title: Ketamine and rapid-acting antidepressants: a window into a new neurobiology for mood disorder therapeutics.
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.
authors.affiliation: 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.
authors.forename: Chadi G
authors.initials: CG
authors.lastname: Abdallah
authors.forename: Gerard
authors.initials: G
authors.lastname: Sanacora
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Duman
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy* / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007649:Ketamine / Q000627:therapeutic use*; D019964:Mood Disorders / Q000188:drug therapy / Q000378:metabolism; D009473:Neuronal Plasticity; D017397:Prefrontal Cortex / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D007649:Ketamine
keywords: BDNF; biomarker; depression; mTOR; synaptic plasticity