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Ketamine and depression

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https://www.readbyqxmd.com/read/29350129/new-medications-for-treatment-resistant-depression-a-brief-review-of-recent-developments
#1
Michael E Thase
There is a great unmet need for new medications with novel mechanisms of action that can effectively treat patients who do not benefit from standard antidepressant therapies. After a period in which it seemed as if the pharmaceutical pipeline for new antidepressants was going dry, the past decade has witnessed renewed interest, beginning with discovery of the antidepressant effects of ketamine. This article briefly highlights more recent research on ketamine and other investigational antidepressants.
December 2017: CNS Spectrums
https://www.readbyqxmd.com/read/29339294/ketamine-for-the-treatment-of-addiction-evidence-and-potential-mechanisms
#2
REVIEW
I Ivan Ezquerra-Romano, W Lawn, E Krupitsky, C J A Morgan
Ketamine is a dissociative anaesthetic drug which acts on the central nervous system chiefly through antagonism of the n-methyl-d-aspartate (NMDA) receptor. Recently, ketamine has attracted attention as a rapid-acting anti-depressant but other studies have also reported its efficacy in reducing problematic alcohol and drug use. This review explores the preclinical and clinical research into ketamine's ability to treat addiction. Despite methodological limitations and the relative infancy of the field, results thus far are promising...
January 12, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29313138/do-psychoactive-drugs-have-a-therapeutic-role-in-compulsivity-studies-on-schedule-induced-polydipsia
#3
Elena Martín-González, Ángeles Prados-Pardo, Santiago Mora, Pilar Flores, Margarita Moreno
RATIONALE: Clinical studies have shown that some psychoactive recreational drugs have therapeutic applications in anxiety, depression, and schizophrenia. However, to date, there are few studies on the therapeutic potential efficacy of recreational drugs in compulsive neuropsychiatric disorders. OBJECTIVES: We explored the therapeutic potential of different psychoactive and psychedelic drugs in a preclinical model of compulsive behavior. METHODS: Outbred male Wistar rats were selected as either high (HD) or low (LD) drinkers according to their behavior in schedule-induced polydipsia (SIP)...
January 8, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29305627/antagonism-at-the-nr2b-subunit-of-nmda-receptors-induces-increased-connectivity-of-the-prefrontal-and-subcortical-regions-regulating-reward-behavior
#4
Natalia Gass, Robert Becker, Markus Sack, Adam J Schwarz, Jonathan Reinwald, Alejandro Cosa-Linan, Lei Zheng, Christian Clemm von Hohenberg, Dragos Inta, Andreas Meyer-Lindenberg, Wolfgang Weber-Fahr, Peter Gass, Alexander Sartorius
RATIONALE: Evidence indicates that ketamine's rapid antidepressant efficacy likely results from its antagonism of NR2B-subunit-containing NMDA receptors (NMDAR). Since ketamine equally blocks NR2A- and NR2B-containing NMDAR, and has affinity to other receptors, NR2B-selective drugs might have improved therapeutic efficiency and side effect profile. OBJECTIVES: We aimed to compare the effects of (S)-ketamine and two different types of NR2B-selective antagonists on functional brain networks in rats, in order to find common circuits, where their effects intersect, and that might explain their antidepressant action...
January 5, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29277196/can-we-confidently-use-ketamine-as-a-clinical-treatment-for-depression
#5
Colleen Loo
No abstract text is available yet for this article.
January 2018: Lancet Psychiatry
https://www.readbyqxmd.com/read/29276735/circuit-and-synaptic-mechanisms-of-repeated-stress-perspectives-from-differing-contexts-duration-and-development
#6
REVIEW
Kevin G Bath, Scott J Russo, Kristen E Pleil, Eric S Wohleb, Ronald S Duman, Jason J Radley
The current review is meant to synthesize research presented as part of a symposium at the 2016 Neurobiology of Stress workshop in Irvine California. The focus of the symposium was "Stress and the Synapse: New Concepts and Methods" and featured the work of several junior investigators. The presentations focused on the impact of various forms of stress (altered maternal care, binge alcohol drinking, chronic social defeat, and chronic unpredictable stress) on synaptic function, neurodevelopment, and behavioral outcomes...
December 2017: Neurobiology of Stress
https://www.readbyqxmd.com/read/29275607/-effect-of-perioperative-multi-day-low-dose-ketamine-infusion-on-prevention-of-postmastectomy-pain-syndrome
#7
Q B Lou, K Nan, F F Xiang, X Z Chen, W S Zhu, X T Zhang, J Li
Objective: To investigate the effects of multi-day low dose ketamine infusion for postmastectomy pain syndrome (PMPS) after breast cancer surgery. Methods: This study was a prospective randomized controlled trial. From June 2015 to May 2016 in Affiliated Yiwu Hospital of Wenzhou Medical University, 66 patients with breast cancer surgery were randomly divided into control group (group C) and ketamine group (group K). Patients in group K were infused with 0.5 mg/kg of ketamine mixed in 250 ml of 0.9% normal saline in 1 h daily for 7 days...
December 12, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29273457/the-effects-of-ketamine-on-sexual-behavior-anxiety-and-locomotion-in-female-rats
#8
Fay A Guarraci, Chantal M F Gonzalez, Devon Lucero, Paige D Womble, Heba Abdel-Rahim, Jennie DeVore, Marcela Nicole Kunkel, Emma Quadlander, Morgan Stinnett, Jessica Boyette-Davis
The present study characterized the effects of ketamine on sexual behavior and anxiety in female rats. In Experiment 1, female subjects received an injection of ketamine (10.0mg/kg) or saline 30min prior to a sexual partner-preference test during which each female subject was given the opportunity to interact with a female stimulus or a sexually vigorous male stimulus. Immediately afterwards, female subjects were tested for locomotion in an open field test. Ketamine-treated subjects spent significantly more time with the male stimulus than saline-treated subjects...
December 19, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29249803/possible-role-of-the-gut-microbiota-brain-axis-in-the-antidepressant-effects-of-r-ketamine-in-a-social-defeat-stress-model
#9
Chun Yang, Youge Qu, Yuko Fujita, Qian Ren, Min Ma, Chao Dong, Kenji Hashimoto
Accumulating evidence suggests that the gut microbiota-brain axis plays a role in the pathogenesis of depression, thereby contributing to the antidepressant actions of certain compounds. (R)-ketamine has a greater potency and longer-lasting antidepressant effects than (S)-ketamine. Here, we investigated whether the gut microbiota plays a role in the antidepressant effects of these two ketamine enantiomers. The role of the gut microbiota in the antidepressant effects of ketamine enantiomers in a chronic social defeat stress (CSDS) model of depression was examined using 16S ribosomal RNA gene sequencing of fecal samples...
December 18, 2017: Translational Psychiatry
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
#10
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
#11
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
#12
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
#13
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
#14
REVIEW
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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