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Kelei Li, Jiaomei Li, Jiaojiao Gu, Xiaofei Guo, Tianlin Gao, Duo Li
Sodium valproate (VPA) is an anti-epileptic drug, but has a strong embryotoxicity due to its induced disturbance of folate-homocysteine (Hcy) metabolism and fatty acid metabolism. The aim of the present study was to investigate whether polyunsaturated fatty acid (PUFA) intake during pregnancy can relieve the embryotoxicity of VPA. VPA (dose: 500 mg kg-1, concentration: 38.5 mg ml-1) was intraperitoneally injected into pregnant mice on day 8.5 of gestation (E8.5d). PUFA intake significantly decreased fetal mortality and NTD incidence induced by VPA: n-3 long chain PUFAs (n-3 LCPUFAs) in fish oil had the best decreasing effect, followed by C18:3n-3 in flaxseed oil and then C18:2n-6 in corn oil...
March 21, 2018: Food & Function
Lanlan Zhang, Chengzhong Wang, Wei Li
Objective: To evaluate clinical efficacy, safety, and tolerability of levetiracetam as mono- or adjunctive therapy in the treatment of children and adolescents with epilepsy. Materials and methods: We performed a meta-analysis of randomized controlled trials published from January 2007 to December 2016 in the databases Web of Science, Medline, Embase, Cochrane Library, and PubMed, Bing, Baidu, Google Scholar, Chinese National Knowledge Infrastructure (CNKI), and Wanfang Data...
2018: Neuropsychiatric Disease and Treatment
Xinyue Zhang, Lichao Sun, Li Cui, Weihong Lin
Background Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in people with epilepsy. The pathogenesis of SUDEP is still unclear. The majority of SUDEP cases occur in intractable epilepsy, especially in the aftermath of a generalized tonic-clonic seizure. We report an atypical SUDEP case with infrequent seizures in frontal lobe epilepsy. Case Report A 14-year-old girl presented with a 13-year history of paroxysmal convulsions. She experienced three episodes within 6-10 months after birth...
January 1, 2018: Journal of International Medical Research
Fiona M Baumer, Brenda E Porter
BACKGROUND: Sunflower Syndrome describes reflex seizures - typically eyelid myoclonia with or without absence seizures - triggered when patients wave their hands in front of the sun. While valproate has been recognized as the best treatment for photosensitive epilepsy, many clinicians now initially treat with newer medications; the efficacy of these medications in Sunflower Syndrome has not been investigated. We reviewed all cases of Sunflower Syndrome seen at our institution over 15 years to describe the clinical course, electroencephalogram (EEG), and treatment response in these patients...
March 3, 2018: Epilepsy Research
Lone Baandrup, Bjørn H Ebdrup, Jesper Ø Rasmussen, Jane Lindschou, Christian Gluud, Birte Y Glenthøj
BACKGROUND: Prolonged treatment with benzodiazepines is common practice despite clinical recommendations of short-term use. Benzodiazepines are used by approximately 4% of the general population, with increased prevalence in psychiatric populations and the elderly. After long-term use it is often difficult to discontinue benzodiazepines due to psychological and physiological dependence. This review investigated if pharmacological interventions can facilitate benzodiazepine tapering. OBJECTIVES: To assess the benefits and harms of pharmacological interventions to facilitate discontinuation of chronic benzodiazepine use...
March 15, 2018: Cochrane Database of Systematic Reviews
Orrin Devinsky, Anup D Patel, Elizabeth A Thiele, Matthew H Wong, Richard Appleton, Cynthia L Harden, Sam Greenwood, Gilmour Morrison, Kenneth Sommerville
OBJECTIVE: To evaluate the safety and preliminary pharmacokinetics of a pharmaceutical formulation of purified cannabidiol (CBD) in children with Dravet syndrome. METHODS: Patients aged 4-10 years were randomized 4:1 to CBD (5, 10, or 20 mg/kg/d) or placebo taken twice daily. The double-blind trial comprised 4-week baseline, 3-week treatment (including titration), 10-day taper, and 4-week follow-up periods. Completers could continue in an open-label extension. Multiple pharmacokinetic blood samples were taken on the first day of dosing and at end of treatment for measurement of CBD, its metabolites 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD, and antiepileptic drugs (AEDs; clobazam and metabolite N -desmethylclobazam [N-CLB], valproate, levetiracetam, topiramate, and stiripentol)...
