Glutamate modulators in major depressive disorder

Current pharmacological methods of treating major depressive disorder are limited by modest efficacy and delayed clinical response, leading investigators to search for novel antidepressant agents. Ketamine is a selective NMDA receptor antagonist that has emerged as a promising experimental antidepressant due to its rapid and robust clinical effects, particularly for treatment-resistant patients or in emergency psychiatry settings. In this chapter, we examine how ketamine’s mechanism of action supports the hypothesis of glutamate dysregulation in major depressive disorder and review the studies in humans on the clinical effects of ketamine and other glutamatergic modulators under investigation for their potential as novel antidepressants.