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https://www.readbyqxmd.com/read/29049083/ketamine-and-pharmacological-imaging-use-of-functional-magnetic-resonance-imaging-to-evaluate-mechanisms-of-action
#1
Eric A Maltbie, Gopinath S Kaundinya, Leonard L Howell
Ketamine has been used as a pharmacological model for schizophrenia as subanesthetic infusions have been shown to produce temporary schizophrenia-like symptoms in healthy humans. More recently, ketamine has emerged as a potential treatment for multiple psychiatric disorders, including treatment-resistant depression and suicidal ideation. However, the mechanisms underlying both the psychotomimetic and the therapeutic effects of ketamine remain poorly understood. This review provides an overview of what is known of the neural mechanisms underlying the effects of ketamine and details what functional MRI studies have yielded at a systems level focused on brain circuitry...
October 18, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29045915/acute-psychoactive-effects-of-intravenous-ketamine-during-treatment-of-mood-disorders-analysis-of-the-clinician-administered-dissociative-state-scale
#2
Gerrit I van Schalkwyk, Samuel T Wilkinson, Larry Davidson, Wendy K Silverman, Gerard Sanacora
INTRODUCTION: Ketamine has rapid-acting antidepressant effects. Frequently, ketamine administration also causes acute psychoactive effects - in trials, these effects are commonly measured using the Clinician Administered Dissociative State Scale (CADSS). However, the CADSS was not designed for this specific purpose, having been validated in other clinical contexts, and anecdotally does not appear to fully capture ketamine's acute psychoactive effects. METHODS: Data were obtained from 110 individuals with mood disorders (predominantly major depressive disorder) who underwent intravenous ketamine infusion...
September 28, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29045739/assessment-of-ketamine-binding-of-the-serotonin-transporter-in-humans-with-positron-emission-tomography
#3
Marie Spies, Gregory M James, Neydher Berroterán-Infante, Harald Ibeschitz, Georg S Kranz, Jakob Unterholzner, Mathis Godbersen, Gregor Gryglewski, Marius Hienert, Johannes Jungwirth, Verena Pichler, Birgit Reiter, Leo Silberbauer, Dietmar Winkler, Markus Mitterhauser, Thomas Stimpfl, Marcus Hacker, Siegfried Kasper, Rupert Lanzenberger
Background: Comprehensive description of ketamine's molecular binding profile becomes increasingly pressing as use in real life patient cohorts widens. Animal studies attribute a significant role in the substance's antidepressant effects to the serotoninergic system. The serotonin transporter (SERT) is a highly relevant target in this context because it is central to depressive pathophysiology and treatment. This is to our knowledge the first study investigating ketamine's SERT binding in-vivo in humans...
October 16, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29045243/use-of-ketamine-in-a-multimodal-analgesia-setting-for-rapid-opioid-tapering-in-a-profoundly-opioid-tolerant-patient-a-case-report
#4
Elise M Strickler, Eric S Schwenk, Mitchell J Cohen, Eugene R Viscusi
Opioids are frequently used for the treatment of chronic pain, and patients taking high doses are at increased risk of complications and adverse opioid-related events. Ketamine is appealing as an opioid adjunct because of its lack of respiratory depression and potential prevention of hyperalgesia and central sensitization. We present a case in which a ketamine infusion was utilized over a 7-day period to provide rapid taper of a daily dose of 400 mg of morphine equivalents to less than one-third of that dose on discharge with unchanged pain levels and no symptoms of opioid withdrawal...
October 17, 2017: A & A Case Reports
https://www.readbyqxmd.com/read/29042527/-biomarkers-for-mood-disorders-and-a-novel-antidepressant-r-ketamine
#5
Kenji Hashimoto
Depression is often misdiagnosed as major depressive disorder in patients with bipolar disorder. Therapeutic drugs for these two disorders are quite different, but the anesthetic ketamine shows fast-acting antidepressant effects in treatment-resistant patients with these disorders. Here, we discuss biomarkers for both disorders, recent findings regarding ketamine, and predictable biomarkers for ketamine's antidepressant actions.
October 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/29039254/the-antidepressant-efficacy-of-subanesthetic-dose-ketamine-does-not-correlate-with-baseline-subcortical-volumes-in-a-replication-sample-with-major-depressive-disorder
#6
Mark J Niciu, Nicolas D Iadarola, Dipavo Banerjee, David A Luckenbaugh, Minkyung Park, Marc Lener, Lawrence Park, Dawn F Ionescu, Elizabeth D Ballard, Nancy E Brutsche, Nirmala Akula, Francis J McMahon, Rodrigo Machado-Vieira, Allison C Nugent, Carlos A Zarate
BACKGROUND: This study sought to reproduce, in a larger sample, previous findings of a correlation between smaller raw 3-Tesla (3T) hippocampal volumes and improved antidepressant efficacy of ketamine in individuals with major depressive disorder (MDD). A secondary analysis stratified subjects according to functional BDNF rs6265 (val66met) genotype. METHODS: Unmedicated subjects with treatment-resistant MDD ( n=55) underwent baseline structural 3T MRI. Data processing was conducted with FSL/FIRST and Freesurfer software...
