Journal
BIOLOGICAL PSYCHIATRY
Volume 78, Issue 1, Pages 10-18Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2014.11.016
Keywords
Major depression; Nitrous oxide; Treatment-resistant depression
Categories
Funding
- Roche Diagnostics
- Abbot
- Express Scripts
- Bristol-Myers Squibb
- Cyberonics
- Stanley Baer Foundation
- Brain and Behavior Research Foundation
- Department of Anesthesiology
- Department of Psychiatry
- Taylor Family Institute for Innovative Psychiatric Research at Washington University School of Medicine
- Taylor Family Institute for Innovative Psychiatric Research at Washington University School of Medicine, St. Louis
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BACKGROUND: N-methyl-D-aspartate receptor antagonists, such as ketamine, have rapid antidepressant effects in patients with treatment-resistant depression (TRD). We hypothesized that nitrous oxide, an inhalational general anesthetic and N-methyl-D-aspartate receptor antagonist, may also be a rapidly acting treatment for TRD. METHODS: In this blinded, placebo-controlled crossover trial, 20 patients with TRD were randomly assigned to 1-hour inhalation of 50% nitrous oxide/50% oxygen or 50% nitrogen/50% oxygen (placebo control). The primary endpoint was the change on the 21-item Hamilton Depression Rating Scale (HDRS-21) 24 hours after treatment. RESULTS: Mean duration of nitrous oxide treatment was 55.6 +/- 2.5 (SD) min at a median inspiratory concentration of 44% (interquartile range, 37%-45%). In two patients, nitrous oxide treatment was briefly interrupted, and the treatment was discontinued in three patients. Depressive symptoms improved significantly at 2 hours and 24 hours after receiving nitrous oxide compared with placebo (mean HDRS-21 difference at 2 hours, -4.8 points, 95% confidence interval [CI], -1.8 to -7.8 points, p = .002; at 24 hours, -5.5 points, 95% CI, -2.5 to -8.5 points, p < .001; comparison between nitrous oxide and placebo, p < .001). Four patients (20%) had treatment response (reduction >= 50% on HDRS-21) and three patients (15%) had a full remission (HDRS-21 <= 7 points) after nitrous oxide compared with one patient (5%) and none after placebo (odds ratio for response, 4.0, 95% CI, .45-35.79; OR for remission, 3.0, 95% CI, .31-28.8). No serious adverse events occurred; all adverse events were brief and of mild to moderate severity. CONCLUSIONS: This proof-of-concept trial demonstrated that nitrous oxide has rapid and marked antidepressant effects in patients with TRD.
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