Real-world observational data show sustained remission
STUDY: Cuomo A et al, Ther Adv Psychopharmacol 2026;16:1–18
STUDY TYPE: Observational cohort study
FUNDING: Independent
Background
Esketamine was supposed to be a short term med, but most of the use is long-term. Only one well-designed trial supports long-term use, so this real world data adds a useful perspective.
The Study
- Single-center Italian study followed 45 patients with treatment-resistant depression on intranasal esketamine for up to five years
- Median of three antidepressant failures
- Most had psychiatric comorbidities including personality disorders and anxiety
- Esketamine was used adjunctively with ongoing antidepressants
- Depression severity was tracked using the depression scale (MADRS)
Mean MADRS scores fell from 40 at baseline to 23 at week 4 and 10 at one year, with scores holding stable around 9–10 through year five. By year three, nearly all continuing patients were on monthly maintenance dosing at 28 mg.
8/45 patients (18%) stopped treatment: 4 for lack of efficacy, 3 for side effects (dissociation in two, hypertensive crisis in one), and 1 lost to follow-up. No manic episodes emerged (they tracked YMRS mania scores, which declined over time).
Limitations: no control group, everyone was on multiple other medications, and the data heavily favor patients who stayed on treatment (survivor bias).
Practice Implications
- This study can’t prove esketamine caused the improvement, but its real-world perspective lines up with the randomized trial that shows people hold steady.
- On the other hand, there are rare reports of tolerance. One size does not fit all.
— Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
