Clinical TrialMajor Depressive Disorder (MDD)Nitrous OxideNitrous OxidePlaceboCompleted

Nitrous Oxide for the Treatment of Major Depressive Disorder

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.

Target Enrollment
81 participants
Study Type
Phase II interventional
Design
Randomized, double Blind

Detailed Description

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.

Study Protocol

Preparation

sessions

Dosing

4 sessions
60 min each

Integration

sessions

Study Arms & Interventions

Nitrous oxide

experimental

Inhaled nitrous oxide at 25% or 50% concentration, administered weekly for 4 weeks (participants randomised to dose).

Interventions

  • Nitrous Oxide50 %
    via Inhalation• weekly• 4 doses total

    50% inhaled concentration (other participants receive 25%); participants randomised to dose.

  • Nitrous Oxide25 %
    via Inhalation• weekly• 4 doses total

    25% inhaled concentration (other participants receive 50%); participants randomised to dose.

Placebo

inactive

Oxygen–air mixture (inspired O2 ~23–30%) administered weekly for 4 weeks.

Interventions

  • Placebo
    via Inhalation• weekly• 4 doses total

    Oxygen–air mixture (sham comparator).

Participants

Ages
18 – 99
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Adult (≥18 years, both sexes), with DSM-IV-TR criteria for MDD without psychosis, as determined using a structured clinical interview [Mini International Neuropsychiatric Interview]
  • 2. MDD, as defined by a pretreatment score >18 on the HDRS-21 scale

Exclusion Criteria

  • Exclusion Criteria:
  • 1. A history of bipolar disorder, schizophrenia, schizoaffective disorder, obsessive-compulsive disorder, panic disorder, or documented Axis II diagnoses; active suicidal intention, as determined by clinical interview
  • 2. Active or recent (<12 months) substance abuse or dependence; excluding nicotine
  • 3. Administration of NMDA-antagonists (e.g., ketamine) in previous 3 months
  • 4. Ongoing treatment with ECT
  • 5. Presence of acute medical illness that could interfere with study participation, including significant pulmonary disease
  • 6. Pregnancy or breastfeeding
  • 7. Any contraindications to the use of nitrous oxide (e.g., pneumothorax, middle ear occlusion, elevated intracranial pressure, chronic cobalamin or folate deficiency unless treated with folic acid or vitamin B12).

Study Details

Locations

University of Chicago Medicine — Chicago, Illinois, United States
Alfred Hospital — Melbourne, Victoria, Australia

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