Pramipexole versus bromocriptine for levodopa-induced complications in Parkinson's disease
Editorial Group: Cochrane Movement Disorders Group
Published Online: 24 APR 2000
Assessed as up-to-date: 23 JAN 2000
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
Clarke CE, Speller J, Clarke JA. Pramipexole versus bromocriptine for levodopa-induced complications in Parkinson's disease. Cochrane Database of Systematic Reviews 2000, Issue 2. Art. No.: CD002259. DOI: 10.1002/14651858.CD002259.
- Publication Status: Edited (no change to conclusions)
- Published Online: 24 APR 2000
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 pramipexole versus bromocriptine therapy 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 and Boehringer Ingelheim.
Randomised controlled trials of pramipexole 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 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 drop outs and adverse events.
One randomised controlled trial has compared pramipexole with bromocriptine using a double-blind, parallel group, multicentre design. It was not powered to examine differences between active treatment arms. There was a larger reduction in off time with pramipexole therapy compared with bromocriptine (weighted mean difference 1.4 hours; 0, 2.8, 95% CI). No differences occurred in dyskinesia rating scale, dyskinesia as an adverse event or UPDRS complication score. The UPDRS ADL and motor scores showed similar improvements compared to placebo with both agonists. Levodopa dose reduction was similar with both agonists. Subscales of the Functional Status Questionnaire showed significant improvements compared to placebo with both agonists. The finding that the EuroQol improved significantly compared with placebo with pramipexole but not bromocriptine should be treated with caution. Dopaminergic adverse events were similar with each agonist, as was the all cause withdrawal rate.
Although pramipexole and bromocriptine improved off time and reduced parkinsonian motor impairments and disability compared with placebo, no conclusions regarding their comparative effectiveness and safety can be drawn as this single trial did not have adequate power to assess such differences. Further larger trials are required to examine this issue in the future.
Plain language summary
In the later stages of Parkinson's disease, side effects occur because of the use of levodopa in its treatment. These consist of involuntary writhing movements (dyskinesia), painful cramps in the legs 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. For this reason, dopamine agonists have for some years been added once these problems develop in the hope of improving them. Pramipexole is a new dopamine agonist recently licensed in the UK for the treatment of later Parkinson's disease. In comparison, bromocriptine has been available since the late 1970s and is a well established agonist. In this review, we will examine the trials performed to see whether pramipexole is better than bromocriptine in terms of effectiveness and side effects.
One trial compared pramipexole with bromocriptine but this was not designed to examine differences between the two treatments as there were too few patients included. However, there was a larger reduction in the time patients spent in the immobile off state with pramipexole therapy compared with bromocriptine by an average of 1.4 hours. No differences occurred in dyskinesia rating scale, dyskinesia as a side effect or Unified Parkinson's Disease Rating Scale (UPDRS) complication score. The UPDRS activities of daily living and motor scores showed similar improvements compared to placebo with both agonists. Levodopa dose reduction was similar with both agonists. Subscales of a quality of life measure, the Functional Status Questionnaire, showed significant improvements compared to placebo with both agonists. The finding that another quality of life scale, the EuroQol, improved significantly compared with placebo with pramipexole but not bromocriptine should be treated with caution. Side effects such as nausea, vomiting, and faintness were similar with each agonist, as was the withdrawal from treatment rate.
No conclusions regarding the comparative effectiveness and safety of pramipexole versus bromocriptine can be drawn as this single trial did not have adequate numbers of patients to assess such differences. Further larger trials are required to examine this issue in the future.
巴金森氏病人長期的levodopa治療和一些動作的副作用相關，像是異常的不自主運動和每劑藥效的縮短(wearing off phenomenon)。有人認為多巴胺受體刺激劑可以減少無法動作期的時間和對於levodopa的需要量，能至少維持甚至改善動作障礙，並只些微地增加多巴胺相關的副作用。
我們電子搜尋了MEDLINE, EMBASE and the Cochrane Controlled Trials Register. 以手工方式搜尋neurology literature as part of the Cochrane Movement Disorders Group's strategy，檢驗了所找到研究和其他評論的參考文獻列表，還聯絡了藥廠Pharmacia Upjohn和Boehringer Ingelheim。
有一個隨機分配試驗以雙盲、平行、多中心的設計比較了pramipexole和bromocriptine。它被設計成有效力能比兩種治療之間的差異。Pramipexole在停止期減少的輻度較bromocriptine大(weighted mean difference 1.4小時; 0, 2.8, 95% CI)。在異動症評分量尺、異動症的副作用、及URDRS副作用指數方面則沒有差異。在UPDRS ADL and motor scores這項指標上兩個效果差不多，都比安慰劑好。兩者減少levodopa劑量的效果也相似。在Functional Status Questionnaire的副量尺方面，兩個藥比較安慰劑都有顯著的進步。有一個發現是pramipexole在EuroQo1這個指標上比安慰劑有顯著的好處，但bromocriptine則沒有，對這個結果我們要小心看待。兩個藥物的多巴胺相關副作用類似，而綜合所有原因的中途退出率也差不多。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。
在巴金森氏病的晚期，會因使用levodopa治療而有一些副作用。這些副作用包含不自主的扭動(異動症)、小腿的抽筋和每次服藥有效時間愈來愈短(稱為“endofdose deterioration”或是“weaningoff effect”)。多巴胺受體刺激劑在腦中的作用類似levodopa，但是它們不會造成上述的長期治療副作用。因此，長年來只要上述副作用產生了，就會使用多巴胺受體刺激劑以期有所改善。Pramipexole是一個新的多巴胺受體刺激劑，最近在英國得到執照用來治療晚期的巴金森氏病。相較之下，bromocriptine從1970年代末就已經存在，是一個使用已久的刺激劑。在這篇評論中，我們檢驗一些用來決定pramipexole是否比bromocriptine有效、副作用較少的試驗。只有一個試驗研究pramipexole和bromocriptine，但它的設計無法比較兩者間的差別，因為病人數目太少。雖然這麼說，使用pramipexole的病人耗在停止期的時間較少，比使用bromocriptine的病人少1.4小時。在異動症評分量尺、異動症副作用、及oUnified ParkinsonDisease Rating Scale (UPDRS)併發症指標方面則沒有顯著差異。UPDRS 日常生活及運動能力指標(UPDRS activities of daily living and motor scores)也顯示兩個刺激劑比起安慰劑都有類似的進步。兩個刺激劑都能造成Levodopa劑量的減少。兩個刺激劑和安慰劑相比，生活品質這個副指標(Subscales of a quality of life measure)和功能狀態問卷(the Functional Status Questionnaire)都有顯著的進步。有一個發現是pramipexole在EuroQo1這個指標上比安慰劑有顯著的好處，但bromocriptine則沒有，對這個結果我們要小心看待。兩個藥物的副作用像是噁心、嘔吐、暈眩都相似，實驗的中途退出率也相似。這個實驗因為沒有足夠的病人數目，沒有辦法告訴我們pramipexole 和bromocriptine相比有效性和安全性如何。將來需要更大的實驗來檢驗這個議題。