How does ketamine elicit a rapid antidepressant response?

Curr Opin Pharmacol. 2015 Feb;20:35-9. doi: 10.1016/j.coph.2014.11.005. Epub 2014 Nov 25.


A single sub-psychotomimetic dose of ketamine, an ionotropic glutamatergic n-methyl-D-aspartate (NMDA) receptor antagonist, produces a fast-acting antidepressant response in patients suffering from major depressive disorder. Depressed patients report alleviation of core symptoms within 2 h of a single low-dose intravenous infusion of ketamine with effects lasting up to 2 weeks. The rapidity of ketamine action implies that major symptoms of depression can be alleviated without substantial structural plasticity or circuit rewiring. Therefore, the ability of ketamine to exert a rapid effect provides a unique opportunity to elucidate the types of acute synaptic plasticity changes that can be recruited to counter depression symptoms.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / pharmacology
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / physiopathology
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / pharmacology
  • Humans
  • Infusions, Intravenous
  • Ketamine / administration & dosage
  • Ketamine / pharmacology*
  • Neuronal Plasticity / physiology
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Time Factors


  • Antidepressive Agents
  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Ketamine