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https://www.readbyqxmd.com/read/29736744/antidepressant-efficacy-and-tolerability-of-ketamine-and-esketamine-a-critical-review
#1
REVIEW
P Molero, J A Ramos-Quiroga, R Martin-Santos, E Calvo-Sánchez, L Gutiérrez-Rojas, J J Meana
Ketamine and its enantiomer S-ketamine (esketamine) are promising candidates to produce a rapid-onset antidepressant effect in treatment-resistant depression. Ketamine causes continued blockade of the glutamate N-methyl-D-aspartate (NMDA) receptor, though this might not primarily mediate the antidepressant effect. Alternative hypotheses include selectivity for the NMDA receptor subtype containing the NMDA receptor subunit 2B (NR2B), inhibition of the phosphorylation of the eukaryotic elongation factor 2 (eEF2) kinase, increased expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrKB), and activation of the mammalian target of rapamycin (mTOR) signaling pathway, alongside other independent actions attributed to the ketamine metabolism to R-hydroxynorketamine (R-HNK)...
May 7, 2018: CNS Drugs
https://www.readbyqxmd.com/read/29661389/esketamine-counters-opioid-induced-respiratory-depression
#2
K Jonkman, E van Rijnsoever, E Olofsen, L Aarts, E Sarton, M van Velzen, M Niesters, A Dahan
BACKGROUND: Opioids can produce life-threatening respiratory depression. This study tested whether subanaesthetic doses of esketamine stimulate breathing in an established human model of opioid-induced respiratory depression. METHODS: In a study with a randomised, double blind, placebo controlled, crossover design, 12 healthy, young volunteers of either sex received a dose escalating infusion of esketamine (cumulative dose 40 mg infused in 1 h) on top of remifentanil-induced respiratory depression...
May 2018: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29661378/differential-role-of-nitric-oxide-in-the-psychedelic-symptoms-induced-by-racemic-ketamine-and-esketamine-in-human-volunteers
#3
K Jonkman, R van der Schrier, M van Velzen, L Aarts, E Olofsen, E Sarton, M Niesters, A Dahan
BACKGROUND: Animal studies suggest that N-methyl-d-aspartate receptor (NMDAR) hypofunction and subsequent decline in intracellular nitric oxide (NO) are responsible for development of ketamine-induced psychedelic symptoms. To examine this mechanism in humans, we administered the NO donor sodium nitroprusside during infusion of racemic ketamine (RS-ketamine), containing equal amounts of S(+)- and R(-)-ketamine isomers, or esketamine, containing just the S(+)-isomer. METHODS: In this randomised, double blind, placebo-controlled crossover study, healthy volunteers were treated with sodium nitroprusside 0...
May 2018: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29656663/efficacy-and-safety-of-intranasal-esketamine-for-the-rapid-reduction-of-symptoms-of-depression-and-suicidality-in-patients-at-imminent-risk-for-suicide-results-of-a-double-blind-randomized-placebo-controlled-study
#4
Carla M Canuso, Jaskaran B Singh, Maggie Fedgchin, Larry Alphs, Rosanne Lane, Pilar Lim, Christine Pinter, David Hough, Gerard Sanacora, Husseini Manji, Wayne C Drevets
OBJECTIVE: The authors compared the efficacy of standard-of-care treatment plus intranasal esketamine or placebo for rapid reduction of symptoms of major depression, including suicidality, among individuals at imminent suicide risk. METHOD: In a double-blind, multicenter, proof-of-concept study, 68 participants were randomly assigned to receive esketamine (84 mg) or placebo twice weekly for 4 weeks, in addition to comprehensive standard-of-care treatment. The primary efficacy endpoint was change in score from baseline to 4 hours after initial dose on the Montgomery-Åsberg Depression Rating Scale (MADRS)...
April 16, 2018: American Journal of Psychiatry
https://www.readbyqxmd.com/read/29465478/glutamatergic-modulators-in-depression
#5
Ioline D Henter, Rafael Teixeira de Sousa, Carlos A Zarate
Both preclinical and clinical studies have implicated glutamatergic system dysfunction in the pathophysiology of mood disorders such as bipolar depression and major depressive disorder. In particular, rapid reductions in depressive symptoms have been noted in response to subanesthetic doses of the glutamatergic modulator ketamine in subjects with major depressive disorder or bipolar depression. These results have prompted the repurposing or development of other glutamatergic modulators, both as monotherapy or adjunctive to other therapies...
February 20, 2018: Harvard Review of Psychiatry
https://www.readbyqxmd.com/read/29392371/effect-of-intranasal-esketamine-on-cognitive-functioning-in-healthy-participants-a-randomized-double-blind-placebo-controlled-study
#6
Randall L Morrison, Maggie Fedgchin, Jaskaran Singh, Joop Van Gerven, Rob Zuiker, Kyoung Soo Lim, Peter van der Ark, Ewa Wajs, Liwen Xi, Peter Zannikos, Wayne C Drevets
BACKGROUND: The effect of intranasal esketamine on cognitive functioning in healthy participants is assessed in this study. METHODS: Twenty-four participants (19-49 years) were randomized to one of two treatment sequences in which either esketamine 84 mg or placebo was intranasally administered in a double-blind, two-period crossover design. Primary measures included five tests of Cogstate® computerized test battery assessed at 1 h predose and 40 min, 2, 4, and 6 h postdose...
April 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29282469/efficacy-and-safety-of-intranasal-esketamine-adjunctive-to-oral-antidepressant-therapy-in-treatment-resistant-depression-a-randomized-clinical-trial
#7
Ella J Daly, Jaskaran B Singh, Maggie Fedgchin, Kimberly Cooper, Pilar Lim, Richard C Shelton, Michael E Thase, Andrew Winokur, Luc Van Nueten, Husseini Manji, Wayne C Drevets
Importance: Approximately one-third of patients with major depressive disorder (MDD) do not respond to available antidepressants. Objective: To assess the efficacy, safety, and dose-response of intranasal esketamine hydrochloride in patients with treatment-resistant depression (TRD). Design, Setting, and Participants: This phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study was conducted in multiple outpatient referral centers from January 28, 2014, to September 25, 2015...
February 1, 2018: JAMA Psychiatry
https://www.readbyqxmd.com/read/29282452/the-promise-of-intranasal-esketamine-as-a-novel-and-effective-antidepressant
#8
Daniel S Quintana, Nils Eiel Steen, Ole A Andreassen
No abstract text is available yet for this article.
February 1, 2018: JAMA Psychiatry
https://www.readbyqxmd.com/read/29240569/paediatric-procedural-sedation-and-analgesia-by-emergency-physicians-in-a-country-with-a-recent-establishment-of-emergency-medicine
#9
Maybritt I Kuypers, Gaël J P Smits, Eva P Baerends, Erick Oskam, Eef P J Reijners, Lisette A A Mignot-Evers, Wendy A M H Thijssen, Frans B Plötz, Erik H M Korsten
OBJECTIVES: Paediatric patients receive less procedural sedation and analgesia (PSA) in the emergency department compared with adults, especially in countries where emergency medicine is at an early stage of development. The objectives of this study were to evaluate the adverse events and efficacy of paediatric PSA in a country with a recent establishment of emergency medicine and to describe which factors aided implementation. METHODS: This is a prospective, multicentre, observational study of paediatric patients undergoing PSA by the first trained emergency physicians (EPs) in The Netherlands...
December 13, 2017: European Journal of Emergency Medicine: Official Journal of the European Society for Emergency Medicine
https://www.readbyqxmd.com/read/29020995/sedation-with-propofol-during-ercp-is-the-combination-with-esketamine-more-effective-and-safer-than-with-alfentanil-study-protocol-for-a-randomized-controlled-trial
#10
Susanne Eberl, Lena Koers, Jeanin E van Hooft, Edwin de Jong, Thomas Schneider, Markus W Hollmann, Benedikt Preckel
BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a gastrointestinal procedure that requires a relatively motionless patient during the intervention. Deep sedation by intravenous propofol combined with an opioid has recently become the preferred sedation technique. However, when high doses of propofol are used, side effects, namely respiratory depression, may occur. Esketamine has hypnotic, analgesic, and sympathomimetic effects. Our assumption is that a combination of propofol with esketamine reduces the dosage of individual drugs, thereby minimizing sedation side effects while keeping the same satisfaction level of patients and endoscopists...
October 11, 2017: Trials
https://www.readbyqxmd.com/read/28940868/effects-of-esketamine-sedation-compared-to-morphine-analgesia-on-hydrostatic-reduction-of-intussusception-a-case-cohort-comparison-study
#11
Jascha A van de Bunt, Esther S Veldhoen, Rutger A J Nievelstein, Caroline C C Hulsker, Antonius N J Schouten, Maud Y A van Herwaarden
BACKGROUND: Hydrostatic or pneumatic reduction of intussusception is an invasive procedure that is stressful and may be painful for a child. Resistance of the child may increase the duration of the procedure and decrease success rate of reduction. Analgesia can help to reduce pain, but not necessarily resistance. General anesthesia increases success rate of reduction. However, it requires the presence of an anesthesiologist, and may lead to anesthesia-related complications. Procedural sedation with esketamine could be a safe alternative...
November 2017: Paediatric Anaesthesia
https://www.readbyqxmd.com/read/28790825/rapid-infusion-of-esketamine-for-unipolar-and-bipolar-depression-a-retrospective-chart-review
#12
Fernanda S Correia-Melo, Felipe C Argolo, Lucas Araújo-de-Freitas, Gustavo Carneiro Leal, Flávio Kapczinski, Acioly Luiz Lacerda, Lucas C Quarantini
BACKGROUND: This study evaluated efficacy and safety of intravenous subanesthetic doses of esketamine using an administration time of 10 minutes in patients with treatment-resistant depression and bipolar depression. METHODS: A retrospective chart review was conducted to identify patients who met the inclusion criteria for treatment-resistant depression and bipolar depression according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria, and these patients received rapid infusion of esketamine between June 2012 and December 2015...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28759464/pharmacokinetics-and-bioavailability-of-inhaled-esketamine-in-healthy-volunteers
#13
Kelly Jonkman, Andreas Duma, Erik Olofsen, Thomas Henthorn, Monique van Velzen, René Mooren, Liesbeth Siebers, Jojanneke van den Beukel, Leon Aarts, Marieke Niesters, Albert Dahan
BACKGROUND: Esketamine is traditionally administered via intravenous or intramuscular routes. In this study we developed a pharmacokinetic model of inhalation of nebulized esketamine with special emphasis on pulmonary absorption and bioavailability. METHODS: Three increasing doses of inhaled esketamine (dose escalation from 25 to 100 mg) were applied followed by a single intravenous dose (20 mg) in 19 healthy volunteers using a nebulizer system and arterial concentrations of esketamine and esnorketamine were obtained...
October 2017: Anesthesiology
https://www.readbyqxmd.com/read/28755104/the-effects-of-intranasal-esketamine-84-mg-and-oral-mirtazapine-30-mg-on-on-road-driving-performance-a-double-blind-placebo-controlled-study
#14
Aurora J A E van de Loo, Adriana C Bervoets, Loes Mooren, Noor H Bouwmeester, Johan Garssen, Rob Zuiker, Guido van Amerongen, Joop van Gerven, Jaskaran Singh, Peter Van der Ark, Maggie Fedgchin, Randall Morrison, Ewa Wajs, Joris C Verster
RATIONALE: The purpose of this study is to evaluate the single dose effect of intranasal esketamine (84 mg) compared to placebo on on-road driving performance. Mirtazapine (oral, 30 mg) was used as a positive control, as this antidepressant drug is known to negatively affect driving performance. METHODS: Twenty-six healthy volunteers aged 21 to 60 years were enrolled in this study. In the evening, 8 h after treatment administration, participants conducted the standardized 100-km on-road driving test...
November 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28733841/analgosedation-of-adult-patients-with-elevated-intracranial-pressure-survey-of-current-clinical-practice-in-austria
#15
Guenther Herzer, Claudia Mirth, Udo M Illievich, Wolfgang G Voelckel, Helmut Trimmel
BACKGROUND: Analgesia and sedation are key items in intensive care. Recently published S3 guidelines specifically address treatment of patients with elevated intracranial pressure. METHODS: The Austrian Society of Anesthesiology, Resuscitation and Intensive Care Medicine carried out an online survey of neurointensive care units in Austria in order to evaluate the current state of practice in the areas of analgosedation and delirium management in this high-risk patient group...
July 21, 2017: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/28682536/ketamine-for-depression-3-does-chirality-matter
#16
REVIEW
Chittaranjan Andrade
Ketamine is a racemic mixture of the enantiomers R-ketamine and S-ketamine (esketamine). S-ketamine has greater analgesic and anesthetic effects than R-ketamine and is less likely to cause psychotomimetic and other adverse effects. There is therefore an emerging interest favoring the use of S-ketamine over racemic ketamine when the drug is used for analgesia or anesthesia. This article examines preclinical and clinical literature on the antidepressant properties of S-ketamine. Animal data suggest potential advantages for R-ketamine over S-ketamine...
June 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28408985/new-drugs-in-psychiatry-focus-on-new-pharmacological-targets
#17
REVIEW
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
https://www.readbyqxmd.com/read/28194724/ketamine-and-beyond-investigations-into-the-potential-of-glutamatergic-agents-to-treat-depression
#18
REVIEW
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
https://www.readbyqxmd.com/read/28194274/moderate-to-deep-sedation-technique-using-propofol-and-ketamine-allowing-synchronised-breathing-for-magnetic-resonance-high-intensity-focused-ultrasound-mr-hifu-treatment-for-uterine-fibroids-a-pilot-study
#19
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
https://www.readbyqxmd.com/read/28092469/investigational-drugs-in-recent-clinical-trials-for-treatment-resistant-depression
#20
REVIEW
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
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