Esketamine Treatment Trajectory of Patients with Treatment-Resistant Depression in the Mid and Long-Term Run: Data from REAL-ESK Study Group.
Gianluca Rosso, Giacomo d'Andrea, Stefano Barlati, Marco Di Nicola, Ileana Andriola, Matteo Marcatili, Vassilis Martiadis, Miriam Olivola, Stefania Di Mauro, Gabriele Di Salvo, Pasquale De Fazio, Massimo Clerici, Bernardo Maria Dell'Osso, Antonio Vita, Giorgio Di Lorenzo, Mauro Pettorruso, Giovanni Martinotti, Giuseppe Maina
Current Neuropharmacology 2025 DOI: 10.2174/011570159X337670241029062524 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational, retrospective, multicentric study Peer reviewed |
|---|---|
| Sample size | 63 |
| Population | Patients with treatment-resistant depression |
| Intervention | Esketamine Nasal Spray |
| Duration | 6-month and 12-month follow-up |
| Topics | Depression Esketamine |
| Keywords | Antidepressants Maintenance treatment Treatment outcome. Depression treatment Antidepressant therapy Mental health breakthrough |
| Citations | 23 |
| Key findings | 76.2% of patients who maintained esketamine nasal spray for at least six months were responders or remitters, and a subgroup of initial non-responders improved by twelve months. |
Abstract
Data on long-term treatment with Esketamine Nasal Spray (ESKNS) in real-world patients with treatment resistant depression (TRD) is scarce. The primary aim of the study is to evaluate the effectiveness and tolerability of ESK-NS treatment at 6 and 12-month follow-ups. This is part of an observational, retrospective, multicentric Italian study (REAL-ESK study). Subjects for the present study underwent psychiatric assessments after 6 and 12 months from the start of ESK-NS treatment. Repeated measures analysis of variance (ANOVA) was used to assess changes in continuous variables, such as scores on psychometric scales from baseline to follow-up time points. Of 63 patients who maintained ESK-NS treatment for at least 6 months, 48 were responders or remitters (76.2%). Among 15 non-responders at 6 months, 4 significantly improved at 12-month follow-up. At least one side effect was reported by 71.8% of subjects with a 6-month follow-up assessment. An overall reduction of side effects was noticed as treatment progressed (42% of patients who continued the treatment reported side effects at 12 months). The most common side effects were sedation (31.7%) and dissociation (28.6%) during ESK-NS sessions. Only 2 patients discontinued ESK-NS for tolerability reasons. The results support the effectiveness and safety of esketamine in the mid and long-term treatment of TRD patients. The late clinical response of a subgroup of patients represents a novel finding. Data needs to be confirmed in larger samples and longer observation periods.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cited by 18
- Treatment-resistant depression and intranasal esketamine: Spanish clinical consensus on practical aspects The European Journal of Psychiatry May 2, 2025
- Esketamine in treatment-resistant depression with and without comorbid borderline personality disorder: A real-world longitudinal study of suicidal ideation and self-harm. Asian Journal of Psychiatry June 1, 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
- Endocannabinoids, depression, and treatment resistance: Perspectives on effective therapeutic interventions Psychiatry Research August 18, 2025
- Sustained effectiveness and safety of esketamine for major depressive disorder: a target trial simulation of real-world data. Translational Psychiatry April 10, 2026
and 13 more in the library
Cites 6
- 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 versus Quetiapine for Treatment-Resistant Depression New England Journal of Medicine October 4, 2023
- Predicting outcome with Intranasal Esketamine treatment: A machine-learning, three-month study in Treatment-Resistant Depression (ESK-LEARNING) Psychiatry Research July 29, 2023
- Predictors of response and remission in patients with treatment-resistant depression: A post hoc pooled analysis of two acute trials of esketamine nasal spray Psychiatry Research March 15, 2023
and 1 more in the library