RCT · 2026
How depression symptoms change over 32 weeks with esketamine nasal spray
- Original title
- Trajectory of response to esketamine nasal spray for treatment resistant depression: Findings from ESCAPE-TRD.
- Authors
- Young AH, Bartova L, Cardoner N, et al.
- Journal
- European psychiatry : the journal of the Association of European Psychiatrists, 2026
- Molecules
- Esketamine
- Conditions
- Treatment-resistant depression
- Participants
- 676
- Evidence grade
- Low
- Source
- Read the original paper
The question
In people whose depression has not responded to previous treatments, how do symptoms change over 32 weeks on esketamine nasal spray, and does an early response predict a better long-term outcome?
What they did
The ESCAPE-TRD study was a randomized, open-label phase IIIb trial comparing esketamine nasal spray with extended-release quetiapine, a commonly used add-on antidepressant medication. Of 676 patients with treatment-resistant depression, 336 were assigned to esketamine and 340 to quetiapine. Depression severity was scored with the Montgomery-Åsberg Depression Rating Scale (MADRS), rated by assessors who did not know the treatment assignment. This analysis tracked the path of symptom change to Week 32 and how quickly individual symptoms resolved.
What they found
Most patients on esketamine improved steadily through Week 32, and improving early was linked to better outcomes later. Among those who responded by Week 4, 89.6% reached remission at some point between Week 4 and Week 32. Among those who responded by Week 8, 78.3% reached remission at some point between Week 8 and Week 32. Individual MADRS symptoms tended to resolve sooner and more often with esketamine than with quetiapine. Patients with only partial or minimal early improvement still improved over the longer term.
The fine print
The trial was open-label, so patients and treating clinicians knew which drug was given, which can influence self-reported symptoms even when raters are blinded. These are secondary analyses of trajectories rather than the trial’s main pre-planned comparison, and no placebo group was included. Follow-up stopped at Week 32, and this summary is based on the abstract alone, which does not report safety data or exact between-group differences.
What it means
In this trial, people with treatment-resistant depression who improved early on esketamine nasal spray were likely to reach remission later, and even slower responders tended to keep improving over eight months.
Evidence grade: Low. This is a secondary analysis of an open-label trial in which patients knew which drug they received, although symptom raters did not.
This summary is based on the study’s published abstract.