title: Prevention of generalized tonic-clonic seizures in refractory focal epilepsy: a meta-analysis.
abstract: OBJECTIVE
  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 (AEDs) 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 AEDs 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 AEDs. Only three AEDs--lacosamide, perampanel and topiramate--showed greater efficacy than placebo. However, confidence intervals of relative risks overlapped for all AEDs 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.
  
  
  CONCLUSIONS
  Indirect comparison of AEDs using randomized placebo-controlled add-on trials does not support robust differences between AEDs to prevent SGTCS. Alternative designs for evaluation of therapeutic interventions in patients at risk for SGTCS-related complications are required.
authors.affiliation: Department of Functional Neurology and Epileptology, Institute of Epilepsies (IDEE), Hospices Civils de Lyon, Lyon, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Hemery
authors.forename: Philippe
authors.initials: P
authors.lastname: Ryvlin
authors.forename: Sylvain
authors.initials: S
authors.lastname: Rheims
mesh_terms: D000081:Acetamides / Q000627:therapeutic use; D000927:Anticonvulsants / Q000627:therapeutic use*; D002908:Chronic Disease; D003645:Death, Sudden / Q000517:prevention & control; D061345:Early Medical Intervention; D004828:Epilepsies, Partial / Q000150:complications / Q000188:drug therapy*; D005632:Fructose / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D000078334:Lacosamide; D009570:Nitriles; D011728:Pyridones / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012307:Risk Factors; D012640:Seizures / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control*; D000077236:Topiramate; D016896:Treatment Outcome
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D009570:Nitriles; D011728:Pyridones; D000077236:Topiramate; D005632:Fructose; D000078334:Lacosamide; C551441:perampanel
keywords: Antiepileptic drugs; Epilepsy; Generalized tonic-clonic seizures; Meta-analysis; Sudden unexpected death in epilepsy