Do antipyretics prevent the recurrence of febrile seizures in children? A systematic review of randomized controlled trials and meta-analysis

Objectives: To determine the effectiveness of antipyretics use in prevention of subsequent febrile seizures in children.

Data sources: A search for all available electronic databases (MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, ACP Journal Club, Database of Abstracts of Reviews of Effects (DARE), Cochrane Central Register of Controlled Trials, Cochrane Methodology Register) from 1950 to July 2011 was done. No language restrictions were applied, but English abstract required.

Study selection: We included randomized controlled trials comparing the efficacy of antipyretic drugs to placebo in reducing the recurrence rate of febrile seizures in children (6-72 months) with previous febrile seizures. We excluded reviews, letters, and uncontrolled or non-randomized studies.

Data extraction and synthesis: The literature search was performed by a professional medical librarian. Based of the preliminary search, two reviewers independently pooled studies for detailed manual review per the inclusion criteria. We used the Cochrane Review Manager software (Revman 5) to calculate the odds ratio and 95% confidence intervals (CI) for seizure recurrence, assuming a random-effects model.

Results: Initial search identified 479 citations, five articles underwent further rigorous evaluation by two reviewers and three papers met the inclusion criteria. In these three studies, 540 children were included, of whom 348 received antipyretics (acetaminophen (15 mg/kg), ibuprofen (5-10mg/kg) or diclofenac (1.5mg/kg)) and 192 received placebo for prevention of subsequent febrile seizures during a 1-2 year follow-up period. Seventy-nine patients (22.7%) in the antipyretics group and forty-seven patients (24.4%) in the placebo group had febrile seizure recurrence during follow up. No statistically significant difference was found between the antipyretics and the placebo groups in the recurrence rate of febrile seizures (OR 0.9, 95% CI: 0.57-1.43).

Conclusion: Antipyretics were ineffective in reducing the recurrence of febrile seizures.