Ketamine and rapid-acting antidepressants: a window into a new neurobiology for mood disorder therapeutics

Annu Rev Med. 2015;66:509-23. doi: 10.1146/annurev-med-053013-062946. Epub 2014 Oct 17.

Abstract

Ketamine is the prototype for a new generation of glutamate-based antidepressants that rapidly alleviate depression within hours of treatment. Over the past decade, there has been replicated evidence demonstrating the rapid and potent antidepressant effects of ketamine in treatment-resistant depression. Moreover, preclinical and biomarker studies have begun to elucidate the mechanism underlying the rapid antidepressant effects of ketamine, offering a new window into the biology of depression and identifying a plethora of potential treatment targets. This article discusses the efficacy, safety, and tolerability of ketamine, summarizes the neurobiology of depression, reviews the mechanisms underlying the rapid antidepressant effects of ketamine, and discusses the prospects for next-generation rapid-acting antidepressants.

Keywords: BDNF; biomarker; depression; mTOR; synaptic plasticity.

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

  • Antidepressive Agents / therapeutic use*
  • Brain / metabolism*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / metabolism
  • Depressive Disorder, Treatment-Resistant / drug therapy*
  • Depressive Disorder, Treatment-Resistant / metabolism
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Glutamic Acid / metabolism
  • Humans
  • Ketamine / therapeutic use*
  • Mood Disorders / drug therapy
  • Mood Disorders / metabolism
  • Neuronal Plasticity*
  • Prefrontal Cortex / metabolism

Substances

  • Antidepressive Agents
  • Excitatory Amino Acid Antagonists
  • Glutamic Acid
  • Ketamine