March 14, 2018: Neurology
Arnaud Boyer, Eddy Pasquier, Pascale Tomasini, Joseph Ciccolini, Laurent Greillier, Nicolas Andre, Fabrice Barlesi, Celine Mascaux
Drug repurposing is the use of known drugs for new indications. Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. So far, few treatments have been approved in this disease. However, its incidence is expected to increase significantly, particularly in developing countries. Consequently, drug repurposing appears as an attractive strategy for drug development in MPM, since the known pharmacology and safety profile based on previous approvals of repurposed drugs allows for faster time-to-market for patients and lower treatment cost...
March 31, 2018: European Respiratory Review: An Official Journal of the European Respiratory Society
Jose de Leon, Edoardo Spina
PURPOSE OF REVIEW: Patients with bipolar disorder are frequently treated with polypharmacy. This article should provide clinicians with an understanding of how polypharmacy can contribute to pharmacokinetic and pharmacodynamic drug-drug interactions (DDIs). RECENT FINDINGS: The pharmacokinetics and pharmacodynamics of lithium and other mood stabilizers (valproate, lamotrigine, carbamazepine, oxcarbazepine, and eslicarbazepine), antipsychotics, and selective serotonin reuptake inhibitors (SSRIs) were reviewed and summarized in the first four tables describing their pharmacokinetic and pharmacodynamic mechanisms...
March 12, 2018: Current Psychiatry Reports
Sophie Dupont
Catamenial epilepsy, defined as the exacerbation of the frequency of seizures in a given phase of the menstrual cycle, affects 35% of women. In women with catamenial epilepsy with perimenstrual seizures, progesterone therapy may be effective. In case of enzyme inducer AEDs, hormonal contraception is deprecated (estroprogestative or progestative pill, progestative implant, patches or hormonal rings). Because of its high malformative teratogenic potential, its possible depressive cognitive effects and the autistic risk, sodium valproate is not indicated during pregnancy...
March 8, 2018: La Presse Médicale
Katherine Elizabeth Triplett, Ronan Murray, Matthew Anstey
A 51-year-old female presented with acute confusion associated with a non-specific headache and lethargy. The patient's history included bipolar disorder on valproate and recent travel to northern Vietnam. The patient was subsequently found to have hyperammonaemia as well as a urinary tract infection and bacteraemia with Klebsiellapneumoniae The patient was presumed to have a multifactorial non-cirrhotic hyperammonaemic encephalopathy due to a combination of a urinary tract infection and bacteraemia with K...
March 9, 2018: BMJ Case Reports
Himani Prajapati, Dinesh Kansal, Rajan Negi
Valproate-related pedal edema is usually regarded as a problem occurring after long-term administration of valproate. Valproate has been a drug of choice for the treatment of generalized or partial seizures as monotherapy or adjunctive therapy, bipolar disorder, for the prophylaxis of migraine headache in adults. This case report described patient-acquiring bilateral pedal edema after long-term use of magnesium valproate. Discontinuing valproate resulted in rapid improvement of the condition. This adverse reaction to the best of our knowledge is first reported a case of bilateral pedal edema cause by magnesium valproate in low dose...
September 2017: Indian Journal of Pharmacology
Lauri J Virta, Reetta Kälviäinen, Kirsti Villikka, Tapani Keränen
BACKGROUND: Documented teratogenic effects of valproate (VPA) prompted restrictions of its use in females of childbearing age in 2014. We investigated possible annual changes in the outpatient use of VPA in Finland during 2008-2016 with a special focus in women. METHODS: We identified all outpatients with VPA purchases between 2008 and 2016 categorizing users due to epilepsy, bipolar disorder or miscellaneous indications. Temporal trends in the annual prevalence rates of VPA use were estimated using Poisson regression analyses...
March 6, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Bushra Parveen, Manjari Tripathi, Divya Vohora
Long-term anti-epileptic drug (AED) therapy compromises bone health. Though vitamin-D deficiency is proposed to be involved, it alone is not held responsible. This accounts for investigating other mechanisms in bone accrual. Recent studies have shown modulation of inhibitors of wnt pathway, sclerostin and dickkopf-1 (DKK-1), in glucocorticoids-induced osteoporosis. We investigated whether AED monotherapy modulates wnt inhibitors in Indian women with epilepsy. Women of age > 20-40 years with the diagnosis of epilepsy and receiving AEDs (carbamazepine, valproate and levetiracetam) for at least a year were enrolled...
