Gabapentin add-on for drug-resistant partial epilepsy

  • Review
  • Intervention

Authors


Abstract

Background

The majority of people with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarize the current evidence regarding a new antiepileptic drug, gabapentin, when used as an add-on treatment for drug-resistant partial epilepsy

Objectives

To evaluate the efficacy and tolerability of gabapentin when used as an add-on treatment for people with drug-resistant partial epilepsy.

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 2, 2007), and MEDLINE (1966 to July 2007). No language restrictions were imposed. We also contacted the manufacturers of gabapentin and researchers in the field to seek any ongoing or unpublished studies.

Selection criteria

Randomized placebo controlled double blind add-on trials of gabapentin in people with drug-resistant partial epilepsy.

Data collection and analysis

Two review authors independently selected trials for inclusion and extracted the relevant data. The following outcomes were assessed: (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) adverse effects. Primary analyses were intention-to-treat. Sensitivity best and worst case analyses were also undertaken. Summary odds ratios were estimated for each outcome. Dose response was evaluated in regression models, and Number Needed to Treat (NNT) was calculated for individual doses.

Main results

Five trials were included representing 997 randomized participants.
Overall odds ratio (OR) with 95% confidence intervals (CIs) for 50% or greater reduction in seizure frequency compared to placebo was 1.93 (95% CI 1.37 to 2.71). Dose regression analysis shows increasing efficacy with increasing dose, with 28.5% (21.5 to 36.7) of people responding to 1800 mg of gabapentin compared to placebo, NNT 6.7 (3.0 to 10.5).
Treatment withdrawal OR (95% CI) compared to placebo was 1.05 (95% CI 0.68 to 1.61).
Adverse effects with OR (99% CI) compared to placebo: dizziness 2.22 (99% CI 1.28 to 3.85); fatigue 2.28 (99% CI 1.15 to 4.52) and somnolence 2.01 (99% CI 1.24 to 3.28) were significanty associated with gabapentin.

Authors' conclusions

Gabapentin has efficacy as an add-on treatment in people with drug-resistant partial epilepsy. However, trials reviewed were of relatively short duration, and provide no evidence for the long-term efficacy of gabapentin. Results cannot be extrapolated to monotherapy or people with other epilepsy types.

摘要

背景

Gabapentin作為添加療法來治療藥物難治的局部發作型癲癇

多數癲癇患者的預後良好,使用單一抗癲癇藥物就可以有效控制其癲癇發作,但是還有將近30%的人發展成為藥物難治的癲癇,尤其是局部發作型的患者。在本次回顧中,我們總結了Gabapentin(一個新一代的抗癲癇藥物)作為藥物難治的局部發作型癲癇的添加療法的臨床證據。

目標

評估Gabapentin作為添加療法來治療藥物難治的局部發作型癲癇的療效和耐受性。

搜尋策略

我們搜尋了Cochrane Epilepsy Group's Specialized Register(2005年5月)以及Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library,2005年第2期) 和MEDLINE (1966年2005年3月)。沒有設定任何語言限制。我們同時聯繫Gabapentin的製造商和該領域的研究者,尋找進行中或未發表的研究。

選擇標準

選擇比較添加Gabapentin或安慰劑來治療藥物難治的局部發作型癲癇患者的隨機雙盲對照試驗。

資料收集與分析

兩位回顧作者各自選擇收納試驗和摘錄數據。評估了下列治療成果:(a) 癲癇發作頻率降低50% 或以上;(b) 停止試驗用藥(不論任何原因);(c) 藥物不良反應。初步分析採用intentiontotreat方法’.同時實施了Sensitivity best and worst case analyses。對每項治療成果評估了總體的odds ratios。使用回歸模型評估劑量與反應的相關性,計算Number Needed to Treat (NNT)。

主要結論

總共收納了5個試驗,包括997位隨機挑選的受試者。相較於安慰劑,Gabapentin在達成癲癇發作頻率降低50% 或以上的odds ratio(OR)是1.93 (95% CI 1.37 −2.71)。劑量回歸分析指出,劑量越大療效越強;相較於安慰劑,28.5% (21.5 – 36.7) 的人對1800 mg Gabapentin的治療有反應,NNT為6.7 (3.0 10.5)。相較於安慰劑,停藥的OR為1.05 (95% CI 0.68 – 1.61)。相對於安慰劑,下列藥物不良反應的OR分別為:頭暈2.22 (99% CI 1.28 – 3.85);疲勞2.28 (99% CI 1.15 – 4.52),嗜睡2.01 (99% CI 1.24 – 3.28) 均顯著和Gabapentin相關。

作者結論

Gabapentin作為添加療法來治療藥物難治的局部發作型癲癇患者時確有其療效。但因本回顧中的臨床試驗,治療期間都相對較短,所以無法提供長期療效的證據。上述的結果也不能外推到單一藥物療法或患有其他癲癇類型的病人。

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

Gabapentin作為短期治療局部發作型癲癇患者的添加療法是有效的。癲癇是一種由於大腦放電異常引起的重覆發作的疾病。本試驗回顧發現,作為一種新一代的抗癲癇藥物,Gabapentin併用其他藥物,短期內可以有效治療藥物難治的局部發作型癲癇。較常見因Gabapentin引起的藥物不良反應包括運動失調(協調性不良,前後搖擺不定)、頭暈、疲勞、噁心、嗜睡和頭疼。至於長期使用Gabapentin的療效則需要更進一步的研究。

Plain language summary

Gabapentin add-on for drug-resistant partial epilepsy

Gabapentin is effective as a short-term add-on treatment for partial epilepsy.

Epilepsy is a disorder where recurrent seizures are caused by abnormal electrical discharges from the brain. The review of trials found that a new antiepileptic drug, gabapentin is effective in the short-term when used with other drugs by people with drug-resistant partial epilepsy. The most common adverse effects caused by gabapentin are ataxia (poor coordination and unsteady gait), dizziness, fatigue, nausea, drowsiness and headaches. Research is needed into the effects of the long-term use of gabapentin.

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