Comparison of the risk of adverse events with pramipexole and ropinirole in patients with Parkinson's disease - A meta-analysis

Background: Pramipexole and ropinirole are relatively new dopamine agonists, both of which have proven efficacy in the treatment of Parkinson's disease. There is, however, uncertainty regarding differences in the adverse event profiles associated with each drug. Objective: To compare the adverse events of pramipexole and ropinirole as. reported in the peer-reviewed medical literature. Methods: We systematically reviewed the medical literature to identify randomised controlled trials of pramipexole and ropinirole used in the management of Parkinson's disease. Computerised databases (including Medline, Embase, the Cochrane Library, and the International Pharmaceutical Abstracts) were used to identify pertinent articles for inclusion in this study. Trials that compared the dopamine agonists to either levodopa or placebo were included. Analysis: Adverse events with these drugs included dizziness, nausea, hypotension, hallucinations, and somnolence. We made two separate analyses. In the first analysis, we estimated the pooled relative risk (RR) of adverse events with either pramipexole or ropinirole as compared with levodopa. In the second analysis, the pooled RRs of adverse events with pramipexole and ropinirole were compared with placebo. We used the random-effects model of DerSimonian and Laird to estimate the RRs and their corresponding 95% CIs. We tested for study heterogeneity using Q statistics. Results: There was no significant difference in the risk of dizziness, nausea, or hypotension with either drug individually or in combination when compared with levodopa. The risk of hypotension was approximately four times higher with ropinirole than pramipexole when each drug was individually compared with placebo (6.46 [95% CI 1.47-28.28] for ropinirole, and 1.65 [0.88-3.08] for pramipexole). The pooled RR (for pramipexole and ropinirole combined) of hallucinations was 1.92 (95% CI 1.08-3.43) when compared with levodopa. Relative to placebo, pramipexole had a significantly higher risk of hallucinations than ropinirole (pramipexole 5.2 [95% CI 1.97-13.72] vs ropinirole 2.75 [95% CI 0.55-13.73]). There was no significant difference in the risk of somnolence between the two drugs when each was individually compared with levodopa. When compared with placebo, the pooled RR (pramipexole and ropinirole combined) of somnolence was 3.16 (95% CI 1.62-6.13). Relative to placebo, the risk of somnolence was 2.01 (95% CI 2.17-3.16) with pramipexole and 5.73 (95% CI 2.34-14.01) with ropinirole. Conclusions: Use of ropinirole seems to be associated with a higher risk of hypotension and somnolence than use of pramipexole when compared with placebo. Use of pramipexole seems to be associated with a higher risk of hallucinations than use of ropinirole when compared with placebo.