Nitrous Oxide: an emerging novel treatment for treatment-resistant depression.
Darin F Quach, Victoria C De Leon, Charles R Conway
Journal of the Neurological Sciences March 15, 2022 DOI: 10.1016/j.jns.2021.120092 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Nitrous oxide |
| Topics | Ketamine Depression |
| Keywords | Interventional psychiatry N-methyl-d-aspartate nmda receptor Nitrous oxide Treatment-resistant depression trd |
| Key findings | Recent clinical studies suggest nitrous oxide may be effective for treatment-resistant depression. |
Abstract
Stemming from the results of the historic STAR-D trial, it is evident that a significant subset of individuals (20-25%) with major depressive disorder (MDD) do not respond to conventional antidepressant medications. As a result, an emphasis has been placed on the development of novel therapeutics for MDD over the last two decades. Recently, substantial research efforts have been focused on the use of ketamine as an antidepressant whose mechanism of action is via the N-methyl-d-aspartate (NMDA) receptor. Another potential therapeutic compound of interest is nitrous oxide, which has been utilized for more than a century in multiple fields of medicine for its analgesic and anesthetic properties. Recent clinical studies suggest that nitrous oxide may be effective for treatment-resistant depression. In this review, we will discuss the administration of nitrous oxide as a psychiatric intervention, current use in psychiatry, putative mechanisms of action, and future directions highlighting knowledge gaps and other potential utilities in the field of psychiatry.
Comparable studies
Other narrative reviews on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine: a paradigm shift for depression research and treatment | 2019 | Review | |
| Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective | 2019 | Review | |
| Ketamine: A tale of two enantiomers | 2020 | Review | |
| Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor | 2021 | Review |
Citations in the library
Cited by 5
- Psychedelics: Future Therapeutics in Major Depression? Advances in experimental medicine and biology 2026
- Nitrous oxide promotes exploratory activity and stimulates neurogenesis in a male rat model of post-traumatic stress disorder. Neuroscience January 26, 2026
- Nitrous oxide for the treatment of depression: a systematic review and meta-analysis. EBioMedicine December 1, 2025
- Changes in cerebral connectivity and brain tissue pulsations with the antidepressant response to an equimolar mixture of oxygen and nitrous oxide: an MRI and ultrasound study. Molecular Psychiatry September 1, 2023
- Nitrous oxide modulates cortical activity, wake–sleep oscillations, and produces antidepressant-like effects in mice
Cites 9
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism American Journal of Psychiatry August 29, 2018
- Clinical applications of hallucinogens: A review. Experimental and Clinical Psychopharmacology August 1, 2016
- Nitrous oxide speeds the reduction of distressing intrusive memories in an experimental model of psychological trauma Psychological Medicine March 3, 2016
- Nitrous oxide as an adjunctive therapy in major depressive disorder: a randomized controlled double-blind pilot trial Brazilian Journal of Psychiatry February 18, 2021
and 4 more in the library