CureusAugust 1, 2025Brett Hughes, Soz Mirza, Manasi Ponamala et al.
The stresses of the Coronavirus Disease of 2019 (COVID-19) pandemic highlighted the burden of psychiatric disorders within the pediatric population, revealing a pre-existing need for rapid-onset therapies that have since driven efforts to expand effective therapeutic interventions. In this narrative review, we utilized the Preferred Reporting Items for Systematic reviews and Meta-Analysis...
Abstract Background Only 18-45% of individuals with treatment-resistant depression (TRD) respond to intravenous ketamine therapy. Although some neurobiological predictors of response to ketamine have been reported, none have been consistently replicated across multiple studies. The imbalance between glutamatergic excitatory and GABAergic inhibitory neurotransmissions is implicated in the...
The rapid and clinically meaningful antidepressant effects of ketamine and esketamine are well-established in major depressive disorder (MDD) and treatment-resistant depression (TRD) as evidenced by improvement in clinician- and patient-reported depression measures. However, there remains a need to determine how these agents affect patient-reported quality of life (QoL). Herein, we aimed to...
Substance Use Disorders (SUDs) involve diminished control, risky use, impaired social interactions, and physical dependence. Despite their global prevalence and burden, treatment options remain limited. Ketamine (KET), an NMDA receptor antagonist, may aid SUD treatment by modulating glutamatergic neurotransmission. This systematic review evaluates KET's role in SUD treatment. This review...
Eating disorders are among the most challenging and fatal mental illnesses and, due to the complication of medical instability caused by malnutrition or other disordered eating behaviors, pose unique treatment challenges for patients with co-occurring depression and mood disorders. Randomized control trials have demonstrated "rapid and robust antidepressant effects" of generic ketamine in...
Ketamine and its enantiomers, esketamine and arketamine, have emerged as promising treatments for treatment-resistant depression (TRD). This cross-sectional study evaluates the regulatory alignment of 40 clinical trials listed on ClinicalTrials.gov, focusing on the methodological challenges. The study highlights methodological inconsistencies, particularly around the challenges of functional...
Ketamine, a psychoactive medication, exerts both analgesic and dissociative effects. However, whether its analgesic effect stems from its dissociative properties is a topic of debate. Our study aimed to determine whether ketamine’s analgesic and dissociative effects are supported by distinct neural mechanisms. In a within-subject, placebo-controlled study, 37 healthy volunteers were...
Pharmacological ResearchJuly 31, 2025C. Pisanu, R. Carvalho Silva, Mattia Meattini et al.6 citations
Treatment-resistant depression (TRD) remains a challenge in psychiatry, necessitating novel therapeutic strategies beyond traditional monoaminergic antidepressants. Ketamine and its S-enantiomer esketamine have demonstrated rapid and robust antidepressant effects in TRD, probably through mechanisms involving glutamatergic modulation, neuroplasticity, and anti-inflammatory properties. However,...
Objective: This study examines the durability (defined as time between treatments) of intravenous ketamine (IV-KET) and intranasal esketamine (IN-ESKET) for treatment-resistant depression (TRD), in a real-world clinical setting with repeated ketamine/esketamine maintenance therapy. Methods: This was a single-center, observational study of adults with TRD who completed acute-phase treatment...
Importance Psilocybin has demonstrated rapid and sustained antidepressant efficacy, with acute-phase effect sizes often more than double those for conventional antidepressants. However, concerns have been raised that high rates of functional unblinding in combination with trial participants with positive expectations of psychedelic use might bias treatment outcomes. Objective To compare...
Catheter-related bladder discomfort (CRBD) is associated with anxiety, pain, and an increased risk of perioperative complications. Esketamine, which exhibits analgesic and anticholinergic properties, may offer therapeutic benefits in this context. This study aims to evaluate the effects of varying sub-anesthetic doses of esketamine on the incidence and severity of CRBD following ureteroscopic...
This research focuses on the promising use of esketamine in perinatal depression, a widespread disorder impacting postpartum women's mental health. Despite esketamine's known rapid antidepressant effects, its precise mechanisms are not fully understood. This study integrates clinical and preclinical approaches to explore esketamine's efficacy in treating perinatal depression and its actions...
Cortical spreading depolarisation (SD) is a pathological wave of depolarisation in the cortex. SDs occur frequently after severe acute brain injury, and SDs in clusters can contribute to secondary brain damage in patients with severe acute brain injury through hypoperfusion and upregulation of cerebral metabolism in vulnerable brain tissue. Ketamine appears to inhibit SDs both in vitro and in...
INTRODUCTION Anhedonia, defined as the diminished ability to experience or anticipate pleasure, is a core symptom of major depressive disorder (MDD) and bipolar depression (BD), and associated with depression severity, suicidality and poor treatment outcomes. Conventional antidepressants demonstrate limited efficacy against anhedonia. Esketamine nasal spray (ESK-NS) - a novel NMDA receptor...
OBJECTIVE: This review explores ketamine's expanding role in managing both chronic pain and mental health conditions, focusing on its pharmacologic mechanisms, clinical applications, and therapeutic potential. We assess its analgesic properties, FDA-approved application in the form of Spravato (esketamine) for depression, and off-label use for analgesia and psychiatric disorders. METHODS: A...
The resurgence of psychedelic-assisted psychotherapy marks a pivotal evolution in mental health treatment, challenging traditional paradigms by integrating compounds such as psilocybin, LSD, MDMA, and ketamine into clinical practice. Historically marginalized due to regulatory and societal concerns, these agents are now gaining recognition for their unique neurobiological mechanisms and...
Endoplasmic reticulum (ER) stress and misfolded proteins accumulation are recognized as central factors in the development of psychiatric disorders. This study evaluated the potential therapeutic effect of fluvoxamine, a potent sigma-1 receptor agonist in alleviating protein misfolding and the subsequent ER stress in ketamine-induced model of schizophrenia. NE100 hydrochloride, a sigma-1...
Subanesthetic doses of ketamine produce complex neuropsychiatric effects, which include rapid psychotomimetic symptoms and antidepressant effects that can last several weeks. Despite over 60 years of research, the mechanism(s) of action underlying ketamine's effects in the brain remains largely mysterious. Neurophysiological field potential recordings provide a direct window into brain...
Ketamine is increasingly used in community clinics as a long-term treatment for different psychiatric and pain conditions, including substance use disorders. Data are lacking, however, regarding the potential influence of ketamine on other substance use. In this secondary analysis, we aimed to explore the relationship between medical ketamine and other substance use among real-world patients by...