A dose-comparison trial of topiramate as monotherapy in recently diagnosed partial epilepsy.
OBJECTIVE
To evaluate topiramate as monotherapy in adults and children with recently diagnosed, localization-related epilepsy, comparing two dosages of topiramate in a multicenter, randomized, double-blind study.


METHODS
Adults and children (>/=3 years of age) were eligible if the maximum interval since epilepsy diagnosis was 3 years and patients had one to six partial-onset seizures during a 3-month retrospective baseline. At study entry, patients (N = 252) were untreated or receiving one antiepileptic drug for less than 1 month. After randomization to 50 or 500 mg/d topiramate (25 or 200 mg/d if weight </= 50 kg), patients remained in the study until 4 months after the last patient was randomized or until patients met seizure-related exit criteria (e.g., had two seizures). The primary efficacy outcome was a univariate analysis of time-to-exit, which was time to second seizure in 96% of patients.


RESULTS
The time-to-exit (median, 422 days vs 293 days) favored the higher dose of topiramate, but this difference was not significant. When time-to-exit was analyzed with time-to-first-seizure as a covariate, the difference between dosage groups was significant (p = 0.01), reflecting the higher seizure-free rates (54% vs 39%, p = 0.02) and longer time-to-first-seizure (median 317 days vs 108 days; p = 0.06) in patients receiving 200 or 500 mg/d topiramate. Higher plasma concentration was associated with increased time-to-first seizure (p < 0.01). Dose-related adverse events included paresthesia, weight loss, diarrhea, and hypoesthesia.


CONCLUSIONS
Although the primary efficacy analysis was negative, time-to-exit analyses that included time-to-first-seizure as a covariate, between-group differences in seizure-free rates, and longer time-to-first-seizure with higher serum concentration provide evidence that topiramate is effective as monotherapy in patients with localization-related epilepsy.
Gilliam
F G
FG
University of Alabama at Birmingham, USA.
Veloso
F
F
Bomhof
M A M
MA
Gazda
S K
SK
Biton
V
V
Ter Bruggen
J P
JP
Neto
W
W
Bailey
C
C
Pledger
G
G
Wu
S-C
SC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D002648:Child; D004244:Dizziness / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D005221:Fatigue / Q000209:etiology; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use*; D006261:Headache / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010292:Paresthesia / Q000209:etiology; D016016:Proportional Hazards Models; D000077236:Topiramate; D016896:Treatment Outcome
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose