A Phase 1 interventional study of Nitrous Oxide and Placebo gas in Major Depressive Disorder, Depression and Mood Disorders, sponsored by Washington University School of Medicine. Enrolling by invitation at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2025-12-22.
Sponsored by Washington University School of Medicine · Phase 1, Interventional, and Treatment
Most clinical major depression responds to standard treatments (medication and psychotherapy); however, a significant subset of depressed patients (15-20%) do not respond to these treatments and are referred to as treatment-resistant major depression (TRMD). New treatments for TRMD are needed, and one promising line of research are drugs known as N-methyl-D-aspartate (NMDA) glutamate receptor antagonists. In a recent pilot study, the investigators of this study demonstrated that the NMDA antagonist nitrous oxide is effective in TRMD, reducing depressive symptoms, guilt, and suicidal thinking.
To more closely investigate suicidal thinking, this study is designed as a double-blind, randomized, prospective, inpatient trial comparing inhaled nitrous oxide (N2O) plus treatment as usual versus inhaled placebo plus treatment as usual. All unipolar depressed, acutely suicidal inpatients will receive standard treatment for their depression/ suicidal thinking (TAU). Additionally, participants will undergo a maximum of four one hour inhalation sessions as inpatients and 2 booster sessions as outpatients during which they will receive either inhaled nitrous oxide (50% nitrous oxide/50% oxygen = active treatment) or placebo gas (50% nitrogen/50% oxygen). A target total of 50 patients with suicidal ideation and unipolar depression will be enrolled, 25 of whom will be assigned to the TAU control group and 25 of whom will be assigned to the N2O + TAU experimental group.
2,741 studies on the registry are indexed under Depressive Disorder, Major; 559 are open to participants now.
This study's planned enrollment of 50 is below the median of 80 across 2,283 interventional studies indexed under Depressive Disorder, Major.
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Of its 324 completed or terminated interventional studies of FDA-regulated products, 212 (65%) have results posted.
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Exclusion Criteria:
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 50% nitrous oxide/50% oxygen in this study. Participants will undergo a maximum of four one hour inhalation sessions as inpatients and 2 booster sessions as outpatients during which they will receive inhaled nitrous oxide.
Drug: Nitrous Oxide
Placebo gas given at 50% nitrogen \[inert\]/50% oxygen. Participants will undergo a maximum of four one hour inhalation sessions as inpatients and 2 booster sessions as outpatients during which they will receive placebo gas.
Drug: Placebo gas
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 50% nitrous oxide/50% oxygen in this study.
Also known as: Laughing Gas
Placebo gas given at 50% nitrogen \[inert\]/50% oxygen.
Severity and number of adverse events in both nitrous oxide and placebo groups
Safety and tolerability of inhaled nitrous oxide will be measured by collecting adverse events in both groups at each study visit throughout the study.
Time frame: Throughout study duration (approximately 60 days)
Differential change in suicidal ideation
Participants receiving inpatient treatment as usual plus nitrous oxide compared to participants receiving inpatient treatment as usual plus placebo as measured by scores on the 19-item Scale for Suicidal Ideation (SSI; total score range is 0 to 38, higher scores indicate greater suicidal ideation).
Time frame: Baseline to Day 7, approximately 7 days (following the inpatient period inhalation sessions)
Identification of pre-treatment key clinical correlates of anti-suicidal response to nitrous oxide
Correlations of change in Scale for Suicidal Ideation score (SSI; total score range is 0 to 38, higher scores indicate greater suicidal ideation) at end of inpatient period with: 1) presence of family history of alcohol dependence; 2) a personal/family history of suicide attempt or a family history of suicide.
Time frame: Change of scores on the SSI for the approximate 7 days of inpatient period
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Washington University School of Medicine