Not Yet RecruitingPhase 3

Sustained Mood Improvement With Laughing Gas Exposure

Canada120 participantsStarted 2026-02-01

Plain-language summary

Multi-centre, parallel group, blinded, 1:1 randomized controlled trial to determine the effect of nitrous oxide on reducing symptoms of depression in patients with treatment resistant depression.

Who can participate

Age range18 Years – 65 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. 18 to 65 years of age
✓. Meeting Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria for Major Depressive Disorder (MDD)
✓. Current major depressive episode as confirmed by the Mini International Neuropsychiatric Interview (MINI) for DSM-5
✓. Experiencing moderate to severe depressive episodes, as defined by the Montgomery-Åsberg Depression Rating Scale (MADRS) \> 21
✓. Failure of two trials of antidepressant therapy of adequate dose and duration, during the current depressive episode
✓. For women of childbearing potential, use of highly effective or double-barrier methods of contraception. Abstinence is acceptable if it is the preferred and usual lifestyle of the female participant
✓. Capacity to provide informed consent.

Exclusion criteria

✕. Acute suicidality defined as score \> 4 on MADRS item 10
✕. Diagnosis of Bipolar Disorder
✕. Current substance abuse or dependence and/or history of alcohol abuse or dependence within the past year
✕. Dementia
✕. Current or lifetime history of schizophrenia or schizoaffective disorder
✕. Known history of hypersensitivity or allergy to nitrous oxide, midazolam or any ingredients in the study formulations
✕. Contraindication to receiving nitrous oxide (e.g. any condition where air is entrapped within a body and its expansion might be dangerous such as, pneumothorax, elevated intracranial pressure, air embolism, recent middle ear, vitreoretinal or bowel obstruction surgeries, etc.)
✕. Known chronic cobalamin or folate deficiency (e.g. signs of anemia or neurological symptoms, with plasma levels of homocysteine over 15 µmol/L and abnormal red blood cells and leukocytes on a complete blood count CBC) or current methotrexate use

What they're measuring

Change in Montgomery-Åsberg Depression Rating Scale (MADRS) score

Timeframe: Baseline to the 2-week follow-up (Visit 6 - Day 35).

Trial details

NCT IDNCT07262008

SponsorWomen's College Hospital

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2027-02-01

Contact for this trial

Anesthesia Clinical Trials Unit

416-340-4800 actu@uhn.ca

View on ClinicalTrials.gov More Major Depressive Disorder trials