Rapid versus slow withdrawal of antiepileptic drugs

  • Review
  • Intervention

Authors


Abstract

Background

The ideal objective of treating a person with epilepsy is to induce remission by usage of antiepileptic drugs (AEDs) and withdraw the AEDs without causing seizure recurrence. Prolonged usage of AEDs may have long-term side effects. Hence when a person with epilepsy is in remission (free of seizures for some time) it is logical to attempt to discontinue the medication. The timing of withdrawal and the mode of withdrawal arise while contemplating withdrawal of AEDs. This review proposes to examine the evidence for the rate of withdrawal of AEDs (whether rapid or slow tapering) and its effect on recurrence of seizure. This review also examines the effect of variables such as age of seizure onset, seizure types, presence of neurological deficits, mental subnormality, aetiology of epilepsy, type of AED, EEG findings or duration of seizure freedom on the risk of recurrence of seizures with the two tapering regimens.

Objectives

(1) To quantify risk of seizure recurrence after rapid (taper period of three months or less) or slow (taper period or more than three months) discontinuation of antiepileptic drugs in adults with epilepsy who are in remission.
(2) To quantify the risk of seizure recurrence after rapid (taper period of three months or less) or slow (taper period of more than three months) discontinuation of antiepileptic drugs in children with epilepsy who are in remission.
(3) To attempt to assess which variables modify the risk of seizure recurrence.

Search methods

We searched the Cochrane Epilepsy Group's Specialized Register (August 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to September 2004) and cross-references from identified studies. No language restrictions were imposed.

Selection criteria

Randomized controlled trials that evaluate withdrawal of AEDs in a rapid or slow manner after varying periods of seizure control in patients with epilepsy.

Data collection and analysis

Both review authors independently assessed the trials for inclusion and extracted the data. The outcomes assessed included seizure relapse (i.e. the percentage of patients experiencing seizure recurrence after withdrawal of AED); time to recurrence of seizure following withdrawal; occurrence of status epilepticus; mortality; morbidity due to seizure such as injuries, fractures, aspiration pneumonia; and quality of life (if assessed by validated scale).

Main results

One trial with weak methodology involving 149 children was included with a mean age of seizure onset of four years, mean age of 11 years at the time of starting the taper. The rapid taper group (six weeks) recruited 81 participants and the slow taper group (nine months) included 68 participants, out of whom 11 and 5 were lost to follow up even before the taper began respectively. The number of participants who were seizure free in the rapid and slow taper groups were 40 and 44 respectively at the end of one year follow up (OR 0.53, 95% CI 0.27 to 1.03); 30 and 29 respectively at the end of two years, (OR 0.79, 95% CI 0.41 to 1.53); 24 and 14 respectively at the end of three years (OR 1.62, 95% CI 0.76 to 3.46); 18 and 8 respectively at the end of four years (OR 2.14, 95% CI 0.87 to 5.3); 10 and 6 respectively at the end of five years (OR 1.46, 95% CI 0.5 to 4.23).

Authors' conclusions

In view of methodological deficiencies and small sample size, in the solitary study identified, we cannot derive any reliable conclusions regarding the optimal rate of tapering of AEDs. Further studies are needed in adults as well as in children to investigate the rate of withdrawal of AEDs and to study the effects of variables such as seizure types, its aetiology, mental retardation, EEG abnormalities, presence of neurological deficits and other co-morbidities on the rate of tapering.

摘要

背景

快速和慢速停用抗癲癇藥物之比較

治療癲癇病患的理想目標是使用抗癲癇藥物 (AEDs)達成緩解,進而停止使用AED後,也不會復發。長時間使用AEDs,可能會產生長期的副作用。因此,當癲癇患者處於緩解期(一段時間不再發作),那麼嘗試停止用藥是合乎邏輯的。在什麼時機與採用何種方式是考慮停藥時該思考的問題。 本回顧預計檢驗有關AEDs停用速度(快速或慢速停藥)的臨床證據與其對於癲癇復發的影響。同時也評估下列各種變數對於癲癇復發風險的影響,包括了發作年齡、發作類型、有無神經功能缺損、心智低下、癲癇病因、AED種類、腦波發現或癲癇無發作的持續期間等。

目標

(1) 量化對緩解期內的成年癲癇患者實施快速(3個月內)或慢速(3個月以上)停藥後癲癇復發的風險。(2) 量化對緩解期內的兒童癲癇患者實施快速(3個月內)或慢速(3個月以上)停藥後癲癇復發的風險。(3) 試圖評估有哪些變數會影響復發的風險。

搜尋策略

我們搜尋了Cochrane Epilepsy Group's Specialized Register(2005年8月)以及Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2005年第3期) 和MEDLINE (1966年2004年12月),並且交叉參照所找到的臨床試驗。沒有設定任何語言限制。

選擇標準

選擇針對已達成某段期間癲癇控制之患者,比較快速或慢速停藥之隨機對照試驗

資料收集與分析

兩位作者單獨評估試驗的收錄和提取了資料。結果的評估包括復發(停止服用AED後復發的比例)、停藥後至首次復發的時間、是否出現癲癇持續狀態、死亡率、因癲癇發作導致受傷、骨折、吸入性肺炎的發病率、及生活品質(使用受驗證過的量表評估者)等面向。

主要結論

我們僅收錄了一個方法學品質較差的試驗,共有149位兒童參加,平均的癲癇發作年齡為4歲,平均於11歲開始減量。快速減量組(6週)收納了81位受試者,慢速減量組(9個月)則有68位受試者參加,其中,分別各有11人和5人在減量開始之前就喪失聯繫或追蹤。在快速減量組和慢速減量組,分別有40和44位受試者在一年後的追蹤時沒有癲癇發作OR 0.53, 95% CI (0.27 – 1.03);分別有30和29人在兩年底沒有癲癇發作OR 0.79, 95% CI (0.41 – 1.53);分別有24和14人在三年底沒有癲癇發作OR 1.62, 95% CI (0.76 – 3.46);分別有18和8人在四年底沒有癲癇發作OR 2.14, 95% CI (0.87 – 5.3); 分別有10和6人在五年底沒有癲癇發作OR 1.46, 95% CI (0.5  4.23)。

作者結論

從方法學缺失和樣本規模小的角度來看,在唯一找出的這項臨床試驗中,對於AEDs減量的最佳速度,我們無法得到可靠的結論。因此我們需要對成年人以及兒童實施進一步的研究,探索AEDs的停藥速度,以及研究各種變數對減量速度產生的影響,這些變數包括發作年齡、發作類型、癲癇病因、智能發育遲滯、腦電圖異常、有無神經功能缺損、及其他共存疾病等。

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

從方法學缺失和樣本規模小的角度來看,在唯一找出的這項臨床試驗中,對於AEDs減量的最佳速度,我們無法得到可靠的結論。因此我們需要對成年人以及兒童實施進一步的研究,探索AEDs的停藥速度,以及研究各種變數對減量速度產生的影響,這些變數包括發作年齡、發作類型、癲癇病因、智能發育遲滯、腦電圖異常、有無神經功能缺損、及其他共存疾病等。

Plain language summary

Rapid versus slow withdrawal of antiepileptic drugs

Epilepsy is a disorder where recurrent seizures are caused by abnormal electrical discharges of the brain.

Antiepileptic drugs (AEDs) are used to prevent these seizures. Regular intake of AEDs may have long-term side effects. When in remission, it is logical to attempt to stop the drugs. Two important issues are how and when to stop them. This review analysed the various studies for evidences regarding rapidity of withdrawal of AEDs. No reliable evidence is available on the optimal rate of tapering of AEDs.

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