RecruitingPhase 2NCT05357040

Antidepressant Effects of Nitrous Oxide

Evaluation of the Antidepressant Effects of Nitrous Oxide in People With Major Depressive Disorder

Sponsor

University of Chicago

Enrollment

172 participants

Start Date

Jun 30, 2021

Study Type

INTERVENTIONAL

Conditions

Major Depressive Disorder Treatment Resistant Depression

Summary

To evaluate the acute and sustained antidepressant effects of nitrous oxide in people with major depressive disorder; and further evaluate these effects by identifying the optimal dose and regimen to guide current practice, and to plan a future large pragmatic trial.

Eligibility

Min Age: 18 Years

Inclusion Criteria2

Adult (≥18 years, both sexes)
DSM-5 criteria for MDD without psychosis, as determined using a structured clinical interview \[Mini International Neuropsychiatric Interview\], MDD, defined by a pre-treatment score \>16 on the HDRS-21 scale and meeting DSM-5 for MDD

Exclusion Criteria9

A current or past history of bipolar disorder, schizophrenia, or schizoaffective disorder.
Current obsessive-compulsive disorder, panic disorder, or documented Axis II diagnoses
Active suicidal intention, as determined by clinical interview assessment tool (Sheehan-STS) and clinical examination
Active or recent (\<12 months) substance use disorder; excluding nicotine
Administration of NMDA-antagonists (e.g., ketamine) in previous 3 months
Ongoing treatment with ECT
Presence of acute medical illness that could interfere with study participation, including significant pulmonary disease
Pregnancy or breastfeeding
Any contraindications to the use of nitrous oxide (e.g., pneumothorax, middle ear occlusion, elevated intracranial pressure, chronic cobalamin or folate deficiency unless treated with folic acid or vitamin B12).

Interventions

DRUGNitrous oxide gas for inhalation

60-minute sessions of inhaled 50% nitrous oxide in oxygen (FiO2 0.5) or 25% nitrous oxide in oxygen (FiO2 0.75), administered weekly for 4-weeks. Administration 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.

DRUGPlacebo

60-minute sessions of inhaled oxygen-air mixture (FiO2 ≈0.3) to be administered weekly for 4-weeks. Administration 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.