Biochemical Pharmacology
December 1, 2021
E. Hess, L. Riggs, Michael Michaelides et al.
167 citations
Treating major depression is a medical need that remains unmet by monoaminergic therapeutic strategies that commonly fail to achieve symptom remission. A breakthrough in the treatment of depression was the discovery that the anesthetic (R,S)-ketamine (ketamine), when administered at sub-anesthetic doses, elicits rapid (sometimes within hours) antidepressant effects in humans that are otherwise...
Annual Review of Clinical Psychology
February 9, 2021
L. Riggs, T. Gould
87 citations
The therapeutic onset of traditional antidepressants is delayed by several weeks and many depressed patients fail to respond to treatment altogether. In contrast, subanesthetic ketamine can rapidly alleviate symptoms of depression within hours of a single administration, even in patients who are considered treatment-resistant. Ketamine is thought to exert these effects by restoring the...
Proceedings of the National Academy of Sciences of the United States of America
February 22, 2019
E. Lumsden, Timothy A. Troppoli, S. J. Myers et al.
159 citations
Significance Standard antidepressant treatments require weeks to show effectiveness. A single subanesthetic dose of ketamine rapidly attenuates many clinical signs and symptoms of depression; however, ketamine treatment also has many adverse effects, including dissociation and potential for abuse, which are mediated by NMDA glutamate receptor (NMDAR) inhibition. Previous work has revealed that...
Pharmacological Reviews
June 26, 2018
Panos Zanos, Ruin Moaddel, Patrick J. Morris et al.
1,272 citations
Ketamine, a racemic mixture consisting of (S)- and (R)-ketamine, has been in clinical use since 1970. Although best characterized for its dissociative anesthetic properties, ketamine also exerts analgesic, anti-inflammatory, and antidepressant actions. We provide a comprehensive review of these therapeutic uses, emphasizing drug dose, route of administration, and the time course of these...
Molecular Psychiatry
March 13, 2018
Panos Zanos, T. Gould
1,112 citations
Clinical studies have demonstrated that a single sub-anesthetic dose of the dissociative anesthetic ketamine induces rapid and sustained antidepressant actions. Although this finding has been met with enthusiasm, ketamine’s widespread use is limited by its abuse potential and dissociative properties. Recent preclinical research has focused on unraveling the molecular mechanisms underlying the...
Molecular Psychiatry
February 27, 2018
Allison C. Nugent, Elizabeth D. Ballard, T. Gould et al.
254 citations
Ketamine’s mechanism of action was assessed using gamma power from magnetoencephalography (MEG) as a proxy measure for homeostatic balance in 35 unmedicated subjects with major depressive disorder (MDD) and 25 healthy controls enrolled in a double-blind, placebo-controlled, randomized cross-over trial of 0.5 mg/kg ketamine. MDD subjects showed significant improvements in depressive symptoms,...
Nature
April 24, 2016
Panos Zanos, Ruin Moaddel, Patrick J. Morris et al.
1,602 citations
Major depressive disorder affects around 16 per cent of the world population at some point in their lives. Despite the availability of numerous monoaminergic-based antidepressants, most patients require several weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive, glutamatergic NMDAR (N-methyl-d-aspartate...