Abstract

Treatment-resistant bipolar depression (TRBD) is a significant but less well-defined and quantified condition compared to treatment-resistant depression (TRD, unipolarity implied). Ketamine, a novel glutamatergic anesthetic agent repurposed as a rapid-acting antidepressant, is considered a third-line treatment with Level 3 evidence for acute bipolar I and II depression.1 While there are numerous studies of the efficacy, safety, and tolerability of off-label intravenous (IV) racemic ketamine and its FDA-approved enantiomer intranasal esketamine for TRD the evidence base of ketamine for TRBD is much less.

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