Efficacy of Esketamine Augmentation in Major Depressive Disorder: A Meta-Analysis

George I. Papakostas, MDa,b,*; Naji C. Salloum, MDa,b; Rebecca S. Hock, PhDa,b; Manish K. Jha, MDc; James W. Murrough, MD, PhDc; Sanjay J. Mathew, MDd; Dan V. Iosifescu, MDe; and Maurizio Fava, MDa,b

Published: May 26, 2020

Article Abstract

Objective: Esketamine, the S-enantiomer of ketamine, was recently approved as a rapid-acting intranasal therapy for depression and is currently under development for suicidality. The authors sought to determine the efficacy of adjunctive intranasal esketamine in major depressive disorder (MDD).

Data Sources: A systematic search of PubMed/MEDLINE was conducted up to January 2019, in addition to abstracts of major psychiatric meetings held since 2010. Searches were conducted by cross-referencing the term intranasal with the term esketamine. Where necessary, authors and/or study sponsors were contacted in order to obtain a copy of the presentation as well as any pertinent study details.

Study Selection: 241 study abstracts were initially identified and reviewed. Selected studies were randomized, double-blind clinical trials comparing adjunctive intranasal esketamine to adjunctive placebo for MDD.

Data Extraction: Data were extracted independently by two of the authors. A random effects model was used to calculate the standardized mean difference (SMD) between esketamine and placebo (intranasal saline) in the Montgomery-Asberg Depression Rating Scale (MADRS) score change from baseline to endpoint, serving as the primary outcome of the study.

Results: Five trials with 774 patients were pooled. Adjunctive esketamine was significantly more effective than placebo for MADRS score change, response, and remission (N = 774, SMD = 0.36, 95% CI = 0.24-0.49, P < .0001; response: risk ratio [RR] = 1.40, 95% CI = 1.22-1.61, P < .0001; remission: RR = 1.45, 95% CI = 1.20-1.75, P < .0001). Results remained statistically significant regardless of differences in the study sample, fixed vs new/optimized baseline antidepressants.

Conclusions: Adjunctive intranasal esketamine for patients with MDD who are either treatment-resistant or acutely suicidal appears to be an effective treatment strategy.

Volume: 81

Quick Links: Depression (MDD)

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