Real-world comparison of intranasal racemic ketamine and esketamine in treatment-resistant depression: A retrospective observational study

BACKGROUND: Treatment-resistant depression (TRD) imposes major individual and societal burden, with few therapeutic options. Intranasal esketamine is approved but limited by cost and accessibility, prompting interest in alternatives. AIMS: To assess non-inferiority of racemic ketamine versus esketamine in a real-world setting. METHODS: We performed a single-centre, retrospective observational study emulating a randomized trial using the target trial framework. Adults with TRD received either intranasal esketamine or off-label racemic ketamine during an eight-session, four-week induction phase. The primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores; secondary outcome was remission (MADRS ≤12). Safety and tolerability were monitored. MADRS changes were analysed via repeated measures ANOVA; non-inferiority was predefined as