Current Status of Ketamine and Related Therapies for Mood and Anxiety Disorders

Major depressive disorder (MDD) is a leading cause of disability worldwide. Despite a plethora of established treatments, less than one third of individuals with MDD achieve stable remission of symptoms. Given limited efficacy and significant lag time to onset of therapeutic action among conventional antidepressants, interest has shifted to treatments that act outside of the monoamine neurotransmitter systems (e.g., serotonin, norepinephrine, and dopamine). Preclinical and clinical research on the glutamate system has been particularly promising in this regard. Accumulating evidence shows support for a rapid antidepressant effect of ketamine—a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist. The present article reviews the pharmacology, safety, and efficacy of ketamine as a novel therapeutic agent for mood and anxiety disorders. The majority of clinical trials using ketamine have been conducted in patients with treatment-resistant forms of MDD; recent work has begun to examine ketamine in bipolar disorder, post-traumatic stress disorder, and obsessive–compulsive disorder. The impact of ketamine on suicidal ideation is also discussed. The current status and prospects for the identification of human biomarkers of ketamine treatment response and hurdles to treatment development are considered. We conclude by considering modulators of the glutamate system other than ketamine currently in development as potential novel treatment strategies for mood and anxiety disorders.