Adding a dopamine agonist to preexisting levodopa therapy vs. levodopa therapy alone in advanced Parkinson’s disease: a meta analysis

Abstract

To perform a meta analysis of randomised placebo-controlled trials evaluating the use of dopamine agonist (DA) or placebo to preexisting levodopa therapy for the treatment of advanced Parkinson's disease (PD). We focused on clinically important efficacy [Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living (ADL) and motor scores as well as change in 'off' time and levodopa dose] and safety outcomes (withdrawal because of adverse drug events (ADEs), dyskinesias, hallucinations and mortality). A systematic literature search was performed between January 1990 and July 2007. The primary outcome measures assessed were the reduction in scores of Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living (ADL) and motor scores as well as reduction in 'off' time and reductions in levodopa dose from baseline. Safety end-points were also evaluated. A total of 15 trials (n = 4380 subjects) were included in the meta analysis. Adjunctive DA use resulted in greater improvement as measured by the UPDRS ADL [weighted mean difference (WMD) -2.20, 95% confidence interval (CI) -2.64 to -1.76; p < 0.0001] and motor score reduction (WMD -5.56, 95% CI -6.82 to -4.31; p < 0.0001) as well as reduction in 'off' time measured in hours/day (WMD -1.20, 95% CI -1.78 to -0.62; p < 0.0001) and reduction in levodopa dose (WMD -128.5 mg, 95% CI -175.0 to -82.1; p < 0.0001) vs. placebo. Incidence of dyskinesia and hallucinations was higher with DAs [odds ratio (OR) 3.27, 95% CI 2.65-4.03; p < 0.0001] and (OR 3.34, 95% CI 2.44-4.58; p < 0.0001). Non-ergot DAs were qualitatively better, although both ergot and non-ergot DAs showed statistically significant improvements in all UPDRS scores. Adjunctive DA use to levodopa is superior to levodopa alone in reducing PD symptoms in patients not controlled with monotherapy. DAs seem especially useful amongst PD patients with wearing-off phenomenon from levodopa therapy, but can cause some adverse events.