Is antiepileptogenesis a realistic goal in clinical trials? Concerns and new horizons.

Any attempt to make antiepileptogenesis a realistic goal in clinical trials should be based on the experience of failures of the past. A wide variety of experimental studies and clinical trials using chronic antiseizure drug therapy during the extended post-injury period have had minimal success. The disappointing results of these studies may be due to several factors including the possibility that antiseizure drugs, despite the fact they suppress seizure activity, do not interfere in any substantial way with the “epileptogenic” process of focal epilepsies. Although the reasons for the failure are not entirely clear, it may be that the antiseizure drugs may have been tested at the wrong doses, for the wrong duration, or at the wrong time after brain injury. Surprisingly, the anti-absence drug ethosuximide has also been shown to be antiepileptogenic in several experimental models of absence epilepsy. In addition, clinical trials aimed at preventing focal post-injury epilepsy have suffered from poor enrolment and other issues related to the comorbidity of severe epilepsies that follow overt brain injury. Testing specific anti-inflammatory and immunological antiepileptogenic agents to prevent focal epilepsies, as well as prevention trials for genetic epilepsies, possibly with anti-absence drugs, may be a way to resolve the dilemma. Although more evidence is needed, there is hope on the horizon for antiepileptogenic therapy that works.