Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression
American Journal of Psychiatry October 1, 2015 D. Jeffrey Newport, Linda L. Carpenter, William M. Mcdonald et al. 594 citations
A systematic review and meta-analysis of placebo-controlled, double-blind, randomized trials found that ketamine produces a rapid but short-lived antidepressant effect. In seven trials with 147 participants, ketamine greatly increased the odds of treatment response and transient remission of symptoms at 24 hours, though it also caused brief psychotomimetic and dissociative effects. When ketamine was added to electroconvulsive therapy (ECT) in five trials with 89 participants, depressive symptoms were reduced after the first treatment but not by the end of the ECT course. Other NMDA receptor antagonists generally did not show consistent efficacy, but two partial agonists, d-cycloserine and rapastinel, reduced depressive symptoms without psychotomimetic or dissociative effects. The fleeting benefit of ketamine, along with its abuse potential and neurotoxicity, warrant caution in clinical use.