Nitrous Oxide as Treatment for Major Depression - a Pilot Study
Condition: Depression; Major Depressive Disorder
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major
Intervention: Nitrous Oxide; Placebo
Intervention description: Patients will receive either up to 50% nitrous oxide/50% oxygen for 1 hour or "placebo" (50% nitrogen [inert]/50% oxygen) in two separate sessions. Both sessions will be 1 week apart.; 50% nitrogen [inert]/50% oxygen - otherwise completely identical administration and setup
Intervention MeSH terms: Nitrous Oxide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Treatment

Summary:

      Major depressive disorder (MDD) is a global medical problem with significant shortcomings in
      current therapy. Chief among these is the delay between initiation of pharmacologic therapy
      and clinical improvement in symptoms. Recently ketamine, an NDMA-receptor antagonist has been
      shown to rapidly and effectively reverse the symptoms of MDD. Nitrous oxide, another
      NMDA-receptor antagonist, may produce the same effect with a cleaner side-effect profile and
      perhaps without the need for intravenous access and anesthesia personnel. Therefore, we
      propose conducting a pilot randomized placebo controlled double-blind crossover study in
      which patients will receive up to 50% nitrous oxide in oxygen or up to 50% oxygen in air for
      a period of one hour in addition to standard medical therapy. Depression severity will be
      assessed by a blinded observer pre-treatment, 30 minutes and 2 hours post treatment using the
      Hamilton depression rating scale.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adults 18-65 years of age

          2. Major depressive disorder without psychosis with as determined by structured interview
             using the Mini-International Neuropsychiatric Interview (MINI).

             (baseline )

          3. HDRS-21 score of >18

          4. Good command of the English language

        Exclusion Criteria:

        History of:

          1. Bipolar disorder

          2. Schizoprenia

          3. Schizoaffective disorder

          4. Obsessive-compulsive disorder, panic disorder

          5. Substance abuse or dependence (except for remote substance abuse or dependence with
             remission at least 1 year prior to the study and except for nicotine use disorders)

          6. Axis II diagnoses that may interfere with the patient's ability to improve on nitrous
             oxide

          7. Acute medical illness that may pose subject at risk during nitrous oxide
             administration

          8. Active suicidal intention (inability to contract for safety)

          9. Active psychotic symptoms

         10. Patients with significant pulmonary disease and/or requiring supplemental oxygen

         11. Contraindication against the use of nitrous oxide:

               1. Pneumothorax

               2. Bowel obstruction

               3. Middle ear occlusion

               4. Elevated intracranial pressure

               5. Chronic cobalamin and/or folate deficiency treated with folic acid or vitamin B12

               6. Pregnant patients

               7. Breastfeeding women

         12. Previous administration of NMDA-receptor antagonists (e.g., ketamine) within the last
             3 months

         13. Current electro-convulsive therapy treatment

         14. Any active suicidal ideation, intention, or planning (clinical assessment of
             suicidality will be used)