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Filippo Caraci, Gian Marco Leggio, Salvatore Salomone, Filippo Drago
The approval of psychotropic drugs with novel mechanisms of action has been rare in recent years. To address this issue, further analysis of the pathophysiology of neuropsychiatric disorders is essential for identifying new pharmacological targets for psychotropic medications. In this report, we detail drug candidates being examined as treatments for psychiatric disorders. Particular emphasis is placed on agents with novel mechanisms of action that are being tested as therapies for depression, schizophrenia, or Alzheimer's disease...
2017: F1000Research
Marc S Lener, Bashkim Kadriu, Carlos A Zarate
Clinical and preclinical studies suggest that dysfunction of the glutamatergic system is implicated in mood disorders such as major depressive disorder and bipolar depression. In clinical studies of individuals with major depressive disorder and bipolar depression, rapid reductions in depressive symptoms have been observed in response to subanesthetic-dose ketamine, an agent whose mechanism of action involves the modulation of glutamatergic signaling. The findings from these studies have prompted the repurposing and/or development of other glutamatergic modulators for antidepressant efficacy, both as monotherapy or as an adjunct to conventional monoaminergic antidepressants...
March 2017: Drugs
Hermanus H B Vaessen, F M Knuttel, J M M van Breugel, M E Ikink, J M Dieleman, M A A J van den Bosch, J T A Knape
BACKGROUND: Magnetic resonance high-intensity focused ultrasound (MR-HIFU) treatment for uterine fibroids is rapidly gaining popularity as a treatment modality. This procedure is generally uncomfortable, painful, and requires minimal or absence of movement and an MR-HIFU synchronised breathing pattern of the patient. Procedural sedation and analgesia protocols have become the standard practice in interventional radiology departments worldwide. The aim of this study was to explore if a sedation regimen with low-dose propofol and ketamine performed by trained non-medical sedation practitioners could result in relief of discomfort for the patient and in adequate working conditions for MR-HIFU treatment for uterine fibroids...
2017: Journal of Therapeutic Ultrasound
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...
June 2017: Expert Review of Neurotherapeutics
Eva Magdalena Korf, Volker Martin Tronnier, Jan Gliemroth, Jan Nils Küchler
We report a misinterpretation of bilateral mydriasis as blown pupils related to elevated intracranial pressure (ICP) under volatile sedation with isoflurane (Anesthetic Conserving Device [AnaConDa], Hudson RCI, Uppland Vasby, Sweden) in a 59-year-old patient with a severe traumatic brain injury with frontal contusion. The patient showed bilateral mydriasis and a missing light reflex 8 hours after changing sedation from intravenous treatment with midazolam and esketamine to volatile administration of isoflurane...
July 2017: Journal of Neurological Surgery. Part A, Central European Neurosurgery
Weili Zhu, Zengbo Ding, Yinan Zhang, Jie Shi, Kenji Hashimoto, Lin Lu
Major depression is a serious psychiatric disorder and remains a leading cause of disability worldwide. Conventional antidepressants take at least several weeks to achieve a therapeutic response and this lag period has hindered their ability to attain beneficial effects in depressed individuals at high risk of suicide. The non-competitive N-methyl-D-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in both rodents and humans. The emergence of ketamine as a fast-acting antidepressant provides promising new insights into the development of a rapid treatment response in patients with clinical depression...
December 2016: Neuroscience Bulletin
Gaël Jp Smits, Maybritt I Kuypers, Lisette Aa Mignot, Eef Pj Reijners, Erick Oskam, Karen Van Doorn, Wendy Amh Thijssen, Erik Hm Korsten
OBJECTIVE: To describe our experience performing ED procedural sedation in a country where emergency medicine (EM) is a relatively new specialty. METHODS: This is a prospective observational study of adult patients undergoing procedural sedation by emergency physicians (EPs) or EM residents in eight hospitals in the Netherlands. Data were collected on a standardised form, including patient characteristics, sedative and analgesic used, procedural success, adverse events (classified according to World SIVA) and rescue interventions...
April 2017: Emergency Medicine Journal: EMJ
Gin S Malhi, Yulisha Byrow, Frederick Cassidy, Andrea Cipriani, Koen Demyttenaere, Mark A Frye, Michael Gitlin, Sidney H Kennedy, Terence A Ketter, Raymond W Lam, Rupert McShane, Alex J Mitchell, Michael J Ostacher, Sakina J Rizvi, Michael E Thase, Mauricio Tohen
SUMMARY: The appeal of ketamine - in promptly ameliorating depressive symptoms even in those with non-response - has led to a dramatic increase in its off-label use. Initial promising results await robust corroboration and key questions remain, particularly concerning its long-term administration. It is, therefore, timely to review the opinions of mood disorder experts worldwide pertaining to ketamine's potential as an option for treating depression and provide a synthesis of perspectives - derived from evidence and clinical experience - and to consider strategies for future investigations...
May 2016: BJPsych Open
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
Anna Höflich, Andreas Hahn, Martin Küblböck, Georg S Kranz, Thomas Vanicek, Sebastian Ganger, Marie Spies, Christian Windischberger, Siegfried Kasper, Dietmar Winkler, Rupert Lanzenberger
Over the last years, a number of studies have been conducted to clarify the neurobiological correlates of ketamine application. However, comprehensive information regarding the influence of ketamine on cortical activity is still lacking. Using resting-state functional MRI and integrating pharmacokinetic information, a double-blind, randomized, placebo-controlled, crossover study was performed to determine the effects of ketamine on neuronal activation. During a 55 min resting-state fMRI scan, esketamine (Ketanest S(®)) was administered intravenously to 35 healthy volunteers...
August 30, 2016: Brain Structure & Function
Kenji Hashimoto, Takeharu Kakiuchi, Hiroyuki Ohba, Shingo Nishiyama, Hideo Tsukada
R-ketamine appears to be a potent, long-lasting and safer antidepressant, relative to esketamine (S-ketamine), since it might be free of psychotomimetic side effects. Using [(11)C]raclopride and positron emission tomography (PET), we investigated whether esketamine and R-ketamine can affect dopamine D2/3 receptor binding in the conscious monkey brain. A single infusion of esketamine (0.5 mg/kg), but not R-ketamine (0.5 mg/kg), caused a reduction of binding availability of dopamine D2/3 receptor in the monkey striatum...
March 2017: European Archives of Psychiatry and Clinical Neuroscience
Chun Yang, Mei Han, Ji-Chun Zhang, Qian Ren, Kenji Hashimoto
Clinical use of the rapid antidepressant drug ketamine is limited, due to psychotomimetic side effects. R-ketamine appears to be a potent, long-lasting and safer antidepressant, relative to S-ketamine (esketamine), since it is free of psychotomimetic side effects. Repeated, intermittent administration of esketamine (10mg/kg, once per week for 8-weeks), but not R-ketamine, caused loss of parvalbumin (PV)-immunoreactivity in the medial prefrontal cortex and hippocampus of mouse brains, regions associated with psychosis...
May 30, 2016: Psychiatry Research
Jaskaran B Singh, Maggie Fedgchin, Ella Daly, Liwen Xi, Caroline Melman, Geert De Bruecker, Andre Tadic, Pascal Sienaert, Frank Wiegand, Husseini Manji, Wayne C Drevets, Luc Van Nueten
BACKGROUND: The purpose of this study was to assess the efficacy and safety and to explore the dose response of esketamine intravenous (IV) infusion in patients with treatment-resistant depression (TRD). METHODS: This multicenter, randomized, placebo-controlled trial was conducted in 30 patients with TRD. Patients were randomly assigned 1:1:1 to receive an IV infusion of .20 mg/kg or .40 mg/kg esketamine or placebo over 40 minutes on day 1. The primary end point was change in Montgomery-Åsberg Depression Rating Scale total score from day 1 (baseline) to day 2...
September 15, 2016: Biological Psychiatry
H Javelot
Pharmacological treatment of acute anxiety still relies on benzodiazepines, while chronic anxiety disorders and depression are treated with different antidepressants, according to specific indications. The monoaminergic axis is represented by two families which are being developed: (i) serotonin-norepinephrine-dopamine reuptake inhibitors (SNDRI), also called triple reuptake inhibitors (TRI), for the treatment of depression (amitifadine), (ii) multimodal antidepressants for depression and anxiety disorders (generalized anxiety disorder mainly) (tedatioxetine, vortioxetine and vilazodone)...
