Functional outcomes with esketamine in treatment-resistant depression: A 6-month multicenter real-world study.
Riccardo Guglielmo, Miriam Olivola, Alberto Inuggi, Elisa Cavanna, Elisa Briasco, Beatriz Pereira da Silva, Andrea Escelsior, Gabriele Giacomini, Giovanni Martinotti, Bernardo Maria Dell'Osso, Mario Amore, Gianluca Serafini
European psychiatry : the journal of the Association of European Psychiatrists June 10, 2026 DOI: 10.1192/j.eurpsy.2026.12233 via PubMed
Summary
AI-generated from the abstractOver six months of routine esketamine treatment for treatment-resistant depression, depressive symptoms and daily functioning both improved progressively. By month six, 78.3% of patients showed a symptomatic response and 46.7% reached symptomatic remission, while 78.3% showed a functional response but only 33.3% achieved functional remission. Functional remission accumulated more slowly than symptomatic remission, with cumulative rates of 5% at one month, 15% at three months, and 33.3% at six months. Higher baseline disability and more previous antidepressant trials were linked to lower odds of functional remission at six months. The findings suggest that functional improvement follows a distinct trajectory from symptom improvement and should be monitored separately in treatment-resistant depression.
Study at a glance
| Characteristics | Prospective multicenter study Peer reviewed |
|---|---|
| Sample size | 60 |
| Population | Patients with treatment-resistant depression initiating intranasal esketamine augmentation |
| Intervention | intranasal esketamine augmentation |
| Duration | 6-month follow-up |
| Topics | Depression Esketamine |
| Keywords | Functional remission Long-term outcomes Real-world study |
| Key finding | Functional remission followed a slower trajectory than symptomatic remission over six months of esketamine treatment, with only 33.3% of patients achieving functional remission compared to 46.7% symptomatic remission, and higher baseline disability and more prior antidepressant trials predicted lower odds of functional remission. |
Abstract
Esketamine has demonstrated efficacy in treatment-resistant depression (TRD), but medium-term real-world functional outcomes remain understudied. This study described 6-month depressive symptoms and functional trajectories during routine esketamine treatment, focusing on functional outcomes and remission correlates. In this prospective multicenter study, 60 patients with TRD initiating intranasal esketamine augmentation were assessed at baseline, Month 1, Month 3, and Month 6 using the Montgomery-Åsberg Depression Rating Scale (MADRS) and Sheehan Disability Scale (SDS). Mixed-effects models, Turnbull interval-censored time-to-remission analysis, logistic regression, and ROC analyses were performed. MADRS and SDS improved significantly at all follow-up time points (p < 0.001). At Month 6, symptomatic response and remission rates were 78.3 and 46.7%, while functional response and remission rates were 78.3 and 33.3%, respectively. Turnbull estimates showed cumulative functional remission rates of 5.0, 15.0, and 33.3% at Months 1, 3, and 6, respectively. MADRS-SDS correlations decreased over time, supporting partial symptomatic-functional dissociation. Higher baseline SDS (OR = 0.73, 95% CI: 0.59-0.89) and more previous antidepressant trials (ADTs; OR = 0.53, 95% CI: 0.35-0.82) were associated with lower odds of Month 6 functional remission; bootstrap internal validation supported coefficient stability. ROC-derived thresholds were considered sample-dependent and not clinically validated. Cumulative esketamine dosage was associated with functional response but not remission. Depressive symptoms and functioning improved progressively over 6 months during esketamine treatment in routine clinical care. Functional remission followed a slower trajectory than symptomatic remission and had partly distinct correlates, supporting functional monitoring as a distinct TRD outcome.