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Ketamine and depression

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https://www.readbyqxmd.com/read/28097909/administration-of-ketamine-for-unipolar-and-bipolar-depression
#1
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%...
January 18, 2017: International Journal of Psychiatry in Clinical Practice
https://www.readbyqxmd.com/read/28092469/investigational-drugs-in-recent-clinical-trials-for-treatment-resistant-depression
#2
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 US 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 16, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28087979/rapid-antidepressant-effect-of-ketamine-correlates-with-astroglial-plasticity-in-the-hippocampus
#3
Maryam Ardalan, Ali H Rafati, Jens R Nyengaard, Gregers Wegener
BACKGROUND AND PURPOSE: Astroglia contributes to the pathophysiology of major depression and the action of antidepressant drugs through modulating synaptic plasticity; therefore, present study investigated whether fast antidepressant action of ketamine is reflected in the rapid alteration of the astrocytes morphology in a genetic animal model of depression. EXPERIMENTAL APPROACH: S-Ketamine (15 mg/kg) or saline was administered as a single injection to Flinders Line (FSL/FRL) rats...
January 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28079589/in-vogue-ketamine-for-neuroprotection-in-acute-neurologic-injury
#4
Josh D Bell
Neurologic deterioration following acute injury to the central nervous system may be amenable to pharmacologic intervention, although, to date, no such therapy exists. Ketamine is an anesthetic and analgesic emerging as a novel therapy for a number of clinical entities in recent years, including refractory pain, depression, and drug-induced hyperalgesia due to newly discovered mechanisms of action and new application of its known pharmacodynamics. In this focused review, the evidence for ketamine as a neuroprotective agent in stroke, neurotrauma, subarachnoid hemorrhage, and status epilepticus is highlighted, with a focus on its applications for excitotoxicity, neuroinflammation, and neuronal hyperexcitability...
January 10, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28057557/anesthetics-inhibit-extracellular-signal-regulated-kinase1-2-phosphorylation-via-nmda-receptor-phospholipase-c-and-protein-kinase-c-in-mouse-hippocampal-slices
#5
Gao Haiying, Han Mingjie, Zhang Lingyu, Wang Qingxiang, Wang Haisong, Zhang Bingxi
BACKGROUND: Extracellular signal-regulated kinase 1/2 (ERK1/2) has been implicated in learning and memory; however, whether intravenous anesthetics modulate ERK1/2 remains unknown. The aim of this study was to examine the effect of several intravenous anesthetics on the phosphorylation of ERK1/2 in the hippocampus of adult mice. METHODS: Western blotting was used to examine cellular levels of phosphorylated and unphosphorylated ERK1/2 in mouse hippocampus slices, which were incubated with or without anesthetics including propofol, etomidate, ketamine and midazolam, a protein kinase C (PKC) activator or inhibitor, or phospholipase C (PLC) activator or inhibitor...
January 3, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28043834/sub-anesthetic-doses-of-ketamine-exert-antidepressant-like-effects-and-upregulate-the-expression-of-glutamate-transporters-in-the-hippocampus-of-rats
#6
Xianlin Zhu, Gang Ye, Zaiping Wang, Jie Luo, Xuechao Hao
Clinical studies on the role of the glutamatergic system in the pathogenesis of depression found that ketamine induces an antidepressant response, but the molecular mechanisms remain unclear. The present study investigated the effects of sub-anesthetic doses of ketamine on the glutamate reuptake function in the rat hippocampus. Chronic unpredictable mild stress (CUMS) was applied to construct animal models of depression. Sixty adult male Sprague-Dawley rats were randomly assigned to 5 groups and received a different regimen of CUMS and ketamine (10, 25, and 50mg/kg) treatment...
December 30, 2016: Neuroscience Letters
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 trial published between September 2003 and September 2014 was conducted...
