Ropinirole versus bromocriptine for levodopa-induced complications in Parkinson's disease

In the later stages of Parkinson's disease, side effects occur because of the use of levodopa treatment. These consist of involuntary writhing movements (dyskinesia), 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 dopamine 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. Ropinirole is a new dopamine agonist recently licensed in the UK for the treatment of early and later Parkinson's disease. In this review, we will examine the trials performed with this drug to see how it compares with one of the older agonists bromocriptine.

Three trials have compared ropinirole with bromocriptine in 482 patients in the later stages of Parkinson's disease. Two studies were conducted over the short term (8 and 16 weeks), and used relatively low doses of ropinirole (9 mg/d) and bromocriptine (17.5 and 22.5mg/d). The other study was medium term (25 weeks) and used ropinirole doses in line with the current UK licensed maximum (24 mg/d).

No significant differences were found between the agonists in the time patients spent in the immobile off state, in dyskinesia reported as a side effect, in measurements of physical difficulties and problems with activities of daily living (such as bathing, shopping, etc.), or in levodopa dose reduction. No differences in side effects or withdrawals from treatment were found apart from less nausea with ropinirole.

In patients with Parkinson's disease and motor complications, ropinirole has similar effects to bromocriptine in terms of improving off time and reducing levodopa dose, without increasing adverse events including dyskinesia. However, these comparitor studies may have been underpowered to detect clinically meaningful differences between the agonists.

Authors' conclusions: 

In patients with Parkinson's disease and motor complications, ropinirole has similar effects to bromocriptine in terms of improving off time and reducing levodopa dose, without increasing adverse events including dyskinesia. However, these comparator studies may have been underpowered to detect clinically meaningful differences between the agonists.

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Background: 

Long-term levodopa therapy for Parkinson's disease is complicated by the development of motor fluctuations and abnormal involuntary movements. One approach is to add a dopamine agonist at this stage of the disease to reduce the time the patient spends immobile or off and to reduce the dose of levodopa in the hope of reducing such problems in the future.

Objectives: 

To compare the efficacy and safety of adjuvant ropinirole therapy with bromocriptine in patients with Parkinson's disease already established on levodopa therapy and suffering from motor complications.

Search strategy: 

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 SmithKline Beecham.

Selection criteria: 

Randomised controlled trials of ropinirole 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 withdrawals and adverse events.

Main results: 

In the 3 trials identified, no significant differences between ropinirole and bromocriptine were found in off time reduction, dyskinesia as an adverse event, motor impairment and disability, or levodopa dose reduction. Withdrawal rates and adverse event frequency were similar with the two agents apart from significantly less nausea with ropinirole (odds ratio 0.50; 0.29, 0.84 95% CI; p =0.01).

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