Perioperative depressive symptoms (PDSs) are common among patients who undergo major surgery and can lead to worse clinical outcomes. Esketamine has been reported to alleviate PDSs in patients undergoing certain types of surgery. However, there is a lack of evidence from large-scale, multisurgery studies to support its therapeutic effects in individuals with preexisting moderate-to-severe PDSs....
NeuropharmacologyJuly 1, 2026Anne Nathalia De Sousa-Silva, Clarissa de Almeida Moura, Carina Ioná De Oliveira Torres et al.1 citation
N,N-dimethyltryptamine (DMT) is an naturally occurring indoleamine with hallucinogenic and antidepressant effects in humans. Here, we compared the effects of DMT and S-ketamine, a fast-acting antidepressant, in helpless mice. To induce helplessness, male single and group-housed mice were exposed to inescapable footshock stress; only helpless animals were subsequently treated with S-ketamine 10...
Background and Objective Ketamine and esketamine have emerged as effective and rapid-acting interventions for treatment-resistant depression. Nevertheless, the best-suited candidates for these treatments are not clear. As such, the ability to personalize treatment selection and parameters would likely improve therapeutic response. This systematic review synthesized the literature on clinical...
Borderline personality disorder (BPD) is a serious mental illness with high rates of morbidity and stigma; however, successful remission is frequently limited by a paucity of accessible treatment options. In an era of growing interest in psychedelics as novel psychiatric treatment modalities, patients with BPD are often excluded from research due to perceived safety risks, particularly...
Treatment resistance (TR) in major depressive disorder (MDD) affects a substantial minority of patients and is hard to recognize early, delaying intensified care. The Esketamine multi-omic biomarker evaluation in MDD (EMBER-MDD) is a non-interventional, investigator-initiated, in-vitro study within the EU Psych-STRATA programme, analyzing biospecimens collected in the randomized INTENSIFY study...
Major depressive disorder, or MDD, is a common cause of disability around the world. Treatment-resistant depression, or TRD, is a tough challenge. Many people do not respond well to treatment, which increases the risk of relapse and suicide. Esketamine is a new treatment that comes as a nasal spray. It works quickly and targets a specific brain receptor. This review looks at research from...
The U.S. Food and Drug Administration (FDA) has increasingly focused on breakthrough molecular mechanisms, rapidly acting medications, and expanded therapeutic indications in the treatment of depression. During this period, psychiatric interventions targeting N-methyl-D-aspartate (NMDA) receptors and intracellular signaling pathways have gained prominence, moving beyond the traditional...
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...
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...
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,...
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...
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...
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Borderline personality disorder (BPD) often occurs alongside treatment-resistant depression (TRD), but the impact of BPD on real-world outcomes with intranasal esketamine is unclear. Consecutive TRD outpatients initiating intranasal esketamine treatment at four Italian centres between 1 September 2024 and 30 September 2025 were enrolled in the study (n = 90): 45 with comorbid BPD and 45 without...
Effective treatments for prolonged disorders of consciousness (pDoC) remain limited. Grounded in the entropic brain hypothesis-that psychedelic agents facilitate consciousness recovery by increasing brain complexity-this study investigated esketamine, a nonclassical psychedelic drug, and its effects on electroencephalographic (EEG) neurophysiological metrics in pDoC patients. In this...