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Ketamine long-term effects

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https://www.readbyqxmd.com/read/29137178/antidepressants-and-mood-stabilizers-novel-research-avenues-and-clinical-insights-for-bipolar-depression
#1
REVIEW
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
https://www.readbyqxmd.com/read/29135596/general-anesthetics-to-treat-major-depressive-disorder-clinical-relevance-and-underlying-mechanisms
#2
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
https://www.readbyqxmd.com/read/29099938/nyx-2925-is-a-novel-nmda-receptor-specific-spirocyclic-%C3%AE-lactam-that-modulates-synaptic-plasticity-processes-associated-with-learning-and-memory
#3
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
https://www.readbyqxmd.com/read/29055748/sex-and-dose-dependent-abuse-liability-of-repeated-subanesthetic-ketamine-in-rats
#4
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
https://www.readbyqxmd.com/read/29030928/pharmacokinetics-of-s-ketamine-during-prolonged-sedation-at-the-pediatric-intensive-care-unit
#5
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
https://www.readbyqxmd.com/read/28994672/low-dose-intravenous-ketamine-for-postcardiac-surgery-pain-effect-on-opioid-consumption-and-the-incidence-of-chronic-pain
#6
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
https://www.readbyqxmd.com/read/28969441/the-effect-of-a-single-dose-of-intravenous-ketamine-on-suicidal-ideation-a-systematic-review-and-individual-participant-data-meta-analysis
#7
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)...
October 3, 2017: American Journal of Psychiatry
https://www.readbyqxmd.com/read/28954811/preclinical-characterization-of-r-3-3s-4s-3-fluoro-4-4-hydroxyphenyl-piperidin-1-yl-1-4-methylbenzyl-pyrrolidin-2-one-bms-986169-a-novel-intravenous-glutamate-n-methyl-d-aspartate-2b-glun2b-receptor-negative-allosteric-modulator-with-potential-in-major-depressive
#8
Linda J Bristow, Jyoti Gulia, Michael R Weed, Bettadapura N Srikumar, Yu-Wen Li, John D Graef, Pattipati S Naidu, Charulatha Sanmathi, Jayant Aher, Tanmaya Bastia, Mahesh Paschapur, Narasimharaju Kalidindi, Kuchibholta Vijaya Kumar, Thaddeus Molski, Rick Pieschl, Alda Fernandes, Jeffrey M Brown, Digavalli V Sivarao, Kimberly Newberry, Mark Bookbinder, Joseph Polino, Deborah Keavy, Amy Newton, Eric Shields, Jean Simmermacher, James Kempson, Jianqing Li, Huiping Zhang, Arvind Mathur, Raja Reddy Kallem, Meenakshee Sinha, Manjunath Ramarao, Reeba K Vikramadithyan, Srinivasan Thangathirupathy, Jayakumar Warrier, Joanne J Bronson, Richard E Olson, John E Macor, Charlie F Albright, Dalton King, Lorin A Thompson, Lawrence R Marcin, Michael Sinz
(R)-3-((3S,4S)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one (BMS-986169), and the phosphate prodrug (BMS-986163), were identified from a drug discovery effort focused on the development of novel, intravenous, glutamate N-methyl-D-aspartate 2B receptor (GluN2B) negative allosteric modulators for treatment resistant depression (TRD). BMS-986169 showed high binding affinity for the GluN2B subunit allosteric modulatory site (Ki = 4.03-6.3 nM) and selectively inhibited GluN2B receptor function in Xenopus oocytes expressing human N-methyl-D-aspartate receptor subtypes (IC50 = 24...
September 27, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28926001/ketamine-differential-neurophysiological-dynamics-in-functional-networks-in-the-rat-brain
#9
A Ahnaou, H Huysmans, R Biermans, N V Manyakov, W H I M Drinkenburg
Recently, the N-methyl-d-aspartate-receptor (NMDAR) antagonist ketamine has emerged as a fast-onset mechanism to achieve antidepressant activity, whereas its psychomimetic, dissociative and amnestic effects have been well documented to pharmacologically model schizophrenia features in rodents. Sleep-wake architecture, neuronal oscillations and network connectivity are key mechanisms supporting brain plasticity and cognition, which are disrupted in mood disorders such as depression and schizophrenia. In rats, we investigated the dynamic effects of acute and chronic subcutaneous administration of ketamine (2...
