Increased risk of somnolence with the new dopamine agonists in patients with Parkinson's disease - A meta-analysis of randomised controlled trials

Background: Recent case reports and letters have alerted practitioners to t he risk of sleep attacks, usually preceded by somnolence, in patients with Parkinson's disease treated with pramipexole and ropinirole. Objective: To quantify the risk of somnolence with the new dopamine agonist s pramipexole and ropinirole in patients with Parkinson's disease. Methods: We searched MEDLINE, EMBASE, International Pharmaceutical Abstract s and Cochrane Library, contacted experts and pharmaceutical manufacturers, and manually reviewed all references retrieved to identify possible articl es to include. Information on randomisation, blinding, type of treatment an d reporting of somnolence were abstracted by 2 independent reviewers. Disag reements were resolved by a third author. Analysis: We made 2 separate analyses. The first analysis compared the risk of somnolence in patients taking either pramipexole or ropinirole to that in patients taking placebo. The second analysis compared the risk of somnol ence with these drugs (plus levodopa) versus that with levodopa alone. We c alculated pooled relative risk estimates using the random effects model and when no heterogeneity was detected we used the fixed effects model. Results: Four trials were included in the analysis of patients taking prami pexole or ropinirole. compared with those taking placebo. The pooled relati ve risk of somnolence in this analysis was 4.98 [95% confidence interval (C I) 1.79 to 13.89]. Seven trials were included in the analysis of patients t aking levodopa and pramipexole or ropinirole compared with those taking lev odopa alone. The pooled relative risk was 2.06 (95% CI 1.47 to 2.88). Conclusion: Patients with Parkinson's disease using pramipexole or ropiniro le are at higher risk of experiencing somnolence relative to patients takin g placebo. Patients taking levodopa plus either one of these dopamine agoni sts are at higher risk than those taking levodopa alone. Clinicians should carefully weigh this risk against the benefit of these agents when prescrib ing these drugs.