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Empirical evidence for the neurocognitive effect of nitrous oxide as an adjunctive therapy in patients with treatment resistant depression: A randomized controlled study.

Jin Liu, Xiaotian Zhao, Xiyu Wei, Danfeng Yan, Wenwen Ou, Mei Liao, Shanling Ji, Yan Peng, Shibin Wu, Mi Wang, Yumeng Ju, Li Zhang, Zexuan Li, Bangshan Liu, Lingjiang Li, Yan Zhang

Psychiatry Research August 1, 2023 DOI: 10.1016/j.psychres.2023.115326 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Placebo-controlled Double-blind Peer reviewed
Sample size 44
Population Patients with treatment-resistant depression
Intervention Nitrous oxide
Dose 50% N2O/50% oxygen for one hour
Duration 1-week and 2-week follow-up
Measures subjective cognitive function, processing speed, attention, executive function
Topics Depression
Keywords Cognitive deficits Executive function Nitrous oxide Randomized controlled trial
Key findings Nitrous oxide improved executive function at 1 week post-treatment compared with placebo, independent of changes in depressive symptoms.

Abstract

Nitrous oxide (N2O) has demonstrated an antidepressant effect for treatment-resistant depression (TRD), but no studies investigated the effects of N2O on different cognition domains. This study aimed to test whether N2O would display pro-cognitive effects. We conducted a double-blinded, placebo-controlled, randomized controlled trial, 44 patients with TRD were randomized to N2O group (one-hour inhalation of 50% N2O/50% oxygen) or placebo group (50% air/50% oxygen). Thirty-four patients completed cognitive tests at the pre-treatment phase, 1-week, and 2 weeks post-treatment including subjective cognitive function, processing speed, attention, and executive function. Although the antidepressant effect of N2O was not significant at 1 week, patients still showed better performance of executive function at 1 week after receiving N2O compared with the placebo. Moreover, this significant improvement still existed at 1 week after controlling for the change in depressive symptoms over-time. Additionally, no significant difference was observed in subjective cognitive function, processing speed, and attention between these two groups across the 2-week follow-up period. As the first study investigating the treatment effects of N2O on improving cognitive function in TRD patients, the current study indicated that N2O has a potential pro-cognitive effect on executive function and this effect might be independent from improvements in depressive symptoms.

Comparable studies

Other randomized controlled trials on depression, most cited first.

Study Year Design Participants
A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Subjects with DSM-IV major depression (treatment resistant) 2006 Randomized, placebo-controlled, double-blind crossover study n = 18
Prevention of relapse/recurrence in major depression by mindfulness-based cognitive therapy. Recovered recurrently depressed patients 2000 Randomized controlled trial n = 145
Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety 2016 Randomized controlled trial n = 51
Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Patients with cancer-related anxiety and depression 2016 Double-blind, placebo-controlled, crossover trial n = 29
Mindfulness-Based Cognitive Therapy for Depression: Replication and Exploration of Differential Relapse Prevention Effects. Recovered recurrently depressed patients 2004 Randomized controlled trial n = 73

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