Journal of Psychopharmacology
March 1, 2020
Paul Glue, Shona Neehoff, A. Sabadel et al.
97 citations
Background: We previously reported that ketamine has anxiolytic effects in patients with treatment-resistant generalized anxiety and social anxiety disorders. Aims: The purpose of this study was to replicate our earlier report about ketamine‘s anxiolytic activity, using a more robust study design. Methods: This was a double-blind, psychoactive-controlled ascending dose study in 12 patients with...
March 1, 2020
Adam Winstock, James W. Rucker
29 citations
Abstract Psychedelics and hallucinogens represent some of the most commonly used drugs in the world, with a history of use steeped in spirituality, counter-culture, and more recently latent therapeutic potential. Sharing a common mechanism of action at the 5-HT2a receptor, drugs such as lysergic acid diethylamide (LSD) and psilocybin, while they can rarely induce significant short-term...
Progress in Neuro-Psychopharmacology and Biological Psychiatry
February 25, 2020
Muris Humo, Beyza Ayazgök, Léa J. Becker et al.
Chronic pain produces psychologic distress, which often leads to mood disorders such as depression. Co-existing chronic pain and depression pose a serious socio-economic burden and result in disability affecting millions individuals, which urges the development of treatment strategies targeting this comorbidity. Ketamine, a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor,...
Neuropsychopharmacology
February 24, 2020
Chadi G. Abdallah, Lynnette A. Averill, Ralitza Gueorguieva et al.
181 citations
Twenty-four hours after administration, ketamine exerts rapid and robust antidepressant effects that are thought to be mediated by activation of the mechanistic target of rapamycin complex 1 (mTORC1). To test this hypothesis, depressed patients were pretreated with rapamycin, an mTORC1 inhibitor, prior to receiving ketamine. Twenty patients suffering a major depressive episode were randomized...
European Archives of Psychiatry and Clinical Neuroscience
February 20, 2020
Gustavo C. Leal, Igor D. Bandeira, Fernanda S. Correia-Melo et al.
257 citations
We aimed to analyze the efficacy and safety of arketamine, the R (−)-enantiomer of ketamine, for treatment-resistant depression (TRD) in humans. Open-label pilot trial, seven subjects with TRD received a single intravenous infusion of arketamine (0.5 mg/kg); primary outcome was change in Montgomery–Åsberg Depression Rating Scale (MADRS) 24 h after. Mean MADRS dropped from 30.7 before infusion...
Chemico-Biological Interactions
February 19, 2020
Guo-Liang Liu, Yun-Feng Cui, Chang Lu et al.
Ketamine is gaining ground as a potential treating depression because it has a distinct mode of action than typical drugs that influence monoamine neurotransmitters including noradrenaline, dopamine, or serotonin. Ketamine is thought to act by blocking N-methyl-d-aspartate (NMDA) receptors in the brain, which interact with the amino acid neurotransmitter glutamate. The resultant chemical...
The Journal of Clinical Pharmacology
February 17, 2020
Paul Glue, Natalie J. Medlicott, Peter Surman et al.
44 citations
Parenteral ketamine has fast‐onset antidepressant and antianxiety effects; however, it causes dissociation, hypertension, and tachycardia shortly after dosing. Ketamine's antidepressant effects may be due to active metabolites rather than to ketamine itself. We hypothesized that oral controlled‐release ketamine tablets would improve safety and tolerability compared with injected ketamine by...
Behavioural Brain Research
February 13, 2020
S. Kokane, Ross J. Armant, Carlos A. Bolaños-Guzmán et al.
Ketamine, a dissociative anesthetic and psychedelic compound, has revolutionized the field of psychopharmacology by showing robust, and rapid-acting antidepressant activity in patients suffering from major depressive disorder (MDD), suicidal tendencies, and treatment-resistant depression (TRD). Ketamine’s efficacy, however, is transient, and patients must return to the clinic for repeated...
Neuropharmacology
February 12, 2020
C. Wilson, Shanshan Li, Anthony J. Hannan et al.
Traditional monoaminergic treatments of depression frequently exhibit suboptimal tolerability and effectiveness. The 'short' (s) allele variant of 5-HTTLPR is known to compromise transcriptional efficacy of the serotonin transporter (5-HTT) and can reduce treatment response to traditional antidepressants (e.g. selective serotonin reuptake inhibitors or SSRIs). This study sought to establish the...
Medicina
February 9, 2020
Adam Włodarczyk, Wiesław Jerzy Cubała
22 citations
The current psychopharmacological treatment approaches for major depression focus on monoaminergic interventions, which are ineffective in a large proportion of patients. Globally, treatment-resistant bipolar depression (TRBD) affects up to 33% of depressive patients receiving treatment. Certain needs are still unmet and require new approaches. Many studies are in favor of treatments with...
