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Amantadine in Parkinson's disease

  • Review
  • Intervention

Authors


Abstract

Background

Although levodopa is the most common drug prescribed to relieve the symptoms of Parkinson's disease it is associated with motor and psychiatric side-effects. Consequently, interest has turned to alternative drugs with improved side-effect profiles to replace or augment levodopa. Amantadine, originally used as an antiviral drug, has been shown to improve the symptoms of Parkinson's disease.

Objectives

To compare the efficacy and safety of amantadine therapy (monotherapy or adjuvant therapy) versus placebo in treating people with Parkinson's disease.

Search methods

Electronic searches of The Cochrane Controlled Trials Register (The Cochrane Library Issue 3, 2001), MEDLINE (1966-2001), EMBASE (1974-2001), SCISEARCH (1974-2001), BIOSIS (1993-2001), GEROLIT (1979-2001), OLDMEDLINE (1957-1965), LILACS (1982-2001), MedCarib (17th Century - 2001), PASCAL (1973-2001), JICST-EPLUS (1985-2001), RUSSMED (1973-2001), DISSERTATION ABSTRACTS (2000-2001), SIGLE (1980-2001), ISI-ISTP (1990-2001), Aslib Index to Theses (2001), Clinicaltrials.gov (2001), metaRegister of Controlled Trials (2001), NIDRR (2001) and NRR (2001) were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of amantadine were contacted.

Selection criteria

Randomised controlled trials comparing amantadine with placebo in the treatment of patients with a clinical diagnosis of idiopathic Parkinson's disease.

Data collection and analysis

Data was abstracted independently by NC and KD onto standardised forms and disagreements were resolved by discussion.

Main results

Six randomised controlled trials were found comparing amantadine monotherapy or adjuvant therapy with placebo in the treatment of idiopathic Parkinson's disease. Five examined amantadine as adjuvant therapy with optimal levels of levodopa or anticholinergics and one examined amantadine as an adjuvant therapy with minimum tolerated levels of anticholinergics or as a monotherapy. Five were double-blind cross-over studies and one was a double-blind parallel group study. In total they examined 215 patients. The parallel group study allowed the randomisation codes to be broken and allowed patients in the placebo group to then receive amantadine. This could have led to bias. One study did not present the results of the placebo arm of the trial, hence we could not determine the difference between the two treatment groups. Two cross-over studies presented the results of the combined data from both treatment and placebo arms. The risk of carry-over effect into the second arm meant that these results could not be analysed. The final two studies presented at least some of their data from the end of the first arm of the trials. However only means were given, without standard deviations, so we could not determine the statistical significance of any difference between the amantadine and placebo groups. Although the authors did report on the side-effects from amantadine (such as livido recticularis, dry mouth and blurred vision), they state that none of them were severe.

Authors' conclusions

A considerable amount of evidence on the effectiveness of amantadine has accrued from non-controlled trials, often in patients with Parkinsonian conditions other than idiopathic Parkinson's disease. However, rigorous analysis of the six randomised controlled trials of amantadine reveals insufficient evidence of its efficacy and safety in the treatment of idiopathic Parkinson's disease.

摘要

背景

以Amantadine治療帕金森氏症

雖然levodopa是目前最常用於緩解帕金森氏症症狀的藥物,它卻也和一些運動或精神上的副作用有關。因此,現在轉向尋球副作用較少的藥物以取代或增強levodopa的作用。Amantadine原來是一個抗病毒藥物,已經有一些證據顯示他對帕金森氏症症狀是有幫助的。

