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M Baulac, W Byrnes, P Williams, S Borghs, E Webster, M De Backer, P Dedeken
OBJECTIVE: To assess prospectively the effectiveness of lacosamide (LCM) added to levetiracetam (LEV) after down-titration of a concomitant sodium channel blocker (SCB) among patients with focal epilepsy not adequately controlled on LEV and SCB. METHODS: In this open-label trial, LCM was initiated at 100 mg/day and up-titrated to 200-600 mg/day over 9 weeks; SCB down-titration started when LCM dose reached 200 mg/day. Patients remained on stable LCM/LEV doses for 12 weeks' maintenance (21-week treatment period)...
October 6, 2016: Acta Neurologica Scandinavica
Francesco Brigo, Nicola Luigi Bragazzi, Raffaele Nardone, Eugen Trinka
BACKGROUND: Brivaracetam (BRV), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) have been recently marketed as adjunctive treatments for focal onset seizures. To date, no randomized controlled trial (RCT) has directly compared BRV with ESL, LCM, or PER. PURPOSE: To compare BRV with the other add-on AEDs in patients with uncontrolled focal epilepsy, estimating their efficacy and tolerability through an adjusted, common-reference based indirect comparison meta-analysis...
September 24, 2016: Seizure: the Journal of the British Epilepsy Association
Mirosław Zagaja, Marta Andres-Mach, Paweł Patrzylas, Daniel Pyrka, Monika Szpringer, Magdalena Florek-Łuszczki, Dorota Żółkowska, Krystyna Skalicka-Woźniak, Jarogniew J Łuszczki
The aim of this study was to determine the effects of xanthotoxin (8-methoxypsoralen) on the protective action of 5 various second- and third-generation antiepileptic drugs (i.e., lacosamide, lamotrigine, oxcarbazepine, pregabalin and topiramate) in the mouse maximal electroshock-induced seizure model. Seizure activity was evoked in adult male albino Swiss mice by a current (25mA, 500V, 0.2s stimulus duration) delivered via auricular electrodes. Drug-related adverse effects were determined in the chimney, grip-strength and passive avoidance tests...
October 1, 2016: Fitoterapia
Krzysztof Kamiński
The multifunctional ligands approach is one of the modern strategies in drug discovery especially in relation to diseases with complex pathomechanism, such as Alzheimer's disease, cancer, or epilepsy. According to this method different molecules with given biological properties are combined in a single chemical entity to provide complex and broad activity. Thus, with the aim of obtaining more efficacious antiepileptic drugs (AEDs) that will suppress different types of human seizures, the new hybrid anticonvulsants based on the pyrrolidine-2,5-dione scaffold have been described...
September 27, 2016: Current Topics in Medicinal Chemistry
Giuseppe d'Orsi, Maria Grazia Pascarella, Tommaso Martino, Elena Carapelle, Francesca Pacillo, Maria Teresa Di Claudio, Daniela Mancini, Marina Trivisano, Carlo Avolio, Luigi M Specchio
PURPOSE: to evaluate the efficacy and safety of intravenous (IV) lacosamide (LCM) in the treatment of seizure clusters (SC) and status epilepticus (SE) in hospitalized adult patients. METHODS: we prospectively analyzed treatment response, seizure outcome, and adverse effects of IV LCM in 38 patients with seizure emergencies (15 with SC, 23 with SE) during a hospital stay. The loading dose of IV LCM was 200-400mg and the maintenance dose was 200-400mg daily. Response to IV LCM was evaluated within 20min, 4h and 24h of LCM infusion...
September 22, 2016: Seizure: the Journal of the British Epilepsy Association
Johan Zelano, Elinor Ben-Menachem
Epileptic emergencies are frequently encountered and include ictal events as status epilepticus or seizure clusters, and non-ictal situations like postictal psychosis or acute drug side effects. The aim of this review was to describe recent pharmacological advances in the treatment of epileptic emergencies. Areas covered: Based on clinically relevant questions, a literature search was performed. The search showed that most pharmacological advances have been made in management of status epilepticus, where substantial literature has accumulated on several AEDs with potentially less side-effects than the traditional choices...
October 14, 2016: Expert Opinion on Pharmacotherapy
Zhen Hong, Yushi Inoue, Weiping Liao, Hongmei Meng, Xuefeng Wang, Wenmin Wang, Liemin Zhou, Liming Zhang, Xinlu Du, Frank Tennigkeit
OBJECTIVE: To evaluate the efficacy and safety of adjunctive lacosamide treatment in Chinese and Japanese adults with uncontrolled focal (partial-onset) seizures (POS), with or without secondary generalization. METHODS: A 24-week, randomized, double-blind, placebo-controlled study (EP0008; NCT01710657) was conducted in patients (aged 16-70 years) with uncontrolled POS and taking 1-3 concomitant antiepileptic drugs from 72 sites across China and Japan. Following an 8-week Baseline period, randomized patients received lacosamide 200mg/day (100mg twice daily), 400mg/day (200mg twice daily), or placebo for 4-week Titration and 12-week Maintenance periods...
