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Pergolide for levodopa-induced complications in Parkinson's disease

  • Review
  • Intervention




In later Parkinson's disease, long-term treatment with levodopa therapy is associated with the development of motor complications which include abnormal involuntary movements (dyskinesia) and a shortening response to each dose (wearing off phenomenon). Dopamine agonists have been used in such patients in the hope that they 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 adjunct pergolide therapy versus placebo in patients with Parkinson's disease suffering from the complications of levodopa therapy.

Search methods

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 Eli Lilly and Company Limited.

Selection criteria

Randomised controlled trials of pergolide 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 each author 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.

Main results

A large number of small RCTs were identified, but these were part of a large multicentre trial which was eventually published in full. The final publication was used as the only subject for this review. The time patients spent 'off' was reduced by 1.8 hours with pergolide compared with 0.2 hours with placebo (p < 0.001). Dyskinesia developed or deteriorated in 62% of pergolide-treated compared with 25% placebo-treated patients (p < 0.05). The excess in dyskinesia prevalence and severity resolved by the end of the study with levodopa reduction. Levodopa dose was reduced more in those receiving pergolide (235 mg v 51 mg; p < 0.001). Pergolide produced significant improvement in Hoehn and Yahr stage (p < 0.05) and both the motor and activities of daily living parts of a modified Columbia rating scale (both p < 0.001). Significantly more patients suffered nausea (24% v 13%; p < 0.001) and hallucinations (14% v 3%; p < 0.01) on pergolide. No difference was found in the numbers remaining on treatment at the end of the study (pergolide 84% v placebo 82%) but withdrawals due to adverse events were greater in those taking pergolide (10% v 4%).

Authors' conclusions

Based on this single large multicentre study, pergolide reduces 'off' time and improves impairment and disability due to Parkinson's disease whilst allowing a reduction in levodopa dose. This is at the expense of dopaminergic adverse events. Further trials are required to compare pergolide with the newer dopamine agonists.



以pergolide 治療levodopa在巴金森氏病人中引起的併發症

在巴金森氏病的晚期,因長期使用levodopa而引起一些動作障礙的併發症,包括了異常的不自主運動(異動症)和每次服藥的效期縮短(wearing off phenomenon)。使這些病人服用多巴胺受體刺激劑是希望它們能使這些病人服用多巴胺受體刺激劑是希望它們能在些微地增加多巴胺刺激的副作用下,卻能減少不能活動靜止期的時間、減少所需要的levodopa藥量,並且能維持甚至改善動作障礙。




以電子搜尋MEDLINE, EMBASE and the Cochrane Controlled Trials Register. 以人工搜尋神經科的文獻: the Cochrane Movement Disorders Group's strategy等資料庫,並檢驗所找到研究和其他評論的參考文獻表。和Eli Lilly 有限公司聯絡。






找到了許多小型的RCTs,但這些是一個大型多中心試驗的一部份,最後一起發表。本篇評論只針對此篇最後發表的版本。服用pergolide的病人出現靜止期的時間可以減少1.8個小時,服用安慰靜的病人只減少0.2個小時(p<0.001)。62%服用pergolide的病人產生異動症或異動症惡化,而服用安慰劑的病人只有25%(p<0.05)。在研究的末期,較高比率的異動症和嚴重度可經由levodopa減量解決。在服用pergolide的病人中,levodopa的劑量減少得較多(235mg 比 51mg; p< 0.001)。在Hoehn and Yahr stage這個指標上,pergolide有顯著的進步,在modified Columbia rating scale中,動作和日常生活的部份都有顯著的進步。服用pergolide組中有比較多的病人有噁心(24%比13%; p< 0.001)、幻覺(14%比3%; p< 0.01)的副作用。在研究末期還留在研究中的病人數目兩組間並沒有差別(pergolide84%比placebo82%),但因為副作用而退出的比率則是pergolide組較高(10%比4%)





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