Frontiers in Molecular Neuroscience
October 21, 2026
Zuzanna Sulej, Magdalena Zielińska
Ketamine has revolutionized psych iatric treatment, challenging monoamine-based paradigms through its capacity for rapid antidepressant action. While N-methyl-D-aspartate receptor (NMDAR) antagonism remains the canonical mechanism, this integrative review proposes a multi-receptor, neuron–glia convergence model to help account for ketamine's therapeutic efficacy. We outline the well-established...
Current Biology
October 19, 2026
John H. Krystal
Ketamine's robust antidepressant effects often appear twenty-four hours after a single dose. A new study now provides evidence suggesting that this timepoint coincides with a quieting of habenula activation and reductions in aversive learning in healthy subjects.
Neuropharmacology
October 19, 2026
U S Drozd, V V Bulygina, G T Shishkina et al.
Exposure to acute, inescapable stress triggers a coordinated neural and endocrine response across corticolimbic and brainstem circuits. Although subanesthetic ketamine has rapid antidepressant effects, it is unclear whether its modulation of the stress-response network depends on the presence of an acute stressor. In this study, naïve rats received subanesthetic ketamine (15 mg/kg) or a...
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...
bioRxiv (Cold Spring Harbor Laboratory)
October 19, 2026
Jack R. Waters, Brian Madeira, Michael Neil Shadlen et al.
preprint
Time estimation is critical to many cognitive operations, including decision-making, working memory, and action planning. Neural correlates of interval timing have been described across multiple cortical and subcortical networks, both at a single-neuron level (as ramping activity) and population level (as dynamical motifs). Low-dose ketamine, a dissociative anesthetic and potent antidepressant,...
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...
Progress in neuro-psychopharmacology & biological psychiatry
October 17, 2026
Fionnghuala L J James, Sayed K Ahamed, Cheng-I Yang et al.
Traumatic memories that are resistant to modification or extinction are a characteristic feature of post-traumatic stress disorder (PTSD). The process of fear memory reconsolidation has been identified as a potential therapeutic target for the treatment of PTSD. Ketamine, an NMDA receptor antagonist with dissociative properties, has been identified as a drug with high therapeutic potential for...
BMC Psychiatry
October 16, 2026
Morfeas Koumas, Markos Apostolakis, Evanthia Bella et al.
Abstract Background Opioid use disorder (OUD) is a chronic relapsing condition associated with substantial mortality. Although medications for opioid use disorder (MOUD) can be effective in reducing opioid use and improving treatment outcomes, relapse to drug use remains common, highlighting the need for adjunctive interventions that address relapse-relevant symptoms not fully targeted by MOUD...
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...
L'Encephale
October 16, 2026
Anne Buot, Jean-Del Burdairon, Luc Mallet et al.
The use of psychedelic substances such as LSD, psilocybin, and dimethyltryptamine is currently being re-evaluated for their therapeutic potential in psychiatry. While international clinical research had started in the 2010s, France only initiated its first psychedelic trials in 2024. This study aimed to explore the knowledge, perceptions, and attitudes of French mental health professionals...
International Journal of Molecular Sciences
October 15, 2026
Ana Zivanovic, Iva Lukic, Emilija Glavonic et al.
Ketamine produces rapid antidepressant-like effects across a range of subanesthetic doses, yet how dose shapes behavioral efficacy and region-specific molecular signaling following adolescent chronic unpredictable stress (CUS) is not well understood. Here, we examined the behavioral and molecular consequences of two subanesthetic ketamine doses in adult mice with depression-like behavior...
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...
Epigenetics
October 15, 2026
Arghavan Nepton, Sonya C. Faber, Zachary A. Kaminsky et al.
Ketamine produces rapid antidepressant effects, but the molecular processes associated with their persistence remain poorly defined in humans. We examined longitudinal DNA methylation changes in 10 adults with major depressive disorder undergoing ketamine-assisted psychotherapy using two pre-treatment assessments (T1, T2) and one post-treatment assessment (T3). Participants received three...
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...
Australasian Psychiatry
October 13, 2026
Adam Bayes, Colleen Loo
ObjectiveThe ideas presented in this paper are based on a presentation at a festschrift event marking the retirement of Professor Gordon Parker from UNSW, Sydney. Drawing on Gordon's depressive subtyping approach and his critiques of a unitary view of major depressive disorder and treatment-resistant depression (TRD), we aim to (i) explore differing models of ketamine for TRD - biomedical...
Journal of Affective Disorders
October 12, 2026
Reinhard Janssen-Aguilar, Jithin Joseph, Huda Al-Shamali et al.
Treatment-resistant depression (TRD) affects 30-60% of individuals with major depressive disorder and carries substantial morbidity and healthcare costs. Intravenous (IV) ketamine (KET) is a rapid-acting antidepressant, but benefits are often transient, prompting augmentation to sustain efficacy or improve tolerability. We conducted a systematic review and meta-analysis of randomized controlled...
Asian Journal of Psychiatry
October 12, 2026
Gia Han Le, Sabrina Wong, Simryn Selby et al.
Ketamine is a rapid-acting antidepressant with demonstrated efficacy in major depressive disorder and treatment-resistant depression, yet the mechanisms by which its molecular actions translate into sustained clinical improvement remain incompletely understood. Prevailing models have emphasized N-methyl-D-aspartate receptor antagonism and downstream glutamatergic signaling; however, convergent...
Cureus
October 12, 2026
Anirudh Bakam
Dissociative neurological symptom disorder (DNSD), termed functional neurological symptom disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), presents with neurological symptoms not explained by structural disease.The first line treatment of DNSD is psychotherapy, but when the conflict maintaining the symptoms cannot be put into words,...
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...