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https://www.readbyqxmd.com/read/28323284/altered-peripheral-immune-profiles-in-treatment-resistant-depression-response-to-ketamine-and-prediction-of-treatment-outcome
#1
D D Kiraly, S R Horn, N T Van Dam, S Costi, J Schwartz, S Kim-Schulze, M Patel, G E Hodes, S J Russo, M Merad, D V Iosifescu, D S Charney, J W Murrough
A subset of patients with depression have elevated levels of inflammatory cytokines, and some studies demonstrate interaction between inflammatory factors and treatment outcome. However, most studies focus on only a narrow subset of factors in a patient sample. In the current study, we analyzed broad immune profiles in blood from patients with treatment-resistant depression (TRD) at baseline and following treatment with the glutamate modulator ketamine. Serum was analyzed from 26 healthy control and 33 actively depressed TRD patients free of antidepressant medication, and matched for age, sex and body mass index...
March 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28322276/identifying-fast-onset-antidepressants-using-rodent-models
#2
M J Ramaker, S C Dulawa
Depression is a leading cause of disability worldwide and a major contributor to the burden of suicide. A major limitation of classical antidepressants is that 2-4 weeks of continuous treatment is required to elicit therapeutic effects, prolonging the period of depression, disability and suicide risk. Therefore, the development of fast-onset antidepressants is crucial. Preclinical identification of fast-onset antidepressants requires animal models that can accurately predict the delay to therapeutic onset. Although several well-validated assay models exist that predict antidepressant potential, few thoroughly tested animal models exist that can detect therapeutic onset...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28318897/efficacy-of-off-label-augmentation-in-unipolar-depression-a-systematic-review-of-the-evidence
#3
REVIEW
Julia Kleeblatt, Felix Betzler, Laura L Kilarski, Tom Bschor, Stephan Köhler
Treatment of unipolar depression with currently available antidepressants is still unsatisfactory. Augmentation with lithium or second generation antipsychotics is an established practice in non-responders to antidepressant monotherapy, but is also associated with a substantial non-response rate and with non-tolerance. Based on a systematic review of the literature, including meta-analyses, randomized controlled trials (RCTs), non-randomized comparative studies and case studies, off-label augmentation agents (administered in addition to an antidepressant, without FDA approval for treatment of MDD) were identified and evaluated regarding their efficacy using levels of evidence...
March 16, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28317392/pharmacotherapy-of-major-depression-in-late-life-what-is-the-role-of-new-agents
#4
Kinjal Patel, Petal S Abdool, Tarek K Rajji, Benoit H Mulsant
Evidence on the pharmacotherapy of late-life major depressive disorder (LLD) is scant. Most of the recommendations in existing clinical guidelines are based on expert opinions, extrapolations from data obtained in younger patients, or theoretical considerations. AREAS COVERED This article summarizes the recommendations from existing clinical guidelines and recent reviews on the treatment of LLD. Next, it discusses the potential role of newer antidepressants -vilazodone, levomilnacipran, and vortioxetine- based on a systematic search of the literature published during the past five years...
March 20, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28303025/targeting-glutamate-signalling-in-depression-progress-and-prospects
#5
REVIEW
James W Murrough, Chadi G Abdallah, Sanjay J Mathew
Major depressive disorder (MDD) is severely disabling, and current treatments have limited efficacy. The glutamate N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine was recently repurposed as a rapidly acting antidepressant, catalysing the vigorous investigation of glutamate-signalling modulators as novel therapeutic agents for depressive disorders. In this Review, we discuss the progress made in the development of such modulators for the treatment of depression, and examine recent preclinical and translational studies that have investigated the mechanisms of action of glutamate-targeting antidepressants...
