title: Risk of Disabling Response Fluctuations and Dyskinesias for Dopamine Agonists Versus Levodopa in Parkinson's Disease.
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.
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.|Parkinson Center Nijmegen (ParC), Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Haaxma
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.|Parkinson Center Nijmegen (ParC), Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Martin W I M
authors.initials: MW
authors.lastname: Horstink
authors.affiliation: Department of Neurology, Amphia Hospital, Breda, The Netherlands.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Zijlmans
authors.affiliation: Department of Epidemiology, Biostatistics and HTA, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Wim A J G
authors.initials: WA
authors.lastname: Lemmens
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.|Parkinson Center Nijmegen (ParC), Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Bastiaan R
authors.initials: BR
authors.lastname: Bloem
authors.affiliation: Department of Epidemiology, Biostatistics and HTA, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: George F
authors.initials: GF
authors.lastname: Borm
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects*; D018491:Dopamine Agonists / Q000009:adverse effects*; D004409:Dyskinesia, Drug-Induced / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy* / Q000453:epidemiology; D013997:Time Factors
chemical_list: D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D007980:Levodopa
keywords: Parkinson’s disease; dopamine agonists; dyskinesia; levodopa; response fluctuations