Epilepsy research
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Randomized Controlled Trial
Lack of effect of perampanel on QT interval duration: Results from a thorough QT analysis and pooled partial seizure Phase III clinical trials.
Perampanel is a selective, noncompetitive AMPA receptor antagonist approved as adjunctive treatment for partial seizures. To assess potential for delayed cardiac repolarization, a Phase I thorough QT study was performed, supplemented by plasma concentration-QT data modeled from 3 pooled Phase III studies. ⋯ Treatment with perampanel 6 mg and 12 mg for 7 days did not delay cardiac repolarization in healthy volunteers. In a population analysis of 1480 patients with partial seizures treated with perampanel doses ≤ 12 mg or placebo, no clinically significant trends in QT interval data were noted. Based on the thorough QT study and evaluations from pooled Phase III studies, there is no evidence of prolonged QT interval duration with perampanel treatment.
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Randomized Controlled Trial
Management of generalised convulsive status epilepticus (SE): A prospective randomised controlled study of combined treatment with intravenous lorazepam with either phenytoin, sodium valproate or levetiracetam--Pilot study.
This study was conducted to compare the efficacy of phenytoin, valproate and levetiracetam in patients with GCSE. ⋯ Phenytoin, valproate, and levetiracetam are safe and equally efficacious following lorazepam in GCSE. The choice of AEDs could be individualised based on co-morbidities. SE could be controlled in 92% of patients with AEDs only and anaesthetics were not required in them.
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Treatment decisions should be informed by high quality evidence of both the potential benefit and harms of treatment alternatives. Randomised controlled trials (RCTs) provide the best evidence regarding benefits; however information relating to serious, rare and long-term harms is usually available only from non-randomised studies (NRSs). The aim of this study was to use a checklist based on the CONSORT (Consolidating Standards for Reporting Trials) extension for harms recommendations to assess the quality of reporting of harms data in both NRSs and RCTs of antiepileptic drugs, using studies of topiramate as an example. ⋯ Reporting of harms is significantly better in RCTs than in NRSs of TPM, but is suboptimal overall and has not improved since the publication of CONSORT extension for harms in 2004. There is a need to improve the reporting of harms in order to better inform treatment decisions.
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The liver plays a major role in the metabolism and elimination of many antiepileptic drugs (AEDs), including perampanel. Some of the metabolites identified for perampanel are likely formed via reactive intermediates, which have the potential to covalently bind to protein and cause idiosyncratic toxicities, including hepatotoxicity. The approved AED perampanel is a selective, noncompetitive AMPA receptor antagonist. The safety and tolerability of perampanel have been well documented in 3 double-blind, randomized, placebo-controlled, phase III studies. Here we report the effects of perampanel on liver function in patients from the phase III studies to assess the potential for liver toxicity. ⋯ Hepatobiliary laboratory data and related TEAEs were not notably different between perampanel and placebo treatment groups, and no dose-related trends were observed. Based on the laboratory results from the 3 Phase III studies, perampanel (2, 4, 8, and 12mg) demonstrated no clinically important effects on liver function tests, indicating perampanel is an AED with a low potential for drug-induced liver toxicity.
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Our goal was to perform a systematic review of the literature on the insertion of vagal nerve stimulators (VNS) for refractory status epilepticus (RSE) and its impact on the control of RSE. ⋯ We currently cannot recommend the use of VNS for RSE. Oxford level 4, GRADE D evidence exists to suggest improvement in seizure control with the use of urgent VNS in generalized RSE. No comments can be made on the utility of VNS in focal RSE. Further prospective study is warranted.