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Intervention Review

Phenytoin versus valproate monotherapy for partial onset seizures and generalized onset tonic-clonic seizures

  1. Catrin Tudur Smith1,*,
  2. Anthony G Marson2,
  3. Paula R Williamson1

Editorial Group: Cochrane Epilepsy Group

Published Online: 23 OCT 2001

Assessed as up-to-date: 26 JUL 2007

DOI: 10.1002/14651858.CD001769


How to Cite

Tudur Smith C, Marson AG, Williamson PR. Phenytoin versus valproate monotherapy for partial onset seizures and generalized onset tonic-clonic seizures. Cochrane Database of Systematic Reviews 2001, Issue 4. Art. No.: CD001769. DOI: 10.1002/14651858.CD001769.

Author Information

  1. 1

    University of Liverpool, Centre for Medical Statistics and Health Evaluation, Liverpool, UK

  2. 2

    Clinical Sciences Centre for Research & Education, University Department of Neurological Science, Liverpool, Merseyside, UK

*Catrin Tudur Smith, Centre for Medical Statistics and Health Evaluation, University of Liverpool, Shelley's Cottage, Brownlow Street, Liverpool, L69 3GS, UK. cat1@liverpool.ac.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 23 OCT 2001

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Phenytoin and valproate are commonly used antiepileptic drugs. It is generally believed that phenytoin is more effective for partial onset seizures, or generalized onset seizures with or without other generalized seizure types.

Objectives

To review the best evidence comparing phenytoin and valproate when used as monotherapy in people with partial onset seizures, or generalized onset tonic-clonic seizures with or without other generalized seizure types.

Search methods

We searched the Cochrane Epilepsy Group's Specialized Register (July 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2007) and MEDLINE (1966 to July 2007). No language restrictions were imposed. We also contacted pharmaceutical companies and researchers in the field.

Selection criteria

Randomized controlled trials in children or adults with partial onset seizures or generalized onset tonic-clonic seizures. Trials must have included a comparison of phenytoin monotherapy with valproate monotherapy.

Data collection and analysis

This was an individual patient data review. Outcomes were time to (a) withdrawal of allocated treatment; (b) 12 month remission; (c) six month remission and (d) first seizure post randomization. Data were analysed using stratified logrank analysis with results expressed as hazard ratios (HR) and 95% confidence intervals (95% CI), where a HR greater than one indicates an event is more likely on phenytoin.

Main results

Data were available for 669 individuals from five trials, representing 60% of the participants recruited into the eleven trials that met our inclusion criteria. One important limitation is that in four of the five trials, for people classified as having generalized onset seizures, tonic-clonic seizures were the only seizure types recorded at follow up. Hence results apply only to generalized tonic-clonic seizures. The main overall results were as follows (HR, HR greater than one indicates a clinical advantage for phenytoin for both remission outcomes and a clinical advantage for valproate for the outcomes time to withdrawal and time to first seizure): (a) time to withdrawal of allocated treatment 1.10 (95% CI 0.79 to 1.54); (b) time to 12 month remission 1.04 (95% CI 0.78 to 1.38); (c) time to six month remission 0.89 (95% CI 0.71 to 1.11) and (d) time to first seizure 0.92 (95% CI 0.74 to 1.14). The results suggest no overall difference between the drugs for these outcomes. No statistical interaction between treatment and seizure type (partial versus generalized) was found.

Authors' conclusions

We have not found evidence that a significant difference exists between phenytoin and valproate for the outcomes examined in this review. Results do not apply to absence or myoclonus. No outright evidence was found to support or overthrow current treatment policies.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Phenytoin versus valproate monotherapy for partial onset seizures and generalized onset tonic-clonic seizures

No evidence to suggest any difference between the drugs phenytoin and valproate for the seizure types studied.

