The efficacy and safety of adjunctive intranasal esketamine treatment in major depressive disorder: a systematic review and meta-analysis

Introduction Intranasal (IN) esketamine represents an innovative treatment for individuals with treatment resistant depression and depression with suicidal ideation and behavior. Herein, we synthesize extant long-term studies (≥ 4 weeks) regarding this treatment.Research design and methods The interventional studies of IN esketamine in patients with depression having a study period of at least four weeks were included for our synthesis. A meta-analysis was undertaken for the efficacy and safety parameters of adjunctive IN esketamine vs IN placebo with an oral antidepressant. The data excluded from meta-analysis were synthesized narratively.Results After pooling data from seven randomized controlled trials, treatment with adjunctive IN esketamine vs IN placebo was safe overall, and more effective at decreasing depressive symptoms (d = −0.239; 95%CI = −0.335,-0.142;p < 0.0001), with higher response (RR = 1.221; 95% CI = 1.055,1.428; p = 0.017) and remission (RR = 1.366; 95% CI = 1.182,1.578; p < 0.0001) rates. The year-long trials showed that treatment with adjunctive IN esketamine led to lower relapse rates with no considerable long-term side effects.Conclusion Intranasal esketamine was demonstrated to be safe, well tolerated, and rapidly effective in individuals with treatment resistant depression, suicidal ideation, and suicidal behavior.