Nitrous oxide inhalation produced time-dependent increases in brain entropy, particularly in the frontal lobe, among patients with treatment-resistant depression. These entropy changes, measured via multivariate multiscale entropy analysis of resting-state EEG, correlated with symptom severity and treatment efficacy, suggesting frontal region temporal-spatial brain entropy may serve as a biomarker for treatment-resistant depression and its treatment outcomes.
In patients with treatment-resistant depression, a single 1-hour inhalation of nitrous oxide improved depressive symptoms more than a placebo, as measured by the 17-Hamilton Depression Rating Scale. The treatment altered brain function, shown by changes in event-related potential components (N1, P1, N2, P2) and increased functional connectivity networks. These brain changes correlated with symptom reduction, suggesting nitrous oxide works by modifying brain function.