Do glutamatergic agents represent a new class of antidepressant drugs? Part 2

Abstract

Both preclinical and early-phase clinical studies suggest that drugs targeting the ionotropic glutamate receptors possess potent antidepressant properties. The seeming effectiveness in previously treatment-resistant patients, the novelty of the mechanism of action, and the rapid antidepressant response associated with the NMDA antagonist drugs have stimulated great interest both at academic centers and within the pharmaceutical industry. However, it is important to acknowledge the limitations of clinical studies reported to date in this area. None of the studies have truly been conducted in a double-blind fashion because the acute effects of the ketamine and even CP-101606 on cognition and perception were discernable by both the subjects and the treaters when compared to a saline placebo. In addition, the studies provide no information on the longer-term effectiveness and safety of the NMDA receptor antagonists in treating depression. This is especially important considering that under certain conditions NMDA receptor antagonists themselves can be neurodestructive. According to clinicaltrials.gov listings, there are 8 ongoing clinical trials examining the antidepressant and mood-stabilizing efficacy of NMDA antagonists, in addition to several others that were recently completed. Undoubtedly, the results of these studies will provide more information on this class of drugs in the near future. © Copyright 2009 Physicians Postgraduate Press, Inc.