title: Bromocriptine/levodopa combined versus levodopa alone for early Parkinson's disease.
abstract: BACKGROUND
  Drugs that mimic dopamine such as bromocriptine were introduced as monotherapy or in a combination with LD in the hope that this approach would prevent or delay the onset of motor complications in patients with Parkinson's disease (PD). However, hitherto, the role of bromocriptine (BR) in this issue has remained controversial. The present study is a systematic review of all randomised controlled trials of bromocriptine/levodopa (BR/LD) combination therapy compared with levodopa (LD) monotherapy in PD.
  
  
  OBJECTIVE
  To assess the efficacy and safety of BR/LD combination therapy in delaying the onset of motor complications associated with LD monotherapy in patients with PD.
  
  
  METHODS
  Sources including the Cochrane Library, the search strategy of the Movement Disorders Group (includes computerised searches of MEDLINE and EMBASE and hand searching of appropriate neurology journals), reference lists of the reviews found by the MEDLINE and EMBASE search-strategy, Sandoz -now Novartis- (manufacturer of BR), PPD Pharmaco, symposia reports, PD handbooks, contacts with colleagues who had co-ordinated trials on BR and reference lists of all included studies were used to identify randomised controlled trials (RCTs) of interest.
  
  
  METHODS
  Randomised trials were eligible for inclusion if they evaluated the efficacy of BR/LD combination therapy for delaying the onset of motor complications compared to LD monotherapy in PD patients. Outcome measures that were evaluated included occurrence and severity of motor complications, scores on impairment and disability, and the occurrence of side effects and dropouts.
  
  
  METHODS
  To determine the feasibility of a quantitative systematic review two independent reviewers evaluated the methodological quality of identified trials.
  
  
  RESULTS
  The methodological quality of five trials showed important shortcomings. All studies failed to adequately describe randomisation procedures. Only two were carried out according to a double-blind design. Differences between studies concerning the mean age of the patients, the BR titration phase, the maximum achieved daily dose of LD (62.5-1000 mg) and BR (5-50 mg), and the applied outcomes were found. Our results show no evidence of consistent differences concerning the occurrence and severity of motor complications, scores of impairment and disability and the occurrence of side effects between both treatment groups.
  
  
  CONCLUSIONS
  This systematic review found no evidence in support of early bromocriptine/levodopa combination therapy as a strategy to prevent or delay the onset of motor complications in the treatment of PD.
authors.affiliation: Department of Neurology, Leiden University Medical Center, P.O. Box 9600, Leiden, Netherlands. J.J.van Hilten@lumc.nl
authors.forename: C
authors.initials: C
authors.lastname: Ramaker
authors.forename: J J
authors.initials: JJ
authors.lastname: Hilten
mesh_terms: D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001971:Bromocriptine / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000978:Antiparkinson Agents; D001971:Bromocriptine; D007980:Levodopa