The efficacy and tolerability of inhaled nitrous oxide in major depressive disorder: a systematic review and meta-analysis.
Youjia Qiu, Longyuan Li, Aojie Duan, Menghan Wang, Minjia Xie, Zhouqing Chen, Zhong Wang
Psychopharmacology October 1, 2023 DOI: 10.1007/s00213-023-06449-w (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Meta-analysis Peer reviewed |
|---|---|
| Sample size | 133 |
| Population | Patients with major depressive disorder |
| Topics | Depression |
| Keywords | Meta-analysis N-methyl-d-aspartate receptor antagonist Nitrous oxide |
| Key findings | Nitrous oxide produced significantly greater reductions in depression severity scores at 2 hours, 24 hours, and 2 weeks or more compared with placebo, along with higher response and remission rates. |
Abstract
Nitrous oxide (N2O) has been initially confirmed by clinical trials to benefit to patients with major depressive disorder (MDD). However, there needs to be a meta-analysis to compare the efficacy and tolerability of N2O in MDD. PubMed, EMBASE, and Cochrane Library were searched for relevant studies up to Jan 1st, 2023. The meta-analysis mainly compared the outcome of the change in depression severity scores, response, remission, and adverse events in patients with MDD receiving 50% N2O and placebo. Four studies with 133 patients were eventually identified. We found that the N2O group and control group showed an overall significant difference in the change in depression severity score for patients at 2 h, 24 h, and 2 weeks or more (2 h, SMD = - 0.64, 95% CI - 0.01 to - 0.28, p < 0.0001) (24 h, SMD = - 0.65, 95% CI - 1.01 to - 0.29, p < 0.0001) (2 weeks, SMD = - 0.76, 95% CI - 1.16 to - 0.36, p < 0.0001). For the response and remission rate, the long-term effect of N2O was also statistically significant (for the response, RR = 2.33, 95% CI 1.23 to 4.44, p = 0.01) (for the remission, RR = 4.68, 95% CI 1.49 to 14.68, p = 0.008). For safety outcomes, patients treated with N2O had higher odds of nausea or vomiting (RR = 10.15, 95% CI 1.96 to 52.59, p = 0.009). Our study suggested that N2O has a rapid and long-lasting antidepressant effect in patients with MDD. However, the efficacy of lower or titrated concentration of N2O should be further investigated.
Comparable studies
Other systematic reviews and meta-analyses on depression, most cited first.
Citations in the library
Cited by 4
- Repurposing General Anesthetic Drugs to Treat Depression: A New Frontier for Anesthesiologists in Neuropsychiatric Care. Anesthesiology August 1, 2024
- Rapid antidepressant potential of nitrous oxide: current state and major questions. Molecular Psychiatry June 1, 2026
- A conceptual framework based on current and emerging treatments for treatment-resistant depression: mechanistic evolution, clinical evidence, and future directions. Expert Review of Neurotherapeutics July 1, 2026
- Nitrous oxide for the treatment of depression: a systematic review and meta-analysis. EBioMedicine December 1, 2025
Cites 18
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- Electrophysiologic Characteristics of Nitrous-Oxide-Associated Peripheral Neuropathy: A Retrospective Study of 76 Patients Journal of Clinical Neurology 2023
- Efficacy and safety of nitrous oxide for patients with treatment-resistant depression, a randomized controlled trial. Psychiatry Research November 1, 2022
and 13 more in the library