Sustained mood improvement with laughing gas exposure (SMILE): a randomised, placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression.

ABSTRACT:

Background

Nitrous oxide may possess antidepressant effects; however, limited data exist on repeated administrations and active placebo-controlled studies in treatment-resistant depression (TRD).

Aims

We aimed to test the feasibility of a randomised controlled trial examining a 4-week course of nitrous oxide or midazolam, an active placebo.

Method

In this randomised, active, placebo-controlled pilot trial, 40 participants with TRD were assigned either a 1-h inhalation of 50% nitrous oxide plus intravenous saline (n = 20) or a 1-h inhalation of 50% oxygen plus intravenous midazolam (0.02 mg/kg, up to 2 mg; n = 20) once weekly, for 4 weeks. Feasibility was assessed by examining rates of recruitment, withdrawal, adherence, missing data and adverse events. T

SUBMITTER: Ladha KS 

PROVIDER: S-EPMC12451564 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature