Randomized controlled antiepileptic drug trials miss almost all patients with ongoing seizures

•Retrospective study•Incidence of drug-resistant patients•Proportion of these patients appropriate for the last phase II and III AED trials•18 of 216 patients (8.3%) would have been acceptable for recruitment.•This may be one reason for the disappointing efficiency of many new AEDs after launch

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.