Nitrous Oxide for Treatment-Resistant Major Depression: A Proof-of-Concept Trial.
Peter Nagele, Andreas Duma, Michael Kopec, Marie Anne Gebara, Alireza Parsoei, Marie Walker, Alvin Janski, Vassilis N Panagopoulos, Pilar Cristancho, J Philip Miller, Charles F Zorumski, Charles R Conway
Biological Psychiatry July 1, 2015 DOI: 10.1016/j.biopsych.2014.11.016 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Patients with treatment-resistant depression |
| Intervention | Nitrous oxide |
| Dose | 50% nitrous oxide/50% oxygen, 1-hour inhalation |
| Duration | 1-hour inhalation, 24-hour follow-up |
| Measures | 21-item Hamilton Depression Rating Scale (HDRS-21) |
| Topics | Depression |
| Keywords | Major depression Nitrous oxide |
| Key findings | Nitrous oxide produced significantly greater improvement in depressive symptoms than placebo at 2 and 24 hours after treatment in patients with treatment-resistant depression. |
Abstract
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. 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. 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. This proof-of-concept trial demonstrated that nitrous oxide has rapid and marked antidepressant effects in patients with TRD.
Comparable studies
Other randomized controlled trials on depression, most cited first.
Citations in the library
Cited by 110
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
- Ketamine: NMDA Receptors and Beyond Journal of Neuroscience November 2, 2016
- Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans Journal of Neuroscience August 19, 2015
- Clinical applications of hallucinogens: A review. Experimental and Clinical Psychopharmacology August 1, 2016
- Psychedelics and Other Psychoplastogens for Treating Mental Illness Frontiers in Psychiatry October 4, 2021
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Cites 8
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- Family history of alcohol dependence and antidepressant response to an N‐methyl‐D‐aspartate antagonist in bipolar depression Bipolar Disorders September 14, 2012
and 3 more in the library