SynthesisBMC medicine2025
Efficacy and safety of esketamine for "treatment resistant depression": registered report for a systematic review with an individual patient data meta-analysis of randomized, double-blind, placebo-controlled trials.
Synthesis in BMC medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Intranasal esketamine plus oral antidepressant for treatment-resistant depression: acute induction and maintenance relapse-prevention outcomes in a systematic review and meta-analysis.Frontiers in psychiatry · 2026Pooled it
- Intranasal administration in modulating depressive-like behavior and reconstructing treatment paradigms through neuroinflammation and neurotrophic pathways.Journal of nanobiotechnology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
backgroundIn 2019, the FDA and EMA approved intranasal esketamine for treatment-resistant depression (TRD). The current study re-evaluated its efficacy and safety.
methodsThis registered report presents a systematic review and individual patient data (IPD) meta-analysis of double-blind, randomised, placebo-controlled trials (RCTs) assessing intranasal esketamine for TRD. Two reviewers independently screened studies from multiple databases and obtained IPD via the Yale Open Data Access Project. Two independent researchers selected studies and assessed risk of bias. The primary outcome was the Montgomery-Åsberg Depression Rating Scale (MADRS) score at ≥ 4 weeks in initiation trials, benchmarked against the 6.5-point clinical significance threshold used in the design of pivotal trials. Evidence certainty was rated using GRADE. Secondary outcomes included additional efficacy and safety endpoints. A two-step IPD meta-analysis was conducted, with separate analyses by trial phase (initiation vs. continuation) and treatment type (combination vs. monotherapy). A one-stage meta-analysis explored moderators (e.g. age and resistance level).
resultsWe re-analysed IPD from 7 RCTs including 1505 patients. In five initiation trials of esketamine plus an antidepressant, esketamine reduced MADRS scores at 4 weeks (mean difference (MD) = - 2.94, 95% CI [- 5.39 to - 0.48]; GRADE: moderate certainty). A continuation trial showed reduced relapse risk (HR = 0.38 [0.26-0.57]), though FDA concerns about one centre could not be addressed due to data privacy restrictions. A monotherapy trial (aggregate data only) showed a larger effect (MD = - 6.32 [- 8.62 to - 4.03]), but there were concerns over selection bias and unblinding. Esketamine increased sedation (RR = 3.70 [2.02-6.78]), dissociation (RR = 2.36 [2.10-2.65]), and adverse events (IRR = 3.91 [2.37-6.45]), with no increase in serious adverse events (IRR = 1.35 [0.54-3.40]). No treatment effect moderation was found by age or resistance level, with most patients displaying low-stage TRD.
conclusionsBased on the IPD used for approval, esketamine in combination with an antidepressant showed an advantage over placebo that was statistically significant but small. The clinical relevance of this benefit is unclear, particularly given the risks of adverse events. STUDY REGISTRATION: PROSPERO: CRD42021290721.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.