Topiramate add-on for drug-resistant partial epilepsy

BACKGROUND: The majority of people with epilepsy have a good prognosis and their seizures are controlled by a single antiepileptic drug. However, up to 20% of patients from population-based studies and up to 30% from clinical series (not population-based) develop drug-resistant epilepsy, especially those with partial onset seizures. In this review we summarize the current evidence regarding a new antiepileptic drug, topiramate, when used as an add-on treatment for drug-resistant partial epilepsy.

OBJECTIVES: To evaluate the efficacy and safety of topiramate when used as an add-on treatment for drug-resistant partial epilepsy.

SEARCH STRATEGY: We searched the Cochrane Epilepsy Group Specialized Register (10 May 2007); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2007). No language restrictions were imposed. We also contacted the manufacturers of topiramate and researchers in the field to see any ongoing or published studies.

SELECTION CRITERIA: Randomized placebo controlled add-on trials of topiramate recruiting people with drug-resistant partial epilepsy.

DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted the relevant data. The following outcomes were assessed: (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention-to-treat. Summary relative risks (RR) with 95% confidence intervals (95% CI) are presented. Dose response was evaluated in regression models.

MAIN RESULTS: Ten trials were included representing 1312 randomized participants. Baseline phases ranged from 4-12 weeks and double-blind phases from 11-19 weeks. The RR for a 50% or greater reduction in seizure frequency compared to placebo was 2.85 (95% CI 2.27 to 3.59). Dose regression analysis shows increasing effect with increasing dose, but found no advantage for doses over 300 or 400 mg per day. The RR for treatment withdrawal compared to placebo was 2.26 (95% CI 1.55 to 3.31). The RR for the following side effects indicate that they are significantly associated with topiramate: ataxia 1.95 (99% CI 1.04 to 3.65); dizziness 1.55 (99% CI 1.08 to 2.22); fatigue 2.19 (99% CI 1.43 to 3.35); nausea 2.35 (99% CI 1.28 to 4.29); somnolence 2.18 (99% CI 1.47 to 3.21) and 'thinking abnormally' 5.77 (99% CI 2.50 to 13.35).

AUTHORS' CONCLUSIONS: Topiramate has efficacy as an add-on treatment for drug-resistant partial epilepsy. However, trials reviewed were of relatively short duration, and provide no evidence for the long-term efficacy of topiramate. Results cannot be extrapolated to monotherapy or treating other epilepsy types.