Proof‐of‐concept randomized controlled trial of single‐session nitrous oxide treatment for refractory bipolar depression: Focus on cerebrovascular target engagement

There remain few efficacious treatments for bipolar depression, which dominates the course of bipolar disorder (BD). Despite multiple studies reporting associations between depression and cerebral blood flow (CBF), little is known regarding CBF as a treatment target, or predictor and/or indicator of treatment response, in BD. Nitrous oxide, an anesthetic gas with vasoactive and putative antidepressant properties, has a long history as a neuroimaging probe. We undertook an experimental medicine paradigm, coupling in‐scanner single‐session nitrous oxide treatment of bipolar depression with repeated measures of CBF.