Role Of Ketamine Research Articles

Morphological correlates of anxiety-related experiences during a ketamine infusion

Objectives: Ketamine exerts rapid antidepressant effects by enhancing neuroplasticity, particularly in the amygdala and hippocampus—regions involved in fear processing and learning. While the role of ketamine’s dissociative effects in its antidepressant response is debated, anxiety experienced during infusion has been negatively correlated with treatment outcomes. Methods: In this single-blind, placebo-controlled study, a subset of 17 healthy volunteers (6 males, 23.12 ± 1.9 years) received intravenously a placebo in the first and 0.5 mg/kg racemic ketamine in the second session. Anxiety-related experiences were assessed by the 5D-ASC score obtained post-infusion, structural magnetic resonance imaging scans were acquired 4 h post-infusion. An anxiety-score was obtained from the 5D-ASC. Relation between post-placebo amygdala volume, hippocampal volume, and its subfields with the anxiety-score were assessed using linear regression models. Results: Results showed a statistically significant negative relation between hippocampal head volume and the anxiety score (β = −0.733, p = 0.006), with trending negative association for each subfield’s head and the score. Conclusion: These findings suggest that anxiety-related experiences during ketamine infusion may be mediated by the hippocampus, with smaller hippocampal volumes leading to more anxiety-related experiences. Thus, hippocampal subfield volumes may be used as a predictor for anxiety-related events during ketamine use and might predict treatment outcome in future approaches.

Ketamine and α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid (AMPA) Receptor Potentiation in the Somatosensory Cortex: A Comprehensive Review.

Ketamine, a dissociative anesthetic primarily recognized for its antagonism of N-methyl-D-aspartate (NMDA) receptors, has gained significant attention for its rapid antidepressant effects and potential in treating mood disorders. However, recent research indicates that ketamine's influence extends beyond NMDA receptor inhibition, affecting α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and sensory processing. This review delves into ketamine's role in enhancing AMPA receptor function and its implications for sensory processing within the somatosensory cortex. AMPA receptors, essential for fast excitatory neurotransmission and synaptic plasticity, play a key role in sensory perception and integration. By examining preclinical and clinical studies, this review sheds light on how ketamine's modulation of AMPA receptors may improve sensory processing and contribute to its therapeutic effects. Additionally, the review explores the potential for ketamine-based therapies to treat sensory processing disorders and refine current treatment strategies. A deeper understanding of ketamine's complex effects on AMPA receptors and sensory processing could provide valuable insights for developing targeted interventions and advancing clinical applications.

Low Dose Lipopolysaccharide-Induced Depressive-Like Phenotype is Mediated by Proinflammatory Cytokines in Mice and Role of Ketamine

Low Dose Lipopolysaccharide-Induced Depressive-Like Phenotype is Mediated by Proinflammatory Cytokines in Mice and Role of Ketamine

Ketamine in Substance Use Disorder Treatment: A Narrative Review.

Substance use disorder (SUD) continues to pose a significant global health challenge, necessitating innovative and effective therapeutic interventions. Ketamine, traditionally recognized for its anesthetic properties, has emerged as a novel and promising avenue for the treatment of SUD. This narrative review critically examines the current body of literature surrounding the use of ketamine in various forms and settings for individuals grappling with substance abuse. The review explores the neurobiological underpinnings of ketamine's potential therapeutic effects in SUD, shedding light on its impact on glutamatergic neurotransmission, neuroplasticity, and reward pathways. Special attention is given to the psychotropic and dissociative properties of ketamine, exploring their implications for both therapeutic outcomes and patient experience. Ultimately, this review aims to provide a comprehensive overview of the current state of knowledge regarding ketamine's role in the treatment of SUD, emphasizing the need for further research and clinical exploration. As we navigate the complex terrain of addiction medicine, understanding the nuances of ketamine's potential in SUD holds promise for the development of more effective and personalized therapeutic strategies.

Ketamine's mechanism of action with an emphasis on neuroimmune regulation: can the complement system complement ketamine's antidepressant effects?

