Abstracts

Rationale: Among all the different seizure types secondary generalized tonic clonic seizures, now called focal-to-bilateral tonic-clonic seizures (FBTCS), are recognized as one of the major risk factors for Sudden Unexpected Death in Epilepsy (SUDEP). Therefore, controlling FBTCS is the best way to reduce the risk of SUDEP. There are almost no data comparing AED efficacy in prevention of FBTCS. Our aim in this systematic review is analysis of the existing evidence of efficacy of specific AEDs for FBTCS reduction. Methods: We searched Pubmed, EMBASE and Cochrane library for all the articles reporting results from randomized, double-blind and placebo controlled clinical trials evaluating the efficacy of anti-epileptic drugs (AEDs) on focal epilepsy with or without secondary generalization, specifically looking at the median reduction in FBTCS compared to placebo. We then hand-searched the references quoted in the identified papers. In addition, we searched the manufacturer websites including, when reported, the papers derived from the pivotal trials of a drug. We only selected papers written in English and excluded the ones with only a pediatric or elderly population. All the abstracts of the articles were reviewed by two reviewers. As a start, both reviewers screened 357 articles by title and abstract. After the search and the screening of the abstracts, 46 papers were selected for full text screening. After the full text screening, 20 papers were excluded. During this phase, the main reason for the exclusion of paper was the lack of reported FBTCS reduction separated from other seizure types. This left inclusion of 26 papers with data on reduction in FBTCS with both the active compound and placebo. Results: The two drugs that yielded the most data were brivaracetam (BRV) and topiramate (TPM). BRV trials showed reduction in FBTCS ranging from 33.9% to 82.1% in the treated patients’ groups versus 24.7% to 42.5% in the placebo groups, with efficacy above placebo of 11.6% to 57.4%. When restricting to doses >= 100 mg/d, efficacy above placebo was 13.7% to 57,4%. TPM trials showed a reduction of FBTCS of 40% to 90% compared to a 1% to 41% with placebo, with efficacy above placebo of 4.1% to 75.2%. With perampanel (PER), decrease in FBTCS was 31.2% with 4mg/day vs 17.6% with placebo and difference of 13.6%, and 32.7% to 76,5% with 8mg/day vs 8.1% to 38,4% with placebo, with a difference of 21.1% to 43.5% above placebo.See the Table for the absolute median reduction compared to placebo for each drug and dose. Conclusions: In a landmark older study, control of convulsive seizures did not differ significantly between phenytoin, carbamazepine, phenobarbital and primidone, and in a second study they observed no significant difference between carbamazepine and valproate. At the present moment, to our knowledge, there are no comparative studies in the literature specifically comparing the effects of new AEDs against FBTCS. Prior literature reported that BRV seems to affect mostly FBTCS compared to focal impaired awareness seizures. At the moment, there are insufficient evidence to determine the superiority of any one AED over another for treatment of FBTCS. Worthy of mention is the fact that none of the studies we analyzed reported the reduction in FBTCS during sleep, which is especially relevant for the prevention of SUDEP. Funding: No funding