Phase III Double Blind Trial of Valproate Sodium for Prophylaxis of Post Traumatic Seizures

PROTOCOL OUTLINE: This is a randomized, double blind trial involving 3 treatment groups. On day 1, controls receive phenytoin IV over 1 hour. On days 2 through 7, controls receive 2 doses each of phenytoin and placebo daily, intravenously. From day 8 through 6 months, controls receive placebo IV 4 times daily, then placebo tablets are administered. On day 1, the experimental group receives a loading dose of valproate sodium intravenously over 1 hour within 24 hours of injury. Then, patients are divided into 2 subgroups. From day 2 through 1 month, one group of patients receives valproate IV 4 times daily over 1 hour until tablets are tolerated. Patients receive placebo tablets by mouth 4 times daily from month 2 through month 6. On day 2, the other group of patients receives valproate IV 4 times daily and continues for 6 months until tablets (same dose) are tolerated. If patients remain seizure free between day 8 and 6 months, the number of valproate or placebo tablets are tapered over 1 week. Each patient receives a full neuropsychological and psychosocial examination at 1, 6, and 12 months after injury. Untreated observation of patients continues until 2 years after injury.