Esketamine, a newly developed antidepressant, is the subject of this research which seeks to explore its impact on depressive symptoms in neuropathic pain mice and the potential molecular mechanisms involved. Through transcriptome sequencing and bioinformatics analysis combined with in vivo studies, it was identified that esketamine markedly boosts the levels of the m6A methyltransferase METTL3...
Dissociation, characterized by altered consciousness and perception, underlies multiple mental disorders, but the specific neuronal subtypes involved remain elusive. In mice, we find that dissociation-inducing doses of ketamine significantly inhibit retrosplenial cortex (RSC) parvalbumin interneurons (PV-INs), enhancing delta oscillations (1-3 Hz) and delta-gamma phase-amplitude coupling (δ-γ...
Objective: This post hoc analysis of the ESCAPE-TRD trial compared work productivity loss (WPL) and related costs among patients with treatment-resistant depression (TRD) receiving esketamine nasal spray or quetiapine extended release in combination with an oral antidepressant. Methods: Adults with TRD randomized to receive esketamine (56/84 mg) or quetiapine (150-300 mg) combined with ongoing...
Background/Objectives: Ketamine/esketamine has a rapid/robust antidepressant effect on treatment-resistant depression (TRD). However, its long-term cognitive effects remain unclear. In this study, we investigated the potential cognitive effects of an esketamine spray on a series of TRD patients. Methods: We evaluated the cognitive performance of eight TRD patients subjected to an esketamine...
Schizophrenia (SZ) a chronic debilitating mental disorder affecting approximately 1% of the population globally. While understanding of pathophysiology, neuropathology and treatment have advance significantly; resistance to therapy and treatment failures necessitate the search for novel compounds like omega-3 fatty acids (OMG). This study investigated the effects of OMG on ketamine-induced...
Preclinical studies and anecdotal case reports support the potential therapeutic benefit of low-dose oral ketamine as a treatment of clinical symptoms in Rett syndrome (RTT); however, no controlled studies have been conducted in RTT to evaluate safety, tolerability and efficacy. This was a sequentially initiated, dose-escalating cohort, placebo-controlled, double blind, randomized sequence,...
ToxicsJanuary 24, 2025Yin Tang, Kang Yang, Jintao Xu et al.5 citations
This study investigates the toxic effects of ketamine on juvenile zebrafish, driven by increasing concerns over ketamine's prevalence and its potential neurotoxic effects that may disrupt behavior and metabolism. Employing a high-throughput behavior tracking system, the research analyzed the locomotor activity of 6-day post-fertilization (6 dpf) zebrafish exposed to various concentrations of...
Plastogens are a class of therapeutics that function by rapidly promoting changes in neuroplasticity. A notable example, ketamine, is receiving great attention due to its combined rapid and long-term antidepressant effects. Ketamine is an N-methyl-D-aspartate receptor (NMDAR) antagonist, and, in addition to its therapeutic activity, it is associated with psychotomimetic and dissociative side...
Journal of Medicinal ChemistryJanuary 23, 2025Allana Cristina Faustino Martins, Bretton Badenoch, Roberto da Silva Gomes2 citations
Treatment-resistant depression responds quickly to ketamine. As an N-methyl-d-aspartate receptor (NMDAR) antagonist, ketamine may affect prefrontal cortex (PFC) neurons. Recent investigations reveal that the (R)-enantiomer is the most effective and least abuseable antidepressant. The Food and Drug Administration approves only the (S)-enantiomer for medical usage. (2R,6R)-Hydroxynorketamine...
Background and Clinical Significance: Treatment resistant psychiatric disorders affect millions of people across the globe. Ketamine has been employed as a treatment option for those with treatment resistant depression, as well as for chronic pain and alcohol use disorder. However, case presentations and research has been limited on the outcomes, and furthermore there is even less on the...
Context: Psychiatric and existential distress are common and difficult-to-treat symptoms that are frequently encountered in the palliative care setting; current treatment options are limited in efficacy and tolerability. Psychedelic-assisted therapies (PAT) have gained public and scientific interest in their potential to induce rapid and effective reductions in psychiatric and existential...
This study investigates repeated oral esketamine as a substitution strategy for maintenance electroconvulsive therapy (M-ECT) in eight patients with treatment-resistant depression (TRD). In a 6-week dosing phase, esketamine was titrated from 0.5 or 1.0 mg/kg to a maximum of 3.0 mg/kg twice weekly. Outcomes included 6-week change in Inventory of Depressive Symptomatology - Self-rated (IDS-SR),...
Since physician-assisted dying (PAD) has become a part of the clinical dialogue in the United States (US) and other Western countries, it has spawned controversy in the moral, ethical, and legal realm, with significant cross-country variation. The phenomenon of PAD includes 2 practices: Euthanasia and medical aid in dying (MAiD). Although euthanasia has been allowed in different parts of the...
There is increasing evidence of ketamine's therapeutic potential in reducing substance use in individuals with substance use disorders. However, its effects on tobacco use disorder are unknown. We investigated the effect of a subanesthetic dose of ketamine on tobacco use. This randomized, single-blind, placebo-controlled, pilot study administered intravenous ketamine to individuals with tobacco...
Auditory steady-state response (ASSR) abnormalities in the 40-Hz (gamma band) frequency have been observed in schizophrenia and in rodent studies of NMDA receptor (NMDAR) hypofunction. However, the extent to which 40-Hz ASSR abnormalities in schizophrenia resemble deficits in 40-Hz ASSR induced by acute administration of ketamine, an NMDAR antagonist, is not yet known. To address this knowledge...
Esketamine nasal spray (ESK) is approved in combination with an oral antidepressant (OAD) for the treatment of adults with treatment-resistant depression (TRD); however, direct comparisons with atypical antipsychotics for TRD are limited. This secondary analysis of the ESCAPE-TRD study compared rates of remission and response, and improvements in depressive symptoms over time, between ESK and...
Post-comatose disorders of consciousness (DoC) represent persistent neurological conditions with limited therapeutic options and a poor prognosis. Recent works advocate for exploring the effects of psychedelics to enhance brain complexity in DoC and ameliorate their consciousness. We investigated sub-anesthetic concentration of the atypical psychedelic ketamine for treating post-comatose...
Depression is a prevalent mental disorder, affecting approximately 300 million people worldwide. Despite decades of research into the underlying mechanisms of depression, a consensus remains elusive. Recent studies have implicated changes in oligodendrocytes and myelin in the pathogenesis of depression. Conventional antidepressants may alleviate symptoms within weeks of use, but approximately...
Subanesthetic ketamine is a rapidly acting antidepressant, yet the effects of ketamine on cognitive function are inconsistent. The primary objective of this study was to explore the effects of esketamine on memory function and plasma levels of nerve growth factor (NGF) in patients with depression. A total of 132 patients with depression completed six intravenous esketamine infusions (0.4 mg/kg)...
Ketamine has gained prominence as one of the most effective therapeutic options in unipolar treatment-resistant depression (TRD). However, most studies related to the antidepressant action of ketamine used intravenous (IV) or intranasal (IN) administration. The subcutaneous (SC) route of administration is a promising alternative, as it results in plasma levels comparable to IV, causes fewer...