Nitrous oxide for late-life depression with inadequate antidepressant response: a randomised controlled trial
Background: O) may offer a new therapeutic avenue with rapid and safe antidepressant effects in late-life depression with inadequate antidepressant response. Methods: O group) or medical air (placebo group). The primary outcome was change in MADRS score from baseline to 2 weeks, analysed under the intention-to-treat principle with a linear mixed-effects model using all available data. Secondary outcomes included clinician- and self-rated depressive symptom scales and safety. The study is complete and registered in ClinicalTrials.gov (NCT05007028). Findings: O experienced a significant and sustained reduction in depressive symptoms compared to the placebo group. The antidepressant effect was rapid, with significant improvements noted as early as 24 h and at one week. At the two-week endpoint, the N2O group showed a significantly greater reduction in MADRS scores (-6.2 points; 95% CI: -9.1 to -3.4; P < 0.001). These positive findings were supported by both clinician- and self-rated questionnaires, and all reported adverse events were mild and transient. Interpretation: O offers a new therapeutic strategy with rapid, sustained and safe antidepressant effects in late-life depression with inadequate antidepressant response. Funding: This study was supported by a grant from the French Ministry of Health and Prevention.
Authors
- Hélène Bourgoin
- Amélie Le Gouge (ORCID: https://orcid.org/0000-0001-6734-5685)
- Thomas Desmidt (ORCID: https://orcid.org/0000-0003-0949-8389)
- Paul Brunault (ORCID: https://orcid.org/0000-0001-9317-228X)
- Quentin Gallet (ORCID: https://orcid.org/0000-0002-1772-7922)
- Victoire Leroy (ORCID: https://orcid.org/0000-0003-4392-3553)
- Jacques‐Alexis Nkodo (ORCID: https://orcid.org/0000-0001-5613-1622)
- Samuel Bulteau (ORCID: https://orcid.org/0000-0003-4855-2173)
- Fabien Espitalier (ORCID: https://orcid.org/0000-0001-6803-0976)
- Marie-Sara Agier
- Valérie Gissot (ORCID: https://orcid.org/0000-0002-0091-8159)
- Anaïs Vandevelde (ORCID: https://orcid.org/0000-0001-5197-6351)
- Nicolas Arlicot (ORCID: https://orcid.org/0000-0001-7087-2312)
- Vincent Camus
- Antony Salamé
- Pierre Poupin
- Gabriel Robert
- Wissam El-Hage
Institutions
- Université de Tours (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut de Recherche en Informatique et Systèmes Aléatoires (FR)
- Centre Hospitalier Universitaire de Tours (FR)
- Clinical Investigation Center Plurithematic Tours (FR)
- Laboratoire de Thermique et Energie de Nantes (FR)
- Centre Hospitalier Universitaire d'Angers (FR)
- CIC Rennes (FR)
- Centre d'Investigation Clinique de Nantes (FR)
- Centre Hospitalier Universitaire de Rennes (FR)
- Empenn (FR)
- Université de Rennes (FR)
- Nantes Université (FR)
Publication Details
- Journal
- EClinicalMedicine
- Published
- 2026-04-01
- DOI
- https://doi.org/10.1016/j.eclinm.2026.103860
- Primary Topic
- Treatment of Major Depression
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Direction Générale de l’offre de Soins
- Ministère des Solidarités et de la Santé