The informed scientist

Population-based studies done in the last 30 years have consistently demonstrated that up to 50% of patients with newly diagnosed epilepsy attain seizure remission immediately after treatment start using first- generation antiepileptic drugs (AEDs). These findings provide scientific evidence of efficacy and tolerability of these drugs when given as the first treatment of epilepsy. In studies assessing the potential benefits of alternative monotherapies or polytherapies in patients failing on a first monotherapy, the proportion of patients attaining remission was negligible regardless of the drug included in the treatment schedule. The poor tolerability profile of old generation drugs given at standard doses is well known. However, the potential of these drugs to cause adverse events can be minimized when using low daily dosages, which have been shown to be equally effective as higher, standard doses in firstly diagnosed patients. Randomized trials comparing recently approved to old generation drugs failed to show any added value of the former in reducing the risk of seizure relapse. Compared to the established compounds, the efficacy and safety of recently approved AEDs has been tested in a limited number of individuals for a limited period of time. In this regard, long-term toxicity and rare adverse events cannot be documented unless sufficient time has elapsed on treatment and the number of exposed individuals has increased to critical levels. Examples are available from patients treated with felbamate, whose hematologic and hepatic toxicity appeared only when about 100,000 patients had been exposed to the drug, with lamotrigine, when only after the marketing of the drug and its use in clinical practice it became obvious that only a slow tapering could prevent (at least in part) the occurrence of rash and severe dermatological syndromes, and with vigabatrin, when only after prolonged use irreversible visual field defects became apparent. Finally, the teratogenic potential of recently approved drugs is virtually unknown. For these reasons, recently approved AEDs should be used only when other, better known drugs have failed, and in patients in whom the use of first generation drugs is contraindicated.