Adjunctive intranasal esketamine for major depressive disorder: A systematic review of randomized double-blind controlled-placebo studies

• Published in: Journal of affective disorders Vol. 265; pp. 63 - 70
• Main Authors: Zheng, Wei, Cai, Dong-Bin, Xiang, Ying-Qiang, Jiang, Wen-Long, Sim, Kang, Ungvari, Gabor S., Huang, Xiong, Huang, Xing-Xiao, Ning, Yu-Ping, Xiang, Yu-Tao
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.03.2020
• Subjects: Administration, Intranasal; Antidepressive Agents - therapeutic use; Depression; Depressive Disorder, Major - drug therapy; Humans; Intranasal esketamine; Ketamine - therapeutic use; Meta-analysis; Psychiatric/Mental Health; Randomized Controlled Trials as Topic; Remission; Response; Response; Depression; Remission; Intranasal esketamine; Meta-analysis
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2020.01.002

•Adjunctive intranasal esketamine has been increasingly studied for treating major depressive disorder (MDD), but the findings have been mixed.•Intranasal esketamine appears to have an ultra-rapid antidepressant effect for MDD, at least lasting by 28 days.•The long-term therapeutic effect and safety of intranasal esketamine needs to be further examined. This is a meta-analysis of randomized double-blind controlled-placebo trials (RCTs) examining the effectiveness, tolerability, and safety of intranasal esketamine in treating major depressive disorder (MDD). Standardized mean difference (SMD), risk ratio (RR) and their 95% confidence intervals (CIs) were calculated using RevMan version 5.3. Four RCTs with 7 active arms covering 708 patients with MDD on intranasal esketamine (n = 419) and placebo (n = 289) were included. Compared with placebo, adjunctive intranasal esketamine was associated with significantly greater study-defined response (RR=1.39, 95%CI: 1.18 to 1.64, P<0.0001) and remission (RR=1.42, 95%CI: 1.17 to 1.72, P = 0.0004) at endpoint assessment. Intranasal esketamine had greater study-defined response starting at 2 h (RR= 2.77, 95%CI: 1.62 to 4.76, P = 0.0002), peaking at 24 h (RR=5.42, 95%CI: 1.38 to 21.20, P = 0.02), and at least lasting for 28 days (RR=1.36, 95%CI: 1.16 to 1.58, P = 0.0001). Similarly, intranasal esketamine had significantly greater study-defined remission starting at 2 h (RR=7.71, 95%CI: 2.16 to 27.55, P = 0.002), peaking at 24 h (RR=6.87, 95%CI: 1.55 to 30.35, P = 0.01), and lasting for 28 days (RR=1.38, 95%CI: 1.11 to 1.72, P = 0.004). Intranasal esketamine had a significantly higher rate of discontinuation due to intolerability (RR=3.50, 95%CI: 1.38 to 8.86, P = 0.008). Discontinuation due to any reasons and inefficacy were similar between the two groups. Intranasal esketamine appears to have an ultra-rapid antidepressant effect for MDD, at least lasting for 28 days. The long-term therapeutic effect and safety of intranasal esketamine need to be further examined in large-scale RCTs.