Department of Neuroscience, Janssen Research and Development, LLC, San Diego, CA.
Department of Neuroscience, Janssen Research and Development, LLC, Titusville, NJ.
Int J Neuropsychopharmacol. 2021 Jan 20;24(1):22-31. doi: 10.1093/ijnp/pyaa068.
Patients with major depressive disorder (MDD) having active suicidal ideation with intent require immediate treatment.
This double-blind study (ASPIRE II) randomized adults (aged 18-64 years) with MDD having active suicidal ideation with intent to esketamine 84 mg or placebo nasal spray twice weekly for 4 weeks, given with comprehensive standard of care (hospitalization ≥5 days and newly initiated or optimized oral antidepressant[s]). Change from baseline to 24 hours post-first dose in Montgomery-Asberg Depression Rating Scale total score (primary efficacy endpoint) was analyzed using ANCOVA. Clinical Global Impression-Severity of Suicidality-revised (key secondary endpoint) was analyzed using ANCOVA on ranks of change.
Of 230 patients who were randomized (115 per arm), 227 received study drug and were included in efficacy/safety analyses; 184 (80.0%) completed double-blind treatment. Greater improvement in Montgomery-Asberg Depression Rating Scale total score was observed with esketamine (mean [SD]: -15.7 [11.56]) vs placebo (-12.4 [10.43]), each with standard of care, at 24 hours (least-squares mean difference [SE]: -3.9 [1.39], 95% CI: -6.60, -1.11; 2-sided P = .006). This was also noted at the earlier (4-hour) timepoint (least-squares mean difference -4.2, 95% CI: -6.38, -1.94). Patients in both treatment groups experienced rapid reduction in Clinical Global Impression-Severity of Suicidality-revised score; the between-group difference was not statistically significant. The most common adverse events among esketamine-treated patients were dizziness, dissociation, nausea, dysgeusia, somnolence, headache, and paresthesia.
This study confirmed rapid and robust reduction of depressive symptoms with esketamine nasal spray in severely ill patients with MDD who have active suicidal ideation with intent. Trial Registration: Clinical Trials.gov identifier: NCT03097133.
有自杀意念且有自杀企图的重度抑郁症（MDD）患者需要立即治疗。
这是一项双盲研究（ASPIRE II），将有自杀意念且有自杀企图的 MDD 成年患者（年龄 18-64 岁）随机分为两组，分别接受 84mg 依他佐辛鼻喷雾剂或安慰剂，每周两次，共 4 周，同时接受综合标准护理（住院≥5 天，新开始或优化口服抗抑郁药）。首次剂量后 24 小时的蒙哥马利-阿斯伯格抑郁评定量表总分（主要疗效终点）变化采用协方差分析。临床总体印象-修订版自杀严重程度（关键次要终点）的变化采用秩和检验进行协方差分析。
230 名随机患者（每组 115 名）中，227 名接受了研究药物治疗并纳入疗效/安全性分析；184 名（80.0%）完成了双盲治疗。依他佐辛（平均[SD]：-15.7[11.56]）与安慰剂（-12.4[10.43]）相比，在接受标准护理时，24 小时时的蒙哥马利-阿斯伯格抑郁评定量表总分改善更明显，差异最小平方均数[SE]为-3.9[1.39]，95%CI：-6.60，-1.11；双侧 P=0.006）。这一结果在更早的（4 小时）时间点也有观察到（最小平方均数差异-4.2，95%CI：-6.38，-1.94）。依他佐辛治疗组和安慰剂组的患者均经历了临床总体印象-修订版自杀严重程度评分的快速降低，两组间的差异无统计学意义。依他佐辛治疗患者最常见的不良事件为头晕、分离、恶心、味觉障碍、嗜睡、头痛和感觉异常。
这项研究证实了依他佐辛鼻喷雾剂在有自杀意念且有自杀企图的重度抑郁症患者中能快速、显著地减轻抑郁症状。
ClinicalTrials.gov 标识符：NCT03097133。
