Preventive Treatments for Recurrences of Febrile Seizures

Summary

A Cochrane review[Abstract] 1 included 32 studies with a total of 4 431 children examining 15 different interventions of continuous or intermittent prophylaxis for febrile seizures. No significant benefit was found for intermittent phenobarbital, phenytoin, valproate, pyridoxine, ibuprofen or zinc sulphate vs. placebo or no treatment; nor for diclofenac vs. placebo followed by ibuprofen, paracetamol or placebo; nor for continuous phenobarbital versus diazepam, intermittent rectal diazepam versus intermittent valproate, or oral diazepam versus clobazam. There was a significant reduction of recurrent febrile seizures with intermittent diazepam vs. placebo or no treatment with a RR of 0.64 (95% CI 0.48 to 0.85; 6 studies, n=1151) at 6 months, RR of 0.69 (95% CI 0.56 to 0.84; 8 studies, n=1 416) at 12 months, RR 0.37 (95% CI 0.23 to 0.60; 1 study,n=289) at 18 months, RR 0.73 (95% CI 0.56 to 0.95; 4 studies, n=739) at 24 months, RR 0.58 (95% CI 0.40 to 0.85; 1 study, n=139) at 36 months, RR 0.36 (95% CI 0.15 to 0.89; 1 study, n=110) at 48 months, with no benefit at 60 to 72 months (RR 0.08, 95% CI 0.00 to 1.31; 1 study, n=60). Phenobarbital 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; 1 study, n=60), an effect found against an extremely high (83.3%) recurrence rate in the controls. When compared to intermittent diazepam, intermittent oral melatonin did not significantly reduce seizures at 6 months (RR 0.45, 95% CI 0.18 to 1.15; 1 study, n=60).When compared to placebo, intermittent oral levetiracetam significantly reduced recurrent seizures at 12 months (RR 0.27, 95% CI 0.15 to 0.52; 1 study, n=115).The recording of adverse effects was variable. Lower comprehension scores in phenobarbital-treated children were found in 2 studies. In general, adverse effects were recorded in up to 30% of children in the phenobarbital-treated groups and in 36% in benzodiazepine-treated groups.