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Garima Shukla, Anupama Gupta, Priya Agarwal, Shivani Poornima
PURPOSE: Levetiracetam (LEV) is often chosen early in the treatment of refractory epilepsy; however, its adverse effects have largely been studied as part of clinical trials. Oxcarbazepine and valproate (VPA) are the other commonly used AEDs and, hence, serve as good comparators. This study was conducted to evaluate behavioral abnormalities and somnolence among patients with epilepsy being treated with LEV and/or OXC compared with those receiving VPA. METHOD: Data of consecutive patients attending our intractable epilepsy clinic over a 2 1/2-year period were reviewed, and patients with at least one seizure a month, who had been initiated on either or a combination of LEV, VPA, or OXC, were included for analysis...
October 15, 2016: Epilepsy & Behavior: E&B
Martin J Bobak, Matthew W Weber, Melissa A Doellman, Douglas R Schuweiler, Jeana M Athens, Steven A Juliano, Paul A Garris
Modafinil (MOD) exhibits therapeutic efficacy for treating sleep and psychiatric disorders, but its mechanism is incompletely understood. Compared to other psychostimulants inhibiting dopamine (DA) uptake, MOD weakly interacts with the dopamine transporter (DAT) and modestly elevates striatal dialysate DA, suggesting additional targets besides DAT. However, the ability of MOD to induce wakefulness is abolished with DAT knockout, conversely suggesting that DAT is necessary for MOD action. Another psychostimulant target, but one not established for MOD, is activation of phasic DA signaling...
October 12, 2016: Journal of Pharmacology and Experimental Therapeutics
S Cohen, G Ifergane, E Vainer, M A Matar, Z Kaplan, J Zohar, A A Mathé, H Cohen
Pharmacotherapeutic intervention during traumatic memory consolidation has been suggested to alleviate or even prevent the development of posttraumatic stress disorder (PTSD). We recently reported that, in a controlled, prospective animal model, depriving rats of sleep following stress exposure prevents the development of a PTSD-like phenotype. Here, we report that administering the wake-promoting drug modafinil to rats in the aftermath of a stressogenic experience has a similar prophylactic effect, as it significantly reduces the prevalence of PTSD-like phenotype...
October 11, 2016: Translational Psychiatry
Xavier Castells, Ruth Cunill, Clara Pérez-Mañá, Xavier Vidal, Dolors Capellà
BACKGROUND: Cocaine dependence is a severe disorder for which no medication has been approved. Like opioids for heroin dependence, replacement therapy with psychostimulants could be an effective therapy for treatment. OBJECTIVES: To assess the effects of psychostimulants for cocaine abuse and dependence. Specific outcomes include sustained cocaine abstinence and retention in treatment. We also studied the influence of type of drug and comorbid disorders on psychostimulant efficacy...
September 27, 2016: Cochrane Database of Systematic Reviews
Christian Bellebaum, Lars Kuchinke, Patrik Roser
Modafinil is becoming increasingly popular as a cognitive enhancer. Research on the effects of modafinil on cognitive function have yielded mixed results, with negative findings for simple memory and attention tasks and enhancing effects for more complex tasks. In the present study we examined whether modafinil, due to its known effect on the dopamine level in the striatum, alters feedback-related choice behaviour. We applied a task that separately tests the choice of previously rewarded behaviours (approach) and avoidance of previously punished behaviours...
September 20, 2016: Journal of Psychopharmacology
Ole Kohler, Jesper Krogh, Ole Mors, Michael Eriksen Benros
Accumulating evidence supports an association between depression and inflammatory processes, a connection that seems to be bidirectional. Clinical trials have indicated antidepressant treatment effects for anti-inflammatory agents, both as add-on treatment and as monotherapy. In particular, nonsteroidal anti-inflammatory drugs (NSAIDs) and cytokine-inhibitors have shown antidepressant treatment effects compared to placebo, but also statins, poly-unsaturated fatty acids, pioglitazone, minocycline, modafinil, and corticosteroids may yield antidepressant treatment effects...
2016: Current Neuropharmacology
Rachael Sv Parker, P Parker
BACKGROUND: Fatigue in military operations leads to safety and operational problems due to a decrease in alertness and performance. The primary method of counteracting the effects of sleep deprivation is to increase nightly sleep time, which in operational situations is not always feasible. History has taught us that surgeons and surgical teams are finite resources that cannot operate on patients indefinitely. METHODS: A systematic review was conducted using the search terms 'sleep' and 'deprivation' examining the impact of sleep deprivation on cognitive performance in military surgical teams...