March 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28301174/differential-characteristics-of-ketamine-self-administration-in-the-olfactory-bulbectomy-model-of-depression-in-male-rats
#6
Zuzana Babinska, Jana Ruda-Kucerova
Ketamine has been extensively studied for its antidepressant potential, with promising results in both preclinical and clinical studies. However, concerns regarding its abuse liabilities greatly limit its potential to become an approved treatment for depression. Therefore, a better understanding the risks and benefits of ketamine use in depression is needed. This study aimed to assess the characteristics of operant intravenous (IV) ketamine self-administration and relapse-like behavior in the olfactory bulbectomy (OBX) model of depression in male rats...
March 16, 2017: Experimental and Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28294453/a-translational-approach-for-nmda-receptor-profiling-as-a-vulnerability-biomarker-for-depression-and-schizophrenia
#7
Handan Gunduz-Bruce, Joshua Kenney, Suravi Changlani, Aldo Peixoto, Ralitza Gueorguieva, Cheryl Leone, Nina Stachenfeld
Altered N-methyl-D-aspartate (NMDA) receptor activity and glutamate signaling may underlie the pathogenesis of both schizophrenia and depression in subgroups of patients. In schizophrenia, pharmacologic modeling, postmortem and imaging data suggest reduced NMDA signaling. In contrast, recent clinical trials demonstrating the efficacy of the NMDA antagonist ketamine in severely depressed patients suggest increased NMDA receptor signaling. We conducted a proof of concept study to assess whether there is any in vivo evidence for an inverse association in depression and schizophrenia with respect to the NMDA receptor function...
March 13, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28294051/further-evaluation-of-mechanisms-associated-with-the-antidepressant-like-signature-of-scopolamine-in-mice
#8
Anna E Martin, Douglas A Schober, Alexander Nikolayev, Vladimir V Tolstikov, Wesley H Anderson, Richard E Higgs, Ming-Shang Kuo, Anastasia Laksmanan, John T Catlow, Xia Li, Christian C Felder, Jeffrey M Witkin
Conventional antidepressants lack efficacy for many patients (treatment-resistant depression or TRD) and generally take weeks to produce full therapeutic response in others. Emerging data has identified certain drugs such as ketamine as rapidly-acting antidepressants for major depressive disorder and TRD. Scopolamine, a drug used to treat motion sickness and nausea, has also been demonstrated to function as a rapidly-acting antidepressant. The mechanisms associated with efficacy in TRD patients and rapid onset of action have been suggested to involve a-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and mammalian target of rapamycin (mTOR) signaling...
March 9, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28285863/low-dose-ketamine-use-in-the-emergency-department-a-new-direction-in-pain-management
#9
A Pourmand, M Mazer-Amirshahi, C Royall, R Alhawas, R Shesser
There is a need for alternative non-opioid analgesics for the treatment of acute, chronic, and refractory pain in the emergency department (ED). Ketamine is a fast acting N-methyl-d-aspartate (NMDA) receptor antagonist that provides safe and effective analgesia. The use of low dose ketamine (LDK) (<1mg/kg) provides sub-dissociative levels of analgesia and has been studied as an alternative and/or adjunct to opioid analgesics. We reviewed 11 studies using LDK either alone or in combination with opioid analgesics in the ED...
March 2, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28284350/ketamine-upregulates-enos-expression-in-human-astroglial-a172-cells-possible-role-in-its-antidepressive-properties
#10
Yael Yuhas, Shai Ashkenazi, Eva Berent, Abraham Weizman
Ketamine is a potent anti-depressive agent. Nitric oxide plays an essential role in neuronal transmission and cerebral blood flow and has been implicated in the pathophysiology of major depressive disorder as well as cardiovascular functioning. We investigated the effect of ketamine on eNOS expression in human A172 astroglial cells. Ketamine (50-500μM) increased eNOS expression at 4-24h in a concentration-dependent manner. This effect was mediated by NMDA receptor, Akt inhibition and ERK1/2 activation and was synergistically augmented by rapamycin...
