Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study
Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study
复制标题
DOI：
10.1016/j.biopsych.2015.10.018
复制
发表时间：
2016-09-15
影响因子：
10.6
通讯作者：
Van Nueten, Luc
中科院分区：
文献类型：
--
作者：
Singh, Jaskaran B.;Fedgchin, Maggie;Van Nueten, Luc
背景：本研究的目的是评估艾司氯胺酮静脉输注治疗难治性抑郁症（TRD）的疗效和安全性，并探讨其剂量反应。患者以1：1：1的比例随机分配，在第1天40分钟内接受0.20 mg/kg或0.40 mg/kg艾司氯胺酮或安慰剂IV输注。主要终点为第1天（基线）至第2天Montgomery-sberg抑郁量表总分的变化。在第1天接受安慰剂的无应答者在第4天再次以1：1随机分配至IV艾司氯胺酮.20 mg/kg或.40 mg/kg组。次要疗效和安全性措施也evaluated.RESULTS：入组患者中，97%（29 30）完成了研究。艾司氯胺酮20 mg/kg和40 mg/kg剂量组第2天蒙哥马利-安氏抑郁评定量表总分较基线的最小二乘平均变化（SE）为216.8（3.00）和216.9（2.61），与安慰剂组（-3.8 [2.97]）相比显示出显著改善（两组单侧p = 0.001）。艾司氯胺酮显示出快速（2小时内）和稳健的抗抑郁作用。治疗后出现的不良事件具有剂量依赖性。最常见的治疗后出现的不良事件是头痛、恶心和分离;最后提到的是一过性的，并且从艾司氯胺酮输注开始后持续不超过4小时。结论：在TRD患者中，在40分钟IV输注0.20 mg/kg或0.40 mg/kg艾司氯胺酮后观察到快速起效的强大抗抑郁作用。较低的剂量可以允许更好的耐受性，同时保持功效。
BACKGROUND:The purpose of this study was to assess the efficacy and safety and to explore the dose response of esketamine intravenous (IV) infusion in patients with treatment-resistant depression (TRD).METHODS:This multicenter, randomized, placebo-controlled trial was conducted in 30 patients with TRD. Patients were randomly assigned 1:1:1 to receive an IV infusion of .20 mg/kg or .40 mg/kg esketamine or placebo over 40 minutes on day 1. The primary end point was change in Montgomery-sberg Depression Rating Scale total score from day 1 (baseline) to day 2. Nonresponders who received placebo on day 1 were randomly assigned again 1:1 to IV esketamine .20 mg/kg or.40 mg/kg on day 4. Secondary efficacy and safety measures were also evaluated.RESULTS:Of the enrolled patients, 97% (29 of 30) completed the study. The least squares mean changes (SE) from baseline to day 2 in Montgomery-angstrom sberg Depression Rating Scale total score for the esketamine.20 mg/kg and .40 mg/kg dose groups were 216.8 (3.00) and 216.9 (2.61), respectively, and showed significant improvement (one-sided p = .001 for both groups) compared with placebo (-3.8 [2.97]). Esketamine showed a rapid (within 2 hours) and robust antidepressant effect. Treatment-emergent adverse events were dose dependent. The most common treatment-emergent adverse events were headache, nausea, and dissociation; the last-mentioned was transient and did not persist beyond 4 hours from the start of the esketamine infusion.CONCLUSIONS:A rapid onset of robust antidepressant effects was observed in patients with TRD after a 40-minute IV infusion of either .20 mg/kg or .40 mg/kg of esketamine. The lower dose may allow for better tolerability while maintaining efficacy.