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Topiramate add-on for drug-resistant partial epilepsy.

Abstract

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.

Authors+Show Affiliations

Department of Clinical Neurosciences, University of Calgary, Foothills Medical Centre, 1403-29 Street NW, Calgary, Alberta, Canada, TN2 2T9. nathalie.jette@calgaryhealthregion.caNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Review
Systematic Review

Language

eng

PubMed ID

18646072

Citation

Jette, Nathalie, et al. "Topiramate Add-on for Drug-resistant Partial Epilepsy." The Cochrane Database of Systematic Reviews, 2008, p. CD001417.
Jette N, Hemming K, Hutton JL, et al. Topiramate add-on for drug-resistant partial epilepsy. Cochrane Database Syst Rev. 2008.
Jette, N., Hemming, K., Hutton, J. L., & Marson, A. G. (2008). Topiramate add-on for drug-resistant partial epilepsy. The Cochrane Database of Systematic Reviews, (3), CD001417. https://doi.org/10.1002/14651858.CD001417.pub2
Jette N, et al. Topiramate Add-on for Drug-resistant Partial Epilepsy. Cochrane Database Syst Rev. 2008 Jul 16;(3)CD001417. PubMed PMID: 18646072.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Topiramate add-on for drug-resistant partial epilepsy. AU - Jette,Nathalie, AU - Hemming,Karla, AU - Hutton,Jane L, AU - Marson,Anthony G, Y1 - 2008/07/16/ PY - 2008/7/23/pubmed PY - 2008/10/16/medline PY - 2008/7/23/entrez SP - CD001417 EP - CD001417 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 3 N2 - 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. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/18646072/Topiramate_add_on_for_drug_resistant_partial_epilepsy_ L2 - https://doi.org/10.1002/14651858.CD001417.pub2 DB - PRIME DP - Unbound Medicine ER -