April 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28275719/a-negative-allosteric-modulator-for-%C3%AE-5-subunit-containing-gaba-receptors-exerts-a-rapid-and-persistent-antidepressant-like-action-without-the-side-effects-of-the-nmda-receptor-antagonist-ketamine-in-mice
#11
Panos Zanos, Mackenzie E Nelson, Jaclyn N Highland, Samuel R Krimmel, Polymnia Georgiou, Todd D Gould, Scott M Thompson
New antidepressant pharmacotherapies that provide rapid relief of depressive symptoms are needed. The NMDA receptor antagonist ketamine exerts rapid antidepressant actions in depressed patients but also side effects that complicate its clinical utility. Ketamine promotes excitatory synaptic strength, likely by producing high-frequency correlated activity in mood-relevant regions of the forebrain. Negative allosteric modulators of GABA-A receptors containing α5 subunits (α5 GABA-NAMs) should also promote high-frequency correlated electroencephalogram (EEG) activity and should therefore exert rapid antidepressant responses...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28272497/the-nucleus-accumbens-and-ketamine-treatment-in-major-depressive-disorder
#12
Chadi G Abdallah, Andrea Jackowski, Ramiro Salas, Swapnil Gupta, João R Sato, Xiangling Mao, Jeremy D Coplan, Dikoma C Shungu, Sanjay J Mathew
Animal models of depression repeatedly showed stress-induced nucleus accumbens (NAc) hypertrophy. Recently, ketamine was found to normalize this stress-induced NAc structural growth. Here, we investigated NAc structural abnormalities in major depressive disorder (MDD) in two cohorts. Cohort A included a cross-sectional sample of 34 MDD and 26 healthy control (HC) subjects, with high-resolution magnetic resonance imaging (MRI) to estimate NAc volumes. Proton MR spectroscopy ((1)H MRS) was used to divide MDD subjects into two subgroups: glutamate-based depression (GBD) and non-GBD...
March 8, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28271731/ketamine-augmentation-rapidly-improves-depression-scores-in-inpatients-with-treatment-resistant-bipolar-depression
#13
Janusz K Rybakowski, Agnieszka Permoda-Osip, Alicja Bartkowska-Sniatkowska
OBJECTIVE: To study the clinical effect of a single ketamine infusion, 0.5 mg/kg body weight, in bipolar depressive patients receiving mood-stabilising drugs, not improving on antidepressants. Previously, in such patients, we had found a correlation between clinical efficacy, serum brain-derived neurotrophic factor and vitamin B12 levels and a rapid improvement in neurocognitive performance. METHODS: The study included 53 patients (13 men, 40 women), aged 22-81 years, receiving ≥1 mood-stabilising medications of the first and/or second generation...
March 8, 2017: International Journal of Psychiatry in Clinical Practice
https://www.readbyqxmd.com/read/28257514/analysis-of-print-news-media-framing-of-ketamine-treatment-in-the-united-states-and-canada-from-2000-to-2015
#14
Melvyn W B Zhang, Ying X Hong, Syeda F Husain, Keith M Harris, Roger C M Ho
OBJECTIVES: There are multifaceted views on the use of ketamine, a potentially addictive substance, to treat mental health problems. The past 15 years have seen growing media coverage of ketamine for medical and other purposes. This study examined the print news media coverage of medical and other uses of ketamine in North America to determine orientations and trends over time. METHODS: Print newspaper coverage of ketamine from 2000 to 2015 was reviewed, resulting in 43 print news articles from 28 North American newspapers...
2017: PloS One
https://www.readbyqxmd.com/read/28254962/ketamine-as-the-anaesthetic-for-electroconvulsive-therapy-the-kanect-randomised-controlled-trial
#15
Gordon Fernie, James Currie, Jennifer S Perrin, Caroline A Stewart, Virginica Anderson, Daniel M Bennett, Steven Hay, Ian C Reid
BackgroundKetamine has recently become an agent of interest as an acute treatment for severe depression and as the anaesthetic for electroconvulsive therapy (ECT). Subanaesthetic doses result in an acute reduction in depression severity while evidence is equivocal for this antidepressant effect with anaesthetic or adjuvant doses. Recent systematic reviews call for high-quality evidence from further randomised controlled trials (RCTs).AimsTo establish if ketamine as the anaesthetic for ECT results in fewer ECT treatments, improvements in depression severity ratings and less memory impairment than the standard anaesthetic...
