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Ketamine and treatment resistant depression

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https://www.readbyqxmd.com/read/28228087/beyond-ketamine-new-approaches-to-the-development-of-safer-antidepressants
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/27718369/change-in-cytokine-levels-is-not-associated-with-rapid-antidepressant-response-to-ketamine-in-treatment-resistant-depression
#16
Minkyung Park, Laura E Newman, Philip W Gold, David A Luckenbaugh, Peixiong Yuan, Rodrigo Machado-Vieira, Carlos A Zarate
Several pro-inflammatory cytokines have been implicated in depression and in antidepressant response. This exploratory analysis assessed: 1) the extent to which baseline cytokine levels predicted positive antidepressant response to ketamine; 2) whether ketamine responders experienced acute changes in cytokine levels not observed in non-responders; and 3) whether ketamine lowered levels of pro-inflammatory cytokines, analogous to the impact of other antidepressants. Data from double-blind, placebo-controlled studies of patients with major depressive disorder (MDD) or bipolar disorder (BD) who received a single infusion of sub-anesthetic dose ketamine were used (N = 80)...
January 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/27692010/exploring-a-post-traumatic-stress-disorder-paradigm-in-flinders-sensitive-line-rats-to-model-treatment-resistant-depression-ii-response-to-antidepressant-augmentation-strategies
#17
Sarel Jacobus Brand, Brian Herbert Harvey
OBJECTIVE: Post-traumatic stress disorder (PTSD) displays high co-morbidity with major depression and treatment-resistant depression (TRD). Earlier work demonstrated exaggerated depressive-like symptoms in a gene×environment model of TRD and an abrogated response to imipramine. We extended the investigation by studying the behavioural and monoaminergic response to multiple antidepressants, viz. venlafaxine and ketamine with/without imipramine. METHODS: Male Flinders sensitive line (FSL) rats, a genetic model of depression, were exposed to a time-dependent sensitisation (TDS) model of PTSD and compared with stress naive controls...
October 3, 2016: Acta Neuropsychiatrica
https://www.readbyqxmd.com/read/27660449/the-interactive-effects-of-ketamine-and-magnesium-upon-depressive-like-pathology
#18
Sara Razmjou, Darcy Litteljohn, Chris Rudyk, Shuaib Syed, Melanie Clarke, Rowan Pentz, Zach Dwyer, Shawn Hayley
Approximately one-third of patients with major depressive disorders (MDDs) are resistant to current treatment methods, and the majority of cases relapse at some point during therapy. This has resulted in novel treatments being adopted, including subanesthetic doses of ketamine, which affects aberrant neuroplastic circuits, glutamatergic signaling, and the production of brain-derived neurotrophic factor. Ketamine rapidly relieves depressive symptoms in treatment-resistant major depressive disorder patients with effects that last for up to 2 weeks even after a single administration...
2016: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/27656788/continuation-phase-intravenous-ketamine-in-adults-with-treatment-resistant-depression
#19
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
BACKGROUND: Little is known about the antidepressive effects of repeated intravenous ketamine infusions beyond the acute phase of treatment in patients with refractory depression. METHODS: Twelve subjects with treatment-resistant non-psychotic unipolar or bipolar major depression and suicidal ideation were given repeated (up to 6) thrice-weekly acute-phase intravenous infusions of ketamine (0.5mg/kg, administered over 100min). Those who remitted during acute-phase treatment received continuation-phase treatment that consisted of 4 weekly ketamine infusions, followed by 4 weeks of post-continuation phase follow-up (during which no further ketamine infusions were administered)...
December 2016: Journal of Affective Disorders
https://www.readbyqxmd.com/read/27648916/metabolomic-signatures-of-drug-response-phenotypes-for-ketamine-and-esketamine-in-subjects-with-refractory-major-depressive-disorder-new-mechanistic-insights-for-rapid-acting-antidepressants
#20
D M Rotroff, D G Corum, A Motsinger-Reif, O Fiehn, N Bottrel, W C Drevets, J Singh, G Salvadore, R Kaddurah-Daouk
Ketamine, at sub-anesthetic doses, is reported to rapidly decrease depression symptoms in patients with treatment-resistant major depressive disorder (MDD). Many patients do not respond to currently available antidepressants, (for example, serotonin reuptake inhibitors), making ketamine and its enantiomer, esketamine, potentially attractive options for treatment-resistant MDD. Although mechanisms by which ketamine/esketamine may produce antidepressant effects have been hypothesized on the basis of preclinical data, the neurobiological correlates of the rapid therapeutic response observed in patients receiving treatment have not been established...
September 20, 2016: Translational Psychiatry
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