The role of glutamate in mood disorders: results from the ketamine in major depression study and the presumed cellular mechanism underlying its antidepressant effects.
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.
Maeng
Sungho
S
Zarate
Carlos A
CA
D000547:Amantadine / Q000494:pharmacology / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000523:psychology*; D015259:Dopamine Agents / Q000494:pharmacology / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D008559:Memantine / Q000494:pharmacology / Q000627:therapeutic use; D019964:Mood Disorders / Q000188:drug therapy* / Q000378:metabolism*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D017470:Receptors, Glutamate / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D000547:Amantadine; D008559:Memantine