Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents

 

Abstract

Background

This is an updated version of the original Cochrane review published in Issue 3, 2003.

Absence seizures are brief epileptic seizures which present in childhood and adolescence. They are characterised by sudden loss of awareness and an electroencephalogram (EEG) typically shows generalised spike wave discharges at three cycles per second. Ethosuximide, valproate and lamotrigine are currently used to treat absence seizures. This review aims to determine the best choice of anticonvulsant for a child with typical absence seizures.

Objectives

To review the evidence for the effects of ethosuximide, valproate and lamotrigine as treatments for children and adolescents with absence seizures, when compared with placebo or each other.

Search methods

We searched the Cochrane Epilepsy Group's Specialised Register (November 2009), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2009), MEDLINE (1950 to November week 3, 2009) and EMBASE (1988 to March 2005). No language restrictions were imposed. In addition, we contacted Sanofi Winthrop, Glaxo Wellcome (now GlaxoSmithKline) and Parke Davis (now Pfizer), manufacturers of sodium valproate, lamotrigine and ethosuximide respectively.

Selection criteria

Randomised parallel group monotherapy or add-on trials which include a comparison of any of the following in children or adolescents with absence seizures: ethosuximide; sodium valproate; lamotrigine or placebo.

Data collection and analysis

Outcome measures were: (1) proportion of individuals seizure free at 1, 3, 6, 12 and 18 months post randomisation; (2) people with a 50% or greater reduction in seizure frequency; (3) normalisation of EEG and/or negative hyperventilation test and (4) adverse effects. Data were independently extracted by two review authors. Results are presented as relative risks (RR) with 95% confidence intervals (95% CI).

Main results

Five small trials were found, four of them were of poor methodological quality. One trial (29 participants) compared lamotrigine with placebo using a response conditional design. Individuals taking lamotrigine were significantly more likely to be seizure free than participants taking placebo during this short trial. Another trial compared lamotrigine with sodium valproate, the study lacked power to detect the difference in efficacy. Three studies compared ethosuximide, but because of diverse study designs and populations studied, we decided not to pool results in a meta-analysis. None of these studies found a difference between valproate and ethosuximide with respect to seizure control, but confidence intervals were wide and the existence of important differences could not be excluded.

Authors' conclusions

Although ethosuximide, lamotrigine and valproate are commonly used to treat people with absence seizures we have insufficient evidence to inform clinical practice, and the few trials included in this review were of poor methodological quality and did not have sufficient number of participants. More trials of better quality are needed.

 

Plain language summary

Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents

Not enough evidence to show which drugs are best for treating seizures in children and adolescents with absence epilepsy

Epilepsy is a disorder where seizures are caused by abnormal electrical discharges from the brain. Absence epilepsy involves seizures that cause a sudden loss of awareness. It often starts in childhood or adolescence. Three antiepileptic drugs are often used for absence epilepsy: valproate; ethosuximide and lamotrigine. Valproate can lead to weight gain, and may cause fetal abnormalities. The review found some evidence that individuals taking lamotrigine are more likely to be seizure free than those using placebos. No difference in effectiveness has been found between valproate and ethosuximide, but more research is needed.

 

摘要

背景

Ethosuximide、Sodium valproate、Lamotrigine用於兒童和青少年的失神型癲癇發作

失神型癲癇發作是發生於兒童和青少年的一種短暫癲癇發作的型式。特點是患者會突然失去意識，腦波(EEG)顯示每秒3次的全盤棘慢複合波。 Ethosuximide、Sodium valproate和Lamotrigine目前用來治療失神型癲癇發作。 本次回顧的目的是決定哪種抗癲癇藥物是治療患有典型失神型癲癇發作的兒童的最佳藥物。

目標

為了回顧Ethosuximide, Sodium valproate和Lamotrigine相對於安慰劑或他種藥物來治療患有失神型癲癇發作的兒童和青少年的療效證據。

搜尋策略

我們搜尋了Cochrane Epilepsy Group's Specialised Register(2007年7月)以及Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library，2007年第3期)、MEDLINE (1966年 2007年7月) 、EMBASE (1988 年 2005年8月)。沒有設定語言限制。另外，我們聯繫了Sanofi Winthrop、Glaxo Wellcome(目前是GlaxoSmithKline)和Parke Davis(目前是Pfizer)等公司，他們分別是製造Sodium valproate, Lamotrigine和Ethosuximide的廠商。

選擇標準

我們選擇了隨機分配平行對照之單一療法或addon試驗，比較Ethosuximide、Sodium valproate、Lamotrigine或安慰劑對治療患有失神型癲癇發作的兒童或青少年的療效。

資料收集與分析

療效成果評估包括：(1) 隨機分配之後，個體在第1、3、6、12和18個月癲癇沒有發作的比例；(2) 發作頻率降低50%或以上的比例；(3) EEG回復正常及／或過度換氣測試不會誘發失神型癲癇發作的比例；(4)不良反應。兩位回顧作者獨立擷取資料。將結果以Relative risks(RR)及95% confidence intervals(95% CI)來呈現。

主要結論

我們找到5個小規模試驗，其中4個試驗的研究方法學品質不佳。在比較Lamotrigine和安慰劑(29位受試者)的某次試驗中，使用response conditional design。 在這個短期的試驗中，服用Lamotrigine的病患比起使用安慰劑的受試者，明顯較能達成癲癇不發作的情況。於另外一個比較Lamotrigine和Sodium valproate的試驗中，該研究無法得知兩者間療效有差異。另有3個研究比較Ethosuximide，但是由於研究設計和研究對象的差異太大，我們決定不將結果合併在metaanalysis中。沒有任何一項研究發現Valproate和Ethosuximide在控制癲癇發作方面有差異，但是由於信賴區間比較寬，所以不排除可能兩者間仍存在重要差異。

作者結論

儘管Ethosuximide、Lamotrigine和Valproate是常見治療失神型癲癇發作的藥物，但是我們沒有充足的證據提供給臨床實務之用。本次回顧中的數個試驗，其研究方法學品質不佳，並且受試者人數不足。因此我們需要更多品質更好的試驗。

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

目前沒有足夠的證據指出哪些藥物是治療的兒童和青少年的失神型癲癇發作的最佳藥物。癲癇是由於大腦放電異常引起的發作性疾病。失神型癲癇發作的特點包括，發作時造成意識障礙，通常發生於兒童或青少年期間。失神型癲癇發作的治療常使用三種抗癲癇藥物：Valproate、Ethosuximide和Lamotrigine。Valproate可能導致體重增加，可能會引起胎兒發育異常。本次回顧發現一些證據指出比起使用安慰劑的患者，使用Lamotrigine的人更可能達成癲癇不發作的狀況。目前沒有發現Valproate和Ethosuximide在療效上有差異，但我們仍然需要有更多相關的研究來支持此點。