Over 300 million people worldwide suffer from major depressive disorder (MDD). Unfortunately, only 30-40% of patients with MDD achieve complete remission after conventional monoamine antidepressant therapy. In recent years, ketamine has revolutionized the treatment of MDD, with its rapid antidepressant effects manifesting within a few hours as opposed to weeks with conventional antidepressants. Many research endeavors have sought to identify ketamine's mechanism of action in mood disorders; while many studies have focused on ketamine's role in glutamatergic modulation, several studies have implicated its role in regulating neuroinflammation. The complement system is an important component of the innate immune response vital for synaptic plasticity. The complement system has been implicated in the pathophysiology of depression, and studies have shown increases in complement component 3 (C3) expression in the prefrontal cortex of suicidal individuals with depression. Given the role of the complement system in depression, ketamine and the complement system's abilities to modulate glutamatergic transmission, and our current understanding of ketamine's anti-inflammatory properties, there is reason to suspect a common link between the complement system and ketamine's mechanism of action. This review will summarize ketamine's anti- inflammatory roles in the periphery and central nervous system, with an emphasis on complement system regulation.

The Role of Ketamine in Calcium Changes in Intracellular Homeostasis and Mitochondrial Dysfunction

: Ketamine was formerly introduced as an anesthesia drug and known as a non-competitive antagonist of the N-methyl-D-aspartate receptor (NMDAR). As knowledge grows, recent studies reveal the antidepressant effect of the drug. Moreover, a few investigations indicate that ketamine might be responsible for multiple calcium-regulated signaling pathways. Ketamine is thought to affect calcium homeostasis through several of its targets, such as N-Methyl-D-Aspartate (NMDA), α-amino-3-hydroxy-5-methylisoxazole-4-propionate acid receptors (AMPA), and voltage-dependent calcium channels (VDCCs).

The Role of Ketamine as a Component of Multimodal Analgesia in Burns: A Retrospective Observational Study

The Role of Ketamine as a Component of Multimodal Analgesia in Burns: A Retrospective Observational Study

Resolution of stuttering during ketamine treatment: a case report

BackgroundStuttering may include repetition of words in whole or part, difficulty saying words, and elongated pauses in speech. Approximately 5% of children stutter for a period lasting 6 months or more. Most of those children stop stuttering as they approach adulthood, but the condition persists in approximately 1% of adults. The cause of stuttering is unknown. Adults who stutter face substantial burdens in many aspects of their lives. Stutterers may choose not to pursue meaningful employment opportunities, may not be hired for positions they seek, or may be denied promotions or positive performance evaluations. Stuttering can cause physical tension from fear of speaking. Social challenges arise when a person who stutters is seen as less capable or of lower intelligence than fluent speakers. Stuttering causes emotional difficulties through the frustration and embarrassment that disfluent speakers feel. Stutterers may experience a general loss of self-esteem and personal satisfaction in life. Speech therapy is the primary intervention for stuttering. Medications have been investigated as treatments for stuttering, but no medication has been identified that has widespread effectiveness.Case presentationA 60-year-old white non-Hispanic woman who had been a near lifelong stutterer was prescribed ketamine for an unrelated condition and experienced an almost immediate resolution of her stuttering.ConclusionsMany possible pharmacological treatments for stuttering have been studied. Some medications appear to be effective in some patients; some appear to be more generally effective but have negative side effects. No reporting in relevant literature has addressed a possible role for ketamine in stuttering treatment. On the basis of this case report, research on the effect of ketamine on stuttering would be useful. Any effective treatment for stuttering would have a significant positive effect on quality of life for persons who stutter.

Ketamine for Chronic Pain and Mental Health: Regulations, Legalities, and the Growth of Infusion Clinics.

In this article, we will review evidence for ketamine's role in chronic pain and mental health conditions, its current legal status and abuse potential, and the regulations related to its administration in stand-alone infusion clinics, as well as future considerations. In the management of chronic pain, ketamine has shown potential to manage neuropathic pain and complex regional pain syndrome and has been used as a treatment for chronic pain management by clinics across the USA. Analogous to the historic rise of lidocaine clinics, ketamine clinics are demonstrating a similar pattern of unregulated growth. Ketamine is an anesthetic and analgesic agent commonly used in the perioperative setting and emergency department for sedation and pain management (Mo et al in West J Emerg Med 21(2):272-281, 2020). It was approved for use by the Federal Drug Administration in the USA in the 1970s as the sole anesthetic agent for short diagnostic and surgical procedures (Coppel et al. in Anaesthesia 28(3):293-296,1973; Schwenk et al. in Reg Anesth Pain Med 43(5):456-466, 2018). Regarding its rising popularity as a treatment option in mental health, ketamine holds promise as a rapidly acting treatment for suicidal ideation and refractory depression.

