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

Abstract Objectives 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). Methods Standardized mean difference (SMD), risk ratio (RR) and their 95% confidence intervals (CIs) were calculated using RevMan version 5.3. Results 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 Conclusion 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 in large-scale RCTs.