Department of Psychiatry and Neurobehavioral Sciences, University of Virginia School of Medicine, Charlottesville (Clayton); Sage Therapeutics, Cambridge, Mass. (Lasser, Jung, Jonas, Kanes, Doherty); Department of Psychiatry, University of Michigan, Ann Arbor (Parikh); Nathan Kline Institute for Psychiatric Research and Department of Psychiatry, New York University School of Medicine, New York (Iosifescu); Biogen, Cambridge, Mass. (Kotecha, Forrestal).
Am J Psychiatry. 2023 Sep 1;180(9):676-684. doi: 10.1176/appi.ajp.20220459. Epub 2023 May 3.
This study assessed the efficacy and safety of a 14-day treatment course of once-daily zuranolone 50 mg, an investigational oral positive allosteric modulator of the γ-aminobutyric acid type A (GABA) receptor, for the treatment of major depressive disorder.
Patients 18-64 years of age with severe major depressive disorder were enrolled in this randomized, double-blind, placebo-controlled trial. Patients self-administered zuranolone 50 mg or placebo once daily for 14 days. The primary endpoint was change from baseline in total score on the 17-item Hamilton Depression Rating Scale (HAM-D) at day 15. Safety and tolerability were assessed by incidence of adverse events.
Of 543 randomized patients, 534 (266 in the zuranolone group, 268 in the placebo group) constituted the full analysis set. Compared with patients in the placebo group, patients in the zuranolone group demonstrated a statistically significant improvement in depressive symptoms at day 15 (least squares mean change from baseline HAM-D score, -14.1 vs. -12.3). Numerically greater improvements in depressive symptoms for zuranolone versus placebo were observed by day 3 (least squares mean change from baseline HAM-D score, -9.8 vs. -6.8), which were sustained at all visits throughout the treatment and follow-up periods of the study (through day 42, with the difference remaining nominally significant through day 12). Two patients in each group experienced a serious adverse event; nine patients in the zuranolone group and four in the placebo group discontinued treatment due to adverse events.
Zuranolone at 50 mg/day elicited a significantly greater improvement in depressive symptoms at day 15, with a rapid time to effect (day 3). Zuranolone was generally well tolerated, with no new safety findings compared with previously studied lower dosages. These findings support the potential of zuranolone in treating adults with major depressive disorder.
本研究评估了每日一次的唑拉诺酮 50mg（一种研究性口服 γ-氨基丁酸 A 型（GABA）受体正变构调节剂）治疗 14 天治疗重度抑郁症的疗效和安全性。
本随机、双盲、安慰剂对照试验纳入了 18-64 岁的重度抑郁症患者。患者自行服用唑拉诺酮 50mg 或安慰剂，每日一次，共 14 天。主要终点为第 15 天 17 项汉密尔顿抑郁量表（HAM-D）总分的基线变化。通过不良反应发生率评估安全性和耐受性。
在 543 名随机患者中，534 名（唑拉诺酮组 266 名，安慰剂组 268 名）构成全分析集。与安慰剂组相比，唑拉诺酮组患者的抑郁症状在第 15 天有统计学意义的改善（HAM-D 总分自基线的最小二乘均值变化，-14.1 与-12.3）。在第 3 天，唑拉诺酮组与安慰剂组相比，抑郁症状的改善程度更大（HAM-D 总分自基线的最小二乘均值变化，-9.8 与-6.8），并且在整个治疗和随访期间一直持续（直至第 42 天，直至第 12 天差异仍具有名义显著性）。两组各有 2 名患者发生严重不良事件；9 名唑拉诺酮组患者和 4 名安慰剂组患者因不良事件停药。
唑拉诺酮 50mg/天在第 15 天可显著改善抑郁症状，起效迅速（第 3 天）。唑拉诺酮总体耐受性良好，与之前研究的较低剂量相比，无新的安全性发现。这些发现支持唑拉诺酮在治疗成人重度抑郁症方面的潜力。