December 30, 2016: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28024909/dose-response-characteristics-of-intravenous-ketamine-on-dissociative-stereotypy-locomotion-sensorimotor-gating-and-nociception-in-male-sprague-dawley-rats
#8
Kennett D Radford, Thomas Y Park, Bong Hyo Lee, Sean Moran, Lisa A Osborne, Kwang H Choi
Clinicians administer subanesthetic intravenous (IV) ketamine infusions for treatment of refractory depression, chronic pain, and post-traumatic stress disorder in humans. However, ketamine is administered via the subcutaneous (SC) or intraperitoneal (IP) routes to rodents in most pre-clinical research, which may limit translational application. The present study characterized the dose-response of a subanesthetic IV ketamine bolus (2 and 5mg/kg) and 1-h infusion (5, 10, and 20mg/kg/h) on dissociative stereotypy, locomotion, sensorimotor gating, and thermal nociception in male Sprague-Dawley rats...
December 24, 2016: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/27979642/severe-carisoprodol-withdrawal-after-a-14-year-addiction-and-acute-overdose
#9
Kathy T Vo, Howard Horng, Craig G Smollin, Neal L Benowitz
BACKGROUND: Carisoprodol, a centrally acting muscle relaxant with a high abuse potential, has barbiturate-like properties at the GABA-A receptor, leading to central nervous system depression and desired effects. Its tolerance and dependence has been previously demonstrated in an animal model, and withdrawal has been described in several recent case reports. Many cases can be effectively managed with a short course of benzodiazepines or antipsychotic agents. However, abrupt cessation in a patient with a history of long-term and high-dose carisoprodol abuse may result in symptoms that are more difficult for providers to treat...
December 12, 2016: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/27966330/therapeutic-effects-of-intralipid-and-medialipid-emulsionsin-a-rat-model-of-verapamil-toxicity
#10
Fatma Akgün Şahin, Sıdıka Hülya Çelebi, İrfan Güngör, Demet Coşkun, Elif Ergüven Kaya
BACKGROUND/AIM: Lipid emulsions are promising as a potential new therapy for severe verapamil overdose. Our purpose is to draw attention to the choice of solution by investigating the efficacy of intralipid 20% or medialipid 20% in verapamil overdose. MATERIALS AND METHODS: Eighteen adult Sprague Dawley rats were randomly divided into three groups: control (saline; Group C), intralipid 20% (Group I), and medialipid 20% (Group M). Rats were anesthetized with ketamine...
November 17, 2016: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/27965856/ketamine-for-depression-relapse-prevention-following-electroconvulsive-therapy-protocol-for-a-randomised-pilot-trial-the-keep-well-trial
#11
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/27965560/ketamine-50-years-of-modulating-the-mind
#12
REVIEW
Linda Li, Phillip E Vlisides
Ketamine was introduced into clinical practice in the 1960s and continues to be both clinically useful and scientifically fascinating. With considerably diverse molecular targets and neurophysiological properties, ketamine's effects on the central nervous system remain incompletely understood. Investigators have leveraged the unique characteristics of ketamine to explore the invariant, fundamental mechanisms of anesthetic action. Emerging evidence indicates that ketamine-mediated anesthesia may occur via disruption of corticocortical information transfer in a frontal-to-parietal ("top down") distribution...
2016: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/27960559/investigational-drugs-for-treating-major-depressive-disorder
#13
Ashish Dhir
Treatment of patients suffering from major depression could be highly challenging for psychiatrists. Intractability as well as relapse is commonly seen among these patients, leading to functional impairment and poor quality of life. The present review discusses some of the novel investigational drugs that are under pre-clinical or clinical phases in the treatment of major depression. Areas covered: Molecules belonging to different classes such as triple reuptake inhibitors, opioid receptors, ionotropic and metabotropic glutamate receptors, and neurotrophin in the treatment of major depression are covered in this article...
January 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27933365/ketamine-decreases-sensitivity-of-male-rats-to-misleading-negative-feedback-in-a-probabilistic-reversal-learning-task
#14
Michal Rychlik, Eva Bollen, Rafal Rygula
RATIONALE: Depression is characterized by an excessive attribution of value to negative feedback. This imbalance in feedback sensitivity can be measured using the probabilistic reversal-learning (PRL) task. This task was initially designed for clinical research, but introduction of its rodent version provides a new and much needed translational paradigm to evaluate potential novel antidepressants. OBJECTIVES: In the present study, we aimed at evaluating the effects of a compound showing clear antidepressant properties-ketamine (KET)-on the sensitivity of rats to positive and negative feedback in the PRL paradigm...