October 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29034354/prefrontal-connectivity-and-glutamate-transmission-relevance-to-depression-pathophysiology-and-ketamine-treatment
#7
Chadi G Abdallah, Christopher L Averill, Ramiro Salas, Lynnette A Averill, Philip R Baldwin, John H Krystal, Sanjay J Mathew, Daniel H Mathalon
BACKGROUND: Prefrontal global brain connectivity with global signal regression (GBCr) was proposed as a robust biomarker of depression, and was associated with ketamine's mechanism of action. Here, we investigated prefrontal GBCr in treatment-resistant depression (TRD) at baseline and following treatment. Then, we conducted a set of pharmacological challenges in healthy subjects to investigate the glutamate neurotransmission correlates of GBCr. METHODS: In study A, we used functional magnetic resonance imaging (fMRI) to compare GBCr between 22 TRD and 29 healthy control...
October 2017: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
https://www.readbyqxmd.com/read/29033793/from-serotonin-to-neuroplasticity-evolvement-of-theories-for-major-depressive-disorder
#8
REVIEW
Bangshan Liu, Jin Liu, Mi Wang, Yan Zhang, Lingjiang Li
The serotonin (5-HT) hypothesis of depression has played an important role in the history of psychiatry, yet it has also been criticized for the delayed onset and inadequate efficacy of selective serotonin reuptake inhibitors (SSRIs). With evolvement of neuroscience, the neuroplasticity hypothesis of major depressive disorder (MDD) has been proposed and may provide a better framework for clarification the pathogenesis of MDD and antidepressant efficacy. In this article, we first summarized the evidence challenging the monoamine hypothesis and proposed that the antidepressant efficacy of SSRIs is not derived from elevated monoamine (5-HT, noradrenaline (NE), or dopamine (DA)) concentration or monoamine neurotransmission...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29029537/the-synergistic-effect-of-dual-use-of-amphetamine-type-stimulants-and-ketamine-on-drug-induced-psychotic-symptoms-in-chinese-synthetic-drug-users
#9
Xue-Bing Liu, Yao Zhang, Xu-Yi Wang, Wei Hao
The use of amphetamine-type stimulants (ATS) and ketamine is of particular clinical concern because of its associated psychotic symptoms. In Chinese clinical practice, ATS and ketamine are commonly used simultaneously, but very few studies have reported the symptom profile of users who use both drugs. This study determined whether the combined use of ATS and ketamine is associated with more psychotic symptoms than either ATS or ketamine alone. According to drug use characteristics, 375 Chinese synthetic drug users were categorized into 2 pairs of comparison groups: ATS-only (n=125) vs...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29020410/the-requirement-of-l-type-voltage-dependent-calcium-channel-l-vdcc-in-the-rapid-acting-antidepressant-like-effects-of-scopolamine-in-mice
#10
Hanjie Yu, Mengmeng Li, Xinbei Shen, Dan Lv, Xin Sun, Jinting Wang, Xinmei Gu, Jingning Hu, Chuang Wang
Background: Previous studies have shown that a low dose of scopolamine produces rapid-acting antidepressant-like actions in rodents. Understanding the mechanisms underlying this effect and the dose-dependent variations of drug responses remains an important task. L-type voltage-dependent calcium channels (L-VDCC) were found to mediate rapid-acting antidepressant effects of certain medications (e.g., ketamine). Therefore, it is of great interest to determine the involvement of L-VDCC in the action of scopolamine...
August 25, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28988615/mechanism-of-synergistic-action-on-behavior-oxidative-stress-and-inflammation-following-co-treatment-with-ketamine-and-different-antidepressant-classes
#11
Gislaine Z Réus, Beatriz I Matias, Amanda L Maciel, Helena M Abelaira, Zuleide M Ignácio, Airam B de Moura, Danyela Matos, Lucineia G Danielski, Fabricia Petronilho, André F Carvalho, João Quevedo
BACKGROUND: Major depressive disorder (MDD) affects many people in the world. However, around 40% of patients do not respond to any pharmacological drugs. An alternative is to use a combination of different pharmacological groups or the combination of a classical antidepressant with a substance that can potentiate its effect. Thus, this study aimed to investigate the synergistic interactions between different antidepressants, including fluoxetine, quetiapine and lamotrigine in combination with ketamine, a N-methyl-d-aspartate (NMDA) receptor antagonist...
