title: Randomized controlled antiepileptic drug trials miss almost all patients with ongoing seizures.
abstract: In spite of the marketing of numerous new antiepileptic drugs (AEDs), their real-life effectiveness has often been disappointing. We therefore retrospectively investigated how many adult patients with drug-resistant epilepsy would have been potential candidates for the last five phase II and III trials that have been performed at our center. Out of a group of 216 consecutively collected patients, only 18 (8.3%) would have been acceptable for recruitment. Treatment with enzyme-inducing AEDs or concomitant medications (47.2%), too few seizures during a baseline period (41.7%), and EEGs showing a pattern not consistent with a diagnosis of focal epilepsy (e.g. generalized spike-wave) (31.5%) were the leading exclusion criteria. If only one criterion prevented recruitment, too few seizures during the baseline period and treatment with enzyme-inducing medications were the most frequent limitations for potential recruitment. Due to the limiting inclusion and exclusion factors of clinical AED trials, only a small fraction of patients with drug-resistant epilepsy is suitable. When new AEDs have passed such trials and are introduced, we have no information about the potential efficacy and tolerability in >90% of our patients with AED-resistant epilepsies. This may be one reason for the disappointing efficacy of many new AEDs after launch.
authors.affiliation: Kork Epilepsy Center, Kehl-Kork, Germany. Electronic address: bsteinhoff@epilepsiezentrum.de.
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Steinhoff
authors.affiliation: Kork Epilepsy Center, Kehl-Kork, Germany.
authors.forename: Anke M
authors.initials: AM
authors.lastname: Staack
authors.affiliation: Kork Epilepsy Center, Kehl-Kork, Germany.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Hillenbrand
mesh_terms: D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D017322:Clinical Trials, Phase II as Topic / Q000592:standards*; D017326:Clinical Trials, Phase III as Topic / Q000592:standards*; D000069279:Drug Resistant Epilepsy / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010043:Outcome and Process Assessment, Health Care; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic / Q000592:standards*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000927:Anticonvulsants
keywords: Antiepileptic drugs; Epilepsy; Practical value; Randomized controlled trials