Small trial tests repeated IV ketamine for treatment-resistant bipolar depression

A randomized clinical trial published online September 2 in JAMA Psychiatry enrolled 68 adults with bipolar I or II depression that had not improved after at least two evidence-based medication trials. Participants continued a stable mood stabilizer or antipsychotic and received four supervised intravenous infusions of either ketamine or the comparison drug midazolam over two weeks. At day 14, the ketamine group had a greater average reduction in clinician-rated depression symptoms.

Why it matters: this adds controlled evidence in a population for whom earlier ketamine research was limited. It is not proof of a durable benefit or a do-it-yourself treatment. The study was small and short, five participants withdrew before the primary endpoint, and nearly half of assessed participants correctly guessed their treatment after the first infusion, which may weaken blinding. The trial evaluated medically supervised IV ketamine added to existing treatment; ketamine is not FDA-approved for bipolar depression.

Primary source (published September 2, 2026): https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2853662

What information about longer-term benefit, relapse, and safety would you want before calling this a meaningful treatment advance? Please discuss treatment decisions with a qualified clinician rather than changing care based on a news post.