Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis.

Intranasal esketamine, approved as an add-on therapy for treatment-resistant major depression with acute suicidal thoughts, shows only modest benefit for depression and no effect on suicidality itself. A systematic review and meta-analysis of 87 studies found a weak but significant positive effect on depression at weeks 2-4 (effect size 0.15-0.23), similar to adding atypical antipsychotics. However, the effect on suicidality was not significant at any time point. The authors highlight esketamine's abuse potential, unknown long-term effects, and alarming signs of deaths and emerging suicidality during testing, urging caution in light of these regulatory and safety concerns.

Study at a glance

Abstract

Intranasal esketamine has been approved as an adjunctive therapy for treatment-resistant major depressive disorder with acute suicidal ideation and behavior. The authors conducted a systematic review and meta-analysis of the available data on its efficacy against depression and suicidality as well as its side effects. MEDLINE was searched with the keyword "esketamine" on March 24, 2024, using the PRISMA method. Data processing and statistical analysis were performed with R, version 4.3.3, and the meta-analysis was performed with the METAFOR package. Of 1,115 articles initially identified, 87 were included for analysis and discussion. At weeks 2-4, randomized controlled trials were mostly negative or failed; however, the meta-analysis returned a weak but significant positive effect for depression (effect size range, 0.15-0.23 at weeks 2-4), similar to augmentation strategies with atypical antipsychotics for treatment-resistant depression. The effect size concerning suicidality was not significant at any time point. The sensitivity analysis produced the same results. The study findings suggest that esketamine's efficacy as an add-on to antidepressants is modest in treatment-resistant depression (similar to augmentation strategies with atypical antipsychotics) and is absent against suicidality itself. These findings need to be considered in light of esketamine's abuse potential and the fact that long-term effects are still not fully known. Some alarming signs concerning deaths and emerging suicidality during the testing phase are discussed, along with other regulatory issues.