The efficacy and tolerability of inhaled nitrous oxide in major depressive disorder: a systematic review and meta-analysis.

BACKGROUND

Nitrous oxide (NO) 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 NO in MDD.

METHODS

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% NO and placebo.

RESULTS

Four studies with 133 patients were eventually identified. We found that the NO 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 NO 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 NO had higher odds of nausea or vomiting (RR = 10.15, 95% CI 1.96 to 52.59, p = 0.009).

CONCLUSION

Our study suggested that NO 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.