Topiramate add-on for drug-resistant partial epilepsy

  • Review
  • Intervention

Authors


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 methods

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.

摘要

背景

Topiramate作為添加療法來治療藥物難治的局部發作型癲癇

多數癲癇患者的預後良好,使用單一抗癲癇藥物就可以有效控制其癲癇發作。但是以一般民眾為對象的研究發現有20% 的病患,及臨床研究(非以一般民眾為對象)發現有30% 的病患會發展成為藥物難治的癲癇,尤其是局部發作型的患者。在本次回顧中,我們總結了Topiramate(一個新的抗癲癇藥物)作為藥物難治的局部發作型癲癇的添加療法的臨床證據。

目標

評估Topiramate作為添加療法來治療藥物難治的局部發作型癲癇的療效和安全性。

搜尋策略

我們搜尋了Cochrane Epilepsy Group Specialized Register(2007年5月10日)以及Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library,2007年第3期)。沒有設定任何語言限制。我們同時聯繫Topiramate的製造商和該領域的研究者,尋找進行中或未發表的研究。

選擇標準

選擇比較添加Topiramate或安慰劑來治療藥物難治的局部發作型癲癇患者的隨機雙盲對照試驗。

資料收集與分析

兩位回顧作者各自選擇收納試驗和摘錄數據。評估了下列治療成果:(a) 癲癇發作頻率降低50% 或以上;(b) 停止試驗用藥(不論任何原因);(c) 藥物不良反應。初步分析採用intentiontotreat方法。將治療成果呈現為總體的relative risks(RR)與95% confidence intervals(95% CI)。使用回歸模型評估劑量與反應的相關性。

主要結論

總共收納了10個試驗,包括1312位隨機挑選的受試者。基準期(baseline phase)是4 – 12週,雙盲治療期是11 – 19週。在癲癇發作頻率降低50% 或以上方面,Topiramate相較於安慰劑的RR是2.85 (95% CI 2.27 – 3.59)。劑量回歸分析指出,劑量越大效果越強,但發現每日使用劑量超過300或400 mg不會有更好的效果。相較於安慰劑,停藥的RR是2.26 (95% CI 1.55 – 3.31)。Topiramate顯著與下列各項藥物不良反應相關,RR分別為:運動失調(ataxia)1.95 (99% CI 1.04 – 3.65);頭暈1.55 (99% CI 1.08 – 2.22);疲勞2.19 (99% CI 1.43 – 3.35);噁心2.35 (99% CI 1.28 – 4.29);嗜睡2.18 (99% CI 1.47 – 3.21) 以及‘思考異常(Thinking abnormally)5.77 (99% CI 2.50 – 13.35)。

作者結論

Topiramate作為添加療法來治療藥物難治的局部發作型癲癇患者時確有其療效。但因本回顧中的臨床試驗,治療期間都相對較短,所以無法提供長期療效的證據。上述的結果也不能外推到單一藥物療法或患有其他癲癇類型的病人。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

Topiramate作為治療藥物難治局部發作型癲癇患者的添加療法是有效的。癲癇是一種由於大腦放電異常引起的重覆發作的疾病。多數發作可以使用單一抗癲癇藥物得以控制。不幸的是,有一些人需要使用不止一種抗癲癇藥物才能控制癲癇發作,特別是當這些人的癲癇來自於大腦的某個區域(即局部發作型癲癇)而非全盤型的發作。本試驗回顧發現,作為一種抗癲癇藥物,Topiramate併用其他藥物,可以有效降低藥物難治的局部發作型癲癇的發作頻率。但是,也存在相關的藥物不良反應如:頭暈、疲勞、噁心、嗜睡和思考異常(Thinking abnormally)。 本回顧中的臨床試驗並未研究Topiramate的長期療效。

Plain language summary

Topiramate add-on for drug-resistant partial epilepsy

Topiramate is effective as an add-on treatment for drug-resistant partial epilepsy.

Epilepsy is a disorder where recurrent seizures are caused by abnormal electrical discharges from the brain. Most seizures can be controlled by a single antiepileptic drug. Unfortunately some people require more than one antiepileptic medication to control their seizures, especially if these originate from one area of the brain (partial epilepsy), instead of being generalized. The review of trials found that topiramate, an antiepileptic drug, is effective when used with other drugs to reduce the number of seizures in drug-resistant partial epilepsy. However, relevant side effects were dizziness; fatigue; nausea; somnolence and 'thinking abnormally'. The trials did not study the long-term effect of topiramate.