NCT05710887

N2O for Acute Suicidality and Depression in the ED

Inhaled Nitrous Oxide for Acute Suicidality and Depression in the Emergency Department

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University of Chicago · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Investigators are conducting this double-blind, randomized control trial (RCT), to compare inhaled N2O+ treatment as usual (TAU) versus inhaled placebo+TAU; demonstrating the feasibility and tolerability of the intervention in an emergency department (ED) setting on an acutely suicidal population.

Detailed description

Past studies have shown that a single dose of ketamine, an NMDA- receptor antagonist has fast and long lasting anti-depressant effect. Although a promising antidepressant and potential anti-suicidal agent, ketamine has very significant side effects including: dissociation, hallucinations, delusional thinking, cognitive impairment, and significant sympathetic nervous system activation. Nitrous Oxide (N2O) is an NMDA-receptor antagonist with a well-known safety profile used as an analgesic. In a proof-of-concept pilot study, this study's investigator recently demonstrated that N2O also has rapid and marked antidepressant effects in patients with severe treatment-resistant depression (TRD); further sub-analyses showed N2O significantly reduced suicidal ideation (SI). While N2O administration may lead to a reduction in SI, it remains unknown whether severely suicidal patients requiring hospitalization on inpatient psychiatric units would benefit. Investigators hypothesize that N2O will rapidly and safely dampen suicidal thinking with minimal side effects in this population. Participants will be randomized to receive either N2O or placebo. The study intervention is in tandem with prescribed treatment-as-usual (TAU) by emergency department physicians relating to diagnosis (depression, anxiety, suicidal ideation); which typically involves anxiolytic medications and/or brief psychotherapy administered by care team psychiatry providers. Study intervention response will be assessed using a self-administered psychiatric diagnostic tool (Computerized Adaptive Testing Mental Health \[CAT-MH\] scores relating to suicide, depression, and anxiety; to determine whether a single 45-minute inhalation of nitrous oxide vs placebo reduces symptoms.

Conditions

• Suicidal Ideation
• Major Depressive Disorder
• Treatment Resistant Depression

Interventions

Type	Name	Description
DRUG	Nitrous oxide gas for inhalation	Administration of inhaled 50% nitrous oxide in oxygen (FiO2 0.5) will be under the direct supervision of a licensed practitioner who is experienced in the use and administration of the study drug, and is familiar with the indications, effects, dosages, methods, and frequency and duration of administration, and with the hazards, contraindications, and side effects and the precautions to be taken (MD, or CRNA); with study patient monitoring of pulse oximetry, heart rate, respiratory, non-invasive blood pressure, and end-tidal carbon dioxide.
DRUG	Placebo	Administration of the placebo (oxygen-air mixture \[FiO2 ≈0.3\]), will be under the direct supervision of a licensed practitioner who is experienced in the use and administration of the study drug, and is familiar with the indications, effects, dosages, methods, and frequency and duration of administration, and with the hazards, contraindications, and side effects and the precautions to be taken (MD, or CRNA); with study patient monitoring of pulse oximetry, heart rate, respiratory, non-invasive blood pressure, and end-tidal carbon dioxide.

Timeline

• Start date: 2026-02-27
• Primary completion: 2026-02-27
• Completion: 2026-02-27
• First posted: 2023-02-02
• Last updated: 2026-03-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study