NCT02139540.

Study name	Nitrous oxide as treatment for major depression ‐ a pilot study
Methods	A pilot randomised placebo‐controlled double‐blind cross‐over 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 HRSD Allocation: randomised Endpoint classification: safety/efficacy study Intervention model: cross‐over assignment Masking: double‐blind (participant, caregiver, investigator, outcomes assessor) Primary purpose: treatment
Participants	Inclusion Criteria: Adults 18 ‐ 65 years of age Major depressive disorder without psychosis with as determined by structured interview using the Mini‐International Neuropsychiatric Interview (MINI). (baseline ) HRSD‐21 score of > 18 Good command of the English language Exclusion criteria History of: Bipolar disorder Schizoprenia Schizoaffective disorder Obsessive‐compulsive disorder, panic disorder 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) Axis II diagnoses that may interfere with the patient's ability to improve on nitrous oxide Acute medical illness that may pose participant at risk during nitrous oxide administration Active suicidal intention (inability to contract for safety) Active psychotic symptoms Patients with significant pulmonary disease and/or requiring supplemental oxygen Contraindication against the use of nitrous oxide:PneumothoraxBowel obstructionMiddle ear occlusionElevated intracranial pressureChronic cobalamin and/or folate deficiency treated with folic acid or vitamin B12Pregnant patientsBreastfeeding women Previous administration of NMDA‐receptor antagonists (e.g., ketamine) within the last 3 months Current electroconvulsive therapy treatment Any active suicidal ideation, intention, or planning (clinical assessment of suicidality will be used)
Interventions	N2O/placebo
Outcomes	Primary outcome measures: Change in HRSD‐21. Time frame: baseline and 24 hours
Starting date	November 2012
Contact information	Peter Nagele, MD, MSc; Washington University School of Medicine
Notes	NCT02139540