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Ketamine and treatment resistant depression

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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/28294051/further-evaluation-of-mechanisms-associated-with-the-antidepressant-like-signature-of-scopolamine-in-mice
#2
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/28271731/ketamine-augmentation-rapidly-improves-depression-scores-in-inpatients-with-treatment-resistant-bipolar-depression
#3
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
#4
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/28250331/elucidation-of-the-role-of-dorsal-raphe-serotonergic-neurons-in-mood-regulation-using-pharmacological-and-viral-vector-based-approaches
#5
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/28228087/beyond-ketamine-new-approaches-to-the-development-of-safer-antidepressants
#6
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
#7
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
https://www.readbyqxmd.com/read/28138040/comparative-effects-of-ly3020371-a-potent-and-selective-mglu2-3-receptor-antagonist-and-ketamine-a-non-competitive-nmda-receptor-antagonist-in-rodents-evidence-supporting-use-for-the-treatment-of-depression
#8
Jeffrey M Witkin, Stephen Mitchell, Keith Wafford, Guy Carter, Gary Gilmour, Jennifer Li, Brian Eastwood, Carl Overshiner, Xia Li, Linda Rorick-Kehn, Kurt Rasmussen, Wesley Anderson, Alexander Nikolayev, Vladamir Tolstikov, Ming-Shang Kuo, John Catlow, Renhua Li, Stephen Smith, Charles Mitch, Paul Ornstein, Stephen Swanson, James Monn
The ability of the NMDA receptor antagonist ketamine to alleviate symptoms in patients suffering from treatment resistant depression (TRD) is well documented. In this report, we directly compare in vivo biological responses in rodents elicited by a recently discovered mGlu2/3 receptor antagonist (LY3020371) with those produced by ketamine. Both LY3020371 and ketamine increased the number of spontaneously active DA cells in the ventral tegmental area of anesthetized rats, increased O2 in the anterior cingulate cortex, promoted wakefulness, enhanced the efflux of biogenic amines in the prefrontal cortex, and produced antidepressant-related behavioral effects in SSRI-sensitive and -insensitive rodent models...
January 30, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28124853/ketamine-future-treatment-for-unresponsive-depression
#9
M Frere, J Tepper
Major Depressive Disorder (MDD) is a debilitating mental health condition which accounts for a significant portion of worldwide disability. Historically, the suggested pharmacotherapy to treat MDD have been monoaminergic-acting antidepressants, such as SSRIs or SNRIs. These drugs can provide relief, but often take weeks to noticeably improve depressive symptoms and are not always effective, leading to a condition known as Treatment-Resistant Depression (TRD). It is believed that 50% MDD sufferers in Ireland suffer from TRD, and thus the development of improved pharmacotherapies is necessary...
September 9, 2016: Irish Medical Journal
https://www.readbyqxmd.com/read/28097909/administration-of-ketamine-for-unipolar-and-bipolar-depression
#10
Christoph Kraus, Ulrich Rabl, Thomas Vanicek, Laura Carlberg, Ana Popovic, Marie Spies, Lucie Bartova, Gregor Gryglewski, Konstantinos Papageorgiou, Rupert Lanzenberger, Matthäus Willeit, Dietmar Winkler, Janusz K Rybakowski, Siegfried Kasper
OBJECTIVE: Clinical trials demonstrated that ketamine exhibits rapid antidepressant efficacy when administered in subanaesthetic dosages. We reviewed currently available literature investigating efficacy, response rates and safety profile. METHODS: Twelve studies investigating unipolar, seven on bipolar depression were included after search in medline, scopus and web of science. RESULTS: Randomized, placebo-controlled or open-label trials reported antidepressant response rates after 24 h on primary outcome measures at 61%...
March 2017: International Journal of Psychiatry in Clinical Practice
https://www.readbyqxmd.com/read/28092469/investigational-drugs-in-recent-clinical-trials-for-treatment-resistant-depression
#11
Ricardo P Garay, Carlos A Zarate, Thomas Charpeaud, Leslie Citrome, Christoph U Correll, Ahcène Hameg, Pierre-Michel Llorca
The authors describe the medications for treatment-resistant depression (TRD) in phase II/III of clinical development in the EU and USA and provide an opinion on how current treatment can be improved in the near future. Areas covered: Sixty-two trials were identified in US and EU clinical trial registries that included six investigational compounds in recent phase III development and 12 others in recent phase II clinical trials. Glutamatergic agents have been the focus of many studies. A single intravenous dose of the glutamatergic modulator ketamine produces a robust and rapid antidepressant effect in persons with TRD; this effect continues to remain significant for 1 week...
January 29, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28035869/comparative-efficacy-and-tolerability-of-pharmacological-and-somatic-interventions-in-adult-patients-with-treatment-resistant-depression-a-systematic-review-and-network-meta-analysis
#12
Katerina Papadimitropoulou, Carla Vossen, Andreas Karabis, Christina Donatti, Nicole Kubitz
OBJECTIVE: Major depressive disorder (MDD) affects about 10-15% of the general population in a lifetime. A considerable number of patients fail to achieve full symptom remission despite adequate treatment and are considered treatment resistant (TRD). The current study compared the relative efficacy and tolerability of pharmacological and somatic TRD interventions by means of a Bayesian network meta-analysis. RESEARCH DESIGN AND METHODS: An electronic literature search of MEDLINE, MEDLINE In-Process, EMBASE, PsycInfo, EconLit and Cochrane Library databases for trials published between September 2003 and September 2014 was conducted...
