Efficacy and Safety of Esketamine Combined with Antidepressants for Treatment-Resistant Depression: A Meta-Analysis

Adding esketamine to an antidepressant improves outcomes for people with treatment-resistant depression more than placebo plus antidepressant. Across seven randomized controlled trials involving 701 patients receiving esketamine plus antidepressant and 551 receiving placebo plus antidepressant, the combination led to greater reductions in depression severity scores (Montgomery-Asberg Depression Rating Scale and self-rating depression scale), higher response and remission rates at the end of the double-blind induction period, and better quality of life and health status ratings. Minor adverse reactions occurred with esketamine.

Study at a glance

Abstract

Objective: To evaluate the efficacy and safety of esketamine + antidepressant in treatment-resistant depression. Methods: We searched PubMed, Web of Science, Embase, CNKI, and Wanfang databases to obtain published information on esketamine + antidepressant from inception to July 2022. We searched for randomized controlled studies on the treatment of depression with a double-blind induction phase. Outcome indicators included changes in Montgomery-Asberg Depression Rating Scale (MADRS) scores before and after treatment, effective response rate, remission rate, and changes in self-rating depression scale (SDS). We analyzed data using Review Manager 5.4 and assessed the quality of evidence using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) analysis. Results: A total of seven articles were included, including 701 patients in the esketamine + antidepressant group and 551 in the placebo group. Meta-analysis results showed that esketamine + antidepressant could improve the MADRS score in patients with treatment-resistant depression (MD = -2.68, 95% CI -3.98 to -1.37, P < 0.0001), SDS (MD = -2.9, 95% CI -4.01 to -1.79, P < 0.00001), response rate at the end of the double-blind induction period (RR = 1.28, 95% CI 1.12 to 1.46, P = 0.0002), remission rate at the end of the double-blind induction period (RR = 1.39, 95% CI 1.18 to 1.63, P < 0.0001), Five-Dimensional Health Scale (EQ-5D-5L) (MD = 0.05, 95% CI 0.02 to 0.08, P = 0.00009), Visual Analogue Scale of Health Status (EQ-VAS) (MD = 5.54, 95% CI 2.37 to 8.71, P = 0.0006). Conclusion: Esketamine + antidepressant has an obvious curative effect in treatment-resistant depression and can rapidly improve depression in patients, quality of life and satisfaction, but minor adverse reactions can occur.