EClinicalMedicine
April 2, 2026
Antony Salamé, Samuel Bulteau, Gabriel Robert et al.
A single 60-minute inhalation of 50% nitrous oxide (N2O) significantly reduced depressive symptoms in older adults (aged 60–90) with late-life depression who had not responded to at least one adequate antidepressant trial. In a double-blind, randomized, placebo-controlled trial with 60 participants, those receiving N2O showed a greater reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) scores at two weeks compared to placebo (−6.2 points; 95% CI: −9.1 to −3.4). Improvements were rapid, appearing within 24 hours and persisting at one week. All adverse events were mild and transient. The findings suggest N2O may be a safe and effective rapid-acting treatment for this difficult-to-treat population, though further studies are needed to confirm long-term efficacy and safety.
International Psychogeriatrics
December 1, 2023
Thomas Desmidt
Nitrous oxide (N2O) shows promise as a fast-acting antidepressant for treatment-resistant depression (TRD), especially in older adults. Its mechanisms may include NMDA receptor antagonism and cerebral vasodilation, which could improve drug delivery and address resistance linked to poor cerebrovascular function. N2O is not metabolized by the kidney or liver, potentially making it safer for older adults. Review of available data on efficacy, safety, and pathophysiology is presented, along with results showing reduced anterior cingulate cortex connectivity and increased brain tissue pulsations during successful N2O treatment. Ongoing RCTs in older adults with TRD and neurocognitive disorders are discussed.
Molecular psychiatry
September 1, 2023
Thomas Desmidt, Paul-Armand Dujardin, Frédéric Andersson et al.
A single one-hour session of a 50:50 nitrous oxide/oxygen mixture (EMONO) rapidly alters functional connectivity in the default mode network and increases brain tissue pulsations in depressed women who respond to the treatment. Among 20 women with treatment-resistant depression, 45% showed at least a 50% reduction in depression scores one week after exposure. Responders exhibited decreased connectivity between the subgenual anterior cingulate cortex and the precuneus, and a larger early increase in brain tissue pulsations, which may enhance drug delivery. Non-responders and healthy controls showed different connectivity changes. The findings suggest potential cerebral mechanisms and markers for antidepressant response to nitrous oxide.