目標

比較amantadine治療﹝單一治療或輔助性治療﹞和安慰劑,在帕金森氏症病患身上的療效和安全性。

搜尋策略

我們搜尋了The Cochrane Controlled Trials Register(The Cochrane Library 2001年,第3期)、 MEDLINE (1966 – 2001)、 EMBASE (1974 – 2001)、SCISEARCH (1974 – 2001)、BIOSIS (1993 – 2001)、GEROLIT (1979 – 2001)、OLDMEDLINE (1957 – 1965)、 LILACS (1982 – 2001)、MedCarib (17世紀2001)、PASCAL (1973 – 2001)、JICSTEPLUS (1985 – 2001)、RUSSMED (1973 – 2001)、DISSERTATION ABSTRACTS (2000 – 2001)、SIGLE (1980 – 2001)、ISIISTP(1990 – 2001)、 Aslib Index to Theses (2001)、Clinicaltrials.gov (2001)、Controlled Trials的metaRegister(2001)、NIDRR (2001)和NRR (2001)等電子資源。手動搜尋了Grey literature以及檢視找到的研究中的參考資料。和amantadine的製造商連絡。

選擇標準

比較以amantadine和安慰劑治療臨床診斷罹患原發性帕金森氏症病患的隨機對照試驗。

資料收集與分析

分別由NC和KD將數據摘錄成標準格式,並經過討論解決意見分歧的部分。

主要結論

我們找到6個和安慰劑比較,以amantadine單一療法或輔助性治療作為原發性帕金森治療的隨機對照試驗。有5個試驗使用最佳levodopa或anticholinergics劑量,並以amantadine作為輔助療法,另一個試驗使用anticholinergic最小耐受劑量併用amantadine作為輔助療法,或使用單一療法。有5個試驗是雙盲交叉研究,1個是雙盲平行小組研究。總共有215位病患。這個平行小組研究破壞原本的隨機分配,容許原本接受安慰劑治療的病患隨後能接受amantadine治療。這可能會導致誤差。有1個研究沒有列出安慰劑組的結果,因此我們無法判定兩個治療組別間的差異。有2個交叉研究有列出兩種療法組別和安慰劑組的合併結果。第二組的殘餘效應風險表示這些結果無法進行分析。剩下的2個研究列出試驗中第一組結果的部分數據。然而只有提供平均數,沒有標準差,所以我們無法評估amantadine和安慰劑在統計上是否有明顯差異。雖然作者沒有回報amantadine的副作用﹝像是網狀青斑、口乾及視力模糊﹞,他們表示這些副作用都不嚴重。

作者結論

我們從非對照試驗中,得到越來越多關於amantadine療效的證據,通常是以有帕金森氏症症狀的病人為樣本,而不是患有原發性帕金森氏症的病人為樣本。然而,這6個隨機對照試驗對於amantadine的分析,凸顯了對於其治療原發性帕金森氏症的療效和安全性證據的缺乏。

翻譯人

本摘要由朱奕蓁翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

目前沒有足夠關於amantadine用於治療帕金森氏症的安全性或療效的證據。帕金森氏症會導致肌肉逐漸僵硬,震顫及其他症狀。最常用於緩解這些症狀的藥物是levodopa,但它有常見的生理和精神上的不良反應。Amantadine是另一個選擇,可以單獨使用或是和levodopa併用。Amantadine可能會有嚴重的不良反應﹝包括精神問題﹞,病人可能會因此對這個藥物產生抗拒。這篇評論發現目前缺乏關於amantadine用於治療帕金森氏症的試驗證據。目前試驗中的不良反應都不嚴重,包括皮膚紅腫,口乾和視力模糊。

Plain language summary

There is not enough evidence about the safety and effectiveness of amantadine for people with Parkinson's disease.

Parkinson's disease causes progressive muscle rigidity, tremors and other symptoms. The most common drug used to try and relieve these symptoms is levodopa, but serious physical and psychiatric adverse effects are common. Amantadine is another option, used alone or with levodopa. Amantadine can have serious adverse effects (including psychiatric problems), and people can become resistant to the drug. The review found that there is not enough evidence from trials about the effects of amantadine for people with Parkinson's disease. Adverse effects in trials so far have not been severe, and included skin rash, dry mouth and blurred vision.

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