Efficacy and safety of esketamine for "treatment resistant depression": registered report for a systematic review with an individual patient data meta-analysis of randomized, double-blind, placebo-controlled trials.
BMC medicine November 28, 2025 Florian Naudet, Claude Pellen, Liviu A Fodor et al. 5 citations
Intranasal esketamine plus an antidepressant reduced depression scores by about 3 points on the MADRS scale after 4 weeks, a statistically significant but small improvement that falls below the 6.5-point threshold for clinical significance used in the pivotal trials. A continuation trial showed reduced relapse risk, but a monotherapy trial had a larger effect with concerns about bias. Esketamine increased risks of sedation, dissociation, and other adverse events without increasing serious adverse events. No moderation by age or treatment resistance level was found. The clinical relevance of the benefit is unclear given the adverse event risks.