Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis.
The American journal of psychiatry March 1, 2025 Konstantinos N Fountoulakis, Athanasios Saitis, Alan F Schatzberg 78 citations
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.