Ketamine treatment for depression: a review
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TLDR
This paper reviewed the clinical evidence regarding single-dose intravenous (IV) administration of the novel glutamatergic modulator racemic (R,S)-ketamine (hereafter referred to as ketamine) as well as its S-enantiomer, intranasal esketamine, for the treatment of major depressive disorder (MDD).Abstract:
This manuscript reviews the clinical evidence regarding single-dose intravenous (IV) administration of the novel glutamatergic modulator racemic (R,S)-ketamine (hereafter referred to as ketamine) as well as its S-enantiomer, intranasal esketamine, for the treatment of major depressive disorder (MDD). Initial studies found that a single subanesthetic-dose IV ketamine infusion rapidly (within one day) improved depressive symptoms in individuals with MDD and bipolar depression, with antidepressant effects lasting three to seven days. In 2019, esketamine received FDA approval as an adjunctive treatment for treatment-resistant depression (TRD) in adults. Esketamine was approved under a risk evaluation and mitigation strategy (REMS) that requires administration under medical supervision. Both ketamine and esketamine are currently viable treatment options for TRD that offer the possibility of rapid symptom improvement. The manuscript also reviews ketamine's use in other psychiatric diagnoses-including suicidality, obsessive-compulsive disorder, post-traumatic stress disorder, substance abuse, and social anxiety disorder-and its potential adverse effects. Despite limited data, side effects for antidepressant-dose ketamine-including dissociative symptoms, hypertension, and confusion/agitation-appear to be tolerable and limited to around the time of treatment. Relatively little is known about ketamine's longer-term effects, including increased risks of abuse and/or dependence. Attempts to prolong ketamine's effects with combined therapy or a repeat-dose strategy are also reviewed, as are current guidelines for its clinical use. In addition to presenting a novel and valuable treatment option, studying ketamine also has the potential to transform our understanding of the mechanisms underlying mood disorders and the development of novel therapeutics. read more
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References
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Journal ArticleDOI
Antidepressant effects of ketamine in depressed patients
Robert M. Berman,Angela Cappiello,Amit Anand,Amit Anand,Dan A. Oren,Dan A. Oren,George R. Heninger,Dennis S. Charney,Dennis S. Charney,John H. Krystal,John H. Krystal +10 more
TL;DR: A first placebo-controlled, double-blinded trial to assess the treatment effects of a single dose of an N-methyl-D-aspartate (NMDA) receptor antagonist in patients with depression suggests a potential role for NMDA receptor-modulating drugs in the treatment of depression.
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Carlos A. Zarate,Jaskaran Singh,Paul J. Carlson,Nancy E. Brutsche,Rezvan Ameli,David A. Luckenbaugh,Dennis S. Charney,Husseini K. Manji +7 more
TL;DR: Robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist; onset occurred within 2 hours postinfusion and continued to remain significant for 1 week.
Journal ArticleDOI
Molecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Undine E. Lang,Stefan Borgwardt +1 more
TL;DR: The neurodegenerative hypothesis of depression explains decreased hippocampal volumes in depressed patients and changes of neurotrophic support by BDNF, erythropoietin, GDNF, FGF-2, NT3, NGF and growth hormone.
Journal ArticleDOI
NMDAR inhibition-independent antidepressant actions of ketamine metabolites
Panos Zanos,Ruin Moaddel,Patrick J. Morris,Polymnia Georgiou,Jonathan Fischell,Greg I. Elmer,Manickavasagom Alkondon,Peixiong Yuan,Heather J. Pribut,Nagendra Singh,Katina Sourou Sylvestre Dossou,Yuhong Fang,Xi Ping Huang,Cheryl L. Mayo,Irving W. Wainer,Edson X. Albuquerque,Scott M. Thompson,Craig J. Thomas,Carlos A. Zarate,Todd D. Gould +19 more
TL;DR: It is shown that the metabolism of (R,S)-ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant-related actions in mice.