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

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

Author information

1
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06511; email: chadi.abdallah@yale.edu , gerard.sanacora@yale.edu , ronald.duman@yale.edu , john.krystal@yale.edu.

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

PMID:
25341010
PMCID:
PMC4428310
DOI:
10.1146/annurev-med-053013-062946
[Indexed for MEDLINE]
Free PMC Article
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