A CONTROLLED TRIAL OF DIAZEPAM ADMINISTERED DURING FEBRILE ILLNESSES TO PREVENT RECURRENCE OF FEBRILE SEIZURES

Background. Phenobarbital, once widely prescribed to prevent febrile s eizures, is now in disfavor because of its side effects and lack of ef ficacy. Diazepam, administered only during episodes of fever, may be a safe, effective agent to prevent the recurrence of febrile seizures. Methods. We conducted a randomized, double-blind, placebo-controlled t rial among 406 children (mean age,24 months) who had at least one febr ile seizure. Diazepam (0.33 mg per kilogram of body weight) or placebo was administered orally every eight hours during all febrile illnesse s. Results. During a mean follow-up of 1.9 years (a period during whic h 90 percent of febrile seizures recur), our intention-to-treat analys is showed a reduction of 44 percent in the risk of febrile seizures pe r person-year with diazepam (relative risk = 0,56; 95 percent confiden ce interval, 0.38 to 0.81; P = 0.002). A survival analysis of the leng th of time to the first recurrent febrile seizure did not show a signi ficant difference between the treatment groups (P = 0.064 by the log-r ank test), but after adjustment for covariates, diazepam was found to have a benefit (P = 0.027 by Cox regression analysis). An analysis res tricted to children who had seizures while actually receiving the stud y medication (7 in the diazepam group and 29 in the placebo group) sho wed an 82 percent reduction in the risk of febrile seizures with diaze pam (relative risk = 0.18; 95 percent confidence interval, 0.09 to 0.3 7; P<0.001). Of the 153 children who took at least one dose of diazepa m, 39 percent had ataxia, lethargy, or irritability or at least one ot her moderate side effect that was reversed after a reduction in the do se. There were no severe side effects. Conclusions. Oral diazepam, giv en only when fever is present, is safe and reduces the risk of recurre nt febrile seizures.