Insights into the Neurobiology of Suicidality: Explicating the role of glutamatergic systems through the lens of ketamine.

Suicidality is a prevalent mental health condition, and managing suicidal patients is one of the most challenging tasks for healthcare professionals due to the lack of rapid-acting, effective psychopharmacological treatment options. According to the literature, suicide has neurobiological underpinnings that are not fully understood, and current treatments for suicidal tendencies have considerable limitations. To treat suicidality and prevent suicide, new treatments are required; to achieve this, the neurobiological processes underlying suicidal behaviour must be thoroughly investigated. Although multiple neurotransmitter systems, particularly serotonergic systems, have been studied in the past, less has been reported in relation to disruptions in glutamatergic neurotransmission, neuronal plasticity and neurogenesis that result from stress-related abnormalities of the hypothalamic-pituitary-adrenal (HPA) system. Informed by the literature which reports robust anti-suicidal and anti-depressive properties of subanaesthetic doses of ketamine, this review aims to provide an examination of the neurobiology of suicidality (and relevant mood disorders) with implications of pertinent animal, clinical and post-mortem studies. We discuss dysfunctions in the glutamatergic system, which may play a role in the neuropathology of suicidality and the role of ketamine in restoring synaptic connectivity at the molecular levels. This article is protected by copyright. All rights reserved.

The Role of Ketamine in the Treatment of Bipolar Depression: A Scoping Review

Bipolar depression remains a clinical challenge with a quarter of patients failing to respond to initial conventional treatments. Although ketamine has been extensively studied in unipolar depression, its role in bipolar disorder remains inconclusive. The aim of our scoping review was to comprehensively synthesize the current clinical literature around ketamine use in bipolar depression. A total of 10 clinical studies (5 randomized controlled trials and 5 open label studies) were selected. The preliminary evidence, albeit weak, suggests that ketamine is a promising treatment and calls for further interest from the research community. Overall, ketamine treatment appeared to be tolerable with minimal risk for manic/hypomanic switching and showed some effectiveness across parameters of depression and suicidality. Moreover, ketamine is a potential treatment agent in patients with treatment-resistant bipolar depression with promising data extracted from extant controlled trials and real-world effectiveness studies. Future studies are needed to identify ketamine’s role in acute and maintenance treatment phases of bipolar depression. Moreover, future researchers should study the recurrence prevention and anti-suicidal effects of ketamine in the treatment of bipolar depression.

The role of ketamine as an antidepressant agent

The role of ketamine as an antidepressant agent

Роль кетаміну у періопераційному знеболюванні (огляд)

В огляді наведено фармакологічні властивості, ефективність та стратегії застосування кетаміну для знеболювання в періопераційному періоді в різних галузях хірургії.

Ketamine as a therapeutic agent for depression and pain: mechanisms and evidence

Ketamine is an anesthetic drug which is now used to treat chronic pain conditions and psychiatric disorders, especially depression. It is an N-methyl-D-aspartate (NMDA) receptor antagonist with additional effects on α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, opioid receptors, and monoaminergic receptors. This article focuses on ketamine's role in treating depression and pain, two commonly comorbid challenging conditions with potentially shared neurobiologic circuitry. Many clinical trials have utilized intravenous or intranasal ketamine for treating depression and pain. Intravenous ketamine is more bioavailable than intranasal ketamine and both are effective for acute depressive episodes. Intravenous ketamine is advantageous for post-operative analgesia and is associated with a reduction in total opioid requirements. Few studies have treated chronic pain or concurrent depression and pain with ketamine. Larger, randomized control trials are needed to examine the safety and efficacy of intravenous vs. intranasal ketamine, ideal target populations, and optimal dosing to treat both depression and pain.

Letter to the Editor: Role of Ketamine in Vaso-Occlusive Crisis of Sickle Cell Disease.

