Intervention Review

Catechol-O-methyltransferase inhibitors versus active comparators for levodopa-induced complications in Parkinson's disease

  1. Katherine Deane2,
  2. Sybille Spieker3,
  3. Carl E Clarke1,*

Editorial Group: Cochrane Movement Disorders Group

Published Online: 18 OCT 2004

Assessed as up-to-date: 7 JUN 2004

DOI: 10.1002/14651858.CD004553.pub2

How to Cite

Deane K, Spieker S, Clarke CE. Catechol-O-methyltransferase inhibitors versus active comparators for levodopa-induced complications in Parkinson's disease. Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD004553. DOI: 10.1002/14651858.CD004553.pub2.

Author Information

  1. 1

    City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Department of Neurology, Birmingham, West Midlands, UK

  2. 2

    Newcastle University, Institute of Health & Society, Newcastle-upon-Tyne, UK

  3. 3

    Marburg, Germany

*Carl E Clarke, Department of Neurology, City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Dudley Road, Birmingham, West Midlands, B18 7QH, UK. c.e.clarke@bham.ac.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 18 OCT 2004

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Abstract

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

Background

As Parkinson's disease progresses the control of the symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of the levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase.

Objectives

To compare the efficacy and safety of adjuvant COMT inhibitor therapy versus active comparators in patients with Parkinson's disease, already established on levodopa and suffering from motor complications.

Search methods

Electronic searches of the Cochrane Controlled Trials Register (The Cochrane Library Issue 1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of COMT inhibitors were contacted.

Selection criteria

Randomised controlled trials of adjuvant COMT inhibitor therapy versus an active comparator in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy.

Data collection and analysis

Data was abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events.

Main results

Two trials were found that examined the efficacy of a COMT inhibitor against an active comparator (n = 349). Koller 1998 compared the efficacy of tolcapone versus pergolide (n = 203) over 12 weeks and TSG 1999 compared the efficacy of tolcapone versus bromocriptine (n = 146) over 8 weeks. No trials were found that compared entacapone with active comparators.

Tolcapone produced similar benefits to bromocriptine in 'off' time reduction, motor impairment and disability ratings over three months of therapy. Tolcapone produced a greater reduction in levodopa dosage than bromocriptine. Tolcapone produced similar benefits to pergolide in levodopa dose reduction, motor impairment and disability ratings, and in generic health-related quality of life scales over the first two months of therapy. Tolcapone produced a greater improvement in the disease-specific quality of life scale PDQ-39 than pergolide. Nausea, constipation and orthostatic complaints were greater with agonist therapy, but otherwise the frequency of adverse events and withdrawals from treatment were similar with the two classes of adjuvant medication. One patient had significantly elevated liver enzymes whilst on tolcapone, but otherwise the frequency of adverse events and withdrawals from treatment were similar.

Authors' conclusions

The two trials comparing tolcapone with the dopamine agonists bromocriptine and pergolide were underpowered to detect clinically relevant differences between them. This is based on medium-term evidence. No evidence was found comparing entacapone with active comparators. Further larger and longer-term trials are required to compare tolcapone with entacapone and COMT inhibitor therapy with alternative adjuvant classes of drug in later Parkinson's disease such as dopamine agonists and monoamine oxidase inhibitors.

 

Plain language summary

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

Insufficient data are available on the benefits of the COMT inhibitor tolcapone compared with the dopamine agonists bromocriptine and pergolide in relieving the symptoms of later Parkinson's disease.

As Parkinson's disease progresses the control of the symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of each levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase. However other drugs such as dopamine agonists can also be used at this stage of the disease. This review found that the COMT inhibitor tolcapone as an adjuvant to levodopa treatment had a similar level of benefits as two dopamine agonists, bromocriptine and pergolide. There was no significant difference in efficacy between the adjuvant tolcapone and adjuvant bromocriptine or pergolide in the medium-term. Tolcapone produced nausea less often than these agonists but there was some evidence of liver function abnormalities with tolcapone. Post-marketing surveillance identified three cases of fatal hepatic toxicity in patients treated with tolcapone. As a result, tolcapone has been withdrawn from some countries and severe restrictions on its use have been imposed in others.