March 5, 2018: Basic & Clinical Pharmacology & Toxicology
Sieta T de Vries, Maartje J M van der Sar, Anna Marie Coleman, Yvette Escudero, Alfonso Rodríguez Pascual, Miguel-Ángel Maciá Martínez, Amelia Cupelli, Ilaria Baldelli, Ivana Šipić, Adriana Andrić, Line Michan, Petra Denig, Peter G M Mol
INTRODUCTION: National competent authorities (NCAs) use Direct Healthcare Professional Communications (DHPCs) to communicate new drug safety issues to healthcare professionals (HCPs). More knowledge is needed about the effectiveness of DHPCs and the extent to which they raise awareness of new safety issues among HCPs. OBJECTIVE: The objective was to assess and compare general practitioners' (GPs'), cardiologists', and pharmacists' familiarity with DHPCs as communication tools, their awareness of specific drug safety issues, and the sources through which they had become aware of the specific issues...
March 2, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
Mila Lovrić, Ivana Čajić, Željka Petelin Gadže, Iva Klarica Domjanović, Nada Božina
AIM: To estimate the effect size of concomitant antiepileptic therapy on the concentrations of lamotrigine, a drug often prescribed in combination with other antiepileptic drugs (AED), which can act as enzyme inducers or inhibitors. METHODS: A total of 304 patients with epilepsy, aged 18-70 years, were divided into a lamotrigine monotherapy group and groups receiving lamotrigine with AEDs that act as enzyme inducers, enzyme inhibitors, or both. We compared lamotrigine monotherapy serum concentrations with those where lamotrigine was administered with a metabolic inhibitor valproate, metabolic inducers carbamazepine, oxcarbazepine, phenobarbital, phenytoin, or topiramate, and both an inducer and an inhibitor...
February 28, 2018: Croatian Medical Journal
Rodrigo Pérez-Esparza, Nelcy Oñate-Cadena, Jesús Ramírez-Bermúdez, Mariana Espínola-Nadurille
Hyperammonemic encephalopathy secondary to the use of valproate is rare without evidence of hepatotoxicity, and it usually presents with confusion, agitation, irritability, cognitive disturbances, lethargy, coma, and death. We present the case of a 21-year-old woman presenting with catatonia as a manifestation of hyperammonemic encephalopathy that resolved with the normalization of ammonia and suspension of valproate.
March 2018: Neurologist
Muhammad S Zafar, Alejandra M Stewart, David N Toupin, Aaron M Cook, Robert J Baumann
OBJECTIVE: This study describes the use of continuous intravenous valproate as an abortive therapy for pediatric status migrainosus. BACKGROUND: Intravenous valproate as a bolus dose has been shown to be an effective abortive therapy for status migrainosus in children; however, Valproate's pharmacokinetic profile suggests that it would be safer and more therapeutic as a continuous infusion. This dosing strategy results in less serum concentration fluctuations, more consistent therapeutic effects, and less adverse effects...
March 2018: Neurologist
M Crettenand, A O Rossetti, T Buclin, U Winterfeld
BACKGROUND: Knowledge about the passage of various antiepileptic drugs into breast milk and its consequences for the infant is limited. Faced with this uncertainty, breastfeeding is often discouraged for these patients. The aim of this study was to comprehensively review the available data regarding antiepileptic drugs during breastfeeding, to compare these data with information provided by the summary of product characteristics (SmPCs), and to provide recommendations for the use of these drugs in breastfeeding women...
February 27, 2018: Der Nervenarzt
Jesse Fishman, Linda Kalilani, Yan Song, Elyse Swallow, Imane Wild
BACKGROUND: Unexpected breakthrough seizures resulting from suboptimal antiepileptic drug (AED) dosing during the titration period, as well as adverse events resulting from rapid AED titration, may influence the titration schedule and significantly increase health care resource use (HRU) and health care costs. OBJECTIVE: To assess the relationship between AEDs, HRU, and costs during AED titration and maintenance. METHODS: Practicing neurologists were recruited from a nationwide panel to provide up to 3 patient records each for this retrospective medical chart review...
February 27, 2018: Journal of Managed Care & Specialty Pharmacy
Usama Bin Zubair, Humza Mumtaz, Sawera Mansoor
Profound deafness is a lifelong impairment, leading to the physical disability as well as poor psychological adjustment. We herein present a mental health disorder rarely seen among the patients of profound deafness. A 16-year deaf and dumb girl, previously treated for depression, presented with unusual laughter, irritability, flight of ideas, decreased sleep, ideas of self importance, and decreased social functioning and educational performance. These problems were understood by the parents via sign language, who interpreted them to the interviewer...
March 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
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