Nitrous Oxide for the Treatment of Major Depressive Disorder

This investigator-initiated Phase 2b randomised, double-blind parallel trial evaluates the antidepressant efficacy of weekly 1-hour inhaled nitrous oxide sessions (25% or 50%) versus an oxygen–air sham, administered for four weeks to participants with MDD.

Primary outcomes are observer-rated depression severity (HDRS-21) assessed weekly during treatment and for four weeks post-treatment; safety excludes participants with significant pulmonary disease or other contraindications to nitrous oxide.