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

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.