ON or OFF?: Modulating the N-Methyl-D-Aspartate Receptor in Major Depression

Since the discovery that a single dose of ketamine, an NMDA receptor (NMDAR) antagonist, had rapid and long-lasting antidepressant effects, there has been increased interest in using NMDAR modulators in the pharmacotherapy of depression. Ketamine’s efficacy seems to imply that depression is a disorder of NMDAR hyperfunctionality. However, studies showing that not all NMDAR antagonists are able to act as antidepressants challenge this notion....