Frontiers in Pharmacology
February 6, 2020
Shan Li, Xiaoxiao Luo, Dongyu Hua et al.
Patients are more likely to suffer from central nervous system (CNS) complications after anesthesia and surgery. However, postoperative depression (POD) has not yet received sufficient attentions, and its pathogenesis and therapeutic strategies remain poorly understood. We here aimed to investigate whether brain derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) signaling...
Pharmacology, Biochemistry, and Behavior
February 5, 2020
Yan Wei, Lijia Chang, Kenji Hashimoto
157 citations
The robust antidepressant effects of (R,S)-ketamine are among the most important discoveries in mood research over the last half century. Off-label use of (R,S)-ketamine, which is an equal mixture of (R)-ketamine and (S)-ketamine, has become especially popular in the United States (US) for treatment-resistant depression. On March 5, 2019, the US Food and Drug Administration approved an...
ACS Chemical Neuroscience
February 3, 2020
Jinghua Zhao, XueJie Liu, Daiyue Chang et al.
About 16% of the world's population has major depressive disorder. Traditional antidepressants have slow effect rates and low response rates. Many studies have shown that low doses of ketamine can produce rapid and effective antidepressant effects. However, its mechanism of action needs further exploration. Lipopolysaccharide (LPS) was used to establish a depression model in rats and PC12 nerve...
Psychiatric Annals
February 1, 2020
Samuel T. Wilkinson, Brandon Kitay
Since the discovery of its rapid-acting antidepressant properties, ketamine has helped stimulate a new line of research in the development of rapid-acting antidepressants based on the glutamate and gamma-aminobutyric acid neurotransmitter systems. An intranasal version of the S-enantiomer of ketamine (esketamine) recently received regulatory approval as a therapy for treatment-resistant...
Psychiatric Annals
February 1, 2020
Hatice Guncu Kurt, Murat Altinay, Amit Anand
Patients who have not responded to two antidepressant trials in their current depressive episode are usually considered to have treatment-resistant depression (TRD). A detailed search on PubMed was conducted for reported response and remission rates for non-ketamine and ketamine treatments for TRD. From a variety of pharmacological and brain stimulation open-label studies, the treatments were...
Psychiatric Annals
February 1, 2020
Lynnette A. Averill, Christopher L. Averill, Chadi G. Abdallah
6 citations
The serendipitous discovery of ketamine's robust antidepressant effects has served as a major catalyst to usher in new era of drug development and a paradigm shift in our understanding of the neurobiology of chronic stress pathology (CSP). This review provides a selective synthesis of (1) the historical foundations of N-methyl-D-aspartate receptor modulators and the path to discovering...
Current Topics in Medicinal Chemistry
January 31, 2020
Domenico de Berardis, Carmine Tomasetti, Maurizio Pompili et al.
38 citations
BACKGROUND: A research on mood disorder pathophysiology has hypothesized abnormalities in glutamatergic neurotransmission, by suggesting further investigation on glutamatergic N-methyl-Daspartate (NMDA) receptor modulators in treating Major Depressive Disorder (MDD). Esketamine (ESK), an NMDA receptor antagonist able to modulate glutamatergic neurotransmission has been recently developed as an...
Journal of Emergency Medicine
January 27, 2020
K. Iserson, Dellon Durga
BACKGROUND Ketamine's application in psychiatry have expanded, but it appears never to have been previously used to diagnose and treat patients with catatonia-like syndrome that occasionally present to emergency departments. CASE REPORT A 23-year-old male was observed to suddenly stop talking. His ED GCS was 8 and had normal vital signs. While verbally unresponsive, he refused to open his eyes,...
Translational Psychiatry
January 27, 2020
Kai Zhang, Chun Yang, Lijia Chang et al.
120 citations
In rodent models of depression, (R)-ketamine has greater potency and longer-lasting antidepressant effects than (S)-ketamine; however, the precise molecular mechanisms underlying the antidepressant actions of (R)-ketamine remain unknown. Using RNA-sequencing analysis, we identified novel molecular targets that contribute to the different antidepressant effects of the two enantiomers. Either...
bioRxiv (Cold Spring Harbor Laboratory)
January 23, 2020
Ca Hales, Jm Bartlett, Roberto Arban et al.
preprint
Abstract Major Depressive Disorder is a significant and costly cause of global disability. Until the discovery of the rapid acting antidepressant (RAAD) effects of ketamine, treatments were limited to drugs that have delayed clinical benefits. The mechanism of action of ketamine is currently unclear but one hypothesis is that it may involve neuropsychological effects mediated through modulation...