Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes.
ABSTRACT The purpose of this report was to update the 2006 International League Against Epilepsy (ILAE) report and identify the level of evidence for long-term efficacy or effectiveness for antiepileptic drugs (AEDs) as initial monotherapy for patients with newly diagnosed or untreated epilepsy. All applicable articles from July 2005 until March 2012 were identified, evaluated, and combined with the previous analysis (Glauser et al., 2006) to provide a comprehensive update. The prior analysis methodology was utilized with three modifications: (1) the detectable noninferiority boundary approach was dropped and both failed superiority studies and prespecified noninferiority studies were analyzed using a noninferiority approach, (2) the definition of an adequate comparator was clarified and now includes an absolute minimum point estimate for efficacy/effectiveness, and (3) the relationship table between clinical trial ratings, level of evidence, and conclusions no longer includes a recommendation column to reinforce that this review of efficacy/evidence for specific seizure types does not imply treatment recommendations. This evidence review contains one clarification: The commission has determined that class I superiority studies can be designed to detect up to a 20% absolute (rather than relative) difference in the point estimate of efficacy/effectiveness between study treatment and comparator using an intent-to-treat analysis. Since July, 2005, three class I randomized controlled trials (RCT) and 11 class III RCTs have been published. The combined analysis (1940-2012) now includes a total of 64 RCTs (7 with class I evidence, 2 with class II evidence) and 11 meta-analyses. New efficacy/effectiveness findings include the following: levetiracetam and zonisamide have level A evidence in adults with partial onset seizures and both ethosuximide and valproic acid have level A evidence in children with childhood absence epilepsy. There are no major changes in the level of evidence for any other subgroup. Levetiracetam and zonisamide join carbamazepine and phenytoin with level A efficacy/effectiveness evidence as initial monotherapy for adults with partial onset seizures. Although ethosuximide and valproic acid now have level A efficacy/effectiveness evidence as initial monotherapy for children with absence seizures, there continues to be an alarming lack of well designed, properly conducted epilepsy RCTs for patients with generalized seizures/epilepsies and in children in general. These findings reinforce the need for multicenter, multinational efforts to design, conduct, and analyze future clinically relevant adequately designed RCTs. When selecting a patient's AED, all relevant variables and not just efficacy and effectiveness should be considered.
- Journal of neurosciences in rural practice. 11/2014; 5(Suppl 1):S5-6.
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ABSTRACT: Epilepsy is one of the most common neurological diseases and it is characterized by the reoccurrence of seizures with variable severity and frequency. The burden of epilepsy, however, is more than having seizures as the disease is frequently associated with comorbid cognitive and behavioral disorders. Diagnosis as well as treatment suffers both from the inadequate understanding of the underlying epileptogenic molecular, cellular and network mechanisms and the related lack of reliable biomarkers for the development, progression, or even the presence and severity of the epileptic condition. Here we summarize the recent advances in both clinical and experimental approach regarding epilepsy, which may create the premise for identification of clinically useful, reliable biomarkers. Identification of the basic patomechanisms of epileptogenesis and epilepsy would potentially create new therapeutic approaches that could not only treat but also prevent and cure epilepsy. Current knowledge regarding the electrophysiological alterations as well as the underlying cellular and molecular mechanisms regarding temporal lobe epilepsy is also critically scrutinized.Brain Research Bulletin 10/2014; · 2.97 Impact Factor
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ABSTRACT: The evidence base for management of childhood epilepsy is poor, especially for the most common specific syndromes such as rolandic epilepsy (RE) and Panayiotopoulos syndrome (PS). Considerable international variation in management and controversy about non-treatment indicate the need for high quality randomised controlled trials (RCT). The aim of this study is, therefore, to describe current UK practice and explore the feasibility of different RCT designs for RE and PS.Archives of Disease in Childhood 09/2014; · 2.91 Impact Factor