Letter to the Editor: Role of Ketamine in Vaso-Occlusive Crisis of Sickle Cell Disease.

The role of ketamine in the treatment of treatment-resistant bipolar depression

Treatment-Resistant Depression (TRD) calls for the development of effective interventions for mood elevation and stabilization. Recently, both ketamine and its S-enantiomer (esketamine) have been investigated with successful clinical trials demonstrating effectiveness in TRD. More specifically, in 2019, intranasally administered esketamine, as opposed to the more effective intravenous ketamine, has been approved by the FDA as a treatment option for TRD. Treatment with esketamine, however, potentially comes with major adverse effects, including risk of psychosis, the possibility of abuse and dependence after repeated use, transient but non-negligible change in blood pressure and the heart rate, and potential toxicity on the urothelium and the liver. These risks are minimized when treatment is kept within the recommended dose range and the drug is administered by experienced medical personnel. Nevertheless, these risks appear to be offset by the effectiveness of esketamine in a wide range of depressive symptoms, such as anhedonia, anxiety, cognitive impairment, suicidality, and general dysfunction. This review highlights the need for more phase 4 clinical studies to evaluate esketamine's performance in real life, including long-term effectiveness and risk studies.

Ketamine in the Past, Present, and Future: Mechanisms, Metabolites, and Toxicity.

While ketamine's analgesia has mostly been attributed to antagonism of N-methyl-D-aspartate receptors, evidence suggests multiple other pathways are involved in its antidepressant and possibly analgesic activity. These mechanisms and ketamine's role in the nociplastic pain paradigm are discussed. Animal studies demonstrating ketamine's neurotoxicity have unclear human translatability and findings from key rodent and human studies are presented. Ketamine's metabolites, and (2R,6R)-hydroxynorketamine in particular, may play a greater role in its clinical activity than previously believed. The activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and the mammalian target of rapamycin by ketamine are mechanisms that are still being elucidated. Ketamine might work best in nociplastic pain, which involves altered pain processing. While much is known about ketamine, new studies will continue to define its role in clinical medicine. Evidence supporting ketamine's neurotoxicity in humans is lacking and should not impede future ketamine clinical trials.

Role of Ketamine in the Treatment of Psychiatric Disorders.

This is a comprehensive review of the literature regarding the use of ketamine as a treatment for treatment-resistant depression (TRD). It covers the epidemiology, risk factors, pathophysiology, and current treatment modalities regarding Major Depressive Disorder (MDD) and TRD. It provides background on the mechanism of action of ketamine, its history, current approved and off-label indications in the field of psychiatry, and then provides an overview of the existing evidence for the use of ketamine in the treatment of TRD. MDD is a mental illness that puts an enormous strain on the affected and a high socio-economic burden on society. The illness is complex and combines genetic, pathophysiologic, and environmental factors that combine to negatively affect neurotransmitter balance in the brain. Additional evidence suggests dysregulation of the hypothalamic-pituitary (HPA) axis, brain-derived neurotrophic factor (BDNF), vitamin D levels, and involvement of pro-inflammatory markers. Core symptoms include depressed mood or anhedonia, combined with neurovegetative symptoms such as sleep impairment, changes in appetite, feelings of worthlessness and guilt, and psychomotor retardation. Current first-line treatment options are antidepressants of the selective serotonin reuptake inhibitor (SSRI) and serotonin-norepinephrine reuptake inhibitor (SNRI) class. Failure to respond to two adequate trials of treatment meets the criteria for TRD. Esketamine (Spravato) is an NMDA-receptor antagonist with additional AMPA-receptor agonist properties, which the FDA approved in 2019 to treat adult TRD in conjunction with an oral antidepressant. It can be administered intranasally, providing a rapid response and proven effective and safe. Additional research suggests that oral ketamine might be effective for PTSD and anxiety disorders. Intravenous administration of ketamine has also shown benefits for acute suicidal ideation and depression and substance use to reduce relapse rates. TRD is associated with huge costs on individual and societal levels. Underlying disease processes are multifactorial and not well understood. Adjunctive therapies for TRD with proven benefits exist, but acutely depressed and suicidal patients often require prolonged inpatient stabilization. Intranasal esketamine is a new FDA-approved alternative with rapid benefit for TRD, which has also shown a rapid reduction in suicidal ideation while maintaining a favorable side-effect profile. Additional potential off-label uses for ketamine in psychiatric disorders have been studied, including PTSD, anxiety disorders, bipolar depression, and substance use disorders.

