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Enrolling by Invitation

NCT Number: NCT03736538

Nitrous Oxide- Suicidal Ideation

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.

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Key information

Conditions

Major Depressive Disorder Behavior Behavioral Symptoms Depression Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders Self-Injurious Behavior Suicidal Ideation Suicide

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients aged 18-65 years old;
  • current diagnosis of unipolar, major depressive disorder (MDD) without psychosis as defined by the Mini-International Neuropsychiatric Interview (MINI) and The Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) DSM-IV determined by clinical interview and by a baseline score of ≥18 on the HDRS-21 (Hamilton Depression Rating Scale 21-item;
  • moderate to severe SI defined as a score ≥3 on the HDRS-21 suicide item (item #3);
  • will have good command of the English language;
  • will have been voluntarily admitted to the inpatient Psychiatric Units at Barnes-Jewish Hospital/Washington University in St. Louis, MO.

Exclusion criteria

  • Lifetime DSM-IV (obtained via MINI) diagnoses of schizophrenia, schizoaffective disorders, bipolar disorder, obsessive-compulsive disorder, evidence of severe personality disorder (e.g., history of recurrent self-mutilation/cutting, significant and recurrent tumultuous relationships), and panic disorders;
  • past 12-month substance abuse/dependence other than nicotine;
  • active psychotic symptoms;
  • significant pulmonary disease and/or requiring supplemental oxygen;
  • administration of other N-Methyl-D-aspartate (NMDA)-receptor antagonist treatment (e.g., ketamine) within two weeks of entry into study;
  • currently receiving electroconvulsive therapy;
  • contraindications for nitrous oxide (pneumothorax, bowel obstruction, middle ear occlusion, elevated intracranial pressure, chronic cobalamin and/or folate deficiency treated with folic acid or vitamin B12);
  • past 12-month history of head trauma;
  • women who are pregnant or breastfeeding;
  • any other factor that in the investigators' judgment may affect patient safety or compliance.

Treatment and study plan

Nitrous Oxide

Drug

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.

Other names: Laughing Gas

Placebo Gas

Drug

Placebo gas given at 50% nitrogen [inert]/50% oxygen.

Primary outcomes

  1. Severity and number of adverse events in both nitrous oxide and placebo groups

    Time frame: Throughout study duration (approximately 60 days)

    Safety and tolerability of inhaled nitrous oxide will be measured by collecting adverse events in both groups at each study visit throughout the study.

  2. Differential change in suicidal ideation

    Time frame: Baseline to Day 7, approximately 7 days (following the inpatient period inhalation sessions)

    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).

  3. Identification of pre-treatment key clinical correlates of anti-suicidal response to nitrous oxide

    Time frame: Change of scores on the SSI for the approximate 7 days of inpatient period

    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.

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Collaborators

  • American Foundation for Suicide Prevention

Registry information

Official study title

Adjunctive Nitrous Oxide for Acute Suicidal Ideation in Unipolar Depressed Hospitalized Patients

Important dates

Study start
2018
Primary completion
2026
Study completion
2026
First posted
Nov 9, 2018
Registry last updated
Dec 22, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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