Efficacy and acceptability of ketamine and esketamine in adults with treatment-resistant major depressive disorder: systematic review and meta-analysis
Open Science Framework January 1, 2026 Annemarie van der Meij, Sotiris Poyiadis, Andrea Cipriani et al.
This preregistration describes an update and extension of a meta-analysis examining ketamine and esketamine for adults with treatment-resistant major depressive disorder. The project is nested within a larger network meta-analysis of next-step strategies for treatment-resistant depression. It restricts interventions to ketamine and esketamine regimens versus placebo, structures outcomes into three time windows (24–72 hours, 1–3 weeks, and 4–12 weeks), and pools results using pairwise random-effects meta-analyses rather than network meta-analysis due to expected lack of direct comparisons between treatment nodes. Short-term outcomes will be extracted from longer-term trials. Subgroup and meta-regression analyses are exploratory.