Affiliations: [a] Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands | [b] Parkinson Center Nijmegen (ParC), Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands | [c] Department of Neurology, Amphia Hospital, Breda, The Netherlands | [d] Department of Epidemiology, Biostatistics and HTA, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Correspondence to: Charlotte A. Haaxma, MD, PhD, Department of Neurology (935), Parkinson Center Nijmegen (ParC), and Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre (Radboudumc), PO Box 9101, 6500 HB, Nijmegen, The Netherlands. Tel.: +31 24 3613394; Fax: +31 24 3541122; E-mails: firstname.lastname@example.org, email@example.com
Note:  We dedicate this article to Dr. Martin Horstink, who performed a substantial part of this research.
Note:  The author has deceased.
Abstract: 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.