Sustained mood improvement with laughing gas exposure (SMILE): a randomised, placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression
Bibliographic record
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: = 20) once weekly, for 4 weeks. Feasibility was assessed by examining rates of recruitment, withdrawal, adherence, missing data and adverse events. The main measure of clinical efficacy was the change in depression severity (Montgomery-Åsberg Depression Rating Scale (MADRS)) score from baseline to day 42. RESULTS: The recruitment rate was 22.3% (95% CI 16.9-29.0). Withdrawal rates were 10% (95% CI 2.8-30.1) in both groups and adherence rates were 100.0% (95% CI 82.4-100) in the nitrous oxide group and 94.4% (95% CI 74.2-99.0) in the placebo group. There were no missing primary clinical outcome data in either group (0.0%, 95% CI 0.0-17.6). MADRS score changed by -20.5% (95% CI -39.6 to -1.3) in the nitrous oxide group and -9.0% (95% CI -22.6 to 4.6) in the placebo group. Nearly all adverse events were mild to moderate and transient. CONCLUSIONS: The findings support the feasibility and necessity of conducting a full-scale trial comparing nitrous oxide and midazolam in patients with TRD.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".