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Prevention of generalized tonic–clonic seizures in refractory focal epilepsy: A meta‐analysis
Author(s) -
Hemery Claire,
Ryvlin Philippe,
Rheims Sylvain
Publication year - 2014
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.12765
Subject(s) - lacosamide , perampanel , topiramate , medicine , epilepsy , placebo , lamotrigine , randomized controlled trial , relative risk , anesthesia , meta analysis , phenytoin , anticonvulsant , confidence interval , psychiatry , alternative medicine , pathology
Summary Objectives Secondary generalized tonic–clonic seizures ( SGTCS ) are among the most severe forms of seizures, and the main risk factor for sudden unexpected death in epilepsy ( SUDEP ). Whether some antiepileptic drugs ( AED s) might be more efficacious than others on SGTCS in patients with drug‐resistant focal epilepsy thus represents an important clinical issue for which no data are currently available. Methods We performed a meta‐analysis of randomized controlled trials of adjunctive AED in which information on efficacy outcomes (i.e., responder rate and/or frequency per 28 days relative to baseline) were available both for all seizure types and for SGTCS . The primary analysis evaluated the efficacy of AED s on all types of seizure and on SGTCS by comparing the responder rates for AED and for placebo. Results Responder rate was available both for all seizure types and for SGTCS in 13 of the 72 eligible trials, evaluating 7 AED s. Only three AED s—lacosamide, perampanel and topiramate—showed greater efficacy than placebo. However, confidence intervals of relative risks overlapped for all AED s but pregabalin, which demonstrated significantly lower efficacy than lacosamide, perampanel, and topiramate. Moreover, there was a nonsignificant trend toward a lower relative risk of responder rate for SGTCS than for all seizure types, which appeared related to a greater response to placebo for this outcome. Significance Indirect comparison of AED s using randomized placebo‐controlled add‐on trials does not support robust differences between AED s to prevent SGTCS . Alternative designs for evaluation of therapeutic interventions in patients at risk for SGTCS ‐related complications are required.