2025-12-01 バーミンガム大学
<関連情報>
- https://www.birmingham.ac.uk/news/2025/clinical-use-of-nitrous-oxide-could-help-treat-depression-major-study-shows
- https://www.thelancet.com/journals/EBIOM/article/PIIS2352-3964(25)00467-0/fulltext
うつ病治療における亜酸化窒素:系統的レビューとメタアナリシス Nitrous oxide for the treatment of depression: a systematic review and meta-analysis
Kiranpreet Gill ∙ Angharad N. de Cates ∙ Chantelle Wiseman ∙ Susannah E. Murphy ∙ Ella Williams ∙ Catherine J. Harmer ∙ et al.
eBiomedicine Published:Published November 30, 2025
DOI:https://doi.org/10.1016/j.ebiom.2025.106023
Summary
Background
Depression remains a global public health challenge, prompting interest in translational targets which allow for more effective and rapidly acting interventions. Nitrous oxide (N2O), an N-methyl-d-aspartate receptor antagonist, has demonstrated potential as a rapid-acting antidepressant. This study synthesised existing data on the efficacy and safety of N2O in depressive disorders.
Methods
We systematically reviewed clinical trials, exploratory studies, and protocol papers evaluating N2O for the treatment of depression, including major depressive disorder (MDD), treatment-resistant depression (TRD), and bipolar depression, following PRISMA guidelines. Meta-analysis was completed where possible. Primary outcomes were change in depressive symptoms and adverse events (AEs). Pooled mean differences (MD) and relative risk ratios were calculated using random- or fixed-effects models. Evidence mapping described trial characteristics across completed and ongoing studies.
Findings
Seven clinical trials involving 247 participants with depressive disorders, and four protocol papers were reviewed. N2O was administered via inhalation at 25% or 50%, as single or repeated sessions, with comparators including air, oxygen, or midazolam. Pooled results from three trials administering 50% N2O in a single session showed significant reductions in depressive symptoms at 2 h (pooled MD -2.74, 95% Confidence Interval (CI): -4.72 to -0.76; p = 0.007) and 24 h (MD -3.32, 95% CI: -5.09 to -1.55; p < 0.0001), but not at 1 week post-inhalation (MD -1.52; 95% CI: -4.07 to 1.03; p = 0.24). AEs were mild and transient, with 25% N2O generally being better tolerated. Evidence mapping showed that most trials are early-phase and focused on short-term outcomes in adults with MDD and TRD.
Interpretation
N2O demonstrates rapid, reproducible antidepressant effects in early-phase trials. Its future clinical value depends on whether these effects can be sustained over time through optimised dosing and extended/repeated use. Improved trial design, outcome standardisation, and population diversity is required to clarify its full potential for the treatment of depression.
Funding
The funder had no role in study design, data collection, analysis, interpretation, or writing.