September 19, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28840469/early-exposure-to-ketamine-impairs-axonal-pruning-in-developing-mouse-hippocampus
#10
Aleksandar Lj Obradovic, Navya Atluri, Lorenza Dalla Massara, Azra Oklopcic, Nikola S Todorovic, Gaurav Katta, Hari P Osuru, Vesna Jevtovic-Todorovic
Mounting evidence suggests that prolonged exposure to general anesthesia (GA) during brain synaptogenesis damages the immature neurons and results in long-term neurocognitive impairments. Importantly, synaptogenesis relies on timely axon pruning to select axons that participate in active neural circuit formation. This process is in part dependent on proper homeostasis of neurotrophic factors, in particular brain-derived neurotrophic factor (BDNF). We set out to examine how GA may modulate axon maintenance and pruning and focused on the role of BDNF...
August 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28828210/short-and-long-term-antidepressant-effects-of-ketamine-in-a-rat-chronic-unpredictable-stress-model
#11
Yinghong Jiang, Yiqiang Wang, Xiaoran Sun, Bo Lian, Hongwei Sun, Gang Wang, Zhongde Du, Qi Li, Lin Sun
OBJECTIVE: This research was aimed to evaluate the behaviors of short- or long-term antidepressant effects of ketamine in rats exposed to chronic unpredictable stress (CUS). BACKGROUND: Ketamine, a glutamate noncompetitive NMDA receptor antagonist, regulates excitatory amino acid functions, such as anxiety disorders and major depression, and plays an important role in synaptic plasticity and learning and memory. METHODS: After 42 days of CUS model, male rats received either a single injection of ketamine (10 mg/kg; day 43) or 15 daily injections (days 43-75)...
August 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28802882/chronic-opioid-therapy-modifies-qst-changes-after-ketamine-infusion-in-chronic-pain-patients
#12
Dermot P Maher, Yi Zhang, Shihab Ahmed, Tina Doshi, Charlene Malarick, Kristin Stabach, Jianren Mao, Lucy Chen
The long-term effects of opioids on sensitization processes are believed to be mediated through the N-methyl-D-aspartate receptor. Quantitative sensory testing (QST) changes observed after a ketamine infusion have been previously described but the effect that chronic opioids will have is not known. The results of this prospective randomized factorial trial compared the thermal QST changes observed after a .05 mg/kg ketamine infusion or a saline placebo in chronic pain subjects who were either opioid-naive or were chronically using opioids for chronic noncancer pain are presented...
December 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28798343/isoflurane-produces-antidepressant-effects-and-induces-trkb-signaling-in-rodents
#13
Hanna Antila, Maria Ryazantseva, Dina Popova, Pia Sipilä, Ramon Guirado, Samuel Kohtala, Ipek Yalcin, Jesse Lindholm, Liisa Vesa, Vinicius Sato, Joshua Cordeira, Henri Autio, Mikhail Kislin, Maribel Rios, Sâmia Joca, Plinio Casarotto, Leonard Khiroug, Sari Lauri, Tomi Taira, Eero Castrén, Tomi Rantamäki
A brief burst-suppressing isoflurane anesthesia has been shown to rapidly alleviate symptoms of depression in a subset of patients, but the neurobiological basis of these observations remains obscure. We show that a single isoflurane anesthesia produces antidepressant-like behavioural effects in the learned helplessness paradigm and regulates molecular events implicated in the mechanism of action of rapid-acting antidepressant ketamine: activation of brain-derived neurotrophic factor (BDNF) receptor TrkB, facilitation of mammalian target of rapamycin (mTOR) signaling pathway and inhibition of glycogen synthase kinase 3β (GSK3β)...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28758582/potential-novel-treatments-for-bipolar-depression-ketamine-fatty-acids-anti-inflammatory-agents-and-probiotics
#14
G H Vázquez, S Camino, L Tondo, Ross J Baldessarini
BACKGROUND: Treatments for depression in bipolar disorder (BD) are far less well developed than for unipolar major depressive disorder. Several innovative and experimental approaches have been emerging recently, including use of the dissociative anesthetic ketamine and other antagonists of central NMDA glutamate receptors, as well as unsaturated fatty acids, anti-inflammatory agents, and possibly probiotic methods. METHODS: We reviewed relevant reports from the past decade...
July 28, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28757132/side-effects-associated-with-ketamine-use-in-depression-a-systematic-review
#15
REVIEW
Brooke Short, Joanna Fong, Veronica Galvez, William Shelker, Colleen K Loo
This is the first systematic review of the safety of ketamine in the treatment of depression after single and repeated doses. We searched MEDLINE, PubMed, PsycINFO, and Cochrane Databases and identified 288 articles, 60 of which met the inclusion criteria. After acute dosing, psychiatric, psychotomimetic, cardiovascular, neurological, and other side-effects were more frequently reported after ketamine treatment than after placebo in patients with depresssion. Our findings suggest a selective reporting bias with limited assessment of long-term use and safety and after repeated dosing, despite these being reported in other patient groups exposed to ketamine (eg, those with chronic pain) and in recreational users...
