Efficacy, tolerability, and safety of rapid initiation of topiramate versus phenytoin in patients with new-onset epilepsy: a randomized double-blind clinical trial.

Authors

• Eugene Ramsay
• Edward Faught
• Allan Krumholz
• Dean Naritoku
• Michael Privitera
• Lesley Schwarzman
• Lian Mao
• Frank Wiegand
• Joseph Hulihan

Publication/Presentation Date

10-1-2010

Abstract

PURPOSE: To evaluate topiramate (TPM) and phenytoin (PHT) monotherapy following rapid oral initiation in new-onset epilepsy.

METHODS: Randomized, double-blind, 28-day trial of TPM (100 mg/day beginning on day 1) versus PHT (1,000 mg on day 1 followed by 300 mg/day maintenance dosing) in 261 patients with new-onset epilepsy. The primary end point was time to seizure, and the primary objective was to establish noninferiority of TPM to PHT in the risk of seizure.

RESULTS: At day 28, the estimated seizure-free rate was 81.1% for TPM treatment in comparison with 90.3% for PHT treatment. Noninferiority of TPM to PHT (primary objective) could not be established [hazard ratio (HR) 2.0, 95% confidence interval (CI), 0.98 to 4.12, p = 0.366), and PHT could not be shown to be superior to TPM. A higher percentage discontinued with PHT compared to TPM for all reasons (21.1 vs. 12.8%) and due to adverse events (13.4 vs. 6.8%). The most common treatment-related adverse events in both groups were dizziness, paresthesia, and somnolence. A post hoc analysis showed that TPM was superior to PHT in time to discontinuation (retention rate) for all causes (89.4% vs. 80.3%, p = 0.047).

CONCLUSION: This study was inconclusive in establishing noninferiority of TPM 100 mg/day compared to a standard regimen of oral PHT in seizure risk in this population of patients with new-onset epilepsy. Given the superiority of TPM in overall retention and favorable tolerability without titration, it may nonetheless be an appropriate option in some patients with new-onset epilepsy requiring rapid treatment initiation.

Volume

51

Issue

10

First Page

1970

Last Page

1977

ISSN

1528-1167

Published In/Presented At

Ramsay, E., Faught, E., Krumholz, A., Naritoku, D., Privitera, M., Schwarzman, L., Mao, L., Wiegand, F., Hulihan, J., & CAPSS-272 Study Group (2010). Efficacy, tolerability, and safety of rapid initiation of topiramate versus phenytoin in patients with new-onset epilepsy: a randomized double-blind clinical trial. Epilepsia, 51(10), 1970–1977. https://doi.org/10.1111/j.1528-1167.2010.02670.x

Disciplines

Medicine and Health Sciences

PubMedID

20633037

Department(s)

Department of Medicine

Document Type

Article