Ketamine: Its Safety, Tolerability, and Impact on Neurocognition
Ketamine, a high-affinity, noncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, has long been used in anesthesiology and also as a drug of recreational abuse. In the last decade, the evidence has shown that a subanesthetic dose of ket
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Ketamine: Its Safety, Tolerability, and Impact on Neurocognition Janusz K. Rybakowski, Agnieszka Permoda-Osip, and Alicja Bartkowska-Sniatkowska
Abstract Ketamine, a high-affinity, noncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, has long been used in anesthesiology and also as a drug of recreational abuse. In the last decade, the evidence has shown that a subanesthetic dose of ketamine has rapid and robust antidepressant effects in patients with treatment-resistant major depressive disorder (MDD) and bipolar depression. For the treatment of depression, the most widely used paradigm is a single 0.5 mg/kg intravenous infusion of ketamine. However, serial infusions, as well as oral and intranasal routes, have also been investigated. This chapter will discuss issues related to ketamine’s safety, tolerability, and effects on neurocognition. In patients with mood disorders, the safety and high tolerability of ketamine used intravenously at subanesthetic doses, and in low doses by other routes, has been demonstrated in many clinical studies. As a result of studies on healthy volunteers and of a ketamine model of schizophrenia (with ketamine-induced positive and negative symptoms and impaired cognition), ketamine has been perceived as a drug that exerts deleterious effects on neurocognition. However, giving ketamine in low doses to depressed patients has not been connected with a negative effect on cognition, and some studies have even shown an improvement in this respect. Possible mechanisms for this phenomenon—for example, ketamine’s ability to modify cognitive-emotional interactions in the brain—have been suggested. This chapter also discusses the issues of ketamine’s safety, tolerability, and effects on neurocognition when used as anesthesia for electroconvulsive therapy.
J.K. Rybakowski, MD, PhD (*) • A. Permoda-Osip Department of Adult Psychiatry, Poznan University of Medical Sciences, ul.Szpitalna 27/33, Poznan 60-572, Poland e-mail: [email protected] A. Bartkowska-Sniatkowska Department of Pediatric Anesthesiology and Intensive Therapy, Poznan University of Medical Sciences, Poznan, Poland © Springer International Publishing Switzerland (outside the USA) 2016 S.J. Mathew, C.A. Zarate Jr. (eds.), Ketamine for Treatment-Resistant Depression, DOI 10.1007/978-3-319-42925-0_5
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Introduction
The introduction of ketamine—a high-affinity, noncompetitive N-methyl-Daspartate (NMDA) glutamate receptor antagonist—for the treatment of depression has, in recent years, been one of the most important events in psychopharmacology. Ketamine, a phencyclidine derivative and an antagonist of the glutamatergic NMDA receptor, also affects the glutamatergic α-amino-3-hydroxyl-5-methyl-4isoxazole-propionate (AMPA) receptors, sigma-1 receptors, and μ-opioid receptors, as well as noradrenaline and serotonin transporters and many others. Ketamine exists as a mixture of two enantiomers (S(+) and R(−)) that have different affinity to the receptors, with S(+)-ketamine ha
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