Randomized trial of adjunctive topiramate therapy in infants with refractory partial seizures.
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.
Novotny
E
E
University of Washington, Seattle, WA, USA. ejn4@u.washington.edu
Renfroe
B
B
Yardi
N
N
Nordli
D
D
Ness
S
S
Wang
S
S
Weber
T
T
Kurland
C L
CL
Yuen
E
E
Eerdekens
M
M
Venkatraman
L
L
Nye
J S
JS
Ford
L
L
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
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose