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SAGE-217治疗重性抑郁障碍患者的试验
Trial of SAGE-217 in Patients with Major Depressive Disorder


Handan Gunduz-Bruce ... 其他 • 2019.09.05
NEJM 动画解读

SAGE-217治疗抑郁
相关阅读
• 艾氯胺酮治疗难治性抑郁症——美国FDA批准首种新型抗抑郁药

摘要


背景

目前已发现γ-氨基丁酸(GABA)神经传递改变与抑郁发病机制相关。SAGE-217(GABA A型受体的口服正向别构调节剂)可否安全、有效地治疗重性抑郁障碍尚不清楚。

 

方法

在这项双盲、2期试验中,我们纳入了重性抑郁患者,并以1∶1的比例将其随机分组,分别接受每日1次30 mg SAGE-217或安慰剂治疗。主要终点是17项汉密尔顿抑郁评定量表(Hamilton Depression Rating Scale,HAM-D;评分范围为0~52分,评分较高表示抑郁较严重)评分从基线至第15日的变化。次要疗效终点(在第2~8日以及第15日、21日、28日、35日和42日评估)包括其他抑郁和焦虑量表评分相对于基线的变化,HAM-D评分相对于基线降低50%以上,HAM-D评分≤7分,以及临床总体印象-改善(Clinical Global Impression of Improvement)评分为1分(非常明显改善)或2分(明显改善)(评分范围为1~7分,7分表示症状非常明显恶化)。

 

结果

共有89例患者被随机分组:45例患者被分配至SAGE-217组,44例被分配至安慰剂组。SAGE-217组和安慰剂组的平均基线HAM-D评分分别为25.2分和25.7分。在SAGE-217组和安慰剂组中,HAM-D评分从基线至第15日的最小二乘均值(±SE)变化分别为-17.4±1.3分和-10.3±1.3分(变化的最小二乘均值差异,-7.0分;95%置信区间,-10.2~-3.9;P<0.001)。次要终点差异一般表现出与主要终点差异相同的方向。无严重不良事件。SAGE-217组最常见的不良事件包括头痛、头晕、恶心和嗜睡。

 

结论

SAGE-217每日给药14日使第15日时的抑郁症状减少。SAGE-217组的不良事件发生率高于安慰剂组。我们需要通过进一步试验来确定SAGE-217治疗重性抑郁障碍的疗效持久性和安全性,并将SAGE-217与现有治疗进行比较(由Sage Therapeutics资助;在ClinicalTrials.gov注册号为NCT03000530)。





作者信息

Handan Gunduz-Bruce, M.D., Christopher Silber, M.D., Inder Kaul, M.D., Anthony J. Rothschild, M.D., Robert Riesenberg, M.D., Abdul J. Sankoh, Ph.D., Haihong Li, Ph.D., Robert Lasser, M.D., Charles F. Zorumski, M.D., David R. Rubinow, M.D., Steven M. Paul, M.D., Jeffrey Jonas, M.D., James J. Doherty, Ph.D., and Stephen J. Kanes, M.D., Ph.D.
From Sage Therapeutics, Cambridge (H.G.-B., C.S., A.J.S., H.L., R.L., S.M.P., J.J., J.J.D., S.J.K.), Kaul Consulting, Concord (I.K.), and the University of Massachusetts Medical School and UMass Memorial Healthcare, Worcester (A.J.R.) — all in Massachusetts; the Atlanta Center for Medical Research, Atlanta (R.R.); Washington University School of Medicine, St. Louis (C.F.Z., S.M.P.); and the University of North Carolina School of Medicine, Chapel Hill (D.R.R.). Address reprint requests to Dr. Gunduz-Bruce at Sage Therapeutics, 215 First St., Cambridge, MA 02142, or at handan.gunduz-bruce@sagerx.com.

 

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