September 13, 2016: Journal of the Royal Army Medical Corps
Richard W Foltin, Margaret Haney, Gillinder Bedi, Suzette M Evans
This study examined how response effort (pressing a keyboard button) for cocaine and the value of an alternative reinforcer (opportunity to play a game of chance for money) combined with 'free' cocaine (with no response effort) affected cocaine choice when participants were maintained on modafinil or placebo. Nontreatment-seeking current cocaine smokers were enrolled in a placebo-controlled, double-blind, within-subject study comprising both inpatient and outpatient phases. Participants were maintained on placebo capsules (0mg/day) during one inpatient phase and modafinil (300mg/day) capsules during another inpatient phase in counter-balanced order...
September 1, 2016: Pharmacology, Biochemistry, and Behavior
Ayşe Kacar Bayram, Hüseyin Per, Sevda Ismailoğullari, Mehmet Canpolat, Hakan Gumus, Murat Aksu
Objective Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic and/or hypnopompic hallucinations, and sleep paralysis. It is one of the most important causes of excessive daytime sleepiness in the pediatric population. The aim of this study is to present the clinical and laboratory findings, and treatment results of pediatric patients with narcolepsy. Materials and Methods We studied five unrelated consecutive children with narcolepsy, focusing on clinical and laboratory features, the therapy and outcome over the 33-month follow-up period...
August 26, 2016: Neuropediatrics
Lucie Barateau, Régis Lopez, Yves Dauvilliers
Narcolepsy type 1 (NT1) and type 2 (NT2) are two rare neurological diseases, classified as central disorders of hypersomnolence. The pathophysiology of NT1 is well known; it is caused by the selective destruction of hypocretin (Hcrt) neurons, by a highly suspected autoimmune process. On the contrary, little is known about NT2 etiology, sharing with NT1 somnolence and signs of dysregulation of rapid eye movement (REM) sleep, but not cataplexy. Management strategies are rather codified, at least in adults, with a lifelong treatment required in NT1, whereas no pharmacological study focused only on NT2 patients, with sometimes spontaneous improvement or disappearance of their symptoms...
October 2016: Current Treatment Options in Neurology
Maddalena Mereu, Lauren E Chun, Thomas Prisinzano, Amy Hauck Newman, Jonathan L Katz, Gianluigi Tanda
Blockade of dopamine (DA) reuptake via the dopamine transporter (DAT) is a primary mechanism identified as underlying the therapeutic actions of (±)-modafinil (modafinil) and its R-enantiomer, armodafinil. Herein, we explored the neurochemical and behavioral actions of modafinil to better characterize its psychostimulant profile. Swiss-Webster mice were implanted with microdialysis probes in the nucleus accumbens shell (NAS) or core (NAC) to evaluate changes in DA levels related to acute reinforcing actions of drugs of abuse...
August 22, 2016: European Journal of Neuroscience
Julia L Chapman, Yasmina Serinel, Nathaniel S Marshall, Ronald R Grunstein
Excessive daytime sleepiness (EDS) is common in obstructive sleep apnea (OSA), but it is also common in the general population. When sleepiness remains after continuous positive airway pressure (CPAP) treatment of OSA, comorbid conditions or permanent brain injury before CPAP therapy may be the cause of the residual sleepiness. There is currently no broad approach to treating residual EDS in patients with OSA. Individual assessment must be made of comorbid conditions and medications, and of lifestyle factors that may be contributing to the sleepiness...
September 2016: Sleep Medicine Clinics
Yves Dauvilliers, Régis Lopez
Central hypersomnias include narcolepsy type 1, type 2 and idiopathic hypersomnia with daytime sleepiness excessive in the foreground of the clinical symptoms. Despite major advances in our understanding of the mechanisms of the narcolepsy type 1 with a low level of hypocretin-1 in cerebrospinal fluid, its current management is only symptomatic. The current management is also only symptomatic for type 2 narcolepsy and idiopathic hypersomnia with an unknown pathophysiology. Treatment options may vary from a single drug targeting several symptoms or several drugs treating a specific symptom...
