( JAMA Network Open . 2025;8(2):e2459331. doi: 10.1001/jamanetworkopen.2024.59331) Postpartum depression (PPD) is a widespread condition affecting about 17.7% of new mothers globally, with an even higher incidence of 21.4% reported in China. Cesarean birth (CB) appears to increase the risk of developing PPD compared to vaginal births. Given the growing recognition of esketamine, a derivative of...
Ketamine was shown to promote synaptogenesis, which is thought to account for its antidepressant effects through the restoration of lost synaptic connections observed in depression. PET imaging using 11C-UCB-J, a radiotracer targeting the synaptic vesicle protein 2 A (SV2A), was investigated as a translational method to monitor ketamine-induced changes in synaptic density in the corticosterone...
Treatment-resistant depression (TRD) is associated with worse clinical outcomes and longer course of illness. However, TRD is more difficult to model in animal phenotypes, suggesting that other experimental and translational models must be considered to properly address and research novel therapeutics. Reelin, an endogenous glycoprotein downregulated in depression, has shown rapid...
Postpartum depression (PPD) is a major global health issue. Although esketamine shows promise for PPD, its preventive effect in cesarean patients with prenatal depression remains unclear. The aim of this trial was to evaluate the effect of perioperative esketamine treatment on PPD incidence in this high-risk population. This dual-center, double-blind, randomized, placebo-controlled trial...
This case report describes the clinical response and safety of intranasal esketamine (Spravato®) in a 61-year-old female with treatment-resistant depression (TRD), a history of electroconvulsive therapy (ECT) poor response, and structural brain abnormalities secondary to left frontal lobe tissue loss from traumatic brain injury in 2008. Despite multiple antidepressant trials, atypical...
This study aims to explore the relationship between the antidepressant effects of drugs (esketamine combined with sertraline) and brain function changes in patients with major depressive disorder. A total of 27 patients with major depressive disorder (MDD) and 27 healthy individuals were included in the study. All MDD patients received a 2-week course of intravenous esketamine infusion (0.25...
Ketamine exhibits superior efficacy compared to conventional antidepressants, yet its clinical application remains limited by dose-dependent side effects. Ascorbic acid (AA) augments ketamine's antidepressant-like effects, suggesting that AA co-administration with subtherapeutic ketamine doses may achieve optimal efficacy while improving safety. Since AA itself lacks independently clinical...
EpigenomicsNovember 7, 2025Ivana Leccisotti, M. Moretti, Mario Altamura et al.
AIM Ketamine antidepressant effects go beyond immediate receptor action, involving lasting transcriptional and epigenomic changes that support its rapid, long-lasting benefits. The present systematic review synthesized existing preclinical and clinical evidence on the epigenetic mechanisms of ketamine in the treatment of depression. METHODS A comprehensive search of three electronic databases...
Twice‐weekly dosing of intranasal esketamine resulted in significant improvement in depressive symptoms compared with placebo in adults with treatment‐resistant depression, a 4‐week trial has found. Esketamine doses of 56 and 84 mg both outperformed placebo in the post‐marketing trial. Study results were published online July 2, 2025, in JAMA Psychiatry.
Abstract Background Behavioural studies in animal models represent a critical component of psychiatric drug development. Positive results in animal studies have identified novel therapeutic targets for major depressive disorder (MDD) but efficacy in humans has largely not been borne out in clinical trials. A possible reason for this failed translation is inappropriate dose selection and the...