Prophylactic drug management for febrile seizures in children

• Published in: Cochrane database of systematic reviews 2017-02, Vol.2 (2), p.CD003031
• Main Authors: Offringa, Martin, Newton, Richard, Cozijnsen, Martinus A, Nevitt, Sarah J
• Format: Article
• Language: English
• Subjects: Anticonvulsants - adverse effects; Anticonvulsants - therapeutic use; Antipyretics - adverse effects; Antipyretics - therapeutic use; Child; Child health; Child, Preschool; Humans; Infant; Neurology; Randomized Controlled Trials as Topic; Recurrence; Seizures, Febrile - prevention & control; Treatment for acute symptomatic seizures
• ISSN: 1469-493X
• DOI: 10.1002/14651858.CD003031.pub3

Febrile seizures occurring in a child older than one month during an episode of fever affect 2% to 4% of children in Great Britain and the United States and recur in 30%. Rapid-acting antiepileptics and antipyretics given during subsequent fever episodes have been used to avoid the adverse effects of continuous antiepileptic drugs. To evaluate primarily the effectiveness and safety of antiepileptic and antipyretic drugs used prophylactically to treat children with febrile seizures; but also to evaluate any other drug intervention where there was a sound biological rationale for its use. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2016, Issue 7); MEDLINE (1966 to July 2016); Embase (1966 to July 2016); Database of Abstracts of Reviews of Effectiveness (DARE) (July 2016). We imposed no language restrictions. We also contacted researchers in the field to identify continuing or unpublished studies. Trials using randomised or quasi-randomised participant allocation that compared the use of antiepileptic, antipyretic or other plausible agents with each other, placebo or no treatment. Two review authors (RN and MO) independently applied predefined criteria to select trials for inclusion and extracted the predefined relevant data, recording methods for randomisation, blinding and exclusions. For the 2016 update a third author (MC) checked all original inclusions, data analyses, and updated the search. Outcomes assessed were seizure recurrence at 6, 12, 18, 24, 36, and 48 months and at age 5 to 6 years in the intervention and non-intervention groups, and adverse medication effects. We assessed the presence of publication bias using funnel plots. We included 40 articles describing 30 randomised trials with 4256 randomised participants. We analysed 13 interventions of continuous or intermittent prophylaxis and their control treatments. Methodological quality was moderate to poor in most studies. We found no significant benefit for intermittent phenobarbitone, phenytoin, valproate, pyridoxine, ibuprofen or zinc sulfate versus placebo or no treatment; nor for diclofenac versus placebo followed by ibuprofen, acetaminophen or placebo; nor for continuous phenobarbitone 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 versus placebo or no treatment, with a risk ratio (RR) o