美国生物制药SAGE公司的Handan Gunduz-Bruce与合作者在最新研究中，分析了SAGE-217治疗抑郁症的有效性和安全性。2019年9月5日出版的《新英格兰医学杂志》发表了这一成果。

在这项双盲、临床2期的试验中，研究组招募了89名抑郁症患者，并按1:1随机分配，45名患者每日口服30毫克的SAGE-217治疗，44名患者口服安慰剂。采用17项汉密尔顿抑郁量表（HAM-D）评分对两组患者的抑郁程度进行评估，得分越高表示抑郁越严重。

SAGE-217组和安慰剂组的平均基线HAM-D评分分别为25.2和25.7。治疗第15天，SAGE-217组的HAM-D评分显著低于安慰剂组，且在第21、28、35、42天亦是如此。两组均无严重不良反应发生。SAGE-217组最常见的不良反应包括头痛、头晕、恶心和嗜睡。

综上，连续14天每日服用SAGE-217可在第15天减轻抑郁症状，不良反应常见，但不严重。由于该研究样本有限，还需进一步试验来确定SAGE-217治疗抑郁症的持久性和安全性，并将其与现有治疗方法进行比较。

据悉，γ-氨基丁酸（GABA）的神经传递改变与抑郁症的发病有关。SAGE-217是一种口服的、阳性的GABA-A型受体变构调节剂，治疗抑郁症的疗效和安全性尚不清楚。

附：英文原文

Title: Trial of SAGE-217 in Patients with Major Depressive Disorder

Author: 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.

Issue&Volume: Vol 381 No 10

Abstract: 

BACKGROUND
Altered neurotransmission of γ-aminobutyric acid (GABA) has been implicated in the pathogenesis of depression. Whether SAGE-217, an oral, positive allosteric modulator of GABA type A receptors, is effective and safe for the treatment of major depressive disorder is unknown.

METHODS
In this double-blind, phase 2 trial, we enrolled patients with major depression and randomly assigned them in a 1:1 ratio to receive 30 mg of SAGE-217 or placebo once daily. The primary end point was the change from baseline to day 15 in the score on the 17-item Hamilton Depression Rating Scale (HAM-D; scores range from 0 to 52, with higher scores indicating more severe depression). Secondary efficacy end points, which were assessed on days 2 through 8 and on days 15, 21, 28, 35, and 42, included changes from baseline in scores on additional depression and anxiety scales, a reduction from baseline of more than 50% in the HAM-D score, a HAM-D score of 7 or lower, and a Clinical Global Impression of Improvement score of 1 (very much improved) or 2 (much improved) (on a scale of 1 to 7, with a score of 7 indicating that symptoms are very much worse).

RESULTS
A total of 89 patients underwent randomization: 45 patients were assigned to the SAGE-217 group, and 44 to the placebo group. The mean baseline HAM-D score was 25.2 in the SAGE-217 group and 25.7 in the placebo group. The least-squares mean (±SE) change in the HAM-D score from baseline to day 15 was −17.4±1.3 points in the SAGE-217 group and −10.3±1.3 points in the placebo group (least-squares mean difference in change, −7.0 points; 95% confidence interval, −10.2 to −3.9; P<0.001). The differences in secondary end points were generally in the same direction as those of the primary end point. There were no serious adverse events. The most common adverse events in the SAGE-217 group were headache, dizziness, nausea, and somnolence.

CONCLUSIONS
Administration of SAGE-217 daily for 14 days resulted in a reduction in depressive symptoms at day 15. Adverse events were more common in the SAGE-217 group than in the placebo group. Further trials are needed to determine the durability and safety of SAGE-217 in major depressive disorder and to compare SAGE-217 with available treatments. (Funded by Sage Therapeutics; ClinicalTrials.gov number, NCT03000530. opens in new tab.)