Proof-of-concept randomized controlled trial of single-session nitrous oxide treatment for refractory bipolar depression: Focus on cerebrovascular target engagement.
Bipolar disorders May 1, 2023 William S H Kim, Mikaela K Dimick, Danielle Omrin et al.
In a double-blind randomized controlled trial, 25 adults with bipolar I or II disorder and treatment-resistant depression received either nitrous oxide (25% concentration for 20 minutes) plus intravenous saline or medical air plus intravenous midazolam (2 mg total). No significant between-group differences emerged in depression severity change or treatment response 24 hours after treatment. However, the nitrous oxide group showed significantly greater same-day reductions in depression severity. Lower baseline regional cerebral blood flow predicted greater 24-hour improvement with nitrous oxide but not midazolam. Midazolam was associated with regional cerebral blood flow reductions compared to nitrous oxide. These secondary findings suggest differential associations of the two agents with depression severity and brain hemodynamics, warranting larger studies.