A phase 2 trial of inhaled nitrous oxide for treatment-resistant major depression.
Peter Nagele, Ben J Palanca, Britt Gott, Frank Brown, Linda Barnes, Thomas Nguyen, Willa Xiong, Naji C Salloum, Gemma D Espejo, Christina N Lessov-Schlaggar, Nisha Jain, Wayland W L Cheng, Helga Komen, Branden Yee, Jacob D Bolzenius, Alvin Janski, Robert Gibbons, Charles F Zorumski, Charles R Conway
Science translational medicine June 9, 2021 DOI: 10.1126/scitranslmed.abe1376 via PubMed
Summary
AI-generated from the abstractA single 1-hour inhalation of 25% nitrous oxide improves depressive symptoms in patients with severe treatment-resistant major depression as effectively as 50% nitrous oxide, but with substantially fewer adverse effects. In a phase 2 crossover trial with 24 patients, both concentrations significantly reduced depression scores on the Hamilton Depression Rating Scale compared to placebo over two weeks. The 25% dose showed significant improvements at week 1 and week 2, while the 50% dose showed significant improvement at week 2. Adverse events declined substantially with the lower dose.
Study at a glance
| Characteristics | Phase 2 clinical trial, crossover Peer reviewed |
|---|---|
| Sample size | 24 |
| Population | Patients with severe treatment-resistant major depression (TRMD) |
| Intervention | Nitrous oxide |
| Dose | 25% nitrous oxide, 50% nitrous oxide |
| Duration | Single 1-hour inhalation, 2-week follow-up |
| Registration | NCT03283670 |
| Key finding | 25% nitrous oxide has comparable efficacy to 50% nitrous oxide in improving treatment-resistant major depression but with a markedly lower rate of adverse effects. |
Abstract
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.