Open-label trial · 2026
Esketamine nasal spray over two extra years: relapse and side effects in hard-to-treat depression
- Original title
- Long-term treatment with esketamine nasal spray in patients with treatment resistant depression: Results from the ESCAPE-LTE study.
- Authors
- Reif A, Anıl YA, Bitter I, et al.
- Journal
- European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2026
- Molecules
- Esketamine
- Conditions
- Treatment-resistant depression
- Participants
- 183
- Evidence grade
- Low
- Source
- Read the original paper
The question
Can esketamine nasal spray keep people with treatment-resistant depression well over the long term, and is it tolerated safely for more than two years?
What they did
ESCAPE-LTE was a two-year (104-week) extension of an earlier 32-week trial that compared esketamine nasal spray plus an ongoing antidepressant with an active comparator. In the extension, 183 patients continued on esketamine nasal spray with no control group. The main measures were treatment-emergent side effects and suicidal thoughts or behaviour, assessed with a standard suicide rating scale. Depression severity and quality of life were also tracked, with results reported from the start of the first trial through 136 weeks of treatment.
What they found
Side effects of some kind occurred in 96.7% of patients, and serious side effects in 8.2%. Of the side effects that happened on dosing days, 98.3% resolved the same day, and 3.3% of patients stopped treatment because of side effects during the extension. Among the 160 patients who were not suicidal at the start, 151 (94.4%) remained non-suicidal at the end. Among those who had reached remission in the first trial, 79.2% neither relapsed nor discontinued during the extension, and the overall relapse rate for patients who achieved remission across both studies was 6.9%.
The fine print
The extension had no comparison group and everyone knew they were receiving esketamine, so expectation effects cannot be ruled out. Only patients who did well enough to continue from the first trial entered this phase, which favours better results. Nearly all participants reported some side effect, and the abstract does not describe what those were. This summary is based on the abstract only.
What it means
In people with treatment-resistant depression who had already responded to esketamine nasal spray, most stayed well over more than two years of continued treatment, and no new safety problems emerged. Because there was no control group, these figures describe what happened to a selected group rather than proving the drug caused the sustained benefit.
Evidence grade: Low. This was a single-arm, open-label extension with no comparison group, so improvements and relapse rates cannot be attributed to the drug alone.
This summary is based on the study’s published abstract.