Anticonvulsant drugs for migraine prophylaxis

 

Abstract

Background

Anticonvulsant drugs seem to be useful in clinical practice for the prophylaxis of migraine. This might be explained by a variety of actions of these drugs in the central nervous system.

Objectives

To describe and assess the evidence from controlled trials on the efficacy and tolerability of anticonvulsants for preventing migraine attacks in adult patients with migraine.

Search methods

We searched PubMed (1966-December 2005), EMBASE (1974-December 2005) and the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2005), and handsearched Headache and Cephalalgia through April 2006.

Selection criteria

Studies were required to be prospective, controlled trials of anticonvulsant drugs taken regularly to prevent the occurrence of migraine attacks and/or to reduce the intensity of those attacks.

Data collection and analysis

Studies were selected and data extracted by two independent reviewers. For migraine frequency data, standardized mean differences (SMDs) were calculated for individual studies and pooled across studies. For dichotomous data on significant reduction in migraine frequency, odds ratios (ORs) and numbers-needed-to-treat (NNTs) were similarly calculated. Adverse events were analyzed by calculating numbers-needed-to-harm (NNHs) for studies using similar agents.

Main results

Twenty-three papers met the inclusion criteria. In total, data from 2927 patients were considered. Analysis of data from 10 trials (n = 902) demonstrates that anticonvulsants, considered as a class, reduce migraine frequency by about 1.3 attacks per 28 days as compared to placebo (WMD -1.31; 95% confidence interval [CI] -1.99 to -0.63). Data from 13 trials (n = 1773) show that anticonvulsants, considered as a class, also more than double the number of patients for whom migraine frequency is reduced by 50% or more relative to placebo (RR 2.25; 95% CI 1.79 to 2.84; NNT 3.9; 95% CI 3.4 to 4.7). For six trials of sodium valproate and divalproex sodium, NNHs for five clinically important adverse events ranged from 7.0 to 18.8. For six trials of topiramate, NNHs for seven adverse events (100 mg dose) ranged from 2.4 to 31.2.

Authors' conclusions

Anticonvulsants appear to be both effective in reducing migraine frequency and reasonably well tolerated. There is noticeable variation among individual agents, but there are insufficient data to know whether this is due to chance or variation in true efficacy. Acetazolamide, clonazepam, lamotrigine and vigabatrin were not superior to placebo (one trial each). Relatively few robust trials are available for agents other than sodium valproate/divalproex sodium and topiramate; gabapentin in particular needs further evaluation. Trials designed with sufficient power to compare different drugs are also necessary.

 

Plain language summary

Anticonvulsant drugs for migraine prophylaxis

Various medicines, collectively termed 'anticonvulsant drugs', are used to treat epilepsy. In recent years, some anticonvulsant drugs have also been used to reduce the frequency of migraine attacks. This review systematically examines the evidence supporting this practice. The authors conclude that anticonvulsant drugs are indeed effective in reducing the frequency of migraine attacks by approximately 1 to 2 attacks per month. Patients are also more than twice as likely to reduce the number of their migraine attacks by 50% or more with anticonvulsants than with an inactive placebo. There is, however, considerable variation among the available anticonvulsant drugs. Further research will be necessary to confirm the value of some drugs, and to compare the efficacy of drugs against each other.

 

摘要

背景

抗痙攣藥物於偏頭痛預防之使用

在臨床應用上抗痙攣藥物對於偏頭痛的預防似乎有益處，這可能可歸因於這類藥物在中樞神經系統中的多種作用。

目標

是為了描述及評估有偏頭痛的成人使用抗痙攣藥物來預防偏頭痛發作之療效及耐受性在對照試驗上的證據。

搜尋策略

我們搜尋了PubMed (1966December 2005), EMBASE(1974December 2005) 及 the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3,2005)，且以人工檢索2006年4月以前與Headache及Cephalalgia有關期刊。

選擇標準

研究必須是前瞻性的且為對照性的試驗，試驗內容為定期服用抗痙攣藥物預防偏頭痛的發作以及(或是)減少發作時的強度。

資料收集與分析

研究的挑選及擷取的數據是由兩位獨立審查員來進行。以標準化平均值差異(standardized mean differences, SMDs)來計算個別研究及彙整所有研究之偏頭痛的頻率數據。對於數據是否顯著降低偏頭痛的頻率，則使用勝算比(odds ratios, Ors)及利一需治數(numbersneededtotreat, NNTs) 來計算。對於使用類似藥物的研究，其不良事件則以計算害一需治數(numbersneededtoharm, NNHs)來分析。

主要結論

共有23篇文獻符合納入標準，總計有2927位病人的數據被分析。由10個試驗(病人數 = 902)數據分析的結果顯示，抗痙攣藥物與安慰劑相較下，每28天能減少1.3次偏頭痛的發作(WMD −1.31; 95% confidence interval [CI] −1.99 to −0.63)。由13個試驗(病人數 = 1773)數據分析的結果顯示，使用抗痙攣藥物偏頭痛發作頻率減少了50%以上(RR 2.25; 95%CI 1.79 to 2.84; NNT 3.9; 95% CI 3.4 to 4.7)的人與安慰劑相較，超過其一倍。在6個使用sodium valproate 及 divalproex sodium的試驗中，5個重大不良事件其NNHs範圍介於7.0 – 18.8之間。在6個使用topiramate的試驗中，7個不良事件(100 mg的劑量)的NNHs範圍介於2.4 – 31.2之間。

作者結論

本研究顯示抗痙攣藥物可以有效減少偏頭痛頻率，病人也有相當程度的藥物耐受性。在個別藥物間有顯著的差異，但無足夠數據可以得知到底是因為機率問題或是實際效果上的差異。Acetazolamide, clonazepam, lamotrigine 及 vigabatrin並未優於安慰劑組(每個藥物都有一個試驗)。除了sodium valproate/divalproex sodium 及topiramate外，其他藥物的高品質臨床試驗相對比較少；其中尤其以gabapentin特別需要進一步評估。同時也需要設計有足夠效力的試驗來比較不同的藥物。

翻譯人

本摘要由三軍總醫院洪乃勻翻譯。

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

總結

抗痙攣藥物能有效減少患有偏頭痛成人之偏頭痛發作次數。一些統稱為「抗痙攣藥物」的藥物用來治療癲癇。近年來，某些抗痙攣藥物也被用於減少偏頭痛發作的頻率。本回顧有系統地檢視了支持此項應用的證據。作者總結抗痙攣藥物確實能有效減少偏頭痛發作的頻率，大約每個月能減少1到2次。使用抗痙攣藥物的病人在減少偏頭痛發作次數達50%以上的人數比安慰劑組病人多了一倍以上。然而，不同抗痙攣藥物之間仍存在相當大的差異性。需要有進一步的研究來確認某些藥物的價值，並且比較不同藥物間的相對療效。