Ketamine as a promising prototype for a new generation of rapid-acting antidepressants

Ann N Y Acad Sci. 2015 May;1344(1):66-77. doi: 10.1111/nyas.12718. Epub 2015 Feb 27.


The discovery of ketamine's rapid and robust antidepressant effects opened a window into a new generation of antidepressants. Multiple controlled trials and open-label studies have demonstrated these effects across a variety of patient populations known to often achieve little to no response from traditional antidepressants. Ketamine has been generally well tolerated across patient groups, with transient mild-to-moderate adverse effects during infusion. However, the optimal dosing and route of administration and the safety of chronic treatment are not fully known. This review summarizes the clinical effects of ketamine and its neurobiological underpinnings and mechanisms of action, which may provide insight into the neurobiology of depression, relevant biomarkers, and treatment targets. Moreover, we offer suggestions for future research that may continue to advance the field forward and ultimately improve the psychopharmacologic interventions available for those individuals struggling with depressive and trauma-related disorders.

Keywords: antidepressant; depression; ketamine; neurobiology; treatment mechanisms.

Publication types

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

MeSH terms

  • Animals
  • Antidepressive Agents, Second-Generation / adverse effects
  • Antidepressive Agents, Second-Generation / pharmacokinetics
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Biomarkers / metabolism
  • Depression / blood
  • Depression / drug therapy*
  • Depression / physiopathology
  • Excitatory Amino Acid Antagonists / adverse effects
  • Excitatory Amino Acid Antagonists / pharmacokinetics
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Humans
  • Ketamine / adverse effects
  • Ketamine / pharmacokinetics
  • Ketamine / therapeutic use*
  • Wounds and Injuries / blood
  • Wounds and Injuries / drug therapy
  • Wounds and Injuries / physiopathology


  • Antidepressive Agents, Second-Generation
  • Biomarkers
  • Excitatory Amino Acid Antagonists
  • Ketamine