March 2016: Annales Pharmaceutiques Françaises
C Yang, Y Shirayama, J-c Zhang, Q Ren, W Yao, M Ma, C Dong, K Hashimoto
Although the efficacy of racemate ketamine, a rapid onset and sustained antidepressant, for patients with treatment-resistant depression was a serendipitous finding, clinical use of ketamine is limited, due to psychotomimetic side effects and abuse liability. Behavioral and side-effect evaluation tests were applied to compare the two stereoisomers of ketamine. To elucidate their potential therapeutic mechanisms, we examined the effects of these stereoisomers on brain-derived neurotrophic factor (BDNF)-TrkB signaling, and synaptogenesis in selected brain regions...
September 1, 2015: Translational Psychiatry
Mie K Lam, Merel Huisman, Robbert J Nijenhuis, Maurice Aaj van den Bosch, Max A Viergever, Chrit Tw Moonen, Lambertus W Bartels
BACKGROUND: Magnetic resonance (MR)-guided high-intensity focused ultrasound has emerged as a clinical option for palliative treatment of painful bone metastases, with MR thermometry (MRT) used for treatment monitoring. In this study, the general image quality of the MRT was assessed in terms of signal-to-noise ratio (SNR) and apparent temperature variation. Also, MRT artifacts were scored for their occurrence and hampering of the treatment monitoring. METHODS: Analyses were performed on 224 MRT datasets retrieved from 13 treatments...
2015: Journal of Therapeutic Ultrasound
Dan Bing, Sze Chim Lee, Dario Campanelli, Hao Xiong, Masahiro Matsumoto, Rama Panford-Walsh, Stephan Wolpert, Mark Praetorius, Ulrike Zimmermann, Hanqi Chu, Marlies Knipper, Lukas Rüttiger, Wibke Singer
BACKGROUND: Accumulating evidence suggests that tinnitus may occur despite normal auditory sensitivity, probably linked to partial degeneration of the cochlear nerve and damage of the inner hair cell (IHC) synapse. Damage to the IHC synapses and deafferentation may occur even after moderate noise exposure. For both salicylate- and noise-induced tinnitus, aberrant N-methyl-d-aspartate (NMDA) receptor activation and related auditory nerve excitation have been suggested as origin of cochlear tinnitus...
2015: Cellular Physiology and Biochemistry
Robert H Howland
Seven topics previously described in this column are revisited. The use of quantitative electroencephalography has been shown in a prospective study to be effective for predicting antidepressant treatment response. A novel antidepressant drug, agomelatine, has generated much controversy, and its development for the U.S. market was discontinued. A long awaited revised system for categorizing the safety of medications during pregnancy and lactation has finally been published by the Food and Drug Administration...
January 2015: Journal of Psychosocial Nursing and Mental Health Services
Sivera A A Berben, Hennie H L M Kemps, Pierre M van Grunsven, Joke A J Mintjes-de Groot, Robert T M van Dongen, Lisette Schoonhoven
Pain management for trauma patients is a neglected aspect in the chain of emergency care in general practices, ambulance services, mobile trauma teams and in hospital emergency departments. The aim of the guideline 'Pain management for trauma patients in the chain of emergency care' is to provide pain management recommendations for trauma patients in the chain of emergency care and thereby improve the assistance that patients receive. Paracetamol is the treatment of choice, if necessary with additional use of NSAIDs or opioids; NSAIDs can be administered in the absence of contra-indications, but should be avoided in cases where the patient history is unknown; fentanyl and morphine can be given for severe pain during emergency care, esketamine can be considered in patients with severe pain and hypovolemia...
2011: Nederlands Tijdschrift Voor Geneeskunde
Er-Ping Zhang, Friedrich Hoffmann
BACKGROUND: Despite technical difficulties caused by the small dimensions, scientific and economic considerations stimulated activities in the murine keratoplasty model. Delicate surgery requires stable anesthesia with rapid postoperative waking. METHODS: For corneal transplantation, all animals were intraperitoneally injected with 0.08 ml of a 1:8 mixture of 2% xylazine and 2.5% esketamine hydrochloride. Thus they all received 0.18 mg of xylazine and 1.8 mg of ketamine...
January 2005: Graefe's Archive for Clinical and Experimental Ophthalmology
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