Abstract
Background
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.
Objectives
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.
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 Pharmacia Upjohn and Boehringer Ingelheim.
Selection criteria
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.
Main results
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.
Authors’ conclusions
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.
