Calcium antagonists as an add-on therapy for drug-resistant epilepsy

 

Abstract

Background

This is an updated version of the original Cochrane review published in The Cochrane Library 2001, Issue 4.

Nearly a third of people with epilepsy do not have their seizures controlled with current treatments. Continuous attempts have been made to find new antiepileptic drugs based on increasing knowledge of cellular and molecular biology involved in the genesis of epilepsy and seizures. Therefore, calcium antagonists that can alter the effects of calcium on brain cells have been investigated for effect on epileptic seizures.

Objectives

To evaluate the effects of calcium antagonists when used as an add-on therapy for people with drug-resistant epilepsy.

Search methods

We searched the Cochrane Epilepsy Group's Specialized Register (12 May 2011), the Cochrane Central Register of Controlled Trials ((CENTRAL) The Cochrane Library 2011, Issue 2) and MEDLINE (1948 to May 2011).

Selection criteria

Randomized placebo-controlled add-on trials of any calcium antagonists in people with drug-resistant epilepsy.

Data collection and analysis

Two review authors (Rungsan Chaisewikul and Nick Baillie) independently selected trials for inclusion and extracted data. Outcomes investigated included 50% or greater reduction in seizure frequency, treatment withdrawal and adverse effects. Analyses were by intention-to-treat.

Main results

We included 11 trials with a total of 424 participants. One parallel and seven cross-over trials of flunarizine, two cross-over trials of nimodipine and one cross-over trial of nifedipine.

For flunarizine, the odds ratio (OR) with 95% confidence intervals (CI) for a 50% or greater reduction in seizure frequency for the parallel trial was 1.64 (95% CI 0.55 to 4.94) indicating a non-significant advantage of flunarizine. We were unable to acquire data for this outcome from the other seven cross-over trials. The overall OR for treatment withdrawal for flunarizine was 5.83 (95% CI 2.06 to 16.45) indicating individuals were significantly more likely to have flunarizine withdrawn than placebo. No adverse effects were statistically associated with flunarizine.

For nifedipine, we were unable to acquire the data we required for our specified outcomes.

For nimodipine, we had data only from the first treatment period from one of the two cross-over trials (17 participants). The ORs for a 50% or greater reduction in seizure frequency was 11.34 (95% CI 1.00 to 128.03) and for treatment withdrawal was 2.46 (95% CI 0.22 to 27.75).

Authors' conclusions

Flunarizine may have a weak effect on seizure frequency, but had a significant withdrawal rate probably due to adverse effects, and should not be recommended for use as an add-on treatment. Similarly, there is no convincing evidence to support the use of nifedipine or nimodipine as add-on treatments for epilepsy.

 

Plain language summary

Calcium antagonists as an add-on therapy for drug-resistant epilepsy

No evidence to suggest that calcium antagonists have a useful effect on seizures.

Nearly a third of people with epilepsy become resistant to antiepileptic drugs. These older drugs do not prevent seizures for everyone, and they have adverse effects. A range of new drugs have been tested as 'add-on' treatments to try and improve the results from older drugs. The calcium antagonist drugs flunarizine, nifedipine and nimodipine have been tested in this way. The review of trials found no evidence to show an effect of these drugs on seizures. Adverse effects include dizziness, fatigue and unsteadiness (ataxia).

 

摘要

背景

鈣離子阻斷劑使用於藥物難治型癲癇的附加使用

約有三分之一的癲癇病患的癲癇發作無法以目前的藥物完全控制住.基於對癲癇發生過程中,細胞學與分子生物學等知識的增加找尋新的抗癲癇藥物仍持續著.鈣離子阻斷劑可改變鈣離子對腦細胞的作用,因此其抗癲癇效果也被研究.

目標

評估鈣離子 阻斷劑作為藥物難治型癲癇的附加治療時的效果

搜尋策略

我們搜尋了Cochrane Epilepsy Group's Specialized Register (7 October 2009)、Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2009) 及 MEDLINE (1950 to September week 4, 2009)

選擇標準

任何使用鈣離子阻斷劑作為藥物難治型癲癇的附加治療的隨機,安慰劑對照試驗

資料收集與分析

兩位獨立的審查者各自選擇合適收錄的試驗與資料.分析結果包括1.大於或等於50%以上的癲癇發作頻率減少2.停藥與藥物不良反應.分析的方法使用intentiontotreat方法

主要結論

總共收錄了11個臨床試驗.利用flunarizine來作為治療,有一個parallel和7個crossover試驗,使用nimodipine的有2個crossover試驗,給予nifedipine的則有一個crossover試驗.對於flunarizine能否減少癲癇發作頻率,由所收錄的一個並行試驗得知.odds ratio 為1.64%(95%(I0.55−4.94).顯示沒有顯著減少發作頻率達到大於或等於5%以上.至於此項結果分析,無法從另外7個crossover試驗得知.另外與安慰劑相比,病患較容易停用flunarizine or 5.83 (95% CI 2.06 to 16.45).然而並未有單一之不良反應試顯著比安慰劑更多的.針對nifedipine我們無法找到合適的資料來進行分析.至於nimodipine,我們僅有從其中1個crossover試驗得到17位病人於早期治療期間的相關資料.對減少癲癇發作的效果上OR為2.46(95% CI 0.22 to 27.75).

作者結論

Flunarizine可能對於減少癲癇發作頻率上有微弱的效果,但是可能會因為副作用而明顯導致病患較易停用,因此不建議作為癲癇的附加治療.同樣的,目前沒有足夠的證據支持使用nifedipine 或nimodipine 作為癲癇的附加治療.

翻譯人

本摘要由高雄長庚醫院曾昱龍翻譯

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

總結

目前沒有足夠證據支持使用鈣離子阻斷劑作為癲癇的附加治療.約有1/3的癲癇病患屬於藥物難治型癲癇.舊有的抗癲癇藥物無法讓所有病患都不再發作,而且經常會造成副作用.有一些新的藥物,已經被試驗來改善治療癲癇的效果其中flunarizine, nifedipine 及 nimodipine這三種鈣離子阻斷劑已經做過試驗,然而本回顧分析發現目前尚未有足夠的證據支持使用鈣離子阻斷劑於癲癇之治療,而副作用常包括頭暈,疲倦及步態不穩(運動失調)