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Topiramate add-on for drug-resistant partial epilepsy
N J Jette1, A G Marson, J L Hutton
1Neurology, Ottawa Hospital - General Campus, 501 Smyth Road, Ottawa, Canada, K1H 8L6. n.jette@sympatico.ca
Background:
The majority of people with epilepsy have a good prognosis and their seizures are controlled by a single antiepileptic drug. However, up to 30 per cent 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 effects of topiramate when used as an add-on treatment for drug-resistant partial epilepsy.
Search Strategy:
We searched the Cochrane Epilepsy Group's specialized register (28 March 2002); the Cochrane Controlled Trials Register (Cochrane Library Issue 1, 2002). In addition, we contacted Johnson and Johnson (makers of topiramate) and experts in the field to seek any ongoing or unpublished studies.
Selection Criteria:
Randomized placebo controlled add-on trials of topiramate recruiting people with drug-resistant partial epilepsy.
Data Collection And Analysis:
Two reviewers independently selected trials for inclusion and extracted the relevant data. The following outcomes were assessed: (a) 50 per cent 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:
Nine trials were included representing 1049 randomized participants. The RR for a 50 per cent or greater reduction in seizure frequency compared to placebo was 3.32(95% CI 2.52 to 4.39). Dose regression analysis shows increasing effect with increasing dose, but found no advantage for doses over 300 mg per day. The RR for treatment withdrawal compared to placebo was 2.06(95% CI 1.38 to 3.08). The RR for the following side effects indicate that they are significantly associated with topiramate: 1.95(99% CI 1.04 to 3.65), dizziness 1.55(99% CI 1.07 to 2.24); fatigue 2.21(99% CI 1.42 to 3.45); nausea 2.75(99% CI 1.36 to 5.57); somnolence 2.26(99% CI 1.48 to 3.46) and 'thinking abnormally' 5.54(99% CI 2.34 to 13.12).
Reviewer'S 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.