May 6, 2017: Pharmacological Reports: PR
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
#12
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/28967437/corrigendum-to-continuation-phase-intravenous-ketamine-in-adults-with-treatment-resistant-depression-j-affect-disord-206-2016-300-304
#13
Jennifer L Vande Voort, Robert J Morgan, Simon Kung, Keith G Rasmussen, Jose Rico, Brian A Palmer, Kathryn M Schak, Susannah J Tye, Matthew J Ritter, Mark A Frye, William V Bobo
No abstract text is available yet for this article.
September 26, 2017: Journal of Affective Disorders
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
#14
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/28947331/ketamine-and-aminoguanidine-differentially-affect-bdnf-and-mtor-gene-expression-in-the-prefrontal-cortex-of-adult-male-rats
#15
Vitor Silva Pereira, Betina Elfving, Sâmia R L Joca, Gregers Wegener
The rapid and sustained antidepressant properties of ketamine provide evidence of the importance of the glutamatergic system in the neurobiology of depression. The antidepressant-like effects of ketamine are dependent on brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR) in limbic brain areas. The nitrergic system is closely related to the glutamatergic system and generates antidepressant-like effects when blocked. The aim of this study was to investigate whether the behavioural effects induced by the inhibition of nitric oxide (NO) synthesis by aminoguanidine or N-methyl-D-aspartate (NMDA) receptor blockade by ketamine would affect the gene expression of Bdnf and Mtor in the ventromedial prefrontal cortex in rats...
September 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28939975/ketamine-induced-glutamatergic-mechanisms-of-sleep-and-wakefulness-insights-for-developing-novel-treatments-for-disturbed-sleep-and-mood
#16
Wallace C Duncan, Elizabeth D Ballard, Carlos A Zarate
Ketamine, a drug with rapid antidepressant effects and well-described effects on slow wave sleep (SWS), is a useful intervention for investigating sleep-wake mechanisms involved in novel therapeutics. The drug rapidly (within minutes to hours) reduces depressive symptoms in individuals with major depressive disorder (MDD) or bipolar disorder (BD), including those with treatment-resistant depression. Ketamine treatment elevates extracellular glutamate in the prefrontal cortex. Glutamate, in turn, plays a critical role as a proximal element in a ketamine-initiated molecular cascade that increases synaptic strength and plasticity, which ultimately results in rapidly improved mood...
September 23, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28926735/ketamine-metabolites-with-antidepressant-effects-fast-economical-and-eco-friendly-enantioselective-separation-based-on-supercritical-fluid-chromatography-sfc-and-single-quadrupole-ms-detection
#17
Georg M Fassauer, Robert Hofstetter, Mahmoud Hasan, Stefan Oswald, Christina Modeß, Werner Siegmund, Andreas Link
Increasing evidence accumulates that metabolites of the dissociative anesthetic ketamine contribute considerably to the biological effects of this drug and could be developed as next generation antidepressants, especially for acute treatment of patients with therapy-refractory major depression. Analytical methods for the simultaneous determination of the plethora of hydroxylated, dehydrogenated and/or demethylated compounds formed after administration of ketamine hydrochloride are a prerequisite for future clinical investigations and a deeper understanding of the individual role of the isomers of these metabolites...
September 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28926001/ketamine-differential-neurophysiological-dynamics-in-functional-networks-in-the-rat-brain
#18
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/28925030/drug-repurposing-may-generate-novel-approaches-to-treating-depression
#19
REVIEW
Mohamed Elsaed Ebada
OBJECTIVES: The breakthrough advancements in scientific medical research have greatly improved our understanding of the pathogenesis of depression, encouraging drug discoverers to take a shorter path than ever through drug repurposing to generate new antidepressant medications. In addition to reduced noradrenergic and serotonergic neurotransmission in the brain, other coincidence features such as glutamate neurotoxicity, inflammation and/or cerebrovascular insufficiency are implicated in the pathogenesis of major depressive disorder and late-life depression...
September 18, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28922961/effect-of-ketamine-dose-on-self-rated-dissociation-in-patients-with-treatment-refractory-anxiety-disorders
#20
Cameron Castle, Andrew Gray, Shona Neehoff, Paul Glue
Patients receiving ketamine for refractory depression and anxiety report dissociative symptoms in the first 60 min post-dose. The most commonly used instrument to assess this is the Clinician-Administered Dissociative States Scale (CADSS), developed based on the assessment of patients with dissociative symptoms. Its psychometric properties for ketamine-induced dissociation have not been reported. We evaluated these from a study using 0.25-1 mg/kg ketamine and midazolam (as an active control) in 18 patients with treatment-resistant anxiety...
October 2017: Journal of Psychopharmacology
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