Pharmaceuticals
October 19, 2026
Daniel Szawarnoga, Joanna Fojcik, Michał Kamil Górski et al.
Treatment-resistant depression (TRD) remains one of the most clinically challenging forms of depressive disorders. In many patients, reduction in symptom severity does not translate into full functional recovery; therefore, assessment of treatment effectiveness should also include health-related quality of life (HRQoL). Objective: The aim of the study was to compare changes in HRQoL in patients...
BMC Medical Ethics
October 18, 2026
Adrian Kind, Josephine Görke, Hannah Smirr et al.
Abstract Background Treatments with acute consciousness-altering effects, such as (es)ketamine, place patients in a state of heightened vulnerability with reduced capacity for self-advocacy and self-regulation. Since feeling safe is a precondition for consenting to begin, and remaining in, treatment, this raises distinct ethical demands on care. Which features of the setting enable patients to...
Frontiers in Pharmacology
October 16, 2026
Qingmei Li, Shuming Liu, Huiling Chen et al.
Objective The molecular mechanisms driving esketamine (ESK) efficacy in the pain-depression dyad (PDD) remain incompletely understood. This study investigated the effects of a sub-anesthetic ESK regimen on cortical expression profiles and exploratory signaling markers within the anterior cingulate cortex (ACC). Methods Male Sprague-Dawley rats were randomized into Sham, PDD, and PDD + ESK...
Frontiers in Psychiatry
October 16, 2026
Gilberto Sousa Alves, Humberto M. M. Dos Santos, Samira D Damasceno et al.
Background Esketamine is a promising therapeutic option for treatment-resistant depression (TRD). Intravenous (IV) administration is the most extensively studied parenteral route. However, subcutaneous (SC) administration may offer simpler, more scalable delivery. Multicenter real-world evidence comparing IV and SC routes of administration remains limited. Objective To report clinical outcomes...
medRxiv
October 15, 2026
Chlöé Müh, Pauline Favre, Isabel Karen Lütkenherm et al.
preprint
Abstract Negative emotional bias, including reduced processing of positive information and negative interpretation of ambiguous stimuli, is a core feature of depression. Esketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist with rapid antidepressant effects in treatment-resistant depression (TRD), reduces depressive symptoms, but its effects on distinct components of emotional...
Preprints.org
October 14, 2026
Domenico de Berardis, Tommaso Barlattani, Alessandro Carano et al.
preprint
Intranasal esketamine has been available for treatment-resistant depression (TRD) since 2019, but the trials that led to its approval answer only some of the questions prescribers face. About 97% of trial participants had failed only one or two antidepressant classes, and patients with bipolar disorder, psychosis, obsessive–compulsive disorder, four personality disorders, moderate-to-severe...
Journal of Child and Adolescent Psychopharmacology
October 9, 2026
Inês Vasconcelos Sousa Magalhães, Daniel N. Lopes, Isabel de Andrade Amato et al.
OBJECTIVE: To describe the feasibility, acute tolerability, and short-term symptom trajectories of adjunctive subcutaneous esketamine in adolescents with severe depressive episodes treated in specialized outpatient care. METHODS: This observational case series included five adolescents aged 15-17 years with severe depressive symptoms, suicidal ideation and/or behavior, and insufficient response...
BMC Psychiatry
October 7, 2026
Qianqian Wu, Weicheng Li, Zhanjie Luo et al.
Abstract Background Anhedonia, a prominent symptom of major depressive disorder (MDD), severely impairs patients’ quality of life and is challenging to treat. Although esketamine has shown potential in treating anhedonia in adult treatment-resistant MDD, its effects on adolescents remain under-explored. Methods In this study, a prospective, randomized, double-blind, controlled trial was...
Brain Research Bulletin
October 6, 2026
Ziyi Hua, Yongqiang Shu, Li Li et al.
INTRODUCTION: This study investigated changes in multiband amplitude of low-frequency fluctuations in patients with major depressive disorder following a 2-week combination treatment regimen of esketamine and sertraline, and examined the associations between ALFF changes and clinical symptom improvement. METHODS: Forty patients with major depressive disorder (MDD) received esketamine (0.25...
Neuropsychiatric Disease and Treatment
October 1, 2026
Anita Słupska, Wiesław Jerzy Cubała, Damian Swieczkowski et al.
Objective: To synthesize evidence for intravenous racemic ketamine and regulated intranasal esketamine in adults with acute suicidal presentations; distinguish the outcomes these interventions have and have not been shown to change; and place any rapid response within a complete emergency suicide-care pathway. Methods: A narrative review of PubMed/MEDLINE-indexed literature was updated through...
