A dose-comparison trial of topiramate as monotherapy in recently diagnosed partial epilepsy

F. G. Gilliam, F. Veloso, M. A M Bomhof, S. K. Gazda, V. Biton, J. P. Ter Bruggen, W. Neto, C. Bailey, G. Pledger, S. C. Wu, J. Alving, S. Arroyo, R. Arts, R. Ayala, R. Barbano, E. Ben-Menachem, W. Blume, E. Brodtkorb, T. R. Browne, D. ChadwickC. Couch, P. K. Crumrine, M. Dam, P. P. De Deyn, C. Dellaportas, H. Desai, K. R. Edwards, B. Engelsen, R. D. Farran, L. M. Frank, J. French, A. J. Friedman, J. Gelbum, C. L. Harden, C. Hart, O. Henriksen, M. D. Hoffstetter, P. J. Holt, J. F. Hulihan, R. P. Hull, T. Husainy, H. Kang, R. Kern, S. S. Kirzinger, M. A. Lee, R. F. Leroy, J. Licht, J. Mai, R. Michelucci, G. L. Morris, R. Mutani, M. Narus, M. Nieto Barrera, M. Nisman-Safirstein, A. Ogunyemi, J. Pak, P. B. Pennell, S. G. Phillips, N. Pillay, R. E. Ramsay, F. J. Ritter, N. T. Rogers-Neame, W. E. Rosenfeld, J. Schneiderman, R. Singer, N. K. So, B. Soederfeldt, I. N. Soryall, M. Sperling, E. Starreveld, B. J. Steinhoff, S. R G Stodiek, J. T J Tans, A. B. Todorov, C. B. Van Orman, M. Veilleux, O. Waltimo, B. B. Wannamaker, D. Weaver, P. Zagnoni

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)196-202
Number of pages7
JournalNeurology
Volume60
Issue number2
Publication statusPublished - Jan 28 2003

ASJC Scopus subject areas

  • Neuroscience(all)

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