Epilepsy is a disorder where recurrent seizures are caused by abnormal electrical discharges from the brain. Phenytoin and valproate are commonly used antiepileptic drugs. The review of trials found no difference between these two drugs for the seizure types studied. The review also found no evidence to support the policy of using valproate for generalized onset tonic-clonic seizures and phenytoin for partial onset seizures. We were unable to address the issue of preferring valproate for generalized onset seizure types other than tonic-clonic.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

比較Phenytoin或Valproate作為單一藥物來治療局部型癲癇發作或全盤型強直陣攣發作

Phenytoin和Valproate是常用的抗癲癇藥物。一般認為,Phenytoin更能有效治療局部型癲癇發作或全盤型強直陣孿發作(不論有無合併其他全盤型癲癇發作類型)。

目標

這裏回顧了比較使用Phenytoin和Valproate作為單一藥物來治療局部型癲癇發作或全盤型強直陣攣發作(不論有無合併其他全盤型癲癇發作類型)的最佳臨床證據。

搜尋策略

我們搜尋了Cochrane Epilepsy Group's Specialized Register(2007年7月)以及 Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library,2007年第3期) 和MEDLINE (1966年2007年7月) 。我們也聯繫製藥公司和該領域的研究者。

選擇標準

選擇對患有局部型癲癇發作或全盤型強直強直陣攣發作的兒童或成年人所進行的隨機對照試驗。 試驗必須包括對Pheytoin單一療法和Valproate單一藥物治療的比較。

資料收集與分析

本研究是取自臨床試驗中個別病患資料的回顧。治療成果的收集包括 (a) 開始治療後至停止試驗用藥的時間 (b) 開始治療後至達成連續12個月緩解的時間 (c) 開始治療後至達成連續6個月緩解的時間 (d) 開始隨機分配治療後至首次癲癇發作的時間。我們使用stratified logrank analysis來分析資料,將結果呈現為hazard ratios (HR) 和95% confidence intervals (CIs)(95% CI),其中HR>1表示該事件較有可能發生在使用Phenytoin時。.

主要結論

我們從5個試驗中取得其中699位受試者的相關資料,佔所有7個符合我們選擇條件的試驗中所有病患的60%。本回顧的一個重要侷限,即在於所收納的4個臨床試驗中,針對患有全盤型癲癇發作的患者,只追蹤他們發生全盤型強直強直陣攣發作的記錄,而未追縱其他種類的全盤型癲癇發作。因此,這些治療成果只適用於患有全盤型強直強直陣攣發作的病人。各項治療成果的HR(HR>1表示Phenytoin在達成緩解期的成果具有臨床優勢,而Valproate在到達停止用藥和首次復發等時間方面具有臨床優勢)如下: (a) 開始治療後至停止試驗用藥的時間為1.10 (95% CI 0.79 – 1.54);(b) 開始治療後至達成連續12個月緩解的時間為1.04 (95% CI 0.78 – 1.38); (c) 開始治療後至達成連續6個月緩解的時間為0.89 (95% CI 0.71 – 1.11);(d) 開始隨機分配治療後至首次癲癇發作的時間為0.92 (95% CI 0.74 – 1.14)。上述的分析顯示,兩種藥物在這些治療成果上不存在整體差異,且藥物與發作類型(局部型癲癇發作對比全盤型發作)之間沒有統計學上顯著的相互影響。

作者結論

我們未發現有證據指出Phenytoin和Valproate在本回顧所檢驗的治療成果方面存在顯著差異。上述的結論不適用於失神型(absence)或肌抽躍型(myoclonus)癲癇發作。目前沒有發現有證據直接支持或反對目前的治療方針。

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

目前沒有證據指出Phenytoin和Valproate在治療所回顧的癲癇發作類型(即局部型癲癇發作或全盤型強直陣攣發作)上有差異。癲癇是一種由於腦部放電異常而引起的反覆發作的疾病。Phenytoin和Valproate是常用的抗癲癇藥物。本回顧發現,兩種藥物在所回顧的癲癇發作類型方面不存在差異。同時,本回顧發現沒有證據能夠支持使用Valproate來治療全盤型強直陣攣發作及使用Phenytoin來治療局部型癲癇發作的治療方針。然而我們無法論述是否Valproate更適合治療強直陣攣發作以外的其他種類全盤型癲癇發作。