Cabergoline versus bromocriptine for levodopa-induced complications in Parkinson's disease
Editorial Group: Cochrane Movement Disorders Group
Published Online: 22 JAN 2001
Assessed as up-to-date: 16 NOV 2000
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
Clarke CE, Deane K. Cabergoline versus bromocriptine for levodopa-induced complications in Parkinson's disease. Cochrane Database of Systematic Reviews 2001, Issue 1. Art. No.: CD001519. DOI: 10.1002/14651858.CD001519.
- Publication Status: Edited (no change to conclusions)
- Published Online: 22 JAN 2001
Long term levodopa therapy in Parkinson's disease is associated with the development of motor complications including abnormal involuntary movements and a shortening response to each dose (wearing off phenomenon). It is thought that dopamine agonists can reduce the duration of immobile off periods and the need for levodopa therapy whilst maintaining or improving motor impairments and only minimally increasing dopaminergic adverse events.
To compare the efficacy and safety of adjuvant cabergoline therapy versus bromocriptine in patients with Parkinson's disease, already established on levodopa and suffering from motor complications.
Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Pharmacia Upjohn Limited.
Randomised controlled trials of cabergoline versus bromocriptine in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy.
Data collection and analysis
Data were 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.
Cabergoline has been compared with bromocriptine in five randomised, double-blind, parallel group studies including 1071 patients. Only one of the phase II studies was medium term (36 weeks), the others all being short term (12 -15 weeks). The non-significant difference in off time reduction produced by cabergoline compared with bromocriptine was 0.29 hours/day in favour of the former (weighted mean difference; 95% CI -0.10, 0.68; p = 0.15). Dyskinesia reported as an adverse event was significantly increased with cabergoline compared with bromocriptine (Peto odds ratio 1.57; 95% CI 1.05, 2.35; p = 0.03). Motor impairment and disability were measured in four of the studies using the UPDRS rating scale but the small differences in UPDRS ADL (part II) and motor (part III) scores were not statistically significant in any study. Similarly, no significant difference in Schwab and England score was seen. The number of patients rated as much or very much improved on a clinician's global impression scale was similar with both agonists. Levodopa dose reduction was no different between cabergoline and bromocriptine. There was more confusion with cabergoline (Peto odds ratio 2.02; 95% CI 1.09, 3.76; p = 0.03). Otherwise, dopaminergic adverse events were comparable with these agonists and no significant difference in all cause withdrawal rate was found.
Cabergoline produces similar benefits to bromocriptine in off time reduction, motor impairment and disability ratings, and levodopa dose reduction over the first three months of therapy. Dyskinesia and confusion were increased with cabergoline but otherwise the frequency of adverse events and withdrawals from treatment were similar with the two agonists.
Plain language summary
In the later stages of Parkinson's disease, side effects occur because of the use of levodopa treatment. These consist of involuntary writhing movements (dyskinesia), painful cramps in the legs (dystonia) and a shortened response to each dose referred to as 'end-of-dose deterioration' or the 'wearing-off effect'. Dopamine agonist drugs act by mimicking levodopa in the brain, but they do not cause these long-term treatment complications when used as initial therapy. For this reason, dopamine agonists have for some years been added once these problems develop in the hope of improving them. Cabergoline is a new dopamine agonist recently licensed in the UK for the treatment of later Parkinson's disease. In this review, we will examine the trials performed with this drug to see how effective it is compared with the older drug bromocriptine and what side effects it causes.
Cabergoline has been compared with the older agonist bromocriptine in five studies including 1071 patients. Only one of the smaller studies was medium term (36 weeks), the others all being short term (12 -15 weeks). The time patients spent in the immobile off state was reduced with both agonists but slightly more by cabergoline compared with bromocriptine. This small advantage of cabergoline did not reach statistical significance. Dyskinesia reported as a side effect was significantly increased with cabergoline compared with bromocriptine. Physical impairment and disability were measured in four of the studies but no statistically significant advantage for cabergoline was found. The number of patients rated as much or very much improved on a clinician's global impression scale was similar with both agonists. Levodopa dose reduction was no different between cabergoline and bromocriptine. There was significantly more confusion with cabergoline. Otherwise, dopaminergic side effects were comparable with these agonists and no significant difference in the withdrawal rate from the trials was found.
