Intranasal esketamine for treatment-resistant depression: real-world effectiveness in electroconvulsive therapy non-responders

• Rocío Gómez Juanes ^[1] ; Guillermo Mompaler Lázaro ^[2] ; Adoración Castro ^[3] ; Guillem Navarra Navarra Ventura ^[4] ; Josep Antoni Mestre Quetglas Quetglas ; Ana Bolon Marset ; Julia Van der Walt Monasterio ; Jaume Andreu Garcias Trullols ; Miquel Roca ; Margalida Gili ; Joan Salvà ; Mauro Garcia Toro
  1. [1] Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS), Carlos III Health Institute, Madrid, Spain University Institute of Health Science Research (IUNICS), University of the Balearic Islands, Palma, Spain Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain Department of Medicine, University of the Balearic Islands, Palma, Spain
  2. [2] on Llatzer University Hospital, Psychiatric Department, Palma, Spain
  3. [3] Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS), Carlos III Health Institute, Madrid, Spain University Institute of Health Science Research (IUNICS), University of the Balearic Islands, Palma, Spain Department of Psychology, University of Balearic Islands, Palma, Spain
  4. [4] Research Network on Chronicity, Primary Care and Health Promotion (RICAPPS), Carlos III Health Institute, Madrid, Spain b University Institute of Health Science Research (IUNICS), University of the Balearic Islands, Palma, Spain c Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain

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• Localización: European journal of psychiatry, ISSN 0213-6163, Vol. 40, Nº 2, 2026, págs. 1-7
• Idioma: inglés
• DOI: 10.1016/j.ejpsy.2026.100349
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  • Background and Objectives: 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 re- mains 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.

    Methods: 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.

    Results: 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.

    Conclusions: This real-world study suggests the opportunity to promptly test intranasal esketamine in ECT re- fractory subtype of TDR patients