No evidence was found comparing entacapone with other adjuvant drugs for Parkinson's disease.

 

摘要

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

背景

兒茶酚O甲基轉移酉每抑制劑以及活性競爭劑治療巴金森氏症使用左多巴引起的副作用

隨著巴金森氏症進行,要控制運動症狀多半需要在左多巴之外另加藥物,COMT抑制劑療法的主要目的是來增加每個左多巴劑量的有效時間因此使病人在停滯相對不動期的時間減少。

目標

在巴金森氏症病人已使用左多巴並有運動副作用的情況,比較輔助COMT抑制劑以及活性競爭劑的效果及安全性

搜尋策略

電子搜尋考科藍對照試驗登錄、(考科藍資料庫議題1, 2003)、MEDLINE (1966 – 2003)、EMBASE(1974 – 2003),手動搜尋灰色文獻,檢視蒐尋出的研究及文獻的參考書目,連絡COMT抑制劑的製造商

選擇標準

在臨床診斷原發性巴金森氏症的病人已使用左多巴並有長期產生副作用的情況,比較輔助COMT抑制劑以及活性競爭劑的隨機對照試驗

資料收集與分析

作者獨立對資料作摘要並討論資料的差異性,預後測量標準包括巴金森氏症分級分數、左多巴劑量、停滯期測量、退出治療以及副作用的頻率

主要結論

有2個試驗測試了COMT抑制劑及活性競爭劑的效力: Koller 1998以12週的時間比較tolcapone與pergolide的效力,TSG 1999以8週的時間比較tolcapone與bromocriptine (n = 146) 的效力,並沒有比較entacapone與活性競爭劑的試驗。在3個月療程後tolcapone與bromocriptine在減少停電時間、運動殘疾及失能分數有相似的益處,tolcapone比bromocriptine減輕更多左多巴劑量;tolcapone與pergolide前2個月療程在減輕左多巴劑量、改善運動殘疾及失能分數、及健康相關生活品質評分皆有相似的益處,tolcapone比pergolide改善更多針對疾病的生活品質分數PDQ39。使用促進劑有較多的噁心、便秘及姿勢性的不適,不過這二類輔助藥物發生副作用及退出藥物使用的頻率是類似的,有1位使用tolcapone的病人肝臟酵素值明顯升高,至於副作用及退出藥物使用的頻率則是相似的。

作者結論

2個比較tolcapone及多巴胺促進劑bromocriptine與pergolide的試驗檢力不足,無法分辨臨床相關的差異,這是依據中等程度的證據,沒有比較entacapone與活性競爭劑的證據。需要進一步大型長期的試驗,比較tolcapone與entacapone,或比較COMT抑制劑療法與在較晚期巴金森氏症的替代輔助藥物例如多巴胺促進劑及單胺氧化酉每抑制劑。

翻譯人

本摘要由新光醫院吳亞縈翻譯。

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

總結

在改善較晚期巴金森氏症症狀方面,沒有足夠證據來支持COMT抑制劑tolcapone比多巴胺促進劑bromocriptine與pergolide更有效,當巴金森氏症疾病進展,為了控制症狀常需要增加左多巴之外的藥物,COMT抑制劑主要目的是延長每個左多巴劑量的有效時間,從而讓病人處在相對無法動作的停電時間減少,不過其他像多巴胺促進劑也可使用在這個疾病時期,這篇回顧發現COMT抑制劑tolcapone作為左多巴療法的輔助與二個多巴胺促進劑bromocriptine及pergolide產生類似的益處,在中期輔以tolcapone及輔以bromocriptine或pergolide並無顯著效力的差異,tolcapone比起這些促進劑產生較少的噁心但有肝臟酵素值升高的證據,藥物上市後監測發現有3位服用tolcapone的病人產生致命的肝毒性,結果在某些國家tolcapone已下架,在其他國家則被嚴格限制使用。並沒有比較entacapone及其他巴金森氏症輔助藥物的證據。