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Ketamine long-term effects

Rachel R Horsley, Tomáš Páleníček, Jan Kolin, Karel Valeš
Short-term moderate doses of serotonergic and dissociative hallucinogens can be useful in the treatment of anxiety. Recently, a trend has developed for long-term intermittent 'microdosing' (usually one-tenth of a 'full' active dose), with reports of long-lasting relief from anxiety and related disorders; however, there is no scientific evidence for the efficacy of therapeutic microdosing nor to show its lasting effects. The objective of this study was to test for lasting effects on anxiety in rats after microdosing with ketamine or psilocin...
March 13, 2018: Behavioural Pharmacology
S D Dolzani, M V Baratta, J M Moss, N L Leslie, S G Tilden, A T Sørensen, L R Watkins, Y Lin, S F Maier
Stress is a potent etiological factor in the onset of major depressive disorder and posttraumatic stress disorder (PTSD). Therefore, significant efforts have been made to identify factors that produce resilience to the outcomes of a later stressor, in hopes of preventing untoward clinical outcomes. The NMDA receptor antagonist ketamine has recently emerged as a prophylactic capable of preventing neurochemical and behavioral outcomes of a future stressor. Despite promising results of preclinical studies performed in male rats, the effects of proactive ketamine in female rats remains unknown...
January 2018: ENeuro
Sufang Jiang, Xuze Li, Wei Jin, Xiaofeng Duan, Lijun Bo, Jiangli Wu, Rui Zhang, Ying Wang, Rongtian Kang, Lining Huang
Ketamine, a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist, is widely used in pediatric clinical practice. However, prolonged exposure to ketamine results in widespread anesthetic neurotoxicity and long-term neurocognitive deficits. The molecular mechanisms that underlie this important event are poorly understood. We investigated effects of anesthetic ketamine on neuroapoptosis and further explored role of NMDA receptors in ketamine-induced neurotoxicity. Here we demonstrate that ketamine induces activation of cell cycle entry, resulting in cycle-related neuronal apoptosis...
March 1, 2018: Neuroscience Letters
Deepak Cyril D'Souza, Richard E Carson, Naomi Driesen, Jason Johannesen, Mohini Ranganathan, John H Krystal
BACKGROUND: Glycine transporter-1 (GlyT1) inhibitors may ameliorate cognitive impairments associated with schizophrenia. The dose-related occupancy and target engagement of the GlyT1 inhibitor PF-03463275 were studied to inform optimal dose selection for a clinical trial for cognitive impairments associated with schizophrenia. METHODS: In substudy 1, the effects of PF-03463275 (10, 20, and 40 mg twice a day) on occupancy of GlyT1 were tested using positron emission tomography and18 F-MK-6577, and visual long-term potentiation (LTP) in schizophrenia patients (SZs) and healthy control subjects...
January 31, 2018: Biological Psychiatry
Allana Munro, Ana Sjaus, Ronald B George
PURPOSE OF REVIEW: High-quality analgesia has been linked to improved patient satisfaction as well as improved short-term and long-term postoperative outcomes. Acute surgical pain is a modifiable risk factor for development of chronic postoperative pain, which is reported by up to 26% of gynecologic surgical patients. In other surgical populations, multimodal analgesia has shown improved pain control and decreased reliance on opioids. This review examines recent evidence for various analgesic modalities applied specifically to the gynecologic surgical population...
February 22, 2018: Current Opinion in Anaesthesiology
Jianli Zhao, Yajing Wang, Dajie Wang
PURPOSE OF REVIEW: Complex regional pain syndrome (CRPS) is a painful debilitating neurological condition that accounts for approximately 1.2% of adult chronic pain population. Ketamine, an NMDA receptor antagonist, is an anesthetic agent that has been used by some pain specialists for CRPS. There is a growing body of clinical evidence to support the use of ketamine in the treatment of neuropathic pain, especially CRPS. This meta-analysis study was aimed to examine the efficacy of ketamine in the treatment of CRPS...
February 5, 2018: Current Pain and Headache Reports
Frank Birklein, Violeta Dimova
Complex regional pain syndrome (CRPS) was described for the first time in the 19th century by Silas Weir Mitchell. After the exclusion of other causes, CRPS is characterised by a typical clinical constellation of pain, sensory, autonomic, motor, or trophic symptoms which can no longer be explained by the initial trauma. These symptoms spread distally and are not limited to innervation territories. If CRPS is not improved in the acute phase and becomes chronic, the visible symptoms change throughout because of the changing pathophysiology; the pain, however, remains...
