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Use of nitrous oxide in the treatment of major depressive disorder and treatment-resistant major depressive disorder: A systematic review and meta-analysis nitrous oxide in depressive disorders.

Peterson Rech, Rodrigo Miranda Custodio, Maria Laura Rodrigues Uggioni, Gabriele Silveira Prestes, Fernanda Marçal, Vitoria Pedroso Silveira, Valdemira Santina Dagostin, Tamy Colonetti, Maria Inês Rosa

Progress in Neuro-Psychopharmacology and Biological Psychiatry February 8, 2024 DOI: 10.1016/j.pnpbp.2023.110869 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Systematic review and meta-analysis Randomized Peer reviewed
Sample size 109
Population Patients with major depressive disorder and treatment-resistant depression
Intervention Nitrous oxide
Topics Depression
Keywords Antidepressive agents Depressive disorder, major Depressive disorder, treatment-resistant Meta-analysis Nitrous oxide
Key findings Nitrous oxide produces a rapid and significant reduction in depression severity at 24 hours and one week in patients with MDD and TRD.

Abstract

Major Depressive Disorder (MDD) has, as a conventional treatment, pharmacological therapy with selective monoamine reuptake inhibitors. However, the medication does not always have a rapid action for exacerbated cases, and moreover, it is estimated that 15 to 30% of patients do not respond effectively to conventional treatment, leading to 'treatment-resistant depressive mood disorder' (TRD). Thus, it is necessary to search for new therapeutic methods for exacerbated and resistant cases. The objective of the study was to evaluate the therapeutic effects of nitrous oxide (N2O) in patients with MDD and TRD. The study was characterized as a systematic review of randomized clinical trials. Search strategy was developed using the keywords "nitrous oxide," "treatment-resistant depression," "Depression disorder," and their synonyms, searched in the databases MEDLINE, EMBASE, LILACS, and American Psychological Association. Four articles were included in the systematic review, with two of them being utilized for the meta-analysis, which comprised a total of 23 patients with MDD and 86 with TRD. A standardized mean difference (SMD) for the HDRS score at 24 h of -2.36 was found, with a 95% confidence interval (CI) of -3.37 to -1.34 (p < 0.0001; I2 = 46%). For the evaluation of the score after one week, an SMD of -0.60, 95% CI of -1.13 to -0.07 (p = 0.03; I2 = 0%) was found. In conclusion, N2O has a rapid action for managing decompensated patients, with a potential therapeutic effect for TRD. However, more studies needed to determine N2O's effectiveness duration.

Comparable studies

Other systematic reviews and meta-analyses on depression, most cited first.

Study Year Design Participants
Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... 2015 Systematic review and meta-analysis
Side-effects associated with ketamine use in depression: a systematic review. Patients with depression 2018 Systematic review
Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Adults with unipolar or bipolar major depression 2020 Systematic review and meta-analysis n = 1,877
Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Patients with major depressive disorder or bipolar depression 2016 Systematic review and meta-analysis n = 588
Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Patients with cancer- or illness-related anxiety and depression, major depressive... 2020 Systematic review n = 188

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