Optimizing Ketamine Infusion Therapy for Treatment-Resistant Bipolar Depression: Commentary on Zhou et al. (2023).

OBJECTIVES: To contextualize the real-world findings of repeated intravenous ketamine infusions for treatment-resistant bipolar depression (TRBPD) and identify priorities for safer, more durable clinical implementation. METHODS: We provide a focused commentary on Zhou et al. (2023) and integrate selected evidence concerning inflammatory and metabolic correlates, neurocognitive outcomes, and continuation-phase ketamine treatment. RESULTS: Repeated subanesthetic ketamine infusions may rapidly improve depressive and anxiety symptoms with an acceptable short-term safety profile. However, the predictive value of C-reactive protein and body mass index varies across cohorts; available cognitive findings are reassuring but limited; and relapse after induction highlights the need for individualized maintenance planning. CONCLUSIONS: Ketamine pathways for TRBPD should combine cautious patient stratification, repeatable cognitive monitoring, and explicit continuation or booster strategies. Prospective bipolar-specific studies are needed to clarify predictors, durability, and stopping rules.