Catechol-O-methyltransferase inhibitors versus active comparators for levodopa-induced complications in Parkinson's disease
Editorial Group: Cochrane Movement Disorders Group
Published Online: 18 OCT 2004
Assessed as up-to-date: 7 JUN 2004
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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.
- Publication Status: Edited (no change to conclusions)
- Published Online: 18 OCT 2004
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.
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.
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.
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.
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.
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
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.
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
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PDQ39。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。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。