Comment: The quality of evidence is downgraded by study limitations (lack of/unclear allocation concealment) and by indirectness (most of the studies were old).
A Cochrane review included 40 studies with a total of 4256 children examining 13 different interventions of continuous or intermittent prophylaxis for febrile seizures. No significant benefit for valproate, pyridoxine, intermittent phenobarbitol, phenytoin, ibuprofen or zinc sulphate vs. placebo or no treatment was found; nor for diclofenac vs. placebo followed by ibuprofen, acetominophen or placebo; nor for intermittent rectal diazepam vs. intermittent valproate, nor phenobarbitone vs. intermittent rectal diazepam, nor for continuous phenobarbitone vs. diazepam or oral diazepam vs. clobazam. There was a significant reduction of recurrent febrile seizures with intermittent oral diazepam vs. placebo with a RR of 0.64 (95% CI 0.48 to 0.85 at 6 months; 6 studies, n=1151), RR of 0.69 (95% CI 0.56 to 0.84) at 12 months (8 studies, n=1416), RR 0.37 (95% CI 0.23 to 0.60) at 18 months (1 study, n=289), RR 0.73 (95% CI 0.56 to 0.95) at 24 months (4 studies, n=739), RR 0.58 (95% CI 0.40 to 0.85) at 36 months (1 study, n=139), RR 0.36 (95% CI 0.15 to 0.89) at 48 months (1 study, n=110), with no benefit at 60 to 72 months. Phenobarbitone vs. placebo or no treatment reduced seizures at 6, 12 and 24 months but not at 18 or 72 month follow up (RR 0.59 , 95% CI 0.42 to 0.83 at 6 months; RR 0.54, 95% CI 0.42 to 0.70 at 12 months; and RR 0.69, 95% CI 0.53 to 0.89 at 24 months). Intermittent clobazam compared to placebo at 6 months resulted in a RR of 0.36 (95% CI 0.20 to 0.64), an effect found against an extremely high (83.3%) recurrence rate in the controls. The recording of adverse effects was variable. Lower comprehension scores in phenobarbitone treated children were found in 2 studies. In general, adverse effects were recorded in up to some 30% of children in the phenobarbitone treated group and in up to 36% in benzodiazepine treated groups.