ArticleBiological psychiatry global open science2025
Antidepressant Effects of Nitrous Oxide in Major Depressive Disorder: A Phase 2b Randomized Clinical Trial.
Article in Biological psychiatry global open science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 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.
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Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Nitrous oxide for the treatment of depression: a systematic review and meta-analysis.EBioMedicine · 2025Pooled it
- Rapid antidepressant potential of nitrous oxide: current state and major questions.Molecular psychiatry · 2026Review
- No Laughing Matter: Nitrous Oxide and Depression.Biological psychiatry global open science · 2025Article
- Novel and emerging anesthetic drugs for the treatments of major depression: a comprehensive review of efficacy, mechanism, and outlook.Frontiers in psychiatry · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Nitrous oxide ("laughing gas") is an NMDA receptor antagonist. In the current study, our aim was to investigate the efficacy, safety, and likely optimal dose of nitrous oxide in adults with major depressive disorder (MDD). Methods: In this phase 2b randomized, double-blind trial, 81 patients with MDD were allocated on a 1:1 basis to receive nitrous oxide or oxygen/air (control); the nitrous group was further randomized to either 50% or 25% inspired nitrous oxide. All participants received four 1-hour-long treatment sessions at 1-week intervals and were followed for an additional 4 weeks. The primary outcome was the change in the 21-item Hamilton Depression Rating Scale (HAM-D) over the 4 treatment sessions. Secondary outcomes included remission (HAM-D ≤7 points), the Computerized Adaptive Test-Depression Inventory (CAT-DI) and Computerized Adaptive Test-Suicide Scale (CAT-SS). Results: The mean averaged change in HAM-D scores over the 4 weeks of treatment was lower with nitrous oxide than with control (-1.9 [95% CI, -3.9 to 0.0], Conclusions: In this study, we confirmed that nitrous oxide has likely beneficial antidepressant effects in people with MDD.
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Registered trials
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