Esketamine nasal spray for treatment-resistant depression: A retrospective multicenter real-world cohort study on effectiveness and suicidal outcomes.
Jesús García-Jiménez, D Nuñez-arias, G Carretero Merelo, A Miller, A Martínez Romero, Luis Gutiérrez-Rojas, J E Mesones Peral
Journal of Psychopharmacology March 21, 2026 DOI: 10.1177/02698811261430495 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective longitudinal cohort study Peer reviewed |
|---|---|
| Sample size | 50 |
| Population | Adults diagnosed with treatment-resistant depression who initiated esketamine nasal spray and completed at least the induction phase |
| Intervention | Esketamine nasal spray |
| Duration | Induction phase plus optimization phase through weeks 8–16, with assessments at baseline, weeks 2, 4, 8, 12, 16, and at discharge; among those discharged, follow-up approximately 10 months |
| Topics | Depression Esketamine |
| Keywords | C-ssrs Madrs Maudsley staging method Sds Real-world evidence Suicide risk |
| Key findings | Esketamine nasal spray produced progressive improvements in depressive symptoms and functioning, with higher baseline treatment refractoriness predicting lower odds of response and remission. |
Abstract
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-Åsberg 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.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cites 20
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study American Journal of Psychiatry April 16, 2018
- Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II) The International Journal of Neuropsychopharmacology August 26, 2020
- Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression The Journal of Clinical Psychiatry April 20, 2020
- Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression New England Journal of Medicine October 4, 2023
and 15 more in the library