Abstract

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.

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.

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 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.

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%).

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.