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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
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.
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.
University of Chicago Medicine
Chicago, Illinois, United States
Treatment Response Based on Changes in Computerized Adaptive Testing Scores
Monitor changes in 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. The CAT-MH is a validated self-reporting electronic diagnostic that adaptively selects a small optimal set of items from a large bank of approximately 1,500 items, targeted to individuals current or historical level of severity and likelihood of 'suicide', 'depression', and 'anxiety'. Generated scores include severity and liklihood percentile: * suicide = (%) low, intermediate, high * depression = (%) normal, mild, moderate, severe * anxiety = (%) normal, mild, moderate, severe
Time frame: Up to 24-hours from baseline
Treatment Compliance
Evaluate compliance of an acutely suicidal population in an Emergency Department (ED) setting, to complete a single 45-minute inhalation of nitrous oxide vs placebo. Determined by 'ability', 'inability', or 'refusal' to complete the entire 45-minute inhalation session (nitrous oxide vs placebo).
Time frame: Intervention completion, 45-minutes
Treatment Response Correlation to Lifetime Predictors Associated with Suicide
Evaluate if lifetime predictors (e.g., personal/family history of suicide attempts or suicide, history of alcohol dependence, and worst lifetime suicidal ideation) of eventual suicide correlate with the acute reduction in symptom severity following treatment. Lifetime predictors will be determined by medical and social history, and family history related to mental health. Symptom reduction is determined by changes in CAT-MH scores, over 24-hours from baseline. The CAT-MH is a validated self-reporting electronic diagnostic that adaptively selects a small optimal set of items from a large bank of approximately 1,500 items, targeted to individuals current or historical level of severity and likelihood of 'suicide', 'depression', and 'anxiety'. Generated scores include severity and liklihood percentile: * suicide = (%) low, intermediate, high * depression = (%) normal, mild, moderate, severe * anxiety = (%) normal, mild, moderate, severe
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Up to 24-hours from baseline
Rapid Treatment Response
Evaluate any acute reduction in symptoms. Based on changes in CAT-MH scores (suicide, depression, anxiety) at 30-minutes to 1-hour following treatment. Study patients ability to complete self-administered CAT-MH following inhalation may impact time-point. The CAT-MH is a validated self-reporting electronic diagnostic that adaptively selects a small optimal set of items from a large bank of approximately 1,500 items, targeted to individuals current or historical level of severity and likelihood of 'suicide', 'depression', and 'anxiety'. Generated scores include severity and liklihood percentile: * suicide = (%) low, intermediate, high * depression = (%) normal, mild, moderate, severe * anxiety = (%) normal, mild, moderate, severe
Time frame: At 30-minutes to 1-hour from intervention conclusion
Sustained Treatment Response
Evaluation of sustained response based on changes in CAT-MH scores at several time-points or until the patient is transferred or discharged from the ED. The CAT-MH is a validated self-reporting electronic diagnostic that adaptively selects a small optimal set of items from a large bank of approximately 1,500 items, targeted to individuals current or historical level of severity and likelihood of 'suicide', 'depression', and 'anxiety'. Generated scores include severity and liklihood percentile: * suicide = (%) low, intermediate, high * depression = (%) normal, mild, moderate, severe * anxiety = (%) normal, mild, moderate, severe
Time frame: Up to 24-hours from intervention conclusion