July 27, 2017: Lancet Psychiatry
https://www.readbyqxmd.com/read/28735534/investigation-and-application-of-a-new-passive-sampling-technique-for-in-situ-monitoring-of-illicit-drugs-in-waste-waters-and-rivers
#16
Changsheng Guo, Tingting Zhang, Song Hou, Jiapei Lv, Yuan Zhang, Fengchang Wu, Zhendong Hua, Wei Meng, Hao Zhang, Jian Xu
Illicit drugs constitute a class of emerging contaminants that has been drawing significant concern due to its potent pharmacological and biological activities. In this study, an in situ passive sampling approach that uses diffusive gradients in thin films (DGT) was successfully tested for measuring ketamine (KET), methamphetamine (METH), and amphetamine (AMP) in water. The diffusion coefficients of KET, METH, and AMP in diffusive gel were (8.13 ± 0.12) × 10(-6), (8.55 ± 0.14) × 10(-6), and (7.72 ± 0.18) × 10(-6) cm(2) s(-1) at 22 °C, respectively...
August 15, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28579941/chronic-ketamine-exposure-causes-white-matter-microstructural-abnormalities-in-adolescent-cynomolgus-monkeys
#17
Qi Li, Lin Shi, Gang Lu, Hong-Luan Yu, Fu-Ki Yeung, Nai-Kei Wong, Lin Sun, Kai Liu, David Yew, Fang Pan, De-Feng Wang, Pak C Sham
Acute and repeated exposures to ketamine mimic aspects of positive, negative, and cognitive symptoms of schizophrenia in humans. Recent studies by our group and others have shown that chronicity of ketamine use may be a key element for establishing a more valid model of cognitive symptoms of schizophrenia. However, current understanding on the long-term consequences of ketamine exposure on brain circuits has remained incomplete, particularly with regard to microstructural changes of white matter tracts that underpin the neuropathology of schizophrenia...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28474988/premedication-with-fentanyl-midazolam-improves-sevoflurane-anesthesia-for-surgical-intervention-in-laboratory-mice
#18
Miriam Lipiski, Margarete Arras, Paulin Jirkof, Nikola Cesarovic
Balanced anesthesia allows for a reduced dosage of each component, while inducing general anesthesia of sufficient depth with potentially fewer side effects. Here, we compare two anesthetic protocols combining sevoflurane anesthesia with pre-medication (ketamine [K] or fentanyl-midazolam [FM]) to a sevoflurane monoanesthesia (S) concerning their ability to provide reliable anesthesia suitable for moderate surgery in laboratory mice. Twenty-one female C57BL/6J mice assigned randomly to one of three protocols underwent a 50-min anesthesia and a sham embryo transfer...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28473755/the-combination-of-long-term-ketamine-and-extinction-training-contributes-to-fear-erasure-by-bdnf-methylation
#19
Ling-Sha Ju, Jiao-Jiao Yang, Lei Lei, Jiang-Yan Xia, Dan Luo, Mu-Huo Ji, Anatoly E Martynyuk, Jian-Jun Yang
A combination of antidepressant drugs and psychotherapy exhibits more promising efficacy in treating fear disorders than either treatment alone, but underlying mechanisms of such treatments remain largely unknown. Here we investigated the role of DNA methylation of the brain-derived neurotrophic factor (Bdnf) gene in the therapeutic effects of ketamine in combination with extinction training in a mouse model of post-traumatic stress disorder (PTSD) induced by inescapable electric foot shocks (IFS). Male mice received ketamine for 22 consecutive days starting 1 h after the IFS (long-term ketamine treatment) or 2 h prior to the extinction training on days 15 and 16 after the IFS (short-term ketamine treatment)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28472198/clozapine-counteracts-a-ketamine-induced-depression-of-hippocampal-prefrontal-neuroplasticity-and-alters-signaling-pathway-phosphorylation
#20
Marion Rame, Dorian Caudal, Esther Schenker, Per Svenningsson, Michael Spedding, Thérèse M Jay, Bill P Godsil
Single sub-anesthetic doses of ketamine can exacerbate the symptoms of patients diagnosed with schizophrenia, yet similar ketamine treatments rapidly reduce depressive symptoms in major depression. Acute doses of the atypical antipsychotic drug clozapine have also been shown to counteract ketamine-induced psychotic effects. In the interest of understanding whether these drug effects could be modeled with alterations in neuroplasticity, we examined the impact of acutely-administered ketamine and clozapine on in vivo long-term potentiation (LTP) in the rat's hippocampus-to-prefrontal cortex (H-PFC) pathway...
2017: PloS One
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