Efficacy of Intranasal Esketamine in Treatment-Resistant Depression: A Six-Month Real-World Follow-Up Study of Depressive Symptoms, Hopelessness, and Suicide Risk.
Maurizio Pompili, Maria Anna Trocchia, Ludovica Longhini, Eva Dispenza, Cristina Di Legge, Salvatore Sarubbi, Denise Erbuto, Isabella Berardelli
Human Psychopharmacology: Clinical and Experimental July 1, 2025 DOI: 10.1002/hup.70008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 21 |
| Population | Patients diagnosed with treatment-resistant depression |
| Intervention | Intranasal esketamine |
| Duration | 6-month follow-up |
| Topics | Depression Esketamine |
| Keywords | Suicide prevention Suicide risk Treatment‐resistant depression Depression treatment |
| Citations | 3 |
| Key findings | Intranasal esketamine was associated with decreased depressive symptoms, reduced suicidal ideation, and lower hopelessness at 3-month and 6-month follow-ups in treatment-resistant depression. |
Abstract
Treatment-resistant depression is one of the most significant clinical challenges in psychiatric practice. The primary aim of the present study was to assess the efficacy and tolerability of intranasal esketamine on depressive symptoms in a real-world outpatient setting. A secondary objective was to explore the potential benefits of intranasal esketamine on hopelessness and suicide risk (suicidal ideation and suicide attempts). Twenty-one patients diagnosed with treatment-resistant depression were treated with intranasal esketamine. Depressive symptoms (MADRS and BDI), suicide risk (C-SSRS), and hopelessness (BHS) were assessed. We conducted a mixed model for repeated measures analysis to evaluate changes from baseline (T0), 3-month follow-up (T1), and 6-month follow-up (T2). Results indicated that depressive symptoms decreased over time. Specifically, both clinician and self-report measures show lower levels of depressive symptoms at 3-month and 6-month follow-up. We also found a significant decrease in the presence of suicidal ideation between T0 and T2. Finally, patients also reported a reduction in hopelessness levels over time. Our findings indicate an overall response regarding depressive symptoms, hopelessness, and suicidal ideation after esketamine in treatment-resistant depression at 3-month and 6-month follow-up assessments.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cited by 5
- 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
- Intranasal esketamine for treatment-resistant depression: real-world effectiveness in electroconvulsive therapy non-responders The European Journal of Psychiatry March 7, 2026
- Profiling intranasal esketamine for adults with major depressive disorder and acute suicidal ideation or behavior: a phenotype-informed drug profile Expert Review of Neurotherapeutics August 18, 2026
- Real-world clinical practice, effectiveness and safety of esketamine nasal spray in major depressive disorder patients: a French prospective cohort (ELLIPSE study) Therapeutic Advances in Psychopharmacology August 1, 2026
- Beyond symptom reduction: Intranasal esketamine is associated with improved quality of life in treatment-resistant depression. Journal of Psychiatric Research September 7, 2026
Cites 18
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- 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 and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression JAMA Psychiatry December 27, 2017
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
and 13 more in the library