Esketamine was recently licensed by the US Food and Drug Administration (FDA) and European Drug Agency (EDA) for use in treatment resistant depression (TRD), and further research indicates ketamine as a possible treatment in other mental health conditions. While the underlying mechanisms remain unclear, it has been hypothesised that ketamine's acute psychoactive effects may be associated with...
Importance: A single subanesthetic dose of ketamine produces an antidepressant response in patients with major depressive disorder (MDD) within hours, but the mechanism of antidepressant effect is uncertain. Objective: To evaluate whether ketamine dose and brain glutamate and glutamine (Glx) and γ-aminobutyric acid (GABA) level responses to ketamine are related to antidepressant benefit and...
There is an ongoing debate as to whether ketamine anesthesia suppresses neurophysiologic complexity at doses sufficient for surgical anesthesia, with previous human studies reporting surrogates of both suppressed and preserved levels of cortical complexity. However, these studies have not assessed cortical dynamics in higher gamma frequencies, which have previously been demonstrated to...
The Food and Drug Administration (FDA) announced Aug. 3 approval of Janssen Pharmaceutical's supplemental new drug application (sNDA) for the expanded use of SPRAVATO esketamine Clll nasal spray for the treatment of major depressive disorder (MDD) with acute suicidal ideation or behavior. SPRAVATO was initially approved by the FDA March 5, 2019, for the treatment of treatment‐resistant depression.
Major depressive disorder (MDD) is a common, serious, debilitating condition affecting 350 million people worldwide, which remains to be unsatisfactorily treated with 53% of patients still complaining of symptoms after completing their courses with the correct dosage. Ketamine, which was approved by the Food and Drug Administration in 2019, is a potential treatment option for those recalcitrant...
Subanesthetic ketamine is found to induce fast-acting and pronounced antidepressant effects, even in treatment resistant depression (TRD). However, it remains unclear how ketamine modulates neural function at the brain systems-level to regulate emotion and behavior. Here, we examined treatment-related changes in the inhibitory control network after single and repeated ketamine therapy in TRD....
Abstract To elucidate the genetic underpinnings of the antidepressant efficacy of S-ketamine (esketamine) nasal spray in major depressive disorder (MDD), we performed a genome-wide association study (GWAS) in cohorts of European ancestry (n = 527). This analysis was followed by a polygenic risk score approach to test for associations between genetic loading for psychiatric conditions, symptom...
OBJECTIVE: Ketamine's effects on different dimensions of depressive symptomatology, including typical/melancholic and atypical depression, remain largely unknown. This study examined the effects of a single intravenous dose of ketamine on general depressive symptoms (measured using the Montgomery-Asberg Depression Rating Scale (MADRS), typical/melancholic symptoms (measured using the MADRS5),...
The objective of this study was to investigate the safety of repeated parenteral ketamine for depression. An electronic survey inquiring about the frequency of adverse events was distributed to providers of parenteral ketamine for depression. In addition, the investigators conducted a search of published studies describing six or more repeated parenteral ketamine treatments administered to...
Augmentative treatment is considered the best second-option when a first-choice drug has partial limitations, particularly by allowing antidepressant dose reduction. Considering that ketamine has significant knock-on effects, this study investigated the effects of single coadministration with subthreshold doses of ketamine plus guanosine in a corticosterone (CORT)-induced animal model of...
Obsessive-Compulsive Disorder (OCD), characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions), is associated with dysfunction in fronto-striatal circuits. There are currently no fastacting pharmacological treatments for OCD. However, recent clinical studies demonstrated that an intravenous infusion of ketamine rapidly reduces OCD symptoms. To probe mechanisms...
Ketamine, an anesthetic developed in the early 1960s, is also a popular abused drug among young people at dance parties and raves and among spiritual seekers, because it produces schizophrenia-like symptoms and dissociation (i.e., out-of-body experience). Regarding mood disorders, ketamine exerts robust antidepressant actions in treatment-resistant patients with depression. Ketamine is a...
Ketamine, a dissociative anesthetic, is experiencing a clinical resurgence as a fast-acting antidepressant. In the central nervous system, ketamine acts primarily by blocking NMDA receptor currents. Although it is generally safe in a clinical setting, it can be addictive, and several of its derivatives are being investigated as preferable alternatives. 2R,6R-Hydroxynorketamine (HNK), a ketamine...
The strategy of repeated ketamine in open-label and saline-control studies of treatment-resistant depression suggested greater antidepressant response beyond a single ketamine. However, consensus guideline stated the lack of evidence to support frequent ketamine administration. We compared the efficacy and safety of single vs. six repeated ketamine using midazolam as active placebo. Subjects...
NeurotoxicologyJune 24, 2020A. C. Ribeiro, Jackie Zhu, Mohamad M. Kronfol et al.
Exposure to organophosphates (OP) during the First Gulf War is among one of the factors for Gulf War Illness (GWI) development in veterans and it has been challenging to treat GWI symptoms with existing therapies. Ketamine produces a rapid-onset and sustained antidepressant response, but there is no evidence whether ketamine treatment is effective for GWI depression. Repeated, low-dose exposure...
The auditory mismatch negativity (MMN) is significantly reduced in schizophrenia. Notably, a similar MMN reduction can be achieved with NMDA receptor (NMDAR) antagonists. Both phenomena have been interpreted as reflecting an impairment of predictive coding or, more generally, the "Bayesian brain" notion that the brain continuously updates a hierarchical model to infer the causes of its sensory...
A significant proportion of patients with major depressive disorder are refractory to approved interventions. The first report of significant and rapid benefit of intravenous (IV) ketamine for treatment resistant depression (TRD) appeared in 2000. Since then, there have been multiple reports on the efficacy and tolerability of ketamine formulations for TRD, in particular for single-dose IV...
Background The use of ketamine in electroconvulsive therapy (ECT) has been examined in the treatment of major depressive disorder (MDD); however, there has been no systematic review and meta-analysis of related randomised controlled trials (RCTs).Aim To examine the efficacy and safety of ketamine augmentation of ECT in MDD treatment.Methods Two reviewers searched Chinese (China National...
Accumulating evidence implicates dysregulation of hippocampal synaptic plasticity in the pathophysiology of depression. However, the effects of ketamine on synaptic plasticity and their contribution to its mechanism of action as an antidepressant, are still unclear. We investigated ketamine’s effects on in vivo dorsal hippocampal (dHPC) synaptic plasticity and their role in mediating aspects of...