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

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.