Introduction: Treatment-resistant depression (TRD) is a major public health and societal challenge, associated with persistent symptoms, functional impairment, and increased healthcare and economic burden. Intranasal esketamine has emerged as a rapid-acting adjunctive therapy with a distinct glutamatergic mechanism of action. This systematic review summarizes current evidence on its...
Background: Intranasal esketamine (ESK-NS) is an effective treatment for treatment-resistant depression (TRD), but whether antidepressant outcomes differ by sex and age remains insufficiently explored. Methods: This secondary analysis of the REAL-ESK study included 210 patients with TRD treated with ESK-NS in routine clinical practice and assessed at baseline (T0), one month (T1), and three...
Oral S-ketamine (S-KETPO) is being explored as an alternative to intravenous maintenance treatment (S-KETIV) in treatment-resistant depression (TRD). However, the first-pass effect with S-KETPO significantly alters S-ketamine's bioavailability and the systemic exposure of its active metabolites, raising potential safety and efficacy concerns. This study characterized the pharmacodynamic and...
Depression and its severe outcomes, suicidal ideation and behavior, are exacerbated by stress. A broad literature links dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) stress response system to depression, suicidal ideation and behavior. Our midazolam-controlled clinical trial of subanesthetic, intravenous ketamine infusion for suicidal depressed patients found rapid reduction...
Ketamine, a dissociative anesthetic, induces behavioral and molecular alterations associated with psychosis-like phenotypes. However, the epigenetic mechanisms bridging its cellular effects with behavioral outcomes are poorly defined. Here, we report that ketamine induces histone H3 Ser10 phosphorylation in both hippocampal neurons (HT22 cells) and the mouse hippocampus, an effect primarily...
Background: Treatment-resistant depression (TRD) is associated with substantial functional impairment, suicide risk, and health-care costs. Ketamine and its S-enantiomer, esketamine, have emerged as rapid-acting glutamatergic treatment options for TRD. Aim: This review aims to synthesize current evidence on the different ketamine administration routes for TRD, with a focus on acute and...
Ketamine has emerged as a promising rapid-acting treatment for mood disorders and suicidality. Notwithstanding its replicated antidepressant efficacy, ketamine-associated risk for abuse, dependence, and misuse remain. We conducted a systematic review of clinical and preclinical studies from database inception to August 2025, including randomized and observational trials, open-label extensions,...
This study aimed to investigate a set of pharmacodynamic biomarkers reflecting acute, delayed and sustained central nervous system effects of S-ketamine, used as a tool compound for rapid-acting antidepressant activity, with the goal of informing biomarker strategies for delayed antidepressant effects. In this randomized, double-blind, double-dummy, placebo-controlled, 4-way crossover study in...
Background Methamphetamine use disorder (MAUD) is associated with substantial psychiatric and physical morbidity, and current treatment options remain limited. Ketamine-assisted psychotherapy (KAP) has shown promise in substance use disorders, but little is known about how individuals experience and interpret this intervention, particularly in MAUD. Qualitative investigation may provide insight...
Protective Effects of Gallic Acid on Oxidative and Inflammatory Markers in the Hippocampus and Prefrontal Cortex of a Ketamine-Induced Schizophrenia-like Model.
European PsychiatryJune 23, 2026Maximilian Preiß, Valentin Popper, Luna Helene Charlotte Faber et al.
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Introduction and purpose. Major depressive disorder is a serious clinical problem. Current treatments are often unsuccessful, and many patients do not achieve full remission. In a reanalysis of the STAR*D study, the cumulative remission rate after up to four treatment steps was about 41%, which highlights the limitations of currently available antidepressant strategies[1]. In recent years,...
Ketamine offers rapid relief for treatment-resistant depression and severe pain in the clinic, providing immediate benefits that traditional medications often fail to deliver. While its antagonistic action at the N-methyl-D-aspartate receptor (NMDAR) is a key mechanism, ketamine's dual nature as both a promising treatment and a drug with abuse potential suggests its therapeutic effects extend...
Esketamine is an effective rapid-acting pharmacological intervention for treatment-resistant depression. However, the temporal dynamics of underlying brain networks associated with the improvement of depressive symptoms remain elusive. This observational study seeks to delineate alteration in network activity within 90 minutes of nasal Esketamine administration, with a focus on exploring its...
Background: In HT-22 cells, 500 μM NMDA was used as a high-concentration oxidative stressor rather than a classical NMDA receptor-mediated excitotoxic stimulus. Because HT-22 cells lack functional ionotropic NMDA receptors, this model cannot test NMDA receptor antagonist-mediated pharmacology. Methods: HT-22 cells and C8-D1A astrocytes were examined in a Transwell co-culture system. CCK-8...
Although esketamine shows efficacy for treatment-resistant depression, its potential effectiveness in cancer-related depression (CRD) has not been well-established. We therefore evaluated the real-world effectiveness and safety of esketamine in CRD using a target trial emulation framework based on anonymized electronic health records from the TriNetX network. Adults aged 18-74 years with CRD...
Despite recent advances in neuropsychiatry, translational development for many targets remains challenging, particularly when receptors exist as families with complex subunit-dependent pharmacology and safety concerns. This is the case for NMDA receptor (NMDAR) antagonists. R,S-ketamine illustrates this issue: although it produces rapid antidepressant effects in the clinic, its use is limited...
Major depressive disorder (MDD) is a leading cause of disability worldwide, and currently available antidepressants remain limited by delayed onset of action, incomplete response, and adverse effects. Ketamine is a rapid-acting antidepressant, whereas xanomeline, an M1/M4 muscarinic receptor agonist, may represent a mechanistically distinct non-monoaminergic strategy. However, the molecular...
The renewal of psychedelic medicine has garnered significant scientific interest, with large efforts dedicated to the understanding of the complex subjective experiences induced by these substances. The Altered States of Consciousness (ASC) questionnaire represents the most comprehensive instrument for measuring such experiences yet lacks a validated French translation despite its centrality to...
BACKGROUND Post-traumatic stress disorder (PTSD) is a common psychological complication after radical lung cancer surgery and has a significant impact on postoperative recovery and quality of life. Esketamine, a new anesthetic agent, may be protective against postoperative PTSD through modulation of neurotransmitter systems and anti-inflammatory actions. AIM To explore the underlying mechanisms...