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ketamine depression

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https://www.readbyqxmd.com/read/29229209/randomized-double-blind-placebo-controlled-dose-escalation-study-investigation-of-the-safety-pharmacokinetics-and-antihyperalgesic-activity-of-l-4-chlorokynurenine-in-healthy-volunteers
#1
Mark Wallace, Alexander White, Kathy A Grako, Randal Lane, Allen Jo Cato, H Ralph Snodgrass
BACKGROUND AND AIMS: Neuropathic pain is a significant medical problem needing more effective treatments with fewer side effects. Overactive glutamatergic transmission via N-methyl-d-aspartate receptors (NMDARs) are known to play a role in central sensitization and neuropathic pain. Although ketamine, a NMDAR channel-blocking antagonist, is often used for neuropathic pain, its side-effect profile and abusive potential has prompted the search for a safer effective oral analgesic. A novel oral prodrug, AV-101 (l-4 chlorokynurenine), which, in the brain, is converted into one of the most potent and selective GlyB site antagonists of the NMDAR, has been demonstrated to be active in animal models of neuropathic pain...
October 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29222646/evidence-for-the-involvement-of-opioid-system-in-the-antidepressant-like-effect-of-ascorbic-acid
#2
Morgana Moretti, Camille M Ribeiro, Vivian B Neis, Luis Eduardo B Bettio, Priscila B Rosa, Ana Lúcia S Rodrigues
Considering the involvement of the opioid system in major depressive disorder (MDD), mainly concerning refractory MDD, and the evidence that ascorbic acid may exert a beneficial effect for the treatment of this disorder, this study investigated the involvement of the opioid system in the antidepressant-like effect of ascorbic acid in the tail suspension test (TST). Treatment of Swiss mice with the non-selective opioid receptor antagonist naloxone (1 mg/kg, i.p.) prevented the reduced immobility time caused by ascorbic acid (1 mg/kg, p...
December 8, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29203848/bdnf-release-and-signaling-are-required-for-the-antidepressant-actions-of-glyx-13
#3
T Kato, M V Fogaça, S Deyama, X-Y Li, K Fukumoto, R S Duman
Conventional antidepressant medications, which act on monoaminergic systems, display significant limitations, including a time lag of weeks to months and low rates of therapeutic efficacy. GLYX-13 is a novel glutamatergic compound that acts as an N-methyl-d-aspartate (NMDA) modulator with glycine-like partial agonist properties; like the NMDA receptor antagonist ketamine GLYX-13 produces rapid antidepressant actions in depressed patients and in preclinical rodent models. However, the mechanisms underlying the antidepressant actions of GLYX-13 have not been characterized...
December 5, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29202655/ketamine-for-rapid-reduction-of-suicidal-thoughts-in-major-depression-a-midazolam-controlled-randomized-clinical-trial
#4
Michael F Grunebaum, Hanga C Galfalvy, Tse-Hwei Choo, John G Keilp, Vivek K Moitra, Michelle S Parris, Julia E Marver, Ainsley K Burke, Matthew S Milak, M Elizabeth Sublette, Maria A Oquendo, J John Mann
OBJECTIVE: Pharmacotherapy to rapidly relieve suicidal ideation in depression may reduce suicide risk. Rapid reduction in suicidal thoughts after ketamine treatment has mostly been studied in patients with low levels of suicidal ideation. The authors tested the acute effect of adjunctive subanesthetic intravenous ketamine on clinically significant suicidal ideation in patients with major depressive disorder. METHOD: In a randomized clinical trial, adults (N=80) with current major depressive disorder and a score ≥4 on the Scale for Suicidal Ideation (SSI), of whom 54% (N=43) were taking antidepressant medication, were randomly assigned to receive ketamine or midazolam infusion...
December 5, 2017: American Journal of Psychiatry
https://www.readbyqxmd.com/read/29199810/ketamine-as-treatment-for-depression
#5
Tero Taiminen
Ketamine infusions administered intravenously 1 to 3 times per week are the quickest and most effective treatment for depression. Short-course ketamine medication is established treatment both for unipolar depression and depressive episodes of bipolar affective disorder. Ketamine is suitable for initiating the treatment for treatment-resistant depression, alleviation of suicidal tendencies, and treatment of depressive patients suffering from simultaneous pain. The safety of prolonged treatment with ketamine is not known to sufficient degree...
2017: Duodecim; Lääketieteellinen Aikakauskirja
https://www.readbyqxmd.com/read/29180675/protein-kinase-m%C3%AE-in-medial-prefrontal-cortex-mediates-depressive-like-behavior-and-antidepressant-response
#6
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
https://www.readbyqxmd.com/read/29178131/the-rapid-onset-antidepressant-effect-of-ketamine-more-surprises
#7
R B Raffa, J V Pergolizzi, R Taylor
WHAT IS KNOWN AND OBJECTIVE: An effective rapid-onset treatment for major depressive disorder could save lives. Extensive preclinical and clinical data demonstrate such an action of ketamine. However, the presumptive mechanism of action, inhibition of NMDA (N-methyl-D-aspartate) receptors, has recently been challenged. Elucidation of the mechanism is important clinically for drug discovery and for understanding the (patho)physiology of depression. COMMENT: The best-known pharmacologic property of ketamine is non-competitive inhibition of the NMDA subtype of glutamate receptor...
