Clinical trials of agents to prevent posttraumatic epilepsy

Posttraumatic epilepsy (PTE) is theoretically preventable since PTE may follow traumatic brain injury (TBI) after months to years. This provides a potential “treatment window” to prevent posttraumatic epileptogenesis after TBI. There have been several clinical trials of antiepileptic drugs to try to prevent PTE. In this chapter, we review these trials in chronological order. Agents that have been tested include phenytoin, phenobarbital, carbamazepine, valproate, magnesium, and levetiracetam. None of these agents prevented the development of late seizures (PTE) after TBI. The absence of any effective antiepileptogenic agents against PTE should stimulate novel clinical trials based on new targets.