Ketamine shows promise as a treatment for bipolar depression, though evidence remains weak. A scoping review of 10 clinical studies (5 randomized controlled trials and 5 open-label studies) found that ketamine was generally tolerable, with minimal risk of triggering manic or hypomanic episodes, and demonstrated some effectiveness in reducing depressive symptoms and suicidality. The treatment may be particularly useful for patients with treatment-resistant bipolar depression. However, more research is needed to establish ketamine's role in both acute and maintenance treatment phases, and to study its potential for preventing recurrence and suicidal behavior.
A systematic review of five neuroimaging studies found that psilocybin therapy transiently increases global connectivity in major neural tracts and activates specific brain areas, and these changes are associated with antidepressant response in depressed patients. The pattern of functional brain changes resembles a 'brain reset' phenomenon and may serve as a predictor of psilocybin's antidepressant effects. Four of the studies were open-label, and one combined an open-label design with a randomized controlled trial. Three studies included psilocybin-assisted psychotherapy, and participants in most studies had treatment-resistant depression.