February 6, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/27965856/ketamine-for-depression-relapse-prevention-following-electroconvulsive-therapy-protocol-for-a-randomised-pilot-trial-the-keep-well-trial
#13
Martha Finnegan, Karen Ryan, Enda Shanahan, Andrew Harkin, Leslie Daly, Declan M McLoughlin
BACKGROUND: Major depressive disorder is a common debilitating illness that is the second leading contributor to the global burden of disease. Unfortunately, about 30 % of patients do not respond to adequate trials of antidepressants and/or psychotherapies. About 45-60 % of such treatment-resistant patients will remit with electroconvulsive therapy (ECT). However, relapse rates are high following ECT-38 % after 6 months. There is a need for better relapse prevention strategies. One possibility is to use ketamine, a competitive glutamate receptor antagonist used for anaesthesia...
2016: Pilot and Feasibility Studies
https://www.readbyqxmd.com/read/27888525/breaking-sad-unleashing-the-breakthrough-potential-of-ketamine-s-rapid-antidepressant-effects
#14
David Feifel
Preclinical Research The surprising results of a small clinical trial on the effects of low dose ketamine, a 65-year old anesthetic drug that is also used off-label for chronic pain and recreationally as a club drug, in eight depressed subjects unleashed the most significant advance in antidepressant drug development in decades. That study and subsequent ones have demonstrated that low dose, infused ketamine is able to induce a remission of depression in patients who have failed conventional medications, within 24 h...
December 2016: Drug Development Research
https://www.readbyqxmd.com/read/27886522/increase-in-pas-induced-neuroplasticity-after-a-treatment-course-of-intranasal-ketamine-for-depression-report-of-three-cases-from-a-placebo-controlled-trial
#15
Verònica Gálvez, Stevan Nikolin, Kerrie-Anne Ho, Angelo Alonzo, Andrew A Somogyi, Colleen K Loo
BACKGROUND: Animal studies suggest that neural plasticity may play a role in the antidepressant effects of a single ketamine dose. However, the potential effects of repeated ketamine treatments on human neuroplasticity are unknown. METHODS: This pilot RCT study measured plasticity-induced changes before and after a ketamine course, in three treatment-resistant depressed subjects, who were randomized to receive 8 intranasal treatments of 100mg ketamine or 4.5mg midazolam...
February 2017: Comprehensive Psychiatry
https://www.readbyqxmd.com/read/27836553/how-much-alcohol-is-in-ketamine-s-antidepressant-action
#16
REVIEW
Udo Bonnet
Ketamine is approved to start and maintain anaesthesia or analgesia. Ketamine is also known to be neurotoxic and an old drug of abuse. Numerous studies have proven a rapid and strong antidepressant response (AR) following parenteral sub-anaesthetic ketamine doses when applied the first time to patients with treatment resistant unipolar or bipolar major depression. This rapid and robust AR is encouraging, though short-lived (usually up to seven days). There is growing evidence that repeated und escalating ketamine administrations exert longer-lasting AR than single infusions...
January 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/27830574/inflammation-effects-on-brain-glutamate-in-depression-mechanistic-considerations-and-treatment-implications
#17
Ebrahim Haroon, Andrew H Miller
There has been increasing interest in the role of glutamate in mood disorders, especially given the profound effect of the glutamate receptor antagonist ketamine in improving depressive symptoms in patients with treatment-resistant depression. One pathway by which glutamate alterations may occur in mood disorders involves inflammation. Increased inflammation has been observed in a significant subgroup of patients with mood disorders, and inflammatory cytokines have been shown to influence glutamate metabolism through effects on astrocytes and microglia...
2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27815416/s-ketamine-rapidly-reverses-synaptic-and-vascular-deficits-of-hippocampus-in-genetic-animal-model-of-depression
#18
Maryam Ardalan, Gregers Wegener, Ali H Rafati, Jens R Nyengaard
BACKGROUND: The neurovascular plasticity of hippocampus is an important theory underlying major depression. Ketamine as a novel glutamatergic antidepressant drug can induce a rapid antidepressant effect within hours. In a mechanistic proof of this concept, we examined whether ketamine leads to an increase in synaptogenesis and vascularization within 24 hours after a single injection in a genetic rat model of depression. METHODS: Flinders Sensitive Line and Flinders Resistant Line rats were given a single intraperitoneal injection of ketamine (15 mg/kg) or saline...
December 8, 2016: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27759570/antidepressant-anxiolytic-and-procognitive-effects-of-subacute-and-chronic-ketamine-in-the-chronic-mild-stress-model-of-depression
#19
Mariusz Papp, Piotr Gruca, Magdalena Lason-Tyburkiewicz, Paul Willner
Ketamine is the prototype of a new generation of antidepressant drugs, which is reported in clinical studies to be effective in treatment-resistant patients, with an effect that appears within hours and lasts for a few days. Chronic mild stress (CMS) is a well-established and widely used animal model of depression, in which anhedonia, anxiogenesis and cognitive dysfunction can be observed reliably. Studies using acute or brief ketamine treatment following withdrawal from CMS have replicated the clinical finding of a rapid onset of antidepressant action...
February 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/27738380/treatment-resistant-depression-with-loss-of-antidepressant-response-rapid-acting-antidepressant-action-of-dextromethorphan-a-possible-treatment-bridging-molecule
#20
Edward C Lauterbach
Dextromethorphan (DM) may have ketamine-like rapid-acting, treatment-resistant, and conventional antidepressant effects.(1,2) This reports our initial experience with DM in unipolar Major Depressive Disorder (MDD). A patient with treatment-resistant MDD (failing adequate trials of citalopram and vortioxetine) with loss of antidepressant response (to fluoxetine and bupropion) twice experienced a rapid-acting antidepressant effect within 48 hours of DM administration and lasting 7 days, sustained up to 20 days with daily administration, then gradually developing labile loss of antidepressant response over the ensuing 7 days...
August 15, 2016: Psychopharmacology Bulletin
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