Intranasal esketamine in treatment-resistant depression: long-term dosing patterns and clinical outcomes in a 5-year observational study.
Alessandro Cuomo, Roger S McIntyre, Despoina Koukouna, Mario Pinzi, Simone Pardossi, Bernardo Firenzuoli, Giovanni Barillà, Pietro Carmellini, Alberto Alamia, Andrea Fagiolini
Therapeutic Advances in Psychopharmacology 2026 DOI: 10.1177/20451253261437597 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort study Peer reviewed |
|---|---|
| Sample size | 45 |
| Population | Patients with treatment-resistant depression treated with intranasal esketamine in a naturalistic setting |
| Intervention | Intranasal esketamine |
| Duration | Up to 260 weeks |
| Topics | Depression Esketamine |
| Keywords | Madrs Dosing patterns Intranasal Long-term outcomes Observational study Person-time analysis Real-world evidence Treatment tolerability |
| Citations | 1 |
| Key findings | Intranasal esketamine used adjunctively was associated with sustained symptom improvement and a favorable long-term safety profile among patients who continued treatment. |
Abstract
Treatment-resistant depression (TRD) remains a major clinical challenge, and long-term real-world data on intranasal esketamine are limited. To describe long-term dosing patterns and clinical outcomes associated with intranasal esketamine in routine clinical practice. Single-center observational cohort study with descriptive analyses. We analyzed 45 patients with TRD treated with intranasal esketamine in a naturalistic setting, with follow-up extending up to 260 weeks. Esketamine was used adjunctively with ongoing oral antidepressants. Outcomes included the Montgomery-Åsberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), and the Glasgow Antipsychotic Side-effect Scale (GASS). Treatment patterns were summarized using person-time (person-weeks). Baseline MADRS was 40.0 (SD 4.63). Mean MADRS decreased to 22.9 (SD 7.99) at week 4 and to 9.70 (SD 5.35) at week 52, with mean scores remaining around 9-10 at later time points among patients with available follow-up. Eight patients (17.8%) discontinued treatment (lack of efficacy n = 4; intolerable adverse effects n = 3; lost to follow-up n = 1). No treatment-emergent hypomania or manic symptoms were observed; YMRS scores decreased over time. GASS scores were low overall, with median values of 0 from week 13 onwards. In a real-world TRD cohort with complex comorbidities, intranasal esketamine used adjunctively was associated with sustained symptom improvement and a favorable long-term safety profile among patients who continued treatment, with dosing evolving from induction to individualized maintenance schedules. Findings are limited by the observational design, concomitant treatments, and survivor bias. Not applicable.
Comparable studies
Other observational and cohort studies on esketamine for depression, most cited first.
Citations in the library
Cites 12
- 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
- Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) The International Journal of Neuropsychopharmacology July 9, 2019
- Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression New England Journal of Medicine October 4, 2023
- Efficacy and Safety of Ketamine vs Electroconvulsive Therapy Among Patients With Major Depressive Episode: A Systematic Review and Meta-analysis. JAMA Psychiatry October 19, 2022
and 7 more in the library