November 26, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29174627/role-of-nmda-receptor-glun2d-subunit-in-the-antidepressant-effects-of-enantiomers-of-ketamine
#8
Soichiro Ide, Yuiko Ikekubo, Masayoshi Mishina, Kenji Hashimoto, Kazutaka Ikeda
We investigated the rapid and sustained antidepressant effects of enantiomers of ketamine in N-methyl-d-aspartate (NMDA) receptor GluN2D subunit knockout (GluN2D-KO) mice. Intraperitoneal administration of ketamine or its enantiomers 10 min before the tail-suspension test exerted significant antidepressant effects on restraint stress-induced depression in both wildtype and GluN2D-KO mice. The antidepressant effects of (RS)-ketamine and (S)-ketamine were sustained 96 h after the injection in both wildtype and GluN2D-KO mice, but such sustained antidepressant effects of (R)-ketamine were only observed in wildtype mice...
November 10, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29171010/prenatal-exposure-to-ketamine-in-rats-implications-on-animal-models-of-schizophrenia
#9
Carlos M Coronel-Oliveros, Renny Pacheco-Calderón
Schizophrenia is a complex neuropsychiatric disorder characterized by hallucinations, delusions, anhedonia, flat affect and cognitive impairments. The aim of this study was to propose a prenatal treatment with ketamine, a psychedelic drug that acts as a non-competitive inhibitor of glutamate NMDA receptors, as a neurodevelopmental animal model of schizophrenia. The drug was applied (i.m. 60 mg.kg(-1)  h(-1) ) in pregnant Sprague-Dawley rats on gestational Day 14. Offspring behavior was studied on pubertal (4 weeks old) and adult (10 weeks old) stages...
November 24, 2017: Developmental Psychobiology
https://www.readbyqxmd.com/read/29162814/trkb-dependent-adult-hippocampal-progenitor-differentiation-mediates-sustained-ketamine-antidepressant-response
#10
Zhenzhong Ma, Tong Zang, Shari G Birnbaum, Zilai Wang, Jane E Johnson, Chun-Li Zhang, Luis F Parada
Adult neurogenesis persists in the rodent dentate gyrus and is stimulated by chronic treatment with conventional antidepressants through BDNF/TrkB signaling. Ketamine in low doses produces both rapid and sustained antidepressant effects in patients. Previous studies have shed light on post-transcriptional synaptic NMDAR mediated mechanisms underlying the acute effect, but how ketamine acts at the cellular level to sustain this anti-depressive function for prolonged periods remains unclear. Here we report that ketamine accelerates differentiation of doublecortin-positive adult hippocampal neural progenitors into functionally mature neurons...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29161812/acute-amino-acid-d-serine-administration-similar-to-ketamine-produces-antidepressant-like-effects-through-the-identical-mechanisms
#11
I-Hua Wei, Kuang-Ti Chen, Mang-Hung Tsai, Ching-Hsiang Wu, Hsien-Yuan Lane, Chih-Chia Huang
D-serine is an amino acid and can work as an agonist at the glycine sites of N-methyl-D-aspartate receptor (NMDAR). Interestingly, both types of glutamatergic modulators, NMDAR enhancers and blockers, can improve depression through common targets, namely alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionaic acid receptors (AMPARs) and mammalian target of rapamycin (mTOR). To elucidate the cellular signaling pathway underlying this counterintuitive observation, we activated NMDARs in rats by using D-serine. Saline, ketamine (NMDAR antagonist), and desipramine (tricyclic antidepressant) were used as controls...
