Outcomes of sustained-release formulation of valproate and topiramate monotherapy in patients with epilepsy: a multi-centre, cohort study

PLoS One. 2012;7(12):e47982. doi: 10.1371/journal.pone.0047982. Epub 2012 Dec 11.

Abstract

Background: New-generation antiepileptic drugs (AEDs) tend to replace traditional AEDs as the first-line choice for epilepsy. However, whether this change results in better outcome, especially in China, remains unknown.

Methodology/principal findings: Two broad spectrum AEDs, the traditional drug of sustained-release formulation of valproate (SRVPA) and the new-generation drug of topiramate, were compared in patients with epilepsy as monotherapy in this multi-centre, observational cohort study from 2000 to 2011. The primary outcome was time to treatment failure. The secondary outcomes included time to first seizure, time to 12-month remission, and time to 24-month remission. Drug tolerability was assessed. Cox proportional hazard models (95% confidence interval [CI]) were used to analyse the relative risks expressed as hazard ratios (HR). Of the 1008 recruited patients, 519 received SRVPA and 489 received topiramate. SRVPA was better than topiramate (28.3% vs. 41.5%; HR = 0.62, [95% CI 0.49-0.77]; p<0.0001) in primary outcome, and in time to first seizure (56.1% vs. 69.3%; HR = 0.73, [95% CI 0.62-0.86]; p = 0.0002). No significant difference was observed between two groups in time to 12-month remission (52.6% vs. 42.5%; HR = 1.01, [95% CI 0.84-1.23]; p = 0.88) and time to 24-month remission (34.7% vs. 25.2%; HR = 1.11, [95% CI 0.88-1.42]; p = 0.38). 36 patients (6.9%) in SRVPA group and 37 patients (7.6%) in topiramate group presented treatment failure associated with intolerable adverse events, there was no significant difference between the two groups (p = 0.70).

Conclusions: The SRVPA is more suitable than topiramate for Chinese epileptic patients, and our results support the viewpoint that traditional AEDs should be the first-line choice for epilepsy rather than new-generation AEDs.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anticonvulsants / administration & dosage*
  • Anticonvulsants / adverse effects
  • Child
  • Child, Preschool
  • China
  • Cohort Studies
  • Epilepsy / drug therapy*
  • Epilepsy / physiopathology
  • Female
  • Fructose / administration & dosage
  • Fructose / adverse effects
  • Fructose / analogs & derivatives*
  • Humans
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Topiramate
  • Treatment Outcome
  • Valproic Acid / administration & dosage*
  • Valproic Acid / adverse effects

Substances

  • Anticonvulsants
  • Topiramate
  • Fructose
  • Valproic Acid

Grants and funding

The data collection and the analysis of this study were funded by National Natural Science of China No. 81071039 (XFW), the Preeminent Medical Doctors' Foundation in Chongqing Medical University (YDH), and the grants of the Chongqing Medical Science and Technology Bureau of Research Projects (2009-2-356) (ZQX). The preparation of this manuscript was funded by the Natural Science Foundation Project of CQ CSTCX1263-0200190012 (ZQX) and the Chongqing Health Bureau funding (2011-2-118) (KBZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.