Does Nitrous Oxide Help Veterans With Posttraumatic Stress Disorder? A Case Series

Varias, Andrea; Roessel, Peter van; Parsiani, Maryam; Filippou-Frye, Maria; Neylan, Thomas C.; Nägele, Peter; Yesavage, Jerome A.; Clark, James D.; Rodriguez, Carolyn I.

doi:10.4088/jcp.20l13393

Cited by 12 publications

(41 citation statements)

References 10 publications

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“…However, these trial results suggest that it may be reasonable to start treatment with a lower dose of nitrous oxide (25%) because of its comparable efficacy and lower risk profile but to consider escalating to 50% when a stronger treatment effect is desired. Since the publication of the first trial investigating the potential use of nitrous oxide in the treatment of TRMD, one case report has shown efficacy of a single inhalation of 50% nitrous oxide beyond 1 month (17) and early promise in the treatment of posttraumatic stress disorder in U.S. veterans (18) and in an experimental model of psychological trauma to simulate posttraumatic stress disorder (19).…”

Section: Adversementioning

confidence: 99%

A phase 2 trial of inhaled nitrous oxide for treatment-resistant major depression

et al. 2021

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Nitrous oxide at 50% inhaled concentration has been shown to improve depressive symptoms in patients with treatment-resistant major depression (TRMD). Whether a lower concentration of 25% nitrous oxide provides similar efficacy and persistence of antidepressant effects while reducing the risk of adverse side effects is unknown. In this phase 2 clinical trial (NCT03283670), 24 patients with severe TRMD were randomly assigned in a crossover fashion to three treatments consisting of a single 1-hour inhalation with (i) 50% nitrous oxide, (ii) 25% nitrous oxide, or (iii) placebo (air/oxygen). The primary outcome was the change on the Hamilton Depression Rating Scale (HDRS-21). Whereas nitrous oxide significantly improved depressive symptoms versus placebo (P = 0.01), there was no difference between 25 and 50% nitrous oxide (P = 0.58). The estimated differences between 25% and placebo were −0.75 points on the HDRS-21 at 2 hours (P = 0.73), −1.41 points at 24 hours (P = 0.52), −4.35 points at week 1 (P = 0.05), and −5.19 points at week 2 (P = 0.02), and the estimated differences between 50% and placebo were −0.87 points at 2 hours (P = 0.69), −1.93 points at 24 hours (P = 0.37), −2.44 points at week 1 (P = 0.25), and −7.00 points at week 2 (P = 0.001). Adverse events declined substantially with dose (P < 0.001). These results suggest that 25% nitrous oxide has comparable efficacy to 50% nitrous oxide in improving TRMD but with a markedly lower rate of adverse effects.

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Section: Adversementioning

confidence: 99%

A phase 2 trial of inhaled nitrous oxide for treatment-resistant major depression

et al. 2021

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Section: Resultsmentioning

confidence: 99%

“…Four studies were from the past 2 years, with two published in 2020 14,22 and two published in 2021 11,12 (Figure 2A). Four studies were from the USA, [12][13][14]22 and one was from Brazil. 11 Two studies enrolled participants with MDD, 11,22 and two recruited patients with TRD 12,13 (Figure 2B).…”

Section: Resultsmentioning

confidence: 99%

“…There was one published case study on PTSD. 14 All five studies had a sample size below 30 participants [11][12][13][14]22 (Figure 2C).…”

Section: Resultsmentioning

confidence: 99%

“…Nitrous oxide (N 2 O) is one such alternative being examined for depression. [11][12][13][14] Also known as the "laughing gas," it is commonly used in medical and dental procedures as an inhalational anesthetic. 15 N 2 O inhalation is associated with limited side effects but can occasionally increase the risk of nausea, vomiting, and headaches.…”

Section: Introductionmentioning

confidence: 99%

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Nitrous oxide for the treatment of psychiatric disorders: A systematic review of the clinical trial landscape

Liu

Kerzner

Demchenko

et al. 2022

Acta Psychiatr Scand

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Objective: To systematically review published research studies and ongoing clinical trials investigating nitrous oxide (N 2 O) in psychiatric disorders, providing an up-to-date snapshot of the clinical research landscape.Methods: A comprehensive literature search was conducted for studies published until June 2021 using the OVID databases (MEDLINE, Embase, APA PsycInfo) and the clinical trial registries (ClinicalTrials.gov, ICTRP). Results:In total, five relevant published articles were identified, among which four investigated N 2 O for depression. One single-dose randomized controlled trial (RCT) for treatment-resistant depression (TRD), one triple crossover RCT comparing 50% vs. 25% N 2 O for TRD, and one repeated-dose RCT for major depressive disorder (MDD) suggest that N 2 O has preliminary feasibility with rapidacting effects on symptoms of depression. From the public registries, 10 relevant ongoing clinical trials were identified. They aim to explore the use of N 2 O for MDD, post-traumatic stress disorder, bipolar disorder, obsessive-compulsive disorder, and suicidal ideation. To date, the typical treatment protocol parameters were a single session of 50% N 2 O delivered for 60 min, although the concentration of 25% is also being explored. Projected enrolment numbers for ongoing trials (M = 55.0) were much higher than sample sizes for published studies (M = 13.0), suggesting that there potentially will be more large-scale RCTs published in the next few years. Conclusion:Preliminary studies support the feasibility of administering N 2 O for depression; however, appropriate blinding is a critical challenge. Larger-scale RCTs with repeated doses of N 2 O and follow-up times beyond 1 month are needed to confirm the feasibility, therapeutic efficacy, and sustainability of response.

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Changed Substance Use After Psychedelic Experiences Among Individuals in Canada

Boehnke

Kruger

Lucas³

2023

Int J Ment Health Addiction

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Does Nitrous Oxide Help Veterans With Posttraumatic Stress Disorder? A Case Series

Cited by 12 publications

References 10 publications

A phase 2 trial of inhaled nitrous oxide for treatment-resistant major depression

A phase 2 trial of inhaled nitrous oxide for treatment-resistant major depression

Nitrous oxide for the treatment of psychiatric disorders: A systematic review of the clinical trial landscape

Changed Substance Use After Psychedelic Experiences Among Individuals in Canada

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