Topiramate titration and tolerability

V. Biton, K. R. Edwards, G. D. Montouris, J. C. Sackellares, C. L. Harden, M. Kamin

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

OBJECTIVE: To evaluate the tolerability and efficacy of two titration rates for topiramate initiated as adjunctive therapy in adults with partial-onset seizures, with or without secondary generalization, in a multicenter, double-blind trial. METHODS: After a two-week baseline phase, 188 patients were randomized to either a 50/50 titration schedule (initial dosage 50 mg/d increased in 50-mg/d increments at weekly intervals; n=93). The maximum dosage of 400 mg/d was therefore achieved in eight weeks or three weeks, respectively. RESULTS: Compared with the 100/200 titration rate, the 50/50 titration rate significantly reduced the cumulative incidence of treatment-emergent adverse events (TEASEs) leading to changes in topiramate therapy (i.e., dosage reductions, interruptions of discontinuations of therapy) (p= 0.048) and significantly reduced interruptions or withdrawals due to TEAEs (p =0.040). Mild or moderate effects involving the central nervous system were the most frequent adverse events. At the final visit, therapeutic responses were comparable in the 50/50 and 100/200 titration groups: median percent seizure reduction was 42% vs. 33% proportion of patients with ≥50% seizure reduction was 42% vs. 38%, and proportion of patients with no seizures during double-blind treatment was 14% vs. 10%, respectively. Seizure frequency was substantially reduced from baseline during topiramate titration. At day 22, with the 50/50 titration group receiving 150 mg/d and the 100/200 titration group receiving 400 mg/d, the median percent seizure reduction was 51% and 54%, respectively. CONCLUSIONS: Gradual initiation of topiramate therapy can significantly enhance patient tolerability without delaying therapeutic response.

Original languageEnglish
Pages (from-to)173-179
Number of pages7
JournalAnnals of Pharmacotherapy
Volume35
Issue number2
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Antiepileptic
  • Epilepsy
  • Titration
  • Topiramate

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