December 8, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27929610/antisuicidal-response-following-ketamine-infusion-is-associated-with-decreased-nighttime-wakefulness-in-major-depressive-disorder-and-bipolar-disorder
#15
Jennifer L Vande Voort, Elizabeth D Ballard, David A Luckenbaugh, Rebecca A Bernert, Erica M Richards, Mark J Niciu, Lawrence T Park, Rodrigo Machado-Vieira, Wallace C Duncan, Carlos A Zarate
OBJECTIVE: Insomnia and disrupted sleep are associated with increased risk of suicide. The N-methyl-D-aspartate antagonist ketamine has been associated with reduced suicidal thoughts, but the mechanism of action is unknown. This study sought to evaluate differences in nocturnal wakefulness in depressed individuals who did and did not have an antisuicidal response to ketamine. METHODS: Thirty-four participants with baseline suicidal ideation diagnosed with either DSM-IV major depressive disorder (n = 23) or bipolar depression (n = 11) between 2006 and 2013 completed nighttime electroencephalography (EEG) the night before and the night after a single ketamine infusion (0...
December 6, 2016: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/27926528/ketamine-rapidly-relieves-acute-suicidal-ideation-in-cancer-patients-a-randomized-controlled-clinical-trial
#16
Wei Fan, HaiKou Yang, Yong Sun, Jun Zhang, Guangming Li, Ying Zheng, Yi Liu
This study was designed to examine the rapid antidepressant effects of single dose ketamine on suicidal ideation and overall depression level in patients with newly-diagnosed cancer. Forty-two patients were enrolled into the controlled trial and randomized into two groups: ketamine group and midazolam group. Patients from the two groups received a sub-anesthetic dose of racemic ketamine hydrochloride or midazolam. Suicidal ideation score, measured with the Beck Scale and suicidal part of the Montgomery-Asberg Depression Rating Scale, significantly decreased on day 1 and day 3 in ketamine-treated patients when compared to those treated with midazolam...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27908572/significant-treatment-effect-of-add-on-ketamine-anesthesia-in-electroconvulsive-therapy-in-depressive-patients-a-meta-analysis
#17
Dian-Jeng Li, Fu-Chiang Wang, Che-Sheng Chu, Tien-Yu Chen, Chia-Hung Tang, Wei-Cheng Yang, Philip Chik-Keung Chow, Ching-Kuan Wu, Ping-Tao Tseng, Pao-Yen Lin
Add-on ketamine anesthesia in electroconvulsive therapy (ECT) has been studied in depressive patients in several clinical trials with inconclusive findings. Two most recent meta-analyses reported insignificant findings with regards to the treatment effect of add-on ketamine anesthesia in ECT in depressive patients. The aim of this study is to update the current evidence and investigate the role of add-on ketamine anesthesia in ECT in depressive patients via a systematic review and meta-analysis. We performed a thorough literature search of the PubMed and ScienceDirect databases, and extracted all relevant clinical variables to compare the antidepressive outcomes between add-on ketamine anesthesia and other anesthetics in ECT...
November 28, 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27892759/the-use-of-ketamine-in-ect-anaesthesia-a-systematic-review-and-critical-commentary-on-efficacy-cognitive-safety-and-seizure-outcomes
#18
Verònica Gálvez, Lucy McGuirk, Colleen K Loo
OBJECTIVES: This review will discuss ECT efficacy and cognitive outcomes when using ketamine as an ECT anaesthetic compared to other anaesthetics, taking into account important moderator variables that have often not been considered to date. It will also include information on safety and other ECT outcomes (seizure threshold and quality). METHODS: A systematic search through MEDLINE, PubMed, PsychINFO, Cochrane Databases and reference lists from retrieved articles was performed...
November 28, 2016: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/27888525/breaking-sad-unleashing-the-breakthrough-potential-of-ketamine-s-rapid-antidepressant-effects
#19
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
#20
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...
November 4, 2016: Comprehensive Psychiatry
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