Cabergoline 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 for levodopa-induced complications in Parkinson's disease. Cochrane Database of Systematic Reviews 2001, Issue 1. Art. No.: CD001518. DOI: 10.1002/14651858.CD001518.
- 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 placebo 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 placebo 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.
Cabergoline has been compared with placebo in two phase II (6 - 12 weeks) and one phase III randomised controlled trials (24 weeks). These were double-blind, parallel group, multicentre studies including 268 patients with Parkinson's disease and motor complications. The reduction of 1.14 hours (WMD; 95% CI -0.06, 2.33; p = 0.06) in off time in favour of cabergoline was not statistically significant. Inadequate data on dyskinesia was collected either on rating scales or as adverse event reporting to allow a conclusion to be drawn. A small but statistically significant advantage of cabergoline over placebo was seen in one study for UPDRS ADL (part II) score and UPDRS motor score. No such advantage was seen in one other study due to small numbers of patients and the comparatively low doses of cabergoline used. No significant differences in Schwab and England scale were seen in two studies. Levodopa dose reduction was significantly greater with cabergoline (WMD 149.6 mg/d; 95% CI 94.1, 205.1; p < 0.00001). There was a trend towards more dopaminergic adverse events with cabergoline but this did not reach statistical significance at the p < 0.01 level. However, there was a trend towards fewer withdrawals from cabergoline.
In the management of the motor complications seen in Parkinson's disease, cabergoline can be used to reduce levodopa dose and modestly improve motor impairment and disability with an acceptable adverse event profile. These conclusions are based on, at best, medium term evidence.
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 (choreoathetosis), 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 and what side effects it causes.
Cabergoline has been compared with inactive placebo in two smaller and shorter (6 - 12 weeks) studies and one larger, medium term trial (24 weeks). These trials included 268 patients with Parkinson's disease and motor complications. The average reduction in the time patients spent in the immobile off state was 1.1 hours greater with cabergoline compared with placebo, although this was not statistically significant. Inadequate data on dyskinesia was collected to allow a conclusion to be drawn. A small but significant advantage of cabergoline over placebo was seen in one study for activities of daily living and physical functioning. No such advantage was seen in one other study due to small numbers of patients and the comparatively low doses of cabergoline used. Levodopa dose reduction was greater with cabergoline by 145 mg per day. There was a trend towards more side effects with cabergoline but towards fewer withdrawals from cabergoline treatment.
In the management of the motor complications seen in Parkinson's disease, cabergoline can be used to reduce levodopa dose and modestly improve motor function and activities of daily living with an acceptable side effect profile. This is based on, at best, medium term evidence. Further long term trials are required to compare the newer with the older dopamine agonists, particularly in terms of quality of life and cost.
長期以levodopa作為帕金森氏症的治療，和運動併發症的形成有關，包括異常的非自主運動以及對每個劑量個反應時間縮短﹝wearing off phenomenon﹞。一般都認為dopamine作用劑能減少不動其和levodopa治療的需求，同時可以維持或是改善運動機能恢復而且只會小幅度增加dopamine相關的不良反應。
我們搜尋了MEDLINE、EMBASE和the Cochrane Controlled Trials Register等電子資料庫。手動檢索The Cochrane Movement Disorders Group's strategy中神經學的相關文章。檢視所有找到的研究中的參考資料。和Pharmacia Upjohn Limited取得連繫。
作者們分別擷取數據，有意見分歧的部分經由討論取得共識。結果量測包括使用Parkinson's disease rating scales、levodopa劑量、不動期的量測以及退出試驗的人數和不良反應的頻率。
有2個第二階段﹝6到12週﹞以及1個第三階段的隨機對照試驗﹝24週﹞，將Cabergoline和安慰劑做比較。它們是雙盲、平行小組、多方參與的研究，包含268位患有帕金森氏症且有運動併發症的病人。Cabergolin能使不動期時間減少1.14小時的現象在統計學上並不顯著﹝WMD；95% CI −0.06，2.33；p = 0.06﹞。從評分表或不良反應報告收集關於運動障礙不充足的數據，以從中獲得結論。有一個試驗，發現cabergoline對於 UPDRS ADL (part II) score 和UPDRS motor score有很小但在統計學上很顯著的優點。由於病人數目很少且使用的cabergoline劑量較低，這樣的優點在其他研究中並沒有看到。有2個試驗，在Schwab和England scale間沒有發現顯著的差異。cabergoline減少levodopa用量的效果很明顯的比較好﹝MD 149.6 mg/d; 95% CI 94.1, 205.1; p <0.00001﹞。Cabergoline似乎有比較多dopamine相關不良反應，但在統計學上並不顯著，p < 0.01。然而，停用Cabergoline人也比較少。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。
在帕金森氏症的末期，會因為使用levodopa作為治療而產生副作用。包括非自主的書寫動作﹝choreoathetosis舞蹈手足徐動症﹞、腿部的抽筋疼痛﹝dystonia肌張力異常﹞以及對每個劑量的反應時間縮短，即所謂的endofdose deterioration或是wearingoff effect。Dopamine作用劑是藉由模仿腦中levodopa作用，但作為初步治療時不會因長期使用而產生併發症。就因為這樣，dopamine 作用劑已經被使用數年，用來作為問題產生時的附加藥物，希望能有所改善。Cabergoline是一個新的dopamine作用劑，最近英國已經核准用於治療末期帕金森氏症。在這篇評論中，我們會檢視以這個藥作為實驗藥物的試驗，以了解其療效及副作用。在2個規模較小且時間較短﹝6到12週﹞的研究以及另一個比較大型、中期﹝24週﹞的試驗中，有以Cabergoline和非活性安慰劑做比較。這些試驗包含268位患有帕金森氏症和運動併發症的病人。使用Cabergoline的人的不動期比使用安慰劑的人平均多縮短了1.1小時，雖然在統計上並不顯著。我們也收集了關於運動障礙的不充足數據以方便做出結論。其中一個試驗發現，比起安慰劑，cabergoline在每日活動力及生理功能上有小但顯著的好處。由於病人數目很少以及cabegoline用量較少，其它研究中並沒有發現類似的好處。使用cabergoline的組別，levodopa的用量每天多減少了145毫克。Cabergoline傾向有較多的副作用，但停用的人也較少。在照護帕金森氏症的運動併發症時，cabergoline能夠在可接受的副作用下，減少levodopa的用量以及適度的改善運動能力和每日活動力。我們需要更進一步的長期試驗，比較新舊dopamine作用劑的差異，特別是針對生活品質和成本做比較。