SynthesisFrontiers in psychiatry2026
Intranasal esketamine plus oral antidepressant for treatment-resistant depression: acute induction and maintenance relapse-prevention outcomes in a systematic review and meta-analysis.
Synthesis in Frontiers in psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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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.
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Who cites it
1 citing paper in PubMed.
- Engineering Advanced Nanomedicine Against Depression: From Treatment Challenges to Delivery Strategies.Advanced healthcare materials · 2026Review
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Authors and funding
3 authors.
Funding
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Abstract
Treatment-resistant depression (TRD) remains a major clinical challenge. Intranasal esketamine, used adjunctively with an oral antidepressant, has been evaluated in randomized trials, but uncertainty persists regarding the magnitude and consistency of benefit, durability, and key harms. This systematic review and meta-analysis included randomized controlled trials comparing intranasal esketamine plus an oral antidepressant versus placebo nasal spray plus the same oral antidepressant in TRD. Acute induction (≈4 weeks) and maintenance randomized-withdrawal phases were analyzed separately. Depression outcomes were assessed primarily using the Montgomery-Åsberg Depression Rating Scale (MADRS), and functional outcomes using the Sheehan Disability Scale (SDS). Two reviewers independently screened studies, extracted data, and assessed risk of bias using RoB 2.0. Random-effects models pooled mean differences (MD) for continuous outcomes, risk ratios (RR) for binary outcomes, and hazard ratios (HR) for relapse prevention. Certainty of evidence was rated using GRADE. From 1,518 records, nine reports representing six unique RCTs (1,836 participants) were included. Four acute induction RCTs (n=937) showed greater symptom reduction at day 28 with esketamine (MADRS MD -2.99, 95% CI -5.10 to -0.89; I²=48.5%). Rapid improvement was evident by day 2 (MD -3.25, 95% CI -4.65 to -1.85). Esketamine increased day-28 response (RR 1.44, 95% CI 1.20-1.74) and remission (RR 1.52, 95% CI 1.20-1.92), corresponding to approximately +154 responders and +106 remitters per 1,000 patients, respectively, based on pooled control risks. Functioning improved (SDS MD -1.70, 95% CI -2.61 to -0.79). Two maintenance randomized-withdrawal RCTs (n=899) demonstrated reduced relapse risk with continued esketamine (HR 0.51, 95% CI 0.42-0.62; I²=0%). In acute induction, esketamine increased any treatment-emergent adverse event (TEAE) (RR 1.37, 95% CI 1.25-1.50) and discontinuation due to adverse events (RR 2.68, 95% CI 1.35-5.29), with notable increases in dissociation (RR 7.33, 95% CI 4.49-11.98) and blood pressure increased events (RR 3.96, 95% CI 2.24-7.01). Maintenance TEAE rates were similar between groups (RR 1.07, 95% CI 0.99-1.17). Intranasal esketamine plus an oral antidepressant provides rapid, modest acute improvement and reduces relapse risk during maintenance among stabilized responders/remitters, but increases acute adverse events, supporting use within supervised care and individualized benefit-risk assessment.
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