Intravenous ketamine for treatment-resistant major depressive disorder

Conventional pharmacologic treatments for major depressive disorder (MDD) generally take several weeks to several months to have a clinically meaningful effect. This time lag to response constitutes a major burden for patients and contributes to increased morbidity and mortality Two published studies in patients with MDD have now provided evidence for rapid and robust antidepressant efficacy of a single intravenous (IV) infusion with a sub-anesthetic dose of ketamine hydrochloride compared with an infusion of saline. In the approximately 60% of patients who responded, ketamine's acute antidepressant effects were maintained for at least several days and up to 2 weeks. This article reviews the pathophysiologic rationale underlying this approach, the clinical evidence for the use of IV ketamine for treatment of MDD, ketamine's safety profile, and areas of uncertainty to be explored in future studies.