Inhaled Nitrous Oxide for Treatment-Resistant Depression: Optimizing Dosing Strategies
Condition: Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major
Intervention: Nitrous Oxide 25%; Nitrous Oxide 50%; Placebo Gas
Intervention description: Nitrous oxide, an odorless, colorless gas typically used as an induction agent for general anesthesia or for dental sedation, is a known N-methyl-D-aspartate (NMDA) antagonist. It will be given at a concentration of 25% nitrous oxide/50% oxygen/25% nitrogen.; Nitrous oxide, an odorless, colorless gas typically used as an induction agent for general anesthesia or for dental sedation, is a known N-methyl-D-aspartate (NMDA) antagonist. It will be given at a concentration of 50% nitrous oxide/50% oxygen.; Placebo gas given at 50% nitrogen [inert]/50% oxygen.
Intervention MeSH terms: Nitrous Oxide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Each participant receives the 3 inhalation types in randomized, one hour sessions separated by at least 4 weeks
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Depression; treatment-resistant

Summary:

      The purpose of the study aims to determine whether different concentrations of nitrous oxide
      (N2O) have different antidepressant effects for adults with treatment-resistant major
      depression.
    

Eligibility criteria:

        Inclusion Criteria

          1. Adults 18-75 years of age;

          2. Current diagnosis of unipolar major depressive disorder (MDD) without psychosis as
             confirmed by structured clinical interview for DSM-IV disorders;

          3. A score of >= 9 on the Montgomery-Åsberg Depression Rating Scale (MADRS);

          4. Documented (i.e., chart review) lifetime failure to respond to >=3 adequate
             dose/duration antidepressant treatment trials, ≥1 medication failure in the current
             depressive episode;

          5. Good command of the English language.

        Exclusion Criteria

          1. Meets criteria for any DSM-IV diagnosis for schizophrenia, bipolar, schizoaffective,
             obsessive-compulsive, personality, or panic disorders;

          2. Any recent (within past 12 months) history of substance dependence or abuse (except
             tobacco), determined by reported history or urine drug screen;

          3. Ability to become pregnant and not using effective contraception;

          4. 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

          5. Inability to provide informed consent;

          6. Any other factor that in the investigators' judgment may affect patient safety or
             compliance