Psychedelics
October 1, 2026
David S. Mathai, Brian Pilecki, Hadi Zaki et al.
In 2019, the U.S. Food and Drug Administration (FDA) approved a patented formulation and delivery method of esketamine, the S-enantiomer of ketamine, for patients with treatment-resistant depression (TRD). While ketamine-based treatments share similarities with serotonin 2 A receptor-mediated “classic psychedelics” like psilocybin regarding subjective drug effects and stimulation of...
Journal of Affective Disorders
September 23, 2026
Erin Curran, Kristina T. Kumpf, Mina Ansari et al.
Ketamine/esketamine produce rapid antidepressant effects, with growing interest in how acute subjective experiences and the surrounding set and setting shape clinical outcomes. Little is known about how audiovisual adjustments during ketamine/esketamine treatment influence comfort, tolerability, or patient experience, despite their common use in clinical practice. Virtual reality (VR) is one...
Journal of Personalized Medicine
September 23, 2026
Aleksandra Metelska, Wojciech Ziemichód, Hanna Karakuła-juchnowicz
Objectives: A significant problem in the treatment of depressive disorders is the growing number of cases of so-called treatment-resistant depression (TRD). There is evidence of ketamine’s effectiveness in treating TRD, with response rates ranging from 40% to 90%. This review aimed to map available studies on peripheral biomarkers of response to ketamine and esketamine in the treatment of...
Discovery medicine
September 23, 2026
Jozélio Freire de Carvalho, Eduardo Pondé de Sena
Background: Treatment-resistant depression (TRD) represents a major clinical challenge, being associated with high morbidity, increased suicide risk, and substantial socioeconomic burden. The need for rapidly acting interventions has driven the development of rapid-acting antidepressants (RAADs), such as ketamine, esketamine, and scopolamine. This study aimed to systematically review the...
Journal of Integrative Neuroscience
September 21, 2026
Yang Wang, Yin Li, Zhe Chen et al.
Repeated propofol exposure during neurodevelopment induces long-term cognitive deficits in rats, potentially through dysregulated hippocampal neuronal autophagy and inhibition of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) pathway. Esketamine has been reported to exert neuroprotective effects; however, the underlying mechanism remains...
Molecular Psychiatry
September 19, 2026
Dijia Wang, Junnan Xu, Zhaoran Wang et al.
Hallucinations are a core feature of several psychiatric disorders, but the circuit mechanisms that separate perception from behavioral output remain poorly defined. Here, we combined an auditory discrimination task with AI-based pose analysis to quantify S-ketamine-induced false auditory threat responses and behavioral disorganization in mice. Control assays, including sucrose preference, loss...
Journal of Huntington's Disease
September 17, 2026
Carsten Saft, Julia Jessen, David Kiefner et al.
Depression and suicidal ideation are common in Huntington's disease (HD). We report a 60-year-old male with HD who suffered from treatment-resistant depression with intermittent suicidal thoughts for 20 years, irritability and apathy. Despite multiple trials of antidepressants, no sustained improvement was achieved. Under nasal esketamine treatment his mood improved dramatically after three...
Psychiatry Research
September 14, 2026
Kelei Xiao, Yealin Woo, Christine E. Dri et al.
Cognitive impairment is a core feature of major depressive disorder (MDD) and bipolar disorder (BD). Most conventional antidepressants do not have direct and clinically relevant procognitive effects. Ketamine and esketamine are effective in treating treatment-resistant depression (TRD). Herein, this systematic review aims to evaluate the effects of both pharmacotherapeutics on cognitive...
International Journal of Innovative Technologies in Social Science
September 11, 2026
Marta Borkowska, Małgorzata Witaszczyk, Alicja Sołtan et al.
Background: Ketamine and esketamine have been studied as rapid-acting interventions in adults with depressive disorders and suicidal ideation, but findings vary across populations, settings, comparators, routes, and outcome measures. Aim: To examine their effects on suicidal ideation within the first 24 hours and to identify factors contributing to variability across studies. Methods: This...
Psychiatry International
September 10, 2026
Tommaso Barlattani, Giorgio Sernia, Chiara D’Amelio et al.
Background: Evidence for repeated intranasal esketamine in obsessive–compulsive disorder (OCD) remains preliminary, particularly when OCD co-occurs with treatment-resistant depression (TRD). Methods: We report a 58-year-old woman treated with intranasal esketamine in routine clinical care for TRD; change in obsessive–compulsive symptoms was followed as a secondary observational outcome. Her...