Risk of Disabling Response Fluctuations and Dyskinesias for Dopamine Agonists Versus Levodopa in Parkinson's Disease

Background: Response fluctuations and dyskinesias develop during the use of both levodopa (LD) and dopamine agonists (DA), but may not be equally disabling. Objective: To compare the risk and time of onset of disabling response fluctuations and dyskinesias (DRFD) among patients with Parkinson's disease (PD) who were initially treated with either LD or DA. Methods: Open cohort study of all consecutive de-novo PD patients in routine clinical practice, included over a period of 15 years (median follow-up: 8.1 years, range 1.1-17.7), since embarking on LD or DA. Older patients and patients with more severe PD were started on LD (n = 77), younger patients on a DA (n = 50). Therapy was adjusted according to generally accepted guidelines. The primary endpoints were: the onset of response fluctuations, dyskinesias, and the moment when these complications became disabling (DRFD). Results: LD-starters developed response fluctuations 0.8 years earlier than DA-starters (p = 0.07), while dyskinesias appeared around 2.5 years earlier (p = 0.003). However, the risk and time of onset of DRFD did not differ statistically between the groups (LD-starters: 60%, median interval 7.3 years, DA-starters: 52%, 6.1 years, p = 0.63). DA-starters displayed a 0.19 points lower adjusted mean improvement in motor scores than LD-starters (p = 0.002). Adjustments for age and severity of PD at start of dopaminergic therapy did not change these results. Conclusions: In routine clinical practice, the risk and time of onset of DRFD is comparable for LD-starters versus DA-starters, but motor functioning is worse in DA-starters. These results support the use of LD as initial therapy for PD.