In the neocortex, neuronal processing of sensory events is significantly influenced by their predictability. A common example is the suppression of responses to repetitive stimuli in sensory cortices, a phenomenon known as habituation. Within a sensory information stream, whenever a novel stimulus deviates from expectations, enhanced brain responses are observed. Mismatch negativity (MMN), the...
(R,S)-Ketamine, a dissociative anesthetic, has shown rapid and sustained antidepressant effects at lower doses than those required for anesthetic effects in patients with treatment-resistant depression. However, its use is limited because it causes side effects, including psychotomimetic symptoms and dependence. The enantiomer (R)-ketamine was reported to promote antidepressant-like effects in...
Background: Posttraumatic stress disorder (PTSD) is a severe and frequent affection that is highly comorbid to major depressive disorder. Comorbid PTSD and depression increase the risk of treatment-resistant depression (TRD), with a high risk of functional impairment and suicide. Esketamine nasal spray is a recent validated treatment for TRD, but its efficacy on comorbid TRD-PTSD remains...
CureusApril 1, 2026Samantha Siu, Peter Hsin, Sarah Simon et al.
Postpartum depression (PPD) is a common condition associated with adverse maternal and infant outcomes. Higher rates have been observed following cesarean delivery, prompting interest in perioperative preventive strategies. Ketamine has demonstrated rapid antidepressant effects and may provide psychiatric benefits beyond analgesia. We conducted a systematic review and meta-analysis of...
Treatment-resistant depression (TRD) remains a major clinical challenge in psychiatric practice and affects a substantial proportion of patients with major depressive disorder (MDD). It is commonly defined as failure to achieve remission after at least two adequately conducted antidepressant trials. TRD is associated with persistent functional impairment, increased morbidity, reduced quality of...
Introduction: Treatment-resistant depression (TRD) represents a significant clinical challenge, particularly when associated with suicidal ideation. Intranasal esketamine has emerged as an effective therapeutic option in refractory cases, while monoamine oxidase inhibitors (MAOIs) remain relevant in the management of severe and resistant conditions. Objective: To describe the clinical course of...
medRxiv Preprint ServerMarch 31, 2026Maia Mallevays, Louise Fuet, Michel Danon et al.1 citation
preprint
Esketamine is a fast-acting antidepressant drug which induces acute psychoactive effects. The most frequent is a dissociative state which seems unrelated to therapeutic efficacy. Other esketamine-induced effects, including psychedelic-like mystical experiences, have been poorly studied in terms of phenomenology and frequency, and may carry specific therapeutic relevance. In this study, we...
Frontiers in NeurologyMarch 30, 2026Jose E. Leon-Rojas, Guido Mascialino, Lizeth Vinueza Mera et al.2 citations
Subanesthetic ketamine shows rapid neuroplastic and antidepressant effects in psychiatric conditions, prompting interest in its potential relevance for cognitive dysfunction in neurological disorders. Cognitive deficits are widespread across traumatic brain injury, stroke, epilepsy, and neurodegenerative diseases, yet treatments remain primarily compensatory. Ketamine's actions on glutamatergic...
Ketamine, a dissociative anesthetic, has been extensively used in clinical anesthesia and sedation. However, its use in general anesthesia is gradually declining because of numerous adverse effects. In 2019, esketamine was introduced to the Chinese market. This narrative review aimed to summarize the current status of clinical applications and research progress of esketamine and to explore its...
Behavioural Brain ResearchMarch 28, 2026Lucas Villar Pedrosa Da Silva Pantoja, Luiza Fernanda Ramos Soares, Brenda Costa Da Conceição et al.
Adolescence is a period of profound behavioral changes associated with high brain vulnerability to negative stimuli including psychotropic drugs misuse which may contribute to the development of psychiatric disorders. Ketamine, an NMDA receptor antagonist, is an anesthetic agent used in a recreational manner in night clubs and raves, especially by intranasal route. The psychedelic effects of...