March 2, 2017: British Journal of Psychiatry: the Journal of Mental Science
https://www.readbyqxmd.com/read/28250331/elucidation-of-the-role-of-dorsal-raphe-serotonergic-neurons-in-mood-regulation-using-pharmacological-and-viral-vector-based-approaches
#16
Kazuki Nagayasu
 Growing evidence indicates that serotonergic neurons play a crucial role in brain function and dysfunction, such as in major depressive disorder. However, the complexity of serotonergic projections severely hampers the elucidation of their precise mechanisms. Here we summarize our recent studies on the effects of ketamine and olanzapine, which have been reported to be effective in treatment-resistant depression, on dorsal raphe nucleus serotonergic neurons, using microdialysis, electrophysiology experiments, and slice cultures...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28246760/-side-effects-of-pain-therapy-sufficient-analgesia-without-unnecessary-complications
#17
F Greul, A Zimmer, W Meißner
Interventions of acute and chronic pain treatment are associated with risks. Therefore, it is important to know about treatment side effects in order to avoid unnecessary complications and therapy interruption. This knowledge, however, is not to prevent/abandon this treatment altogether. Rather, it is intended to use pain treatment interventions rationally. The following article is to deepen the knowledge of unintended effects of analgetic treatments. Moreover, it will help find an optimal pain therapy in terms of efficacy and tolerable risks as well as limitations...
February 28, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28236848/the-fibrinolytic-system-a-new-target-for-treatment-of-depression-with-psychedelics
#18
R D Idell, G Florova, A A Komissarov, S Shetty, R B S Girard, S Idell
Current understanding of the neurobiology of depression has grown over the past few years beyond the traditional monoamine theory of depression to include chronic stress, inflammation and disrupted synaptic plasticity. Tissue plasminogen activator (tPA) is a key factor that not only promotes fibrinolysis via the activation of plasminogen, but also contributes to regulation of synaptic plasticity and neurogenesis through plasmin-mediated activation of a probrain derived neurotrophic factor (BDNF) to mature BDNF...
March 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28228087/beyond-ketamine-new-approaches-to-the-development-of-safer-antidepressants
#19
Shigeyuki Chaki
Ketamine has been reported to exert rapid and sustained antidepressant effects in patients with depression, including patients with treatment-resistant depression. However, ketamine has several drawbacks such as psychotomimetic/dissociative symptoms, abuse potential and neurotoxicity, all of which prevent its routine use in daily clinical practice. Therefore, development of novel agents with fewer safety and usage concerns for the treatment of depression has been actively investigated. From this standpoint, searching for active substances (stereoisomers and metabolites) and agents acting on the N-methyl-D-aspartate (NMDA) receptor have recently gained much attention...
February 20, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28222822/electroconvulsive-therapy-with-s-ketamine-anesthesia-for-catatonia-in-coexisting-depression-and-dementia
#20
Zsuzsa Litvan, Martin Bauer, Siegfried Kasper, Richard Frey
Information on efficacy and safety of electroconvulsive therapy in patients with dementia is sparse. The current case report describes a patient suffering from severe depression and dementia who received electroconvulsive therapy with S-ketamine anesthesia at our psychiatric intensive care unit for the treatment of her therapy-resistant catatonic stupor. The patient's condition improved remarkably through the treatment. By the end of 16 electroconvulsive therapy sessions, her catatonic symptoms remitted entirely, her affect was brighter and she performed markedly better at the cognitive testing...
February 22, 2017: International Psychogeriatrics
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