Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics
This review (2014) examines 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.
Authors
- Gerard Sanacora
- John Krystal
- Chadi Abdallah
Published
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.
Research Summary of 'Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics'
Introduction
Major depressive disorder (MDD) is a leading global cause of disability with an estimated lifetime prevalence of about 17% in the United States. Existing antidepressant medications largely target monoaminergic systems, but their efficacy is limited for a substantial subgroup of patients and clinical benefit typically requires weeks to months to emerge. This delay and incomplete response in many patients create an urgent need for rapid-acting treatments with efficacy in treatment-refractory cases. Ari and colleagues present a narrative synthesis of clinical, preclinical, and biomarker research on ketamine as a prototype rapid-acting, glutamate-based antidepressant. The review summarises evidence for ketamine’s rapid antidepressant and antisuicidal effects, examines proposed neurobiological mechanisms (notably synaptic plasticity involving BDNF and mTORC1), and discusses biomarkers, safety, and the prospects for next-generation rapid-acting therapeutics for mood disorders.
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Study Details
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- APA Citation
Abdallah, C. G., Sanacora, G., Duman, R. S., & Krystal, J. H. (2015). Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics. Annual Review of Medicine, 66(1), 509-523. https://doi.org/10.1146/annurev-med-053013-062946
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López-Díaz, A., Fernández-González, J. L., Luján-Jiménez, J. E. et al. · Therapeutic Advances in Psychopharmacology (2017)
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Abdallah, C. G., Averill, L. A., Krystal, J. H. · Annals of the New York Academy of Sciences (2015)
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