Wang Zhibin, Jiang Lili, Ma Wenzhuang, Li Xingyue, Gao Qiushi, Lian Siyu, Yu Weiwei
Department of Pain Management, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
Clin Pharmacol Ther. 2025 Jun;117(6):1637-1649. doi: 10.1002/cpt.3555. Epub 2025 Jan 10.
Despite being approved by the US FDA and the EU European Medicines Agency, the performance of esketamine nasal spray as an adjunctive therapy with an antidepressant in major depressive disorder is still controversial. Comprehensive retrieval in Embase, Pubmed, and Web of Science was conducted to identify randomized controlled trials comparing esketamine nasal spray versus control in major depressive disorder or treatment-resistant depression. The primary efficacy outcome was a reduction of the Montgomery-Asberg Depression Rating Scale, from baseline to Day 2 or Day 28 for patients with or without suicidal ideation, respectively. The long-term efficacy outcome was the relapse rate of patients who achieved stable remission. The certainty of evidence was assessed according to the Cochrane recommendation. Esketamine nasal spray was superior to placebo in reduction of Montgomery-Asberg Depression Rating Scale from baseline to Day 28 in patients without suicidal ideation (standardized mean difference: -0.24, 95% confidence interval: -0.38, -0.09, P = 0.001, I = 24%), and on Day 2 in patients with suicidal ideation (standardized mean difference: -0.30, 95% confidence interval: -0.47, -0.12, P = 0.0008, I = 0%). The long-term relapse rate was significantly lower in the esketamine nasal spray group than in the placebo/quetiapine group (risk ratio: RR: 0.60, 95% confidence interval: 0.45-0.80, I = 0%). The rate of suicidal ideation was similar between the two groups. The certainty of evidence was graded as "moderate" or "high" in the abovementioned results. Esketamine nasal spray in conjunction with an antidepressant effectively controls short-term and long-term depressive symptoms in major depressive disorder and treatment-resistant depression, with a manageable trade-off between efficacy and safety.
尽管艾氯胺酮鼻喷雾剂已获得美国食品药品监督管理局（FDA）和欧盟欧洲药品管理局的批准，但作为重度抑郁症抗抑郁药辅助疗法的疗效仍存在争议。我们在Embase、Pubmed和科学网进行了全面检索，以确定比较艾氯胺酮鼻喷雾剂与对照组治疗重度抑郁症或难治性抑郁症的随机对照试验。主要疗效指标是蒙哥马利-艾斯伯格抑郁量表（Montgomery-Asberg Depression Rating Scale）的降低，对于无自杀意念的患者，从基线到第2天；对于有自杀意念的患者，从基线到第28天。长期疗效指标是实现稳定缓解的患者的复发率。根据Cochrane推荐评估证据的确定性。在无自杀意念的患者中，从基线到第28天，艾氯胺酮鼻喷雾剂在降低蒙哥马利-艾斯伯格抑郁量表评分方面优于安慰剂（标准化均数差：-0.24，95%置信区间：-0.38，-0.09，P = 0.001，I² = 24%）；在有自杀意念的患者中，在第2天也优于安慰剂（标准化均数差：-0.30，95%置信区间：-0.47，-0.12，P = 0.0008，I² = 0%）。艾氯胺酮鼻喷雾剂组的长期复发率显著低于安慰剂/喹硫平组（风险比：RR：0.60，95%置信区间：0.45 - 0.80，I² = 0%）。两组间自杀意念发生率相似。上述结果中证据的确定性等级为“中等”或“高”。艾氯胺酮鼻喷雾剂联合抗抑郁药可有效控制重度抑郁症和难治性抑郁症的短期和长期抑郁症状，疗效和安全性之间的权衡可控。
