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

Nov 28, 2025BMC medicine

Esketamine's effectiveness and safety for hard-to-treat depression: a detailed analysis of patient data from controlled trials

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Abstract

Re-analysis of data from 1505 patients shows that esketamine combined with an antidepressant reduced depression scores by an average of 2.94 points at 4 weeks compared to placebo.

  • Esketamine in combination with an antidepressant is associated with a moderate reduction in depression scores as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS).
  • A continuation trial indicates a reduced risk of relapse with esketamine treatment.
  • Monotherapy with esketamine appears to show a larger effect on depression scores, though concerns regarding selection bias exist.
  • Esketamine is linked to increased sedation, dissociation, and adverse events, although serious adverse events were not found to be more frequent.
  • No significant differences in treatment effects were observed based on patient age or level of treatment resistance.

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Key numbers

0.38
for Relapse
Efficacy observed in continuation trials for esketamine.
3 points
Mean Difference on
Primary outcome of efficacy in the meta-analysis.
7 times
Increase in Adverse Events
Comparative increase in adverse events reported in trials.

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