Current Psychiatry Reports

, Volume 9, Issue 6, pp 467-474

First online:

The role of glutamate in mood disorders: Results from the ketamine in major depression study and the presumed cellular mechanism underlying its antidepressant effects

  • Sungho Maeng
  • , Carlos A. ZarateJrAffiliated with10 Center Drive, CRC Email author 

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In this article, we first review a study showing that the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine leads to rapid, robust, and relatively sustained antidepressant effects in patients with treatment-resistant major depression. We then discuss our hypothesis that the therapeutic effects of monoaminergic antidepressants and ketamine may be mediated by increased AMPA-to-NMDA glutamate receptor throughput in critical neuronal circuits. We hypothesize that ketamine directly mediates this throughput, whereas monoaminergic antidepressants work indirectly and gradually; this may explain, in part, the lag of onset of several weeks to months that is observed with traditional antidepressants.