Treatment-resistant depression (TRD) represents an unmet challenge, accounting for disproportionate morbidity, disability, and healthcare burden in depression. Limitations of monoaminergic antidepressants have prompted a conceptual shift toward models emphasizing impaired neuroplasticity, synaptic dysfunction, and network dysregulation. This expert review synthesizes preclinical, translational,...
Treatment-resistant depression and anxiety remain major challenges in psychiatry, particularly in female patients, who are disproportionately affected yet remain underrepresented in preclinical ketamine research. The present study investigated short- and long-term anxiolytic effects of acute subanesthetic ketamine administration in female Wistar-Kyoto (WKY) rats, a validated genetic model of...
Ketamine is increasingly prescribed in an off-label manner to treat psychiatric disorders, raising concerns about direct-to-consumer advertising and the proliferation of clinics offering ketamine for at-home use without direct medical supervision. We aimed to identify and characterize clinics advertising ketamine for psychiatric conditions online in the New York metropolitan area (New York, New...
JAMA PsychiatryJuly 1, 2026Sung Ryul Shim, Hye Su Jeong, Tanner J. Bommersbach et al.1 citation
While intravenous ketamine is not approved by the US Food and Drug Administration, it is increasingly used with off-label indications as a novel treatment for suicidal and depressive symptoms. To systematically review and metasynthesize the efficacy and safety data for intravenous ketamine in treating major depressive episodes (MDEs). PubMed, PsycInfo, Cochrane Library, and Embase were...
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...
PsychopharmacologyJuly 1, 2026Sarah Ann Smith, Haseeb Mohammad, Lik Hang N Lee et al.
Interest in psychedelic drugs has increased rapidly because of their potential therapeutic role in psychiatric disorders. Impairments in the sociocognitive skills needed to build and maintain social relationships are prominent features of many psychiatric and neurodevelopmental disorders. Emerging evidence suggests that compounds such as 3,4-methylenedioxymethamphetamine (MDMA), lysergic acid...
Relevance. Depression is one of the leading causes of disability worldwide, and a significant proportion of patients suffer from treatment-resistant forms of the disorder. An innovative approach involves the use of ketamine and esketamine, which are capable of inducing a “window of neuroplasticity” – a period of enhanced synaptogenesis and the formation of new neural connections. Theoretically,...
Background. Ketamine provides rapid but short-lived antidepressant effects for treatment-resistant depression (TRD). To prolong this response, ketamine-assisted therapy (KAT) combines the drug's pharmacological effects with psychotherapy. Aim. This study aims to analyze scientific evidence regarding the synergistic interaction between ketamine's pharmacological effects and modern...
Ketamine, a dissociative anesthetic introduced in the 1960s, has re-emerged as a versatile therapeutic agent extending beyond its traditional perioperative role. Its rapid antidepressant action in treatment-resistant depression and efficacy in acute and chronic pain syndromes have driven what is termed the “ketamine renaissance.” Unlike conventional monoaminergic antidepressants, ketamine...
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...
Preprints.orgJune 30, 2026Dirk Revenstorf, Joost (j.b.c.) Mertens, Martin Schipplick
preprint
The therapeutic use of ketamine and other psychoactive substances in psychiatry is attracting growing research interest, particularly in treatment-resistant depression and related conditions refractory to conventional care. Ketamine exerts direct pharmacological antidepressant effects through NMDA receptor antagonism and downstream neuroplastic mechanisms; its combination with structured...
Ketamine and its structural analog, 2-Fluorodeschloroketamine, both potent stimulants, can induce euphoria but also cause neurotoxicity, cognitive decline, and neurodevelopmental deficits in the fetus. However, the molecular mechanisms responsible for these neurodevelopmental abnormalities are not yet fully elucidated, particularly concerning effects that are specific to certain cell types....
NeuropsychiatrieJune 30, 2026Cielo A Estela-Fernandez, Reem Mohamed Yousif Elsheikh, Dal Bianco Beatrice et al.
Major depressive disorder (MDD) is a heterogeneous, debilitating disorder. A distinct subgroup within the MDD spectrum is identified to have treatment-resistant depression (TRD). There is an impetus to find alternative treatments for TRD to reduce disease burden and improve quality of life. Psychedelics have been used in the treatment of various psychiatric disorders since the 1950s, with...
Background: Ensuring participants understand informed consent forms (ICFs) is a core ethical requirement of clinical research, particularly in psychiatry, where cognitive and affective symptoms can compromise decisional capacity. As ketamine-based interventions are increasingly studied for mental health conditions, the readability of consent materials in these trials warrants systematic...
Major depressive disorder (MDD) ranks among the foremost contributors to disability worldwide, yet its neurophysiological mechanisms remain poorly understood. Excitation-inhibition (E/I) imbalance has been implicated in MDD pathophysiology, but cortex-wide E/I ratio and its molecular substrates in MDD remain unknown. Resting-state functional magnetic resonance imaging data from 254 MDD patients...
Ketamine is an indispensable therapeutic in emergency medicine, yet its pharmacologic profile carries a unique constellation of adverse effects that emergency medicine clinicians must recognize and manage. This focused clinical review examines four categories of these ketamine-specific adverse effects encountered in the emergency department (ED): acute psycho-perceptual adverse effects (PPAEs)...
Ketamine is an antagonist of the N-Methyl-D-aspartate (NMDA) receptor with the effect of inducing aberrant excitatory-inhibitory neurotransmission and oxidative neurotoxicity, which mimic the cognitive impairments found in schizophrenia. This study explored the potential of mangiferin, a strong antioxidant xanthone polyphenol, to normalize neurotransmitter levels and mitigate oxidative and...