Myles Paul S, Kulkarni Jayashri, Kasza Jessica, Wallace Sophie, Deng Carolyn, Turbić Alisa, Aykanat Verna, Conway Charles R, Brown Frank, Lee Royce, Gibbons Robert D, Nagele Peter
Department of Anaesthesiology and Perioperative Medicine, Alfred Hospital, Melbourne, Australia.
Department of Anaesthesiology and Perioperative Medicine, Monash University, Melbourne, Australia.
Biol Psychiatry Glob Open Sci. 2025 Apr 15;5(4):100504. doi: 10.1016/j.bpsgos.2025.100504. eCollection 2025 Jul.
Nitrous oxide ("laughing gas") is an NMDA receptor antagonist. In the current study, our aim was to investigate the efficacy, safety, and likely optimal dose of nitrous oxide in adults with major depressive disorder (MDD).
In this phase 2b randomized, double-blind trial, 81 patients with MDD were allocated on a 1:1 basis to receive nitrous oxide or oxygen/air (control); the nitrous group was further randomized to either 50% or 25% inspired nitrous oxide. All participants received four 1-hour-long treatment sessions at 1-week intervals and were followed for an additional 4 weeks. The primary outcome was the change in the 21-item Hamilton Depression Rating Scale (HAM-D) over the 4 treatment sessions. Secondary outcomes included remission (HAM-D ≤7 points), the Computerized Adaptive Test-Depression Inventory (CAT-DI) and Computerized Adaptive Test-Suicide Scale (CAT-SS).
The mean averaged change in HAM-D scores over the 4 weeks of treatment was lower with nitrous oxide than with control (-1.9 [95% CI, -3.9 to 0.0], = .051). In the first week, 15 of 39 (38%) in the nitrous oxide group and 5 of 39 (13%) in the control group were remitted ( = .031). The mean averaged change in CAT-DI scores was -7.7 (95% CI, -14.1 to -1.4), = .017; the mean averaged change in CAT-SS scores was -8.3 (95% CI, -14.4 to -2.1), = .008, both favoring nitrous oxide.
In this study, we confirmed that nitrous oxide has likely beneficial antidepressant effects in people with MDD.
一氧化二氮（“笑气”）是一种N-甲基-D-天冬氨酸（NMDA）受体拮抗剂。在本研究中，我们的目的是调查一氧化二氮对重度抑郁症（MDD）成人患者的疗效、安全性及可能的最佳剂量。
在这项2b期随机双盲试验中，81例MDD患者按1:1比例分配，分别接受一氧化二氮或氧气/空气（对照组）治疗；一氧化二氮组再随机分为吸入50%或25%一氧化二氮两组。所有参与者每隔1周接受4次每次1小时的治疗，并随访4周。主要结局是在4次治疗期间21项汉密尔顿抑郁量表（HAM-D）的变化。次要结局包括缓解（HAM-D≤7分）、计算机化自适应测试抑郁量表（CAT-DI）和计算机化自适应测试自杀量表（CAT-SS）。
治疗4周期间，一氧化二氮组HAM-D评分的平均变化低于对照组（-1.9[95%CI，-3.9至0.0]，P = 0.051）。在第一周，一氧化二氮组39例中有15例（38%）缓解，对照组39例中有5例（13%）缓解（P = 0.031）。CAT-DI评分的平均变化为-7.7（95%CI，-14.1至-1.4），P = 0.017；CAT-SS评分的平均变化为-8.3（95%CI，-14.4至-2.1），P = 0.008，两者均有利于一氧化二氮组。
在本研究中我们证实，一氧化二氮对MDD患者可能具有有益的抗抑郁作用。
