Liu Helen, Kerzner Jaimie, Demchenko Ilya, Wijeysundera Duminda N, Kennedy Sidney H, Ladha Karim S, Bhat Venkat
Interventional Psychiatry Program, Mental Health and Addictions Service, St. Michael's Hospital, Toronto, Ontario, Canada.
Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Ontario, Canada.
Acta Psychiatr Scand. 2022 Aug;146(2):126-138. doi: 10.1111/acps.13432. Epub 2022 Apr 11.
To systematically review published research studies and ongoing clinical trials investigating nitrous oxide (N O) in psychiatric disorders, providing an up-to-date snapshot of the clinical research landscape.
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).
In total, five relevant published articles were identified, among which four investigated N O for depression. One single-dose randomized controlled trial (RCT) for treatment-resistant depression (TRD), one triple crossover RCT comparing 50% vs. 25% N O for TRD, and one repeated-dose RCT for major depressive disorder (MDD) suggest that N O has preliminary feasibility with rapid-acting effects on symptoms of depression. From the public registries, 10 relevant ongoing clinical trials were identified. They aim to explore the use of N 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 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.
Preliminary studies support the feasibility of administering N O for depression; however, appropriate blinding is a critical challenge. Larger-scale RCTs with repeated doses of N O and follow-up times beyond 1 month are needed to confirm the feasibility, therapeutic efficacy, and sustainability of response.
系统回顾已发表的关于一氧化二氮（N₂O）在精神疾病中的研究及正在进行的临床试验，提供临床研究现状的最新概况。
使用OVID数据库（MEDLINE、Embase、APA PsycInfo）和临床试验注册库（ClinicalTrials.gov、ICTRP）对截至2021年6月发表的研究进行全面文献检索。
共识别出5篇相关已发表文章，其中4篇研究了N₂O治疗抑郁症的情况。一项针对难治性抑郁症（TRD）的单剂量随机对照试验（RCT）、一项比较50%与25% N₂O治疗TRD的三交叉RCT以及一项针对重度抑郁症（MDD）的重复剂量RCT表明，N₂O具有初步可行性，对抑郁症状有快速起效作用。从公共注册库中，识别出10项相关正在进行的临床试验。它们旨在探索N₂O用于治疗MDD、创伤后应激障碍、双相情感障碍、强迫症和自杀意念。迄今为止，典型的治疗方案参数是单次给予50% N₂O持续60分钟，不过25%的浓度也在探索中。正在进行的试验预计入组人数（M = 55.0）远高于已发表研究的样本量（M = 13.0），这表明未来几年可能会有更多大规模RCT发表。
初步研究支持N₂O用于治疗抑郁症的可行性；然而，适当的盲法是一项关键挑战。需要进行更大规模的重复给予N₂O且随访时间超过1个月的RCT，以确认其可行性、治疗效果和反应的可持续性。
