Abstract
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.
Publication types
-
Research Support, N.I.H., Intramural
-
Review
MeSH terms
-
Amantadine / pharmacology
-
Amantadine / therapeutic use
-
Depressive Disorder, Major / psychology*
-
Dopamine Agents / pharmacology
-
Dopamine Agents / therapeutic use
-
Excitatory Amino Acid Antagonists / administration & dosage
-
Excitatory Amino Acid Antagonists / pharmacology*
-
Excitatory Amino Acid Antagonists / therapeutic use*
-
Humans
-
Ketamine / administration & dosage
-
Ketamine / pharmacology*
-
Ketamine / therapeutic use*
-
Memantine / pharmacology
-
Memantine / therapeutic use
-
Mood Disorders / drug therapy*
-
Mood Disorders / metabolism*
-
Receptors, AMPA / antagonists & inhibitors
-
Receptors, Glutamate / drug effects*
-
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
Substances
-
Dopamine Agents
-
Excitatory Amino Acid Antagonists
-
Receptors, AMPA
-
Receptors, Glutamate
-
Receptors, N-Methyl-D-Aspartate
-
Ketamine
-
Amantadine
-
Memantine