Marie Naughton1, Gerard Clarke2, Olivia F O'Leary3, John F Cryan4, Timothy G Dinan5. 1. Department of Psychiatry, University College Cork, Western Road, Cork City, Cork, Ireland. Electronic address: marienaughton@beaumont.ie. 2. Department of Psychiatry, University College Cork, Western Road, Cork City, Cork, Ireland; Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. Electronic address: g.clarke@ucc.ie. 3. Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland. Electronic address: o.oleary@ucc.ie. 4. Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland. Electronic address: j.cryan@ucc.ie. 5. Department of Psychiatry, University College Cork, Western Road, Cork City, Cork, Ireland; Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. Electronic address: t.dinan@ucc.ie.
Abstract
INTRODUCTION: Recent research has seen low-dose ketamine emerge as a novel, rapid-acting antidepressant. Ketamine, an N-methy-d-aspartate (NMDA) receptor antagonist, leads to effects on the glutamatergic system and abnormalities in this neurotransmittor system are present in depression. This article aims to (1) review the clinical literature on low-dose ketamine as a rapid-acting antidepressant in affective disorders, (2) provide a critical overview of the limitations of ketamine and research attempts to overcome these (3) discuss the proposed mechanisms of action of ketamine and (4) point towards future research directions. METHOD: The electronic database Pubmed, Web of Science and sciencedirect were searched using the keywords: ketamine, N-methyl-d-aspartate receptor antagonist, rapid-acting antidepressant, depression, treatment-resistant depression, bipolar depression, suicidal ideation, electroconvulsive therapy, mechanism of action. RESULT: The literature demonstrates evidence supporting a rapid-acting antidepressant effect of low-dose intravenous ketamine in major depressive disorder, in bipolar depression and in depression with suicidal ideation. There are mixed results as to whether ketamine leads to a reduction in time to remission in patients undergoing electroconvulsive therapy (ECT). Efforts to unravel ketamine's therapeutic mechanism of action have implicated the mammalian target of rapamycin (mTOR)-dependent synapse formation in the rat prefrontal cortex, eukaryotic elongation factor 2 phosphorylation (p-eEF2) and glycogen synthase kinase (GSK-3). Ketamine's limiting factors are the transient nature of its antidepressant effect and concerns regarding abuse, and research efforts to overcome these are reviewed. CONCLUSION: Current and future research studies are using ketamine as a promising tool to evaluate the glutamatergic neurotransmittor system to learn more about the pathophysiology of depression and develop more specific rapid-acting antidepressant treatments.
INTRODUCTION: Recent research has seen low-dose ketamine emerge as a novel, rapid-acting antidepressant. Ketamine, an N-methy-d-aspartate (NMDA) receptor antagonist, leads to effects on the glutamatergic system and abnormalities in this neurotransmittor system are present in depression. This article aims to (1) review the clinical literature on low-dose ketamine as a rapid-acting antidepressant in affective disorders, (2) provide a critical overview of the limitations of ketamine and research attempts to overcome these (3) discuss the proposed mechanisms of action of ketamine and (4) point towards future research directions. METHOD: The electronic database Pubmed, Web of Science and sciencedirect were searched using the keywords: ketamine, N-methyl-d-aspartate receptor antagonist, rapid-acting antidepressant, depression, treatment-resistant depression, bipolar depression, suicidal ideation, electroconvulsive therapy, mechanism of action. RESULT: The literature demonstrates evidence supporting a rapid-acting antidepressant effect of low-dose intravenous ketamine in major depressive disorder, in bipolar depression and in depression with suicidal ideation. There are mixed results as to whether ketamine leads to a reduction in time to remission in patients undergoing electroconvulsive therapy (ECT). Efforts to unravel ketamine's therapeutic mechanism of action have implicated the mammalian target of rapamycin (mTOR)-dependent synapse formation in the rat prefrontal cortex, eukaryotic elongation factor 2 phosphorylation (p-eEF2) and glycogen synthase kinase (GSK-3). Ketamine's limiting factors are the transient nature of its antidepressant effect and concerns regarding abuse, and research efforts to overcome these are reviewed. CONCLUSION: Current and future research studies are using ketamine as a promising tool to evaluate the glutamatergic neurotransmittor system to learn more about the pathophysiology of depression and develop more specific rapid-acting antidepressant treatments.
Authors: Eric J Lenze; Nuri B Farber; Evan Kharasch; Julie Schweiger; Michael Yingling; John Olney; John W Newcomer Journal: World J Biol Psychiatry Date: 2016-02-26 Impact factor: 4.132
Authors: Ricardo P Garay; Carlos A Zarate; Thomas Charpeaud; Leslie Citrome; Christoph U Correll; Ahcène Hameg; Pierre-Michel Llorca Journal: Expert Rev Neurother Date: 2017-01-29 Impact factor: 4.618