Current antipsychotics have limited efficacy in controlling cognitive and negative symptoms of schizophrenia (SZ). Glutamatergic dysregulation has been implicated in the pathophysiology of SZ, based on the capacity of N-methyl-D-aspartate receptor (NMDAR) antagonists such as ketamine (KET) to induce SZ-like behaviors. This could be related to their putative neuropathological effect on...
PURPOSE/BACKGROUND: Major depressive disorder (MDD) and obesity commonly co-occur. We sought to assess the impact of body mass index (BMI) on the acute antidepressant effects of ketamine in patients with treatment-resistant depression. METHODS/PROCEDURES: Post hoc analyses were conducted from a multisite, randomized, double-blind, placebo-controlled trial designed to assess the rapid-onset...
Substance abuse disorder continues to have devastating consequences for individuals and society and current therapies are not sufficient to provide the magnitude of medical impact required. Although some evidence suggests the use of ketamine in treating various substance use related- symptoms, its adverse event profile including dissociation, dysphoria, and abuse liability limit its potential...
OBJECTIVE: To evaluate long-term safety and efficacy of esketamine nasal spray plus a new oral antidepressant (OAD) in patients with treatment-resistant depression (TRD). METHODS: This phase 3, open-label, multicenter, long-term (up to 1 year) study was conducted between October 2015 and October 2017. Patients (≥ 18 years) with TRD (DSM-5 diagnosis of major depressive disorder and nonresponse...
Due to unmet clinical needs for efficient drugs with a rapid onset of antidepressant effects, we aimed to evaluate the efficacy of single-dose ketamine in different subgroups of patients with major depression and establish whether repeated ketamine administration could be a viable strategy to maintain treatment gains. Electronic databases (Medline via PubMed, Embase, Cochrane Library, Trip...
Cerebral CortexApril 14, 2020Rebecca B Hughes, Jayde Whittingham-Dowd, Rachel E Simmons et al.
2p16.3 deletions, involving heterozygous NEUREXIN1 (NRXN1) deletion, dramatically increase the risk of developing neurodevelopmental disorders, including autism and schizophrenia. We have little understanding of how NRXN1 heterozygosity increases the risk of developing these disorders, particularly in terms of the impact on brain and neurotransmitter system function and brain network...
Abstract Background Increasing evidence suggests that multiple or long-time exposure to general anaesthesia (GA) could be detrimental to cognitive development in young subjects and might also contribute to accelerated neurodegeneration in the elderly. Iron is essential for normal neuronal function, and excess iron in the brain is implicated in several neurodegenerative diseases. However, the...
Over the past decade, various N-Methyl-D-Aspartate modulators have failed in clinical trials, underscoring the challenges of developing novel rapid-acting antidepressants based solely on the receptor or regional targets of ketamine. Thus, identifying the effect of ketamine on the brain circuitry and networks is becoming increasingly critical. In this longitudinal functional magnetic resonance...
BACKGROUND: Esketamine nasal spray was recently approved for treatment-resistant depression. The current analysis evaluated the impact of symptom-based treatment frequency changes during esketamine treatment on clinical outcomes. METHODS: This is a post-hoc analysis of an open-label, long-term (up to 1 year) study of esketamine in patients with treatment-resistant depression (SUSTAIN 2). During...
Research has found that the vividness of conscious experience is related to brain dynamics. Despite both being anesthetics, propofol and ketamine produce different subjective states: we explore the different effects of these two anaesthetics on the structure of dynamic attractors reconstructed from electrophysiological activity recorded from cerebral cortex of two macaques. We used two methods:...
AnesthesiologyApril 2020Jesus J Ballesteros, Pamela Huang, Shaun R Patel et al.
Ketamine is a noncompetitive N-methyl-D-aspartate antagonist and is known for unique electrophysiologic profiles in electroencephalography. However, the mechanisms of ketamine-induced unconsciousness are not clearly understood. The authors have investigated neuronal dynamics of ketamine-induced loss and return of consciousness and how multisensory processing is modified in the primate...
Abstract: Background: Targeting of glutamate receptors is a novel approach for the treatment of major depressive disorder (MDD). This study aimed to review the usefulness for esketamine nasal spray for the management of treatment-resistant depression (TRD) using the tools of evidence-based medicine: number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed...
Whether the brain operates at a critical ‘‘tipping” point is a long standing scientific question, with evidence from both cellular and systems-scale studies suggesting that the brain does sit in, or near, a critical regime. Neuroimaging studies of humans in altered states of consciousness have prompted the suggestion that maintenance of critical dynamics is necessary for the emergence of...
Background: Rapid-acting antidepressants ketamine and (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) have overcome some of the major limitations of classical antidepressants. However, little is known about sex-specific differences in the behavioral and molecular effects of ketamine and (2R,6R)-HNK in rodents. Methods: We treated mice with an intraperitoneal injection of either saline, ketamine (30 mg...
Subanesthetic ketamine evokes rapid and long-lasting antidepressant effects in human patients. The mechanism for ketamine’s effects remains elusive, but ketamine may broadly modulate brain plasticity processes. We show that single-dose ketamine reactivates adult mouse visual cortical plasticity and promotes functional recovery of visual acuity defects from amblyopia. Ketamine specifically...
bioRxiv Preprint ServerMarch 11, 2020M Wu, S Minkowicz, V Dumrongprechachan et al.3 citations
preprint
Escaping aversive stimuli is essential for complex organisms, but prolonged exposure to stress leads to maladaptive learning. Stress alters plasticity, neuromodulatory signaling, and neuronal activity in distributed networks, yet the field lacks a unifying framework for its varied consequences. Here we describe neuromodulatory and plasticity changes following aversive learning by using a...
New methods for using ketamine in patients with propofol-electroconvulsive therapy-resistant depression (ECT-RD) are needed in the clinic. This study aimed to investigate the therapeutic efficacy of ketamine plus ECT in ECT-RD patients, along with the treatment-induced brain alterations. A total of 28 ECT-RD patients were intravenously injected with ketamine six times and treated with...
Psilocybin shows efficacy to alleviate depression in human clinical trials for six or more months after only one or two treatments. Another hallucinogenic drug, esketamine, has recently been U.S. Food and Drug Administration (FDA)-approved as a rapid-acting antidepressant. The mechanistic basis for the antidepressant effects of psilocybin and ketamine appear to be conserved. The efficacy of...
The relationship between ketamine's hallucinogenic- and dissociative-type effects and antidepressant mechanism of action is poorly understood. This paper reviewed the correlation between subjective effects defined by various psychometric scales and observed clinical outcomes in the treatment of patients with Major Depressive Disorder (MDD). Based on PRISMA guidelines, we reviewed the...
Elderly patients with treatment‐resistant depression did not see overall improvement in depression symptoms over 28 days with use of esketamine nasal spray plus an oral antidepressant, a placebo‐controlled Phase 3 study has found. A younger subgroup of the overall study sample, as well as patients with earlier onset of depression, showed some improvement with esketamine, the researchers...