Treating Treatment-resistant Depression with Esketamine Nasal Spray When All Therapeutic Options Have Been Exhausted: Clinical Experience from a Spanish Cohort of Expanded Use
Júlia Vendrell-Serres1,2,3, Óscar Soto-Angona1,2,3, Amanda Rodríguez-Urrutia1,2,3,4, Benedetta Inzoli1, Antonia López González1, Josep Antoni Ramos-Quiroga1,2,3,4
1Department of Mental Health, Hospital Universitari Vall d’Hebron, Barcelona, Spain
2Group of Psychiatry, Mental Health and Addictions, Vall d’Hebron Research Institute (VHIR), Barcelona, Spain
3Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
4Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain
Correspondence to: Óscar Soto-Angona
Department of Mental Health, Hospital Universitari Vall d’Hebron, Passeig de la Vall d’Hebron, 119-129, Barcelona 08035, Spain
Received: May 24, 2023; Revised: July 24, 2023; Accepted: August 1, 2023; Published online: September 6, 2023.
© The Korean College of Neuropsychopharmacology. All rights reserved.

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objective: Treatment Resistant Depression (TRD) is commonly defined as the lack of response to two or more antidepressants with different mechanisms of action. Up to 30% of patients diagnosed with major depressive disorder might be considered to present TRD. The objective of this study was to assess the effectiveness and tolerability of esketamine in patients diagnosed with TRD, who were referred to our program after exhausting all available treatments. A secondary objective consisted in researching the relationship between response and previous use of electroconvulsive therapy.
Methods: A prospective, observational study was carried out in patients enrolled in the expanded use of esketamine in our center. They received esketamine prior to its marketing authorisation, for therapeutic purposes. Sixteen subjects were analyzed. Effectiveness was assessed with the Montgomery-Asberg depression rating scale (MADRS). Patients were followed up to 4 months after the administration.
Results: Esketamine showed a rapid, robust effect in improving depressive symptoms, with no specific correlation between outcome and any demographic or clinical traits evaluated. No differences were found between patients that previously received Electroconvulsive Therapy, and those that didn’t. 10 out of 16 patients responded (> 50% change in baseline MADRS scores), but only five achieved remission (< 12 points in the global MADRS score). We provide some recommendations, based on clinical experience, to improve tolerability and adherence, and to manage adverse effects.
Conclusion: Results suggest that esketamine is a safe, effective and rapid-acting option for TRD. More studies are needed to properly assess predictors of response outcome.
Keywords: Esketamine; Depressive disorder, Treatment-resistant; Prospective study; Compassionate use

This Article