Intranasal esketamine for treatment-resistant depression: real-world effectiveness in electroconvulsive therapy non-responders
Rocío Gómez-juanes, Guillermo Mompaler Lázaro, Adoración Castro, Guillem Navarra-Ventura, Josep Antoni Mestre Quetglas, Ana Bolon Marset, Julia van der Walt Monasterio, Jaume Andreu Garcias Trullols, Miquel Roca, Margalida Gili, Joan Salvà, Mauro Garcia-Toro
The European Journal of Psychiatry March 7, 2026 DOI: 10.1016/j.ejpsy.2026.100349 via OpenAlex
Summary
AI-generated from the abstractIntranasal esketamine is a newer treatment for Treatment-Resistant Depression (TRD), but its long-term benefits in real-world settings remain uncertain. A 6-month observational study of 60 highly chronic and complex TRD patients (average episode length 41.2 months, 61.6% with psychiatric comorbidity) found that depression scores (MADRS) dropped from an average of 33.9 at baseline to 15.7 at 6 months. Patients who had not responded to prior electroconvulsive therapy (ECT) showed no significant difference in therapeutic response compared to those who had not tried ECT. The findings suggest that intranasal esketamine may be worth testing promptly in TRD patients who have not responded to ECT.
Study at a glance
| Characteristics | Observational study Peer reviewed |
|---|---|
| Sample size | 60 |
| Population | Patients with Treatment-Resistant Depression (TRD) who had not responded to prior electroconvulsive therapy or for whom ECT had not been attempted |
| Intervention | Intranasal esketamine |
| Duration | 6-month intervention and follow-up |
| Citations | 1 |
| Key finding | Intranasal esketamine reduced depression scores over 6 months, but prior non-response to ECT did not significantly affect therapeutic outcomes. |
Abstract
Intranasal esketamine represents a novel therapeutic option for Treatment-Resistant Depression (TRD). However, its medium-to-long-term risk-benefit profile in real-world clinical practice remains controversial. Limited data is available regarding its effectiveness, particularly in patients who have not responded to electroconvulsive therapy (ECT), which is the focus of this study. We conducted a 6-month observational study investigating intranasal esketamine treatment in the first TRD patients managed at our care centers. We compared outcomes between patients who had not responded to prior ECT and those for whom ECT had not been attempted. The sample comprised 60 patients exhibiting high chronicity (mean episode duration: 41.2 ± 54.7 months) and complexity, with psychiatric comorbidity observed in 37 cases (61.6%). The mean Montgomery-Åsberg Depression Rating Scale (MADRS) score decreased from a baseline of 33.9 ± 7.8 to 15.7 ± 9.6 at 6 months. No significant differences in therapeutic responses were observed in patients who had not responded to ECT during the current episode. This real-world study suggests the opportunity to promptly test intranasal esketamine in ECT refractory subtype of TDR patients.