Clinical TrialMajor Depressive Disorder (MDD)Nitrous OxidePlaceboCompleted

Nitrous Oxide as Treatment for Major Depression – a Pilot Study

Randomised, placebo-controlled, double-blind crossover pilot study (n=21) testing up to 50% nitrous oxide in oxygen versus placebo (50% nitrogen/50% oxygen) for one hour in patients with major depressive disorder.

Target Enrollment
21 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

This pilot study randomises participants with major depressive disorder to receive 50% nitrous oxide/50% oxygen or placebo (50% nitrogen/50% oxygen) in a double-blind crossover design with two 1-hour sessions one week apart.

Depression severity is assessed by blinded raters using the Hamilton Depression Rating Scale at baseline, 30 minutes and 2 hours post-treatment; rationale is that nitrous oxide, an NMDA-receptor antagonist like ketamine, may produce rapid antidepressant effects with simpler administration.

Population includes non-treatment-resistant and treatment-resistant MDD subjects; safety monitoring and standard medical therapy are continued throughout.

Study Protocol

Preparation

sessions

Dosing

2 sessions
60 min each

Integration

sessions

Study Arms & Interventions

Nitrous oxide vs placebo

experimental

Randomised, double-blind crossover comparing 50% nitrous oxide/50% oxygen with 50% nitrogen/50% oxygen (placebo) in two 1-hour sessions one week apart.

Interventions

  • Nitrous Oxide50 %
    via Inhalation• single dose• 1 doses total

    Up to 50% N2O in oxygen administered for 60 minutes.

  • Placebo50 %
    via Inhalation• single dose• 1 doses total

    Placebo: 50% nitrogen (inert)/50% oxygen for 60 minutes; identical administration and setup.

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Adults 18-65 years of age
  • 2. Major depressive disorder without psychosis as determined by structured interview using the Mini-International Neuropsychiatric Interview (MINI)
  • 3. HDRS-21 score of >18
  • 4. Good command of the English language

Exclusion Criteria

  • Exclusion Criteria:
  • 1. Bipolar disorder
  • 2. Schizophrenia
  • 3. Schizoaffective disorder
  • 4. Obsessive-compulsive disorder, panic disorder
  • 5. Substance abuse or dependence (except remote with remission ≥1 year and nicotine use disorders)
  • 6. Axis II diagnoses that may interfere with improvement on nitrous oxide
  • 7. Acute medical illness posing risk during nitrous oxide administration
  • 8. Active suicidal intention (inability to contract for safety)
  • 9. Active psychotic symptoms
  • 10. Significant pulmonary disease and/or requiring supplemental oxygen
  • 11. Contraindications to nitrous oxide (pneumothorax; bowel obstruction; middle ear occlusion; elevated intracranial pressure; chronic cobalamin/folate deficiency treated with folic acid or vitamin B12; pregnancy; breastfeeding)
  • 12. Previous NMDA-antagonist (e.g., ketamine) within last 3 months
  • 13. Current electro-convulsive therapy
  • 14. Any active suicidal ideation, intention, or planning (clinical assessment used)

Study Details

Locations

Barnes-Jewish Hospital — St Louis, Missouri, United States

Your Library