Nitrous Oxide- Suicidal Ideation

NCT ID: NCT03736538

Last Updated: 2025-12-22

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-30
• Study Completion Date: 2026-12-31

Brief Summary

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.

Conditions

Major Depressive Disorder; Depression; Mood Disorders; Suicidal Ideation

Keywords

Nitrous Oxide; Anesthetics

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Nitrous Oxide

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.

Group Type: EXPERIMENTAL

Nitrous Oxide

Intervention Type: 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.

Placebo Gas

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.

Group Type: PLACEBO_COMPARATOR

Placebo gas

Intervention Type: DRUG

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

Interventions

Nitrous Oxide

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.

Intervention Type: DRUG

Placebo gas

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

Intervention Type: DRUG

Other Intervention Names

Laughing Gas

Eligibility Criteria

Inclusion Criteria

1. Patients aged 18-65 years old;

2. 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;

3. moderate to severe SI defined as a score ≥3 on the HDRS-21 suicide item (item #3);

4. will have good command of the English language;

5. will have been voluntarily admitted to the inpatient Psychiatric Units at Barnes-Jewish Hospital/Washington University in St. Louis, MO.

Exclusion Criteria

1. 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;

2. past 12-month substance abuse/dependence other than nicotine;

3. active psychotic symptoms;

4. significant pulmonary disease and/or requiring supplemental oxygen;

5. administration of other N-Methyl-D-aspartate (NMDA)-receptor antagonist treatment (e.g., ketamine) within two weeks of entry into study;

6. currently receiving electroconvulsive therapy;

7. 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);

8. past 12-month history of head trauma;

9. women who are pregnant or breastfeeding;

10. any other factor that in the investigators' judgment may affect patient safety or compliance.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Foundation for Suicide Prevention

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charles R Conway, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

Other Identifiers

201710183

Identifier Type: -

Identifier Source: org_study_id