A meta-analytic review of the preventive treatment of recurrences of febrile seizures

Objective: To assess the efficacy of various medications in the prevention of recurrent febrile seizures. Study design: A meta-analysis of all published randomized, placebo-controlled trials of the preventive treatment of febrile seizures published in English; 45 articles were found, but only 9 trials were randomized and placebo-controlled-4 using phenobarbital; 3, diazepam; 1, pyridoxine; and 1, phenytoin. In one of the phenobarbital trials, valproate was also compared with placebo. Results: The risk of recurrences was significantly lower in children receiving continuous phenobarbital therapy than placebo (odds ratio 0.54, 95% confidence intervals 0.33 to 0.90, p = 0.017). The odds ratio for recurrences in the valproate group was 0.09, 95% CI 0.01 to 0.78, p = 0.011. No difference in the risk was found for recurrences between children receiving intermittent diazepam and placebo (odds ratio 0.81, 95% CI 0.54 to 1.22, p = 0.31). The risk for recurrences in children receiving pyridoxine or phenytoin did not differ from the risk among children receiving placebo. Four children would have to be treated with valproate (95% CI 2 to 11) or eight children would have to be treated with phenobarbital (95% CI5 to 27), continuously, to prevent one febrile seizure. Conclusions: Because both agents found to be effective in prevention of recurrent febrile seizures have known adverse effects, prophylaxis of febrile seizures cannot be recommended.