University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• Does there exist a medication regimen that does not require daily administration that can prevent the recurrence of febrile seizures throughout an episode of fever?

Clinical Bottom Lines

1. Convulsions triggered by fever (febrile seizures) are the most common type of seizure, with a prevalence of 3 to 4 percent. Febrile seizures frequently recur with a recurrence rate of 33 percent overall and 50 percent when the first febrile seizure occurs before one year of age.
2. Prevention of febrile seizures is highly desirable since seizures are upsetting to both parents and children, and since medical costs can be considerable. Any child with a convulsion is at risk for brain injury due to falls caused by seizures or due to hypoxia if there is accompanying respiratory compromise. Most studies, though not all, have found a relation between the number of febrile seizures, particularly those that are complex, and the risk of later afebrile seizures. Hence, prevention of febrile seizures might also lessen that risk.
3. For two decades, daily phenobarbital has been the drug of choice for the prevention of febrile seizures, and in most studies it has been effective. More recently, however, its role in prophylaxis has been questioned. Concern has centered on the frequency of behavioral side effects, consistently poor compliance with the drug regimen, and evidence of some accompanying decline in IQ. Finally, assessments of the efficacy of daily phenobarbital, based on the intention to treat, have shown no advantage over placebo.
4. The study summarized suggested that oral diazepam, given only when fever is present, is safe and reduces the risk of recurrent febrile seizures.¹

Summary of Key Evidence

1. A randomized, double-blind, placebo-controlled trial among 406 children (mean age, 24 months) who had at least one febrile seizure was conducted. Placebo and control groups had similar characteristics at the onset.¹
2. The protocol called for the subjects to continue to receive their assigned medications until their fifth birthdays or until the end of the study.
3. An analysis of the occurrence of febrile seizures while the study medicine was actually being taken indicates a striking and significant effect of diazepam with an 82 percent reduction rate of recurrent febrile seizures with diazepam.

Additional Comments

• Among the 153 children who took at least one dose of diazepam, 59 (39 percent) reported at least one moderate side effect. The side effects most frequently seen were ataxia, lethargy, and irritability (reported in approximately one quarter to one third of the children given diazepam). A much smaller proportion of children receiving diazepam (roughly 1 in 20) had moderate side effects involving speech, activity level, or sleep. The frequency of mild side effects in children receiving diazepam paralleled that of side effects of moderate severity.
• In a recent update, the Subcommittee on Febrile Seizures of the American Academy of Pediatrics, has determined that a simple febrile seizure is a benign and common event in children between the ages of 6 months and 5 years. Most children have an excellent prognosis. Although there are effective therapies that could prevent the occurrences of additional febrile seizures, the potential adverse effects of such therapy are not commensurate with the benefit. In situations in which parental anxiety associated with febrile seizures is severe, intermittent oral diazepam at the onset of febrile illness may be effective in preventing recurrence. There is no convincing evidence, however, that any therapy will alleviate the possibility of future epilepsy (a relatively unlikely event). Antipyretics, although may improve the comfort of the child, will not prevent febrile seizures.²

Citation

1. Rosman NP, Colton T, et al. A controlled trial of diazepam administered during febrile illnesses to prevent recurrence of febrile seizures. N Engl J Med. 1993; 329: 79-84.
2. American Academy of Pediatrics: Committee on Quality Improvement, Subcommittee on Febrile Seizures. Practice Parameters: Long-Term Treatment of the Child with Simple Febrile Seizures. Pediatrics 1999; 103:1307-1309.

CAT Author: Luisa F. Madronero, MD

CAT Appraisers: John G. Frohna, MD

Date appraised: August 2, 1999