NMDA Antagonists and Their Role in the Management of Bipolar Disorder: a Review

Purpose of Review This manuscript aims to review the role of NMDA antagonists in the treatment of mood disorders, more specifically in bipolar disorder. Recent Findings Different sources of evidence have implicated glutamatergic abnormalities in the pathophysiology of bipolar disorder. In particular, rapid and robust antidepressant effects of NMDA antagonist ketamine and its enantiomer esketamine have been consistently reported by several controlled trials. In last years, considerable research efforts have been destined to identify glutamatergic drugs with a better safety and tolerability profile. However, efforts to develop “ideal” glutamatergic antidepressant have proven challenging. Summary Considering several glutamatergic targets with promising findings in the treatment of mood disorders and innumerous mechanisms of action associated, NMDA antagonists have been raised as the subclass of glutamatergic agents with the most robust evidence. Among them, the agents classified as “broad glutamatergic modulators” such as ketamine and esketamine appear to be the most promising among NMDA antagonists.