title: Randomized trial of adjunctive topiramate therapy in infants with refractory partial seizures.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of adjunctive topiramate (sprinkle capsules or oral liquid) in reducing daily rates of partial-onset seizures (POS) in infants with refractory POS.
  
  
  METHODS
  In this double-blind, placebo-controlled, parallel-group, international study, infants (n = 149) with clinical or EEG evidence of refractory POS were randomly allocated (1:1:1:1) to receive adjunctive topiramate 5, 15, or 25 mg/kg/d or placebo for 20 days. The primary variable was the median percentage reductions in daily POS rate from baseline to final assessment as recorded on a 48-hour video-EEG.
  
  
  RESULTS
  Of the 149 infants (mean age 12 months) included in the intent-to-treat analysis set, 130 completed the study. Median percentage reduction from baseline in daily POS rate was not significantly different (p = 0.97) between topiramate 25 mg/kg (20.4%) and placebo (13.1%). Lower doses were not formally tested, but nominal p values for comparisons with placebo were not significant (15-mg/kg/d dose: p = 0.97; 5-mg/kg/d dose: p = 0.91). Treatment-emergent fever, diarrhea, vomiting, anorexia, weight decrease, somnolence, and viral infection occurred more frequently (> or = 10% difference) with topiramate than with placebo.
  
  
  CONCLUSIONS
  In infants aged 1-24 months, topiramate 5, 15, or 25 mg/kg/d was not effective as adjunctive treatment for refractory partial-onset seizures. No new safety concerns associated with topiramate use were noted.
  
  
  METHODS
  This interventional study provides Class I evidence that topiramate 5, 15, or 25 mg/kg/d compared with placebo does not significantly reduce seizure rates in infants aged 1 month to 2 years with refractory partial-onset seizures.
authors.affiliation: University of Washington, Seattle, WA, USA. ejn4@u.washington.edu
authors.forename: E
authors.initials: E
authors.lastname: Novotny
authors.forename: B
authors.initials: B
authors.lastname: Renfroe
authors.forename: N
authors.initials: N
authors.lastname: Yardi
authors.forename: D
authors.initials: D
authors.lastname: Nordli
authors.forename: S
authors.initials: S
authors.lastname: Ness
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Weber
authors.forename: C L
authors.initials: CL
authors.lastname: Kurland
authors.forename: E
authors.initials: E
authors.lastname: Yuen
authors.forename: M
authors.initials: M
authors.lastname: Eerdekens
authors.forename: L
authors.initials: L
authors.lastname: Venkatraman
authors.forename: J S
authors.initials: JS
authors.lastname: Nye
authors.forename: L
authors.initials: L
authors.lastname: Ford
mesh_terms: D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D017024:Chemotherapy, Adjuvant; D004311:Double-Blind Method; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008297:Male; D012640:Seizures / Q000188:drug therapy* / Q000503:physiopathology; D000077236:Topiramate; D016896:Treatment Outcome; D014741:Video Recording
chemical_list: D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose