Esketamine nasal spray for treatment-resistant depression: A retrospective multicenter real-world cohort study on effectiveness and suicidal outcomes.

The trajectory and predictors of response under routine clinical care of esketamine nasal spray (ESK NS) over treatment-resistant depression (TRD) require elucidation. This retrospective, longitudinal cohort study was conducted across three Spanish centers. Adults diagnosed with TRD who initiated ESK NS and completed at least the induction phase were included. Assessments occurred at baseline, weeks 2, 4, 8, 12, 16, and at discharge. Primary outcomes included depressive severity assessed with the Montgomery- sberg Depression Rating Scale (MADRS), functioning assessed with the Sheehan Disability Scale (SDS), and suicidal risk assessed with the Columbia-Suicide Severity Rating Scale (C-SSRS). Multivariable logistic regression examined several response predictors. The study included 50 patients (52% women). Significant improvements were observed in MADRS and SDS scores at every time point (all p < 0.001), with notable increases during weeks 8-16, coinciding with optimization phase. The median time to response was 8 weeks, and to remission was 16 weeks. The last observation across the entire cohort indicated response and remission rates of 70% and 68%, respectively. C-SSRS risk categories shifted early toward lower risk with no suicide attempts during monitored treatment. Higher Maudsley Staging Model scores, indicating greater refractoriness, independently predicted lower odds of response (OR: 0.50, 95% CI: 0.29-0.86) and remission (OR: 0.59, 95% CI: 0.36-0.97). Among those discharged, 86% remained clinically stable over approximately 10 months. In real-world clinical setting, ESK NS produces progressive improvements in depressive symptoms and functioning that often consolidating beyond the induction phase, especially during optimization phase.