Antipyretic agents for preventing recurrences of febrile seizures: randomized controlled trial

Arch Pediatr Adolesc Med. 2009 Sep;163(9):799-804. doi: 10.1001/archpediatrics.2009.137.


Objective: To evaluate the efficacy of different antipyretic agents and their highest recommended doses for preventing febrile seizures.

Design: Randomized, placebo-controlled, double-blind trial.

Setting: Five hospitals, each working as the only pediatric hospital in its region.

Participants: A total of 231 children who experienced their first febrile seizure between January 1, 1997, and December 31, 2003. The children were observed for 2 years.

Interventions: All febrile episodes during follow-up were treated first with either rectal diclofenac or placebo. After 8 hours, treatment was continued with oral ibuprofen, acetaminophen, or placebo.

Main outcome measure: Recurrence of febrile seizures.

Results: The children experienced 851 febrile episodes, and 89 of these included a febrile seizure. Febrile seizure recurrences occurred in 54 of the 231 children (23.4%). There were no significant differences between the groups in the main measure of effect, and the effect estimates were similar, as the rate was 23.4% (46 of 197) in those receiving antipyretic agents and 23.5% (8 of 34) in those receiving placebo (difference, 0.2; 95% confidence interval, -12.8 to 17.6; P = .99). Fever was significantly higher during the episodes with seizure than in those without seizure (39.7 degrees C vs 38.9 degrees C; difference, 0.7 degrees C; 95% confidence interval, -0.9 degrees C to -0.6 degrees C; P < .001), and this phenomenon was independent of the medication given.

Conclusions: Antipyretic agents are ineffective for the prevention of recurrences of febrile seizures and for the lowering of body temperature in patients with a febrile episode that leads to a recurrent febrile seizure.

Trial registration: NCT00568217.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / therapeutic use
  • Administration, Oral
  • Analysis of Variance
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Chi-Square Distribution
  • Child, Preschool
  • Diclofenac / administration & dosage
  • Diclofenac / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Ibuprofen / administration & dosage
  • Ibuprofen / therapeutic use
  • Infant
  • Male
  • Placebos
  • Secondary Prevention
  • Seizures, Febrile / prevention & control*
  • Suppositories
  • Time Factors
  • Treatment Outcome


  • Anti-Inflammatory Agents, Non-Steroidal
  • Placebos
  • Suppositories
  • Diclofenac
  • Acetaminophen
  • Ibuprofen

Associated data