Intranasal esketamine in treatment-resistant depression: long-term dosing patterns and clinical outcomes in a 5-year observational study.
Alessandro Cuomo, Roger Mcintyre, Despoina Koukouna, Mario Pinzi, Simone Pardossi, Bernardo Firenzuoli, Giovanni Barillà, Pietro Carmellini, Alberto Alamia, Andrea Fagiolini
Therapeutic advances in psychopharmacology January 1, 2026 Peer reviewed DOI: 10.1177/20451253261437597 via PubMed
Summary
In a cohort of 45 patients with treatment-resistant depression (TRD), long-term use of intranasal esketamine led to significant symptom improvement, with Montgomery-Åsberg Depression Rating Scale (MADRS) scores decreasing from a baseline of 40.0 to 9.70 at week 52. Most patients maintained low scores over time, and only 17.8% discontinued treatment due to lack of efficacy or adverse effects. The study indicates that esketamine can be effective and well-tolerated in real-world settings.
Study at a glance
| Design | observational cohort |
|---|---|
| Sample size | 45 |
| Population | patients with treatment-resistant depression |
| Key finding | Intranasal esketamine 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.