Meta-analysis · 2026
Pooled real-world data on nasal esketamine for hard-to-treat depression
- Original title
- Systematic review and meta-analysis of intranasal esketamine for treatment-resistant depression: Evidence from real-world studies.
- Authors
- de Oliveira Lapa C, Viola T, Delfino R, et al.
- Journal
- Journal of affective disorders, 2026
- Molecules
- Esketamine
- Conditions
- Treatment-resistant depression
- Evidence grade
- Low
- Source
- Read the original paper
The question
Does intranasal esketamine work as well in everyday clinical practice as it did in randomized trials for people whose depression has not responded to other treatments?
What they did
Researchers searched three research databases up to April 2025 for observational studies (real-world records of patients being treated, with no placebo comparison) of nasal spray esketamine in adults with treatment-resistant depression. Nine studies met their criteria. They pooled the results statistically to estimate changes in depression symptoms, the odds of remission over time, and how often side effects occurred. The plan was registered in advance.
What they found
Depression scores dropped substantially, with a pooled effect size of Hedges’ g = -1.98 (95% confidence interval -2.94 to -1.03; p < 0.0001). Patients were about five times more likely to be in remission at three months than at the earlier induction phase (odds ratio 5.1, 95% CI 2.29 to 11.39). Results did not appear to differ by gender or by the presence of anxiety, personality or substance use disorders. Among studies reporting safety data, 82% of patients had at least one side effect (95% CI 69 to 92), most commonly dissociation, a temporary sense of detachment from oneself or one’s surroundings, in 49% (95% CI 37 to 62).
The fine print
All included studies were observational with no control or placebo group, so improvement cannot be attributed to esketamine alone. Only nine studies were pooled, and the abstract does not report the total number of patients or the length of follow-up beyond three months. Results varied enough that the confidence intervals are wide. This summary is based on the abstract only.
What it means
In routine care, people taking nasal esketamine for treatment-resistant depression showed meaningful symptom reduction and increasing remission over three months, but without comparison groups the size of the drug’s own contribution remains uncertain.
Evidence grade: Low. It pools nine observational studies with no control groups, so the large effect size cannot be separated from natural improvement, expectation or other care.
This summary is based on the study’s published abstract.