Randomized clinical trial on the efficacy of antiepileptic drugs in reducing the risk of relapse after a first unprovoked tonic-clonic seizure. First Seizure Trial Group (FIR.S.T. Group).

We conducted a randomized multicenter clinical trial on 397 patients ranging in age from 2 to 70 years to assess the effectiveness of treatment of the first unprovoked epileptic seizure. Subjects seen within 7 days after a first witnessed tonic-clonic seizure with or without partial onset were randomized to immediate treatment (carbamazepine, phenytoin, phenobarbital, or sodium valproate) or to treatment with the same drugs only after seizure recurrence. We excluded individuals with acute symptomatic seizures, progressive neurologic disorders, or gross psychiatric illness. Thirty-six of 204 subjects randomized to treatment and 75 of 193 randomized to delayed treatment experienced seizure recurrence during follow-up. The cumulative time-dependent risk of relapse among treated subjects was 25% by 24 months. The corresponding figure for untreated subjects was 51%. The risk of relapse was 2.8 times higher (95% CI, 1.9 to 4.2) for untreated subjects. There were no interactions between age and EEG findings (the only predictors of risk of relapse) and treatment effects. We conclude that treatment of the first seizure with antiepileptic drugs leads to a significant reduction of the risk of relapse.