Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil.
Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Ribeirão Preto, SP, Brazil.
Braz J Psychiatry. 2021 Sep-Oct;43(5):484-493. doi: 10.1590/1516-4446-2020-1543.
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.
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.
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.
N2O treatment led to a statistically significant reduction in HAM-D17 scores compared to placebo.
Brazilian Register of Clinical Trials, RBR-5rz5ch.
重度抑郁症（MDD）与谷氨酸能功能障碍有关。谷氨酸能 N-甲基-D-天冬氨酸受体（NMDAR）拮抗剂，如氯胺酮，具有抗抑郁作用。一氧化二氮（N2O）也是一种 NMDAR 拮抗剂。因此，本研究旨在评估用 N2O 增强抗抑郁治疗的效果。
这是一项双盲、安慰剂对照、随机平行试验，于 2016 年 6 月至 2018 年 6 月在巴西圣保罗大学里贝朗普雷图医学院附属医院的医院诊所进行。23 名 MDD 患者（年龄 18-65 岁，正在服用抗抑郁药，汉密尔顿抑郁量表 17 项评分[HAM-D17]＞17）接受 N2O（n=12；37.17±13.59 岁）或安慰剂（100%氧气）（n=11；37.18±12.77 岁）治疗，每周两次各 60 分钟，持续 4 周。主要结局是从基线到第 4 周 HAM-D17 的变化。
N2O 组的抑郁症状显著改善（N2O：从 22.58±3.83 降至 5.92±4.08；安慰剂：从 22.44±3.54 降至 12.89±5.39，p＜0.005）。N2O 组分别有 91.7%和 75%的患者达到了反应（HAM-D17 评分降低≥50%）和缓解（HAM-D17＜7）。N2O 治疗的主要不良反应是恶心、呕吐和头痛。
与安慰剂相比，N2O 治疗可使 HAM-D17 评分显著降低。
巴西临床试验注册处，RBR-5rz5ch。
