Randomised, double-blind, parallel-group Phase 2 trial (n=81 actual) comparing weekly 1-hour inhaled nitrous oxide (25% or 50%) versus placebo (oxygen–air) for 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.
Inhaled nitrous oxide at 25% or 50% concentration, administered weekly for 4 weeks (participants randomised to dose).
50% inhaled concentration (other participants receive 25%); participants randomised to dose.
25% inhaled concentration (other participants receive 50%); participants randomised to dose.
Oxygen–air mixture (inspired O2 ~23–30%) administered weekly for 4 weeks.
Oxygen–air mixture (sham comparator).