November 2017: Pain Reports (Baltimore, Md.)
J H Kwon, W S Sim, J P Hong, I S Song, J Y Lee
WHAT IS KNOWN AND OBJECTIVE: Ketamine in a subanaesthetic dose has been shown to produce rapid antidepressant effects. Here, we describe a long-term follow-up case of a Korean patient with severe major depression who received repeated ketamine intravenous therapy (KIT). CASE DESCRIPTION: A 49-year-old woman with a 6-year history of treatment-resistant major depression was given KIT once every 1 or 2 weeks over 10 months, for a total of 36 treatments. Her mood stabilized, and she showed a nearly 50% reduction in the severity of her depressive symptom...
January 25, 2018: Journal of Clinical Pharmacy and Therapeutics
C Fantacci, G C Fabrizio, P Ferrara, F Franceschi, A Chiaretti
OBJECTIVE: Pain relief is a very important aspect in Pediatrician's clinical practice. It is often thought that young children, particularly infants, do not perceive as much pain as adults because of their immature nervous system and that untreated pain would not have adverse long-term consequences. Instead, it has been demonstrated that infants and children experience pain in a similar manner to adults. Many factors, particularly emotional factors, can increase the child's pain perception...
January 2018: European Review for Medical and Pharmacological Sciences
L Aparicio-Nava, L A Márquez-García, A Meneses
Previously the effects (0.01-3.0 mg/kg) of post-training SB-699551 (a 5-HT5A receptor antagonist) were reported in the associative learning task of autoshaping, showing that SB-699551 (0.1 mg/kg) decreased lever-press conditioned responses (CR) during short-term (STM; 1.5-h) or (3.0 mg/kg) long-term memory (LTM; 24-h); relative to the vehicle animals. Moreover, as pro-cognitive efficacy of SB-699551 was reported in the ketamine-model of schizophrenia. Hence, firstly aiming improving performance (conditioned response, CR), in this work autoshaping lever-press vs...
January 9, 2018: Behavioural Brain Research
W Yan, J-F Liu, Y Han, W Zhang, Y-X Luo, Y-X Xue, W-L Zhu, C Yang, W-H Chen, H-L Guo, Y-N Ma, K Yuan, J-S Wang, J Shi, L Lu
Neuronal atrophy and alterations of synaptic structure and function in the medial prefrontal cortex (mPFC) have been implicated in the pathogenesis of depression, but the underlying molecular mechanisms are largely unknown. The protein kinase Mζ (PKMζ), a brain-specific atypical protein kinase C isoform, is important for maintaining long-term potentiation and storing memory. In the present study, we explored the role of PKMζ in mPFC in two rat models of depression, chronic unpredictable stress (CUS) and learned helplessness...
November 28, 2017: Molecular Psychiatry
N Yao, O Skiteva, X Zhang, P Svenningsson, K Chergui
Low doses of ketamine trigger rapid and lasting antidepressant effects after one injection in treatment-resistant patients with major depressive disorder. Modulation of AMPA receptors (AMPARs) in the hippocampus and prefrontal cortex is suggested to mediate the antidepressant action of ketamine and of one of its metabolites (2R,6R)-hydroxynorketamine ((2R,6R)-HNK). We have examined whether ketamine and (2R,6R)-HNK affect glutamatergic transmission and plasticity in the mesolimbic system, brain regions known to have key roles in reward-motivated behaviors, mood and hedonic drive...
November 21, 2017: Molecular Psychiatry
John Hartberg, Simone Garrett-Walcott, Angelo De Gioannis
RATIONALE: Depressive episodes are the leading cause of mental health-related hospital admissions in Australia, and 44% of those admitted have a previous history of hospitalisations for depression (Admitted patient mental health-related care: (Australian Institute of Health and Welfare Aust Hospital Stat 2011-12, 2013). Despite numerous available antidepressant treatments, many patients do not respond to conventional therapy, having what is called 'treatment resistance' (Fava Biol Psychiatry 53:649-659, 2003)...
November 18, 2017: Psychopharmacology
In Hee Shim, Young Sup Woo, Moon-Doo Kim, Won-Myong Bahk
The concept of the bipolar-spectrum and of mixed features being a bridge between major depressive disorders and bipolar disorders (BDs) has become increasingly important in mood-disorder diagnoses. Under these circumstances, antidepressants (ADs) and mood stabilizers (MSs) should be used with caution in the treatment of major depressive episodes (MDEs) and to obtain long-term stability in BDs. Before treating MDEs, screening tools, specific symptom evaluation and medical history should be used to distinguish between bipolarity and mixed features in patients for whom AD monotherapy may present a risk...
