Ketamine as an NMDA-modulating therapy in bipolar disorder: rationale and evidence

Ketamine and esketamine represent mechanistically novel and clinically effective treatments for bipolar depression. Their rapid antidepressant action and low switch liability distinguish them from traditional antidepressants. Esketamine, with its favorable tolerability and intranasal administration, offers a promising adjunctive option for treatment-resistant bipolar depression. Long-term data are warranted to optimize maintenance strategies and confirm sustained safety and efficacy.