Rapid-onset antidepressant action of ketamine: potential revolution in understanding and future pharmacologic treatment of depression

J Clin Pharm Ther. 2015 Apr;40(2):125-30. doi: 10.1111/jcpt.12238. Epub 2014 Dec 26.


What is known and objective: The current pharmacotherapeutic treatment of major depressive disorder (MDD) generally takes weeks to be effective. As the molecular action of these drugs is immediate, the mechanistic basis for this lag is unclear. A drug that has a more rapid onset of action would be a major therapeutic advance and also be a useful comparator to provide valuable mechanistic insight into the disorder and its treatment.

Comment: Recent evidence suggests that ketamine produces rapid-onset antidepressant action. Important questions are as follows: is it specific or coincidental to other effects; is there a dose-response relationship; and is the mechanism related to that of current antidepressants. NMDA receptor antagonism is unlikely the explanation for ketamine's antidepressant action.

What is new and conclusion: It is not an exaggeration to state that the new findings, if validated, might produce a revolution in understanding and treating depressive disorders.

Keywords: antidepressant; ketamine; major depressive disorder (MDD); mechanism of action.

MeSH terms

  • Animals
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / chemistry
  • Antidepressive Agents / therapeutic use*
  • Clinical Trials as Topic
  • Depressive Disorder, Major / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Humans
  • Ketamine / administration & dosage
  • Ketamine / chemistry
  • Ketamine / therapeutic use*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors


  • Antidepressive Agents
  • Receptors, N-Methyl-D-Aspartate
  • Ketamine