This review highlights major methodological problems and sources of heterogeneity that not only hamper the comparability of trials but also preclude a conclusion on the efficacy of BR in the adjunct treatment of PD patients with motor complications.
Motor Complications are an important issue in the management of patients with Parkinson's disease and dopamine agonists have been introduced to ameliorate this problem.
To assess the efficacy and safety