Cortical spreading depolarizations in the context of subarachnoid hemorrhage and the role of ketamine

Delayed cerebral ischemia (DCI) is one of the main complications of spontaneous subarachnoid haemorrhage and one of its causes is the cortical spreading depolarizations (CSDs). Cortical spreading depolarizations are waves of neuronal and glial depolarizations in which there is loss of neuronal ionic homeostasis with potassium efflux and sodium and calcium influx. In damaged brain areas and brain areas at risk, such as those adjacent to subarachnoid haemorrhage (SAH), CSDs induce microvascular vasoconstriction and, therefore, hypoperfusion and spread of ischemia. Several studies have been devoted to minimize secondary injuries that occur hours to days after an acute insult. Ketamine, a drug until recently contraindicated in the neurosurgical population for potentially causing intracranial hypertension, has re-emerged as a potential neuroprotective agent due to its pharmacodynamic effects at the cellular level. These effects include anti-inflammatory mechanisms, and those of microthrombosis and cell apoptosis controls, and of modulation of brain excitotoxicity and CSDs. A literature review was performed at PubMed covering the period from 2002 to 2019. Retrospective studies confirmed the effects of ketamine on the control of CSDs and, consequently, of DCI in patients with SAH, but did not show improvement in clinical outcome. The influence of ketamine on the occurrence/development of DCI needs to be further confirmed in prospective randomized studies.

The role of ketamine in opioid-free spinal deformity surgery: is it possible and beneficial?

As the opioid epidemic in the United States has continued to gain momentum in recent years, the current study aims to explore the efficacy of ketamine in a traditionally challenging setting regarding pain control, and contribute toward developing an opioid-free intraoperative pain protocol in spinal deformity surgery. Fifty-four patients who underwent spinal deformity surgery between January 1, 2017 and December 31, 2017 by one senior surgeon were included. Demographic data and preoperative opioid use was collected. Surgical details including number of levels fused, estimated blood loss, and operative time was also collected. All patients received a hydromorphone patient-controlled anesthesia (PCA) device postoperatively. 36/54 patients received perioperative ketamine during their procedure, both intraoperatively and postoperatively. The consumption of postoperative hydromorphone and the ratio of doses given by doses attempted postoperatively were recorded. Patient charts were also reviewed for documented ileus during their inpatient stay. Mean age was 49 years, and 31% were male. Average BMI was 24.3 kg/m2. The average number of levels fused was 11.6. Mean operative time was 10.7 hrs, and average EBL was 1,522 mL. The mean length of stay was 8 days. Average postoperative PCA use of hydromorphone in the no ketamine group (NK) (n=18) was 5.99 mg compared to 6.91 mg for those who received perioperative ketamine (K) (n=36); there was no significant difference between populations (P=0.57), although the variances was significant (P=0.044). There was no correlation between intraoperative ketamine and postoperative PCA use (r=-0.05; P=0.72). Additionally, there was no correlation between postoperative PCA use and dose of postoperative ketamine received (r=-0.15; P=0.27). The ratio of doses given: attempted was 0.61 in the NK group and 0.59 in those in the K group (P=0.79). Average postoperative hydromorphone use was 5.48 mg in patients that did not use opioids preoperatively (n=39) compared to 12.77 mg in those who used opioids preoperatively (n=9; P=0.0003). 9/54 patients had a documented ileus during their admission, while 4/9 (11%) had received ketamine (P=0.095). Though our study showed no significant change in postoperative opioid requirement in our population, our results show that integration of ketamine in these extensive operations fare similarly to traditional opioid-based regimens. There was also no significant association seen between ketamine use and adverse side effects such as ileus. At our institution we are currently establishing opioid-free intraoperative pain protocols that use ketamine as an adjunct, and further study will explore the effect this may have on postoperative opioid consumption for spinal surgery patients as well as postoperative patients in general.