Background: Depression is a significant mental health condition affecting numerous individuals worldwide, leading to disability within society and posing a heightened risk of suicide, thereby diminishing overall quality of life. Depression, often a contributing factor in suicides, is associated with various prevalent medical conditions such as obesity, diabetes, stroke, Parkinson's disease, and...
PsychopathologyMarch 27, 2026Xiaoran Ding, Yaping Wu, Juan Yang et al.1 citation
Ketamine has emerged as a promising rapid-acting antidepressant with distinct advantages for the treatment of treatment-resistant depression (TRD). Its therapeutic effects are mediated through multi-target modulation of the glutamatergic system. Unlike conventional antidepressants, ketamine exerts a markedly faster onset of action; however, its long-term safety profile and potential risk of...
Medicine AdvancesMarch 27, 2026Thomas Edward Cutting, Richard Evans Hartman
ABSTRACT Numerous studies have demonstrated the efficacy of (R, S)‐ketamine as a treatment for post‐traumatic stress disorder (PTSD), treatment‐resistant depression, and comorbid occurrences of these conditions. The (R) and (S) stereoisomers of ketamine have also demonstrated efficacy in attenuating stress and depressive symptoms, with (R)‐ketamine demonstrating reduced abuse potential and side...
Ugeskrift for LægerMarch 26, 2026Anders Borg Andersen, Reem Falah Kadhum Alrubaie, Morten Jønler et al.
A 29-year-old male with prior testicular cancer and daily ketamine use developed severe lower urinary tract symptoms due to bladder fibrosis. Despite multiple treatments – botulinum toxin type A , bladder distension, and medications - his condition progressed to hydronephrosis, recurrent urosepsis, and acute kidney injury requiring nephrostomies. Eventually, a Bricker bladder was created. The...
Ketamine holds promise for the treatment of post-traumatic stress disorder (PTSD), but challenges remain in delivery and sustained effects. This controlled study evaluates a novel intranasal formulation, employing AmyloLipid nanovesicles (ALN) to enhance ketamine’s therapeutic efficacy in a predator-scent stress (PSS) rat model of PTSD. A total of 130 rats underwent PSS or sham-PSS exposure,...
Behavioral SciencesMarch 24, 2026J. Richard Kendrick, Ghonwa Ahmad, Audrey Wood et al.
The use of ketamine for the management of neuropsychiatric conditions outside clinical settings has rapidly expanded, creating a critical need to understand diverse individual experiences. We conducted a qualitative content analysis of posts from the r/TherapeuticKetamine subreddit. From 3302 threads, the 500 highest-engagement threads (12,852 comments) were analyzed by independent coders...
Treatment-resistant depression affects up to one third of patients with major depressive disorder and is frequently accompanied by persistent cognitive impairments that significantly hinder functional recovery. Emerging evidence suggests that sub-anesthetic esketamine does not appear to be associated with cognitive deterioration and may be associated with procognitive effects; however, no...
BiomoleculesMarch 24, 2026Veronica Begni, Floriana de Cillis, Natascha Pfeiffer et al.
Pharmacological antidepressant treatments alter the molecular and functional reactivity of stress-sensitive neural networks. However, how classical versus rapid-acting antidepressants differentially modulate acute stress-induced transcriptional responses across brain regions remains unclear. Here, we compared imipramine and ketamine in mice exposed to acute swim stress, assessing...
We investigated ketamine's neuroplastic effects in healthy human subjects using integrated Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) measures before and 1-8 days after a single psychedelic dose of ketamine (1 mg/kg, intravenous). Eleven male participants underwent two PET/MRI scans with [11C]-UCBJ (synaptic density/plasticity), 1H-MRS (glutamate and GABA) and...
The trajectory and predictors of response under routine clinical care of esketamine nasal spray (ESK NS) over treatment-resistant depression (TRD) require elucidation. This retrospective, longitudinal cohort study was conducted across three Spanish centers. Adults diagnosed with TRD who initiated ESK NS and completed at least the induction phase were included. Assessments occurred at baseline,...