Compassionate use of esketamine intranasal in patients with severe major depressive disorder resistant to the treatment.
Luis Gutiérrez-Rojas, Julia Vendrell-Serres, Josep Antoni Ramos‐quiroga, Jon Iñaki Etxeandia-Pradera, Eduardo Aguilar, Ana Isabel De Santiago-Díaz, Daniel Hernández-Huerta, Vicente Tordera, Carlos Vázquez-Ventoso, Moisés Bolívar, Asunción Abril, Rubén Catalán-Barragán, Jesús García-Jiménez
Journal of Psychopharmacology 2025 DOI: 10.1177/02698811241267837 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Retrospective observational study Peer reviewed |
|---|---|
| Sample size | 71 |
| Population | Patients with treatment-resistant depression enrolled in an early access program for intranasal esketamine across nine centers |
| Interventions | Esketamine intranasal psychotherapy |
| Duration | 180 days |
| Topics | Depression Esketamine |
| Keywords | Compassionate use Functional impairment Psychotherapy #depression-treatment antidepressants Mental health interventions #esketamine-therapy intranasal esketamine Ketamine treatment Nasal spray antidepressant #treatment-resistant- |
| Citations | 8 |
| Key findings | Intranasal esketamine treatment was associated with a statistically and clinically significant reduction in depressive symptom severity at all time points, and concurrent psychotherapy further improved outcomes at 90 and 180 days. |
Abstract
Treatment-resistant depression (TRD) is defined as the failure of at least two antidepressants in adequate doses and timing during a major depressive episode. Esketamine intranasal (ESK-IN) has been approved by the Food and Drug Administration and the European Medicines Agency for the treatment of TRD in combination with other antidepressants. To assess the effectiveness and tolerability of a sample of TRD patients who received treatment with ESK-IN as part of the compassionate use program. A retrospective, observational study was carried out on patients with a diagnosis of TRD enrolled in the early access program of ESK-IN in nine centers. Effectiveness was assessed with the Montgomery-Asberg depression rating scale (MADRS) at four time points: baseline, 28, 90, and 180 days of treatment. The sample included 71 patients (70% women) with a mean baseline MADRS score of 38.27 ± 5.9 and total or partial work disability rates of 85%. ESK-IN treatment was associated with a statistically and clinically significant reduction in the severity of depressive symptoms at all time points assessed. The presence of side effects was common but the majority were mild in severity and resolved after the observation period. Those patients who received psychotherapy in combination with ESK-IN showed a significantly lower MADRS score at 90 and 180 days than those patients who did not undergo psychotherapy. ESK-IN has proven to be effective and safe in a clinical sample of patients with severe TRD. To optimize clinical outcomes, the pharmacological treatment for TRD should always be integrated into a comprehensive therapeutic plan that encompasses strategies such as psychotherapy, social support, and family interventions.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cited by 7
- A Real-World Study on the Use, Effectiveness, and Safety of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression: INTEGRATE Study. Advances in Therapy May 1, 2025
- Ketamine-assisted psychotherapies for mental disorders: A historical overview and systematic review. Clinical Psychology Review February 2, 2026
- Systematic review and meta-analysis of intranasal esketamine for treatment-resistant depression: Evidence from real-world studies. Journal of Affective Disorders January 28, 2026
- Intranasal esketamine for treatment-resistant depression: real-world effectiveness in electroconvulsive therapy non-responders The European Journal of Psychiatry March 7, 2026
- Esketamine and Acceptance and Commitment Therapy (ACT) for Treatment-Resistant Depression: An Intervention-Development Framework and Treatment Manual Psychedelics October 1, 2026
and 2 more in the library
Cites 16
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
- 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
- Practical recommendations for the management of treatment-resistant depression with esketamine nasal spray therapy: Basic science, evidence-based knowledge and expert guidance The World Journal of Biological Psychiatry November 3, 2020
and 11 more in the library