Nitrous oxide as an adjunctive therapy in major depressive disorder: a randomized controlled double-blind pilot trial
Mara C. Guimarães, Tiago M. Guimarães, Jaime E. C. Hallak, João Abrão, João P. Machado‐de‐Sousa
Brazilian Journal of Psychiatry February 18, 2021 DOI: 10.1590/1516-4446-2020-1543 (opens in new tab) via OpenAlex
Summary
AI-generated from the abstractIn a small pilot trial, adding nitrous oxide (N2O) to ongoing antidepressant treatment for major depressive disorder produced significantly greater improvement in depressive symptoms than placebo (100% oxygen). After four weeks of twice-weekly 60-minute sessions, depression scores on the Hamilton Depression Rating Scale dropped from an average of 22.58 to 5.92 in the N2O group, compared with a drop from 22.44 to 12.89 in the placebo group. Most participants receiving N2O met criteria for response (91.7%) and remission (75%). Common side effects included nausea, vomiting, and headache. The results suggest N2O may be a useful augmentation strategy for treatment-resistant depression.
Study at a glance
| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Pilot study Peer reviewed |
|---|---|
| Sample size | 23 |
| Population | Adults aged 18 to 65 with major depressive disorder, on antidepressants, with HAM-D17 score > 17 |
| Intervention | Nitrous oxide |
| Dose | 50% N2O for 60 minutes twice a week for 4 weeks |
| Duration | 4-week intervention |
| Topics | Depression |
| Keywords | Placebo Nausea Internal medicine Adverse effect |
| Citations | 41 |
| Key finding | Nitrous oxide augmentation significantly reduced depressive symptoms compared to placebo, with 91.7% of the N2O group achieving response and 75% achieving remission. |
Abstract
OBJECTIVE: Major depressive disorder (MDD) is related to glutamatergic dysfunction. Antagonists of glutamatergic N-methyl-D-aspartate receptor (NMDAR), such as ketamine, have antidepressant properties. Nitrous oxide (N2O) is also a NMDAR antagonist. Thus, this study aimed to evaluate the effects of augmenting antidepressant treatment with N2O. METHODS: This double blind, placebo-controlled randomized parallel pilot trial was conducted from June 2016 to June 2018 at the Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. Twenty-three subjects with MDD (aged 18 to 65, on antidepressants, with a score > 17 on the 17-item-Hamilton Depression Rating Scale [HAM-D17]) received 50% N2O (n=12; 37.17±13.59 years) or placebo (100% oxygen) (n=11; 37.18±12.77 years) for 60 minutes twice a week for 4 weeks. The primary outcome was changes in HAM-D17 from baseline to week 4. RESULTS: Depressive symptoms improved significantly in the N2O group (N2O: from 22.58±3.83 to 5.92±4.08; placebo: from 22.44±3.54 to 12.89±5.39, p < 0.005). A total of 91.7% and 75% of the N2O group subjects achieved response (≥ 50% reduction in HAM-D17 score) and remission (HAM-D17 < 7), respectively. The predominant adverse effects of N2O treatment were nausea, vomiting, and headache. CONCLUSION: N2O treatment led to a statistically significant reduction in HAM-D17 scores compared to placebo. CLINICAL TRIAL REGISTRATION: Brazilian Register of Clinical Trials, RBR-5rz5ch.