November 22, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29158578/ketamine-and-its-metabolite-2r-6r-hydroxynorketamine-induce-lasting-alterations-in-glutamatergic-synaptic-plasticity-in-the-mesolimbic-circuit
#12
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
https://www.readbyqxmd.com/read/29158577/vgf-function-in-depression-and-antidepressant-efficacy
#13
C Jiang, W-J Lin, M Sadahiro, B Labonté, C Menard, M L Pfau, C A Tamminga, G Turecki, E J Nestler, S J Russo, S R Salton
Brain-derived neurotrophic factor (BDNF) is a critical effector of depression-like behaviors and antidepressant responses. Here, we show that VGF (non-acronymic), which is robustly regulated by BDNF/TrkB signaling, is downregulated in hippocampus (male/female) and upregulated in nucleus accumbens (NAc) (male) in depressed human subjects and in mice subjected to chronic social defeat stress (CSDS). Adeno-associated virus (AAV)-Cre-mediated Vgf ablation in floxed VGF mice, in dorsal hippocampus (dHc) or NAc, led to pro-depressant or antidepressant behaviors, respectively, while dHc- or NAc-AAV-VGF overexpression induced opposite outcomes...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29155993/lack-of-antidepressant-effects-of-2r-6r-hydroxynorketamine-in-a-rat-learned-helplessness-model-comparison-with-r-ketamine
#14
Yukihiko Shirayama, Kenji Hashimoto
Background: (R)-Ketamine exhibits rapid and sustained antidepressant effects in animal models of depression. It is stereoselectively metabolized to (R)-norketamine, and subsequently to (2R,6R)-hydroxynorketamine (HNK) in the liver. The metabolism of ketamine to HNK was recently demonstrated to be essential for ketamine's antidepressant actions. However, no study has compared the antidepressant effects of these three compounds in animal models of depression. Methods: The effects of a single intraperitoneal injection of (R)-ketamine, (R)-norketamine, and (2R,6R)-HNK in a rat learned helplessness (LH) model were examined...
November 15, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29151192/impact-of-oral-ketamine-augmentation-on-hospital-admissions-in-treatment-resistant-depression-and-ptsd-a-retrospective-study
#15
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
https://www.readbyqxmd.com/read/29150633/ketamine-s-antidepressant-effect-is-mediated-by-energy-metabolism-and-antioxidant-defense-system
#16
Katja Weckmann, Michael J Deery, Julie A Howard, Renata Feret, John M Asara, Frederik Dethloff, Michaela D Filiou, Jamie Iannace, Christiana Labermaier, Giuseppina Maccarrone, Christian Webhofer, Larysa Teplytska, Kathryn Lilley, Marianne B Müller, Christoph W Turck
Fewer than 50% of all patients with major depressive disorder (MDD) treated with currently available antidepressants (ADs) show full remission. Moreover, about one third of the patients suffering from MDD does not respond to conventional ADs and develop treatment-resistant depression (TRD). Ketamine, a non-competitive, voltage-dependent N-Methyl-D-aspartate receptor (NMDAR) antagonist, has been shown to have a rapid antidepressant effect, especially in patients suffering from TRD. Hippocampi of ketamine-treated mice were analysed by metabolome and proteome profiling to delineate ketamine treatment-affected molecular pathways and biosignatures...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29149755/a-randomized-clinical-trial-of-adjunctive-ketamine-anesthesia-in-electro-convulsive-therapy-for-depression
#17
Minling Zhang, Robert Rosenheck, Xiaoming Lin, Qirong Li, Yanling Zhou, Yunshan Xiao, Xiong Huang, Ni Fan, Hongbo He
BACKGROUND: Electroconvulsive therapy (ECT) is a rapid acting and effective treatment for both major depressive disorder (MDD) and bipolar disorder (BP). Both propofol and ketamine are commonly used anesthetic agents but recent clinical studies suggest that ketamine has rapid-acting antidepressant properties, itself, at sub-anesthetic doses. METHODS: A total of 77 inpatients (41 MDD and 36 BP) were randomly assigned to receive ECT with propofol (1mg/kg) anesthesia or with ketamine (0...
November 10, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29147024/comparison-of-r-ketamine-and-lanicemine-on-depression-like-phenotype-and-abnormal-composition-of-gut-microbiota-in-a-social-defeat-stress-model
#18
Youge Qu, Chun Yang, Qian Ren, Min Ma, Chao Dong, Kenji Hashimoto
Accumulating evidence suggests a key role of the gut-microbiota-brain axis in the antidepressant actions of certain compounds. Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, showed rapid and sustained antidepressant effects in treatment-resistant depressed patients. In contrast, another NMDAR antagonist, lanicemine, did not exhibit antidepressant effects in such patients. (R)-ketamine, the (R)-enantiomer of ketamine, has rapid-acting and long-lasting antidepressant effects in rodent models of depression...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138992/use-of-ketamine-in-elderly-patients-with-treatment-resistant-depression
#19
REVIEW
Carolina Medeiros da Frota Ribeiro, Patricio Riva-Posse
PURPOSE OF REVIEW: The purpose of this paper is to provide a review of the use of ketamine as an antidepressant for treatment-resistant depression (TRD) in the geriatric population. Available treatment options for late-life treatment-resistant depression are limited and include electroconvulsive therapy and transcranial magnetic stimulation as well as possible pharmacologic augmentation. Ketamine has been shown to be a promising treatment in TRD; however, data regarding the use of ketamine in the elderly includes only five case reports...
November 15, 2017: Current Psychiatry Reports
https://www.readbyqxmd.com/read/29137178/antidepressants-and-mood-stabilizers-novel-research-avenues-and-clinical-insights-for-bipolar-depression
#20
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
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