Current Neuropharmacology
March 10, 2016
Eric S. Wohleb, Danielle M. Gerhard, Alex Thomas et al.
148 citations
Major depressive disorder (MDD) is a prevalent neuropsychiatric disease that causes profound social and economic burdens. The impact of MDD is compounded by the limited therapeutic efficacy and delay of weeks to months of currently available medications. These issues highlight the need for more efficacious and faster-acting treatments to alleviate the burdens of MDD. Recent breakthroughs...
eNeuro
March 1, 2016
A. Soumier, Ray M. Carter, Timothy J. Schoenfeld et al.
Abstract Virtually all antidepressant agents increase the birth of granule neurons in the adult dentate gyrus in rodents, providing a key basis for the neurogenesis hypothesis of antidepressant action. The novel antidepressant ketamine, however, shows antidepressant activity in humans within hours, far too rapid for a mechanism involving neuronal birth. Ketamine could potentially act more...
eNeuro
March 1, 2016
Victoria Phoumthipphavong, Florent Barthas, Samantha Hassett et al.
142 citations
A single subanesthetic dose of ketamine, an NMDA receptor antagonist, leads to fast-acting antidepressant effects. In rodent models, systemic ketamine is associated with higher dendritic spine density in the prefrontal cortex, reflecting structural remodeling that may underlie the behavioral changes. However, turnover of dendritic spines is a dynamic process in vivo, and the longitudinal...
The World Journal of Biological Psychiatry
February 26, 2016
Eric J Lenze, Nuri B Farber, E. Kharasch et al.
ABSTRACT Objectives We examined the feasibility of a high-dose, 96-h infusion of ketamine in treatment-resistant depression. Methods Ten participants were randomised to receive a 96-h ketamine infusion, titrated as tolerated to a target rate of 0.6 mg/kg/h, while 10 received a 40-min ketamine infusion (0.5 mg/kg). Both groups received clonidine, titrated to a maximum of 0.6 mg orally daily,...
Human Brain Mapping
February 25, 2016
Milan Scheidegger, Anke Henning, Martin Walter et al.
78 citations
Increased amygdala reactivity might lead to negative bias during emotional processing that can be reversed by antidepressant drug treatment. However, little is known on how N-methyl-d-aspartate (NMDA) receptor antagonism with ketamine as a novel antidepressant drug target might modulate amygdala reactivity to emotional stimulation. Using functional magnetic resonance imaging (fMRI) and...
Translational Psychiatry
February 23, 2016
H-L Sun, Z-Q Zhou, G.-F. Zhang et al.
87 citations
Although ketamine shows a rapid and sustained antidepressant effect, the precise mechanisms underlying its effect are unknown. Recent studies indicate a key role of p11 (also known as S100A10) in depression-like behavior in rodents. The present study aimed to investigate the role of p11 in the antidepressant-like action of ketamine in chronic unpredictable mild stress (CUMS) rat model. The...
Behavioural Brain Research
February 15, 2016
Lakshmi Rajagopal, Jeffrey S Burgdorf, Joseph R Moskal et al.
GLYX-13 (rapastinel), a tetrapeptide (Thr-Pro-Pro-Thr-amide), has been reported to have fast acting antidepressant properties in man based upon its N-methyl-D-aspartate receptor (NMDAR) glycine site functional partial agonism. Ketamine, a non-competitive NMDAR antagonist, also reported to have fast acting antidepressant properties, produces cognitive impairment in rodents and man, whereas...
Psychological Medicine
February 12, 2016
Taishiro Kishimoto, J. M. Chawla, K. Hagi et al.
363 citations
Background Ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists (NMDAR antagonists) recently demonstrated antidepressant efficacy for the treatment of refractory depression, but effect sizes, trajectories and possible class effects are unclear. Method We searched PubMed/PsycINFO/Web of Science/clinicaltrials.gov until 25 August 2015. Parallel-group or cross-over randomized...
Medical Hypotheses
February 1, 2016
Ming-Chyi Huang, Lian-Yu Chen, Chih-Ken Chen et al.
Ketamine is an anesthetic derivative of phencyclidine (PCP; 'Angel dust') with dissociative, analgesic and psychedelic properties. Ketamine has become a popular recreational drug of abuse in many parts of the world in recent years. The preclinical studies demonstrate the reinforcing effects of ketamine and long-term ketamine abuse induces a delayed and persistent upregulation of dopamine...
The British Journal of Psychiatry
February 1, 2016
Robert A Schoevers, Tharcila V. Chaves, Sonya M. Balukova et al.
80 citations
BACKGROUND: Recent studies with intravenous (i.v.) application of ketamine show remarkable but short-term success in patients with MDD. Studies in patients with chronic pain have used different ketamine applications for longer time periods. This experience may be relevant for psychiatric indications. AIMS: To review the literature about the dosing regimen, duration, effects and side-effects of...