September 1, 2016: Epilepsy Research
Rolla Shbarou
The management of early-onset, genetically determined epilepsies is often challenging. First-line anti-epileptic drugs (AEDs) often include phenobarbital, phenytoin, oxcarbazepine, carbamazepine, clonazepam, levetiracetam, and valproic acid. Combinations of medications are used in these patients with often intractable seizures, and they include topiramate, clobazam, felbamate, lacosamide, lamotrigine, rufinamide, vigabatrin, ACTH, oral steroids, and the ketogenic diet. Vagus nerve stimulator therapy offers some relief in selected patients...
October 2016: Current Treatment Options in Neurology
Sherif Hanafy Mahmoud
Continuous renal replacement therapy (CRRT) is used for managing acute kidney injury in critically ill patients. Removal of antiepileptic drugs (AEDs) by CRRT could be significant and may complicate patients' intensive care unit stay. The objective of the current review was to summarize the available evidence for AED removal by CRRT. An electronic literature search of PubMed (1946 to May 2016), Medline (1946 to May 2016), and Embase (1974 to May 2016) databases for studies discussing AED removal by CRRT was conducted...
September 1, 2016: Clinical Drug Investigation
Francesco Brigo, Eugen Trinka, Nicola Luigi Bragazzi, Raffaele Nardone, Alberto Milan, Elisabetta Grillo
OBJECTIVE: Eslicarbazepine acetate (ESL) and lacosamide (LCM) have recently emerged as add-on treatments in patients with focal epilepsy experiencing seizures despite adequate monotherapy. Both drugs enhance slow inactivation of voltage-gated sodium channels. To date no randomized controlled trial (RCT) has directly compared ESL with LCM as add-on treatments for focal epilepsy. Our aim was to indirectly compare the efficacy of ESL and LCM used as add-on treatments in patients with focal epilepsy using common reference-based indirect comparison meta-analysis...
August 11, 2016: Epilepsy Research
David G Vossler, Robert T Wechsler, Paulette Williams, William Byrnes, Sheila Therriault
OBJECTIVE: To assess long-term use and safety of lacosamide (LCM) ≤800 mg/day monotherapy in patients with partial-onset seizures (POS) enrolled previously in a historical-controlled, conversion-to-monotherapy study (SP902; NCT00520741). METHODS: Patients completing or exiting SP902 with LCM as monotherapy or as adjunctive therapy were eligible to enter this 2-year open-label extension (OLE) trial (SP904; NCT00530855) at a starting dose ±100 mg/day of their final SP902 dose...
October 2016: Epilepsia
Karine Abou Khaled, Jean Khoury, Gabrielle Macaron, Sami Richa
No abstract text is available yet for this article.
October 2016: Seizure: the Journal of the British Epilepsy Association
Kimford J Meador, David W Loring, Alan Boyd, Javier Echauz, Suzette LaRoche, Naymee Velez-Ruiz, Pearce Korb, William Byrnes, Deanne Dilley, Simon Borghs, Marc De Backer, Tyler Story, Peter Dedeken, Elizabeth Webster
Differential effectiveness of antiepileptic drugs (AEDs) is more commonly determined by tolerability than efficacy. Cognitive effects of AEDs can adversely affect tolerability and quality of life. This study evaluated cognitive and EEG effects of lacosamide (LCM) compared with carbamazepine immediate-release (CBZ-IR). A randomized, double-blind, double-dummy, two-period crossover, fixed-dose study in healthy subjects compared neuropsychological and EEG effects of LCM (150mg, b.i.d.) and CBZ-IR (200mg, t.i.d...
September 2016: Epilepsy & Behavior: E&B
Mesut Mete, Beyhan Gurcu, Fatih Collu, Ulkun Unlu Unsal, Yusuf Kurtulus Duransoy, Mehmet Ibrahim Tuglu, Mehmet Selcuki
INTRODUCTION: Antiepileptic drugs (AEDs) are teratogens and confer a risk of congenital malformation. The estimated prevalence of major congenital malformations such as cardiac defects, facial clefts, hypospadias, and neural tube defects in epileptic women is 4-10 %, which represents a two- to fourfold increase in pregnant women compared to the general population. However, there are no clear data for newer drugs. Lacosamide (LCM), a novel AED, is the first of the third-generation AEDs to be approved as adjunctive therapy for the treatment of partial-onset seizures...
September 2016: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
Alicia Mirás Veiga, David Conejo Moreno, Ana Isabel Gómez Menéndez, Ignacio Muñoz Siscart, Marta Del Olmo Fernández, Esteban Gómez Sánchez, María García González, Fernando Gómez Sáez
Febrile infection-related epilepsy syndrome (FIRES) is a rare condition which evolves into refractory status epilepticus (SE), with poor outcome in most cases. Conventional antiepileptic drugs fail to control SE in FIRES patients. We report the case of a previously healthy 4-year-old boy who was diagnosed with FIRES. One week after pharyngitis and high fever he started seizures, followed by refractory SE. Benzodiazepines, phenytoin, high-dose barbiturates that induce burst suppression, high doses of corticosteroids, plasmapheresis, immunoglobulins, propofol, lidocaine, ketamine, inhaled desflurane, ketogenic diet, lacosamide, and therapeutic hypothermia were tried at different times in a period of 8 weeks, but all of them were ineffective...
July 19, 2016: Neuropediatrics
Emily McGinnis, Sudha Kilaru Kessler
OBJECTIVES: To evaluate the effectiveness of lacosamide (LCM) in pediatric patients, using time to treatment failure as the outcome measure, and to assess the impact of concomitant sodium channel blocker (SCB) use on LCM retention. METHODS: This is a retrospective cohort study of patients <21 years old receiving LCM from 2010 to 2015. Kaplan-Meier survival curves were generated for time to LCM failure, defined as discontinuation of LCM or addition of another antiepileptic therapy...
September 2016: Epilepsia
Christian E Elger, Michael Rademacher, Christian Brandt, Sami Elmoufti, Peter Dedeken, Klaus Eckhardt, Frank Tennigkeit, Marc De Backer
Treatment with enzyme-inducing antiepileptic drugs (AEDs) such as carbamazepine (CBZ) can lead to changes in reproductive, endocrine, and lipid parameters, resulting in clinical symptoms for some patients. Previous studies indicate that these changes can be reversed by switching to a nonenzyme-inducing AED. Lacosamide is a newer-generation AED, not known to induce or strongly inhibit cytochrome P450 (CYP450) enzymes. In this phase IIIb, prospective, multicenter, open-label, single-arm trial (NCT01375374), the serum concentrations of CYP-related reproductive hormones, thyroid hormones, and lipids were assessed in otherwise healthy male patients with focal seizures (N=11), before and after a switch from CBZ (600-1200mg/day at baseline) to lacosamide (target dose: 400mg/day by the end of titration) as adjunctive treatment to the nonenzyme-inducing AED levetiracetam (LEV, stable dosage of >1000mg/day throughout)...
September 2016: Epilepsy & Behavior: E&B
Annika Hilgers, Marion Schaefer
BACKGROUND: Based on data of clinical trials, new agents are receiving approval to the pharmaceutical market, for which information concerning safety issues under real-life conditions is not yet available. OBJECTIVES: The aim was to evaluate the tolerability of newer antiepileptic drugs (AEDs), such as topiramate, levetiracetam, zonisamide, pregabalin, extended-release oxcarbazepine, lacosamide and eslicarbazepine, under real-life conditions by means of an assessment of routine clinical data of inpatients...
June 2016: Drugs—Real World Outcomes
Josta de Jong, Ester Garne, Lolkje T W de Jong-van den Berg, Hao Wang
BACKGROUND: More information is needed about possible associations between the newer anti-epileptic drugs (AEDs) in the first trimester of pregnancy and specific congenital anomalies of the fetus. OBJECTIVES: We performed a literature review to find signals for potential associations between newer AEDs (lamotrigine, topiramate, levetiracetam, gabapentin, oxcarbazepine, eslicarbazepine, felbamate, lacosamide, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, vigabatrin, and zonisamide) and specific congenital anomalies...
June 2016: Drugs—Real World Outcomes
Bianca T A de Greef, Ingemar S J Merkies, Margot Geerts, Catharina G Faber, Janneke G J Hoeijmakers
BACKGROUND: Small fiber neuropathy generally leads to considerable pain and autonomic symptoms. Gain-of-function mutations in the SCN9A- gene, which codes for the Nav1.7 voltage-gated sodium channel, have been reported in small fiber neuropathy, suggesting an underlying genetic basis in a subset of patients. Currently available sodium channel blockers lack selectivity, leading to cardiac and central nervous system side effects. Lacosamide is an anticonvulsant, which blocks Nav1.3, Nav1...
2016: Trials
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