November 13, 2017: International Journal of Molecular Sciences
Laszlo Vutskits
Major depressive disorder is a frequent and devastating psychological condition with tremendous public health impact. The underlying pathophysiological mechanisms involve abnormal neurotransmission and a relatedly impaired synaptic plasticity. Since general anesthetics are potent modulators of neuronal activity and, thereby, can exert long-term context-dependent impact on neural networks, an intriguing hypothesis is that these drugs could enhance impaired neural plasticity associated with certain psychiatric diseases...
November 10, 2017: Anesthesia and Analgesia
M Amin Khan, David R Houck, Amanda L Gross, Xiao-Lei Zhang, Cassia Cearley, Torsten M Madsen, Roger A Kroes, Patric K Stanton, Jeffrey Burgdorf, Joseph R Moskal
Background: N-methyl-D-aspartate receptors (NMDAR) are one member of a family of ionotropic glutamate receptors that play a pivotal role in synaptic plasticity processes associated with learning and have become attractive therapeutic targets for diseases such as depression, anxiety, schizophrenia, and neuropathic pain. NYX-2925 ((2S, 3R)-3-hydroxy-2-((R)-5-isobutyryl-1-oxo-2,5-diazaspiro[3.4]octan-2-yl)butanamide) is one member of a spiro--lactam-based chemical platform that mimics some of the dipyrrolidine structural features of rapastinel (formerly GLYX-13: threonine-proline-proline-threonine) and is distinct from known NMDAR agonists or antagonists such as D-cycloserine, ketamine, MK-801, kynurenic acid or ifenprodil...
November 1, 2017: International Journal of Neuropsychopharmacology
Kristin J Schoepfer, Caroline E Strong, Samantha K Saland, Katherine N Wright, Mohamed Kabbaj
RATIONALE: Subanesthetic ketamine (KET) elicits rapid, robust, but transient antidepressant effects. KET's antidepressant actions can be augmented and maintained for a longer duration when repeatedly delivered. However, KET is recreationally abused, raising long-term treatment safety concerns. Women are more likely than men to seek treatment for depression, escalate from casual to compulsive drug use, and are more sensitive to antidepressants. Similarly, female rodents are more sensitive than males to KET's rapid antidepressant-like behavioral effects; dose-response thresholds in these assays equal 2...
October 18, 2017: Physiology & Behavior
Robert B Flint, Carole N M Brouwer, Anne S C Kränzlin, Loraine Lie-A-Huen, Albert P Bos, Ron A A Mathôt
BACKGROUND: S-ketamine is the S(+)-enantiomer of the racemic mixture ketamine, an anesthetic drug providing both sedation and analgesia. In clinical practice, significant interpatient variability in drug effect of S-ketamine is observed during long-term sedation. AIMS: The aim of this study was to evaluate the pharmacokinetic variability of S-ketamine in children aged 0-18 years during long-term sedation. Twenty-five children (median age: 0.42 years, range: 0...
November 2017: Paediatric Anaesthesia
Jennifer Cogan, Geneviève Lalumière, Grisell Vargas-Schaffer, Alain Deschamps, Zeynep Yegin
BACKGROUND: Recent meta-analyses have concluded that low-dose intravenous ketamine infusions (LDKIs) during the postoperative period may help to decrease acute and chronic postoperative pain after major surgery. AIMS: This study aims to evaluate the level of pain at least 3 months after surgery for patients treated with a postoperative LDKI versus patients who were not treated with a postoperative LDKI. METHODS: Administrative and Ethics Board approval were obtained for this study...
October 2017: Annals of Cardiac Anaesthesia
Samuel T Wilkinson, Elizabeth D Ballard, Michael H Bloch, Sanjay J Mathew, James W Murrough, Adriana Feder, Peter Sos, Gang Wang, Carlos A Zarate, Gerard Sanacora
OBJECTIVE: Suicide is a public health crisis with limited treatment options. The authors conducted a systematic review and individual participant data meta-analysis examining the effects of a single dose of ketamine on suicidal ideation. METHOD: Individual participant data were obtained from 10 of 11 identified comparison intervention studies that used either saline or midazolam as a control treatment. The analysis included only participants who had suicidal ideation at baseline (N=167)...
February 1, 2018: American Journal of Psychiatry
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