Cabergoline produces similar benefits to bromocriptine in off time reduction, physical impairment and disability ratings, and levodopa dose reduction over the first three months of therapy. The frequency of side effects and withdrawals from treatment were similar with the two agonists apart from increased dyskinesia and confusion with cabergoline.
電子查尋MEDLINE, EMBASE 和 the Cochrane Controlled Trials Register。手工查尋the Cochrane Movement Disorders Group strategy的部分神經學文獻。檢閱確認出的研究和其他回顧的參考目錄。聯絡Pharmacia Upjohn Limited。
對臨床診斷為自發性帕金森氏症且有因levodopa療法產生長期併發症的病人比較Cabergoline 與 bromocriptine的隨機對照試驗
比較cabergoline和bromocriptine用於總共1071個病人的五個隨機取樣、雙盲平行組研究。只有在二階段研究其中一組是中期(36週)，其他都是短期(12 – 15週)。cabergoline和bromocriptine減少停電期並無顯著差異，前者減少多了0.29時/日(加權平均值差異; 95% CI −0.10, 0.68; p = 0.15)。使用cabergoline比使用bromocriptine增加更多異動症的副作用(Peto odds ratio 1.57; 95% CI 1.05,2.35; p = 0.03)。其中四個研究有用UPDRS評定量表加以測量運動障礙和殘疾，但是UPDRS ADL (part II)和UPDRS運動分數(part III)上的小差異都無統計學上的意義。同樣地，Schwab和England分數也不見重大差異。臨床醫生全面印象分級中改善很多及非常多的病人數在這二組增效劑結果是類似的。cabergoline和bromocriptine對於左多巴劑量的減輕沒有不同，cabergoline (Peto odds ratio 2.02;95% CI 1.09, 3.76; p = 0.03)的結果比較令人困惑，除此之外，dopaminergic副作用和這些增效劑引起的是相當的，在所有原因退出研究的比率上沒有明顯差異。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。
在帕金森氏症的後期，因為使用左多巴治療會發生副作用。包含不自主的扭動(異動症)、腿部痛苦的痙攣(肌張力異常)、以及稱為「藥量末期的症狀惡化」或「藥效漸消效果」的對於每一次劑量的有效反應時間縮短。多巴胺增效劑在腦部模仿左多巴發生作用，但在治療初期不會造成長期治療併發症。因此有幾年的時間使用多巴胺增效劑期望當這些副作用出現時，副作用可以有所改善。Cabergoline是一種最近在英國領有執照的新多巴胺增效劑來治療晚期帕金森氏症。在這篇回顧，我們將檢閱用這種藥物的試驗，和以前的bromocriptine加以比較會是多麼有效以及造成什麼副作用。比較cabergoline和以前的增效劑bromocriptine用於總共1071個病人的五個研究中。只有較小型研究的其中一個是中期(36週)，其他都是短期(12 – 15週)。二種增效劑皆使得病人的停電時間減少了，cabergoline減少更多但沒有達到統計學上的意義。報告出的異動症副作用在使用cabergoline比bromocriptine增加許多。其中四個研究有測量身體損傷和失能，但是使用cabergoline並沒有發現統計學上的重大優勢。臨床醫生全面印象分級中改善很多及非常多的病人數在這二種增效劑是類似的。Cabergoline和bromocriptine對於左多巴藥量減輕沒有不同，但cabergoline造成更多顯著的意識混亂。反過來，dopaminergic副作用在這二種增效劑是類似的，且在這些試驗中，退出藥物使用的頻率沒有顯著不同。在治療的前三個月，在減輕停電時間、身體損傷和失能等級、左多巴藥量減輕等方面產生和bromocriptine類似的益處。除了Cabergoline增加異動症與意識混亂之外，發生副作用和退出治療的頻率在這二種增效劑是類似的。