Intervention Review

Carbamazepine versus phenobarbitone monotherapy for epilepsy

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

Editorial Group: Cochrane Epilepsy Group

Published Online: 20 JAN 2003

Assessed as up-to-date: 30 SEP 2006

DOI: 10.1002/14651858.CD001904


How to Cite

Tudur Smith C, Marson AG, Williamson PR. Carbamazepine versus phenobarbitone monotherapy for epilepsy. Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD001904. DOI: 10.1002/14651858.CD001904.

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: 20 JAN 2003

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Abstract

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

Background

In developing countries, phenobarbitone is commonly used but its use in Europe and the USA has decreased due to concerns over adverse effects. Carbamazepine is recommended as the drug of choice for partial onset seizures, and there is concern that it may worsen some generalized onset seizure types. We report a review using individual patient data in which carbamazepine and phenobarbitone are compared.

Objectives

To review the effects of carbamazepine compared to phenobarbitone monotherapy for people with partial onset seizures or generalized onset tonic-clonic seizures.

Search methods

We searched the Cochrane Epilepsy Group's Specialized Register (October 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2006) and MEDLINE (Ovid, 1950 to August 2006). We contacted experts in the field, original trial investigators, and the manufacturers of carbamazepine.

Selection criteria

Randomized or quasi-randomized, blinded or unblinded controlled trials in children or adults with partial onset seizures or generalized onset tonic-clonic seizures.

Data collection and analysis

Outcome measures were (i) time to withdrawal of allocated treatment, (ii) time to 12-month remission, and (iii) time to first seizure. Data were analysed using a stratified logrank analysis with results expressed as hazard ratios (HR) and 95% confidence intervals (CIs), where a HR>1 indicates an event is more likely on phenobarbitone. A test for interaction between treatment and seizure type (partial versus generalized onset) was also undertaken.

Main results

Data are available for 684 participants from four trials, representing 59% of the participants recruited into the nine trials that met our inclusion criteria. The main overall results (HR 95% CI) adjusted for seizure type were, (i) time to withdrawal 1.63(1.23 to 2.15), (ii) time to 12-month remission 0.87 (0.65 to 1.17), (iii) time to first seizure 0.85 (0.68 to 1.05). The review suggests that time to withdrawal is significantly improved with carbamazepine compared to phenobarbitone. No overall difference between drugs is identified for the outcomes 'time to 12-month remission' and 'time to first seizure'. Statistical heterogeneity was not encountered. An interaction between treatment and seizure type, confirmed statistically, was identified for time to first seizure, where phenobarbitone was favoured for partial onset seizures and carbamazepine for generalized onset tonic-clonic seizures.

Authors' conclusions

We found no overall difference between carbamazepine and phenobarbitone for time to 12-month remission or time to first seizure, however, subgroup analyses for time to first seizure suggest an advantage with phenobarbitone for partial onset seizures and a clinical advantage with carbamazepine for generalized onset tonic-clonic seizures. Phenobarbitone is significantly more likely to be withdrawn, indicating that it is less well tolerated than carbamazepine.

 

Plain language summary

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

Carbamazepine versus phenobarbitone monotherapy for epilepsy

Epilepsy is a disorder where recurrent seizures are caused by abnormal electrical discharges from the brain. Carbamazepine and phenobarbitone are commonly used antiepileptic drugs. The review of trials found that carbamazepine is better tolerated than phenobarbitone. No reliable evidence was found of a difference in the overall seizure control between these two drugs. For the seizure types investigated, time to first seizure was longer for people with partial onset seizures taking phenobarbitone whilst carbamazepine tended to be better for people with generalized onset seizures.

 

摘要

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

背景

以Carbamazepine或Phenobarbitone 作為癲癇的單一藥物治療之比較

發展中國家常使用Phenobarbitone,但是在歐洲和美國由於考慮到不良反應,其用量呈下降趨勢。Carbamazepine為被推薦作為治療局部型癲癇發作的首選藥物,但是存在著可能使某些全盤型癲癇發作惡化的疑慮。在此,我們運用統計學方法從現有臨床試驗中取得之個別病人資料累積來回顧比較Carbamazepine和Phenobarbitone治療癲癇的結果。

目標

這裏回顧了使用Carbamazepine或Phenobarbitone作為單一藥物治療患有局部型癲癇發作的病人或全盤型強直陣攣發作病人的治療成果。

搜尋策略

我們搜尋了Cochrane Epilepsy Group's Specialized Register(2006年10月)以及Cochrane Central Register of Controlled Trials (The Cochrane Library,2006年第4期), MEDLINE、EMBASE等資料庫,也利用人工搜尋、聯繫癲癇專家和參與臨床試驗的研究人員,也聯繫Carbamazepine的製造廠商。

選擇標準

選擇對患有局部型癲癇發作或全盤型強直陣攣發作的兒童或成人進行的隨機或半隨機盲法或非盲法對照試驗。

資料收集與分析

治療成果的收集包括 (i) 開始治療後至停止試驗用藥的時間 (ii) 開始治療後至達成連續12個月緩解的時間 (iii) 開始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),其中HR>1表示該事件較可能發生在使用Phenobarbitone時。我們也檢驗了治療藥物和發作類型(局部型癲癇發作對比全盤型發作)之間的相互影響。

主要結論

我們從4個試驗中取得其中684位受試者的相關資料,佔所有9個符合我們選擇條件的試驗中所有病患的59%。根據不同發作類型加以調整後的治療成果及其HR與95% CI如下:(i) 開始治療後至停止試驗用藥的時間為1.63 (1.23 – 2.15);(ii) 開始治療後至達成連續12個月緩解的時間為0.87 (0.65 – 1.17);(iii) 開始治療後至首次癲癇發作的時間為0.85 (0.68 – 1.05)。本回顧顯示比起Phenobarbitone,使用Carbamazepine能夠顯著改善開始治療後至停止試驗用藥的時間。然而就開始治療後至達成連續12個月緩解的時間和開始治療後至首次癲癇發作的時間等項目的比較而言,兩種藥物間沒有顯著差異。資料分析上並未出現統計學異質性。 至於治療藥物和發作類型之間的相互影響方面,統計學上有意義的發現僅出現於開始治療後至首次癲癇發作的時間上,其中以henobarbitone來治療局部型癲癇發作時的結果較佳,而以Carbamazepine來治療全盤型強直陣攣發作時較好。

作者結論

我們發現使用Carbamazepine和Phenobarbitone在開始治療後至達成連續12個月緩解的時間及開始治療後至首次癲癇發作的時間兩方面沒有整體差異,但是於開始治療後至首次癲癇發作的時間的子群體分析中,使用henobarbitone對局部型癲癇發作而Carbamazepine對全盤型強直陣攣發作具有臨床上的優勢。使用Phenobarbitone的患者明顯較早停止使用試驗用藥,這說明它的耐受度較Carbamazepine差。

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

癲癇是一種由於腦部放電異常而引起的反覆發作的疾病。Carbamazepine和Phenobarbitone是常見治療癲癇的抗癲癇藥物。本回顧發現使用Carbamazepine比Phenobarbitone更有耐受性。目前沒有發現可靠的證據指出兩種藥物對於控制整體癲癇發作有顯著差異。至於針對不同發作類型的治療效果比較上Phenobarbitone比較能延後患有局部型癲癇發作病人在接受治療後首次發作的時間,而Carbamazepine則對患有全盤型癲癇發作的病人有類似的效果。