June 2016: La Revue du Praticien
Thomas Lillicrap, Venkatesh Krishnamurthy, John Attia, Michael Nilsson, Christopher R Levi, Mark W Parsons, Andrew Bivard
BACKGROUND: Fatigue is a common symptom in stroke survivors for which there is currently no proven therapy. Modafinil is a wakefulness-promoting agent with established benefits in other disease models. We aim to test if modafinil will improve patient's self-reported fatigue scores when compared to placebo and if therapy results in increased quality of life. METHODS/DESIGN: MIDAS is a phase II, single-centre, prospective, double-blinded, randomised, crossover trial of modafinil for the treatment of persistent fatigue in survivors of ischaemic stroke...
2016: Trials
Jorge Zimbron, Golam M Khandaker, Chiara Toschi, Peter B Jones, Emilio Fernandez-Egea
Metabolic complications are commonly found in people treated with clozapine. Reviews on the management of this problem have generally drawn conclusions by grouping different types of studies involving patients treated with various different antipsychotics. We carried out a systematic review and meta-analysis of pharmacological and non-pharmacological treatments for clozapine-induced obesity or metabolic syndrome. Two researchers independently searched PubMed and Embase for randomised controlled trials (RCTs) of treatments for clozapine-induced obesity or metabolic syndrome...
September 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Michael B Maksimowski, Rajesh R Tampi
BACKGROUND: The objective of this systematic review is to summarize data from published randomized controlled trials (RCTs) on the efficacy of stimulants for psychiatric symptoms in individuals with traumatic brain injury (TBI). METHODS: A literature search was conducted of 5 major databases (PubMed, MEDLINE, PsycINFO, Embase, and Cochrane Collaboration) that identified RCTs on the use of stimulants for human patients with a diagnosis of TBI. RESULTS: A total of 176 articles were identified, of which 18 matched the inclusion criteria and were reviewed in their entirety...
August 2016: Annals of Clinical Psychiatry: Official Journal of the American Academy of Clinical Psychiatrists
Yohei Sagawa, Masatoshi Sato, Noriaki Sakai, Sachiko Chikahisa, Shintaro Chiba, Takashi Maruyama, Junki Yamamoto, Seiji Nishino
Prostaglandin (PG)D2 is an endogenous sleep substance, and a series of animal studies reported that PGD2 or PGD2 receptor (DP1) agonists promote sleep, while DP1 antagonists promote wakefulness. This suggests the possibility of use of PG DP1 antagonists as wake-promoting compounds. We therefore evaluated the wake-promoting effects of ONO-4127Na, a DP1 antagonist, in a mouse model of narcolepsy (i.e., orexin/ataxin-3 transgenic mice) and compared those to effects of modafinil. ONO-4127Na perfused in the basal forebrain (BF) area potently promoted wakefulness in both wild type and narcoleptic mice, and the wake-promoting effects of ONO-4127Na at 2...
November 2016: Neuropharmacology
Susan Willavize, Jill Fiedler-Kelly, Elizabeth Ludwig, Lingling Guan
Population pharmacokinetic models for armodafinil and its major metabolites, R-modafinil acid and modafinil sulfone, were developed and selected covariates were investigated. Data from 583 healthy subjects and patients with bipolar I disorder in 11 phase 1-3 studies (8027 concentrations) of armodafinil, given as single or multiple once-daily doses (50-400 mg tablet or capsule), were pooled. A previously developed one-compartment model with first-order absorption, without covariate effects, was initially applied to pooled phase 1 and 2 data...
July 19, 2016: Journal of Clinical Pharmacology
Corinna Roschlau, Angeline Votteler, Wolfgang Hauber
Here we tested in rats effects of the procognitive drugs modafinil and methylphenidate on post-acquisition performance in an object-location paired-associates learning (PAL) task. Modafinil (32; 64 mg/kg) was without effect, while higher (9 mg/kg) but not lower (4.5 mg/kg) doses of methylphenidate impaired PAL performance. Likewise, higher but not lower doses of amphetamine (0.4; 0.8 mg/kg) and MK-801 (0.08; 0.12 mg/kg) decreased PAL performance. Impaired PAL performance induced by methylphenidate, amphetamine, and MK801 most likely reflects compromised cognitive function, e...
August 2016: Learning & Memory
Emma Beard, Lion Shahab, Damian M Cummings, Susan Michie, Robert West
A wide range of support is available to help smokers to quit and to aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications with (1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and (2) 24 alternative products: cytisine (novel outside Central and Eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e...
October 2016: CNS Drugs
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