调节 GABAA 受体表达来增强抑制性 GABA 信号传导的能力。综上所述，初步证据表明 Zuranolone 具有抗抑郁作用的潜力。 Zuranolone 已被 FDA 批准用于治疗产后抑郁症，并且在治疗重度抑郁症方面显示出疗效。未来的研究前景应寻求确定这种治疗方法的持久性及其对特定领域结果（例如快感缺乏、昼夜节律、唤醒系统）的影响以及在其他诊断实体（例如双相抑郁症）中的应用。
Major depressive disorder (MDD) is a common mental disorder with a high rate of morbidity and mortality. Dysfunctional signaling of gamma-aminobutyric acid (GABA) has been implicated in some studies in the etiology of MDD. Zuranolone (SAGE-217) is a novel, oral neuroactive steroid and an investigational positive allosteric modulator of synaptic and extrasynaptic GABAA receptors. Herein, we aimed to evaluate the efficacy and safety of Zuranolone in individuals with MDD. We reviewed seven studies including 1662 participants with MDD. Zuranolone was investigated as an oral, once-daily, 14-day treatment course. The results of our synthesis indicate that the antidepressant effects of Zuranolone are rapid, clinically meaningful, and replicated across multiple randomized clinical trials. In addition to replicated efficacy, Zuranolone is associated with an acceptable level of treatment-emergent adverse events and discontinuation without serious adverse events. It is believed that Zuranolone's antidepressant effects arise from its ability to enhance inhibitory GABAergic signaling by increasing synaptic and extrasynaptic GABAA activity and regulation of GABAA receptor expression. Taken together, preliminary evidence suggests the potential for antidepressant effects of Zuranolone. Zuranolone has been approved by FDA for postpartum depression, and is showing efficacy in major depressive disorder. Future research vistas should seek to determine the durability of this treatment approach as well as its effects on domain-specific outcomes (e.g., anhedonia, circadian rhythm, arousal systems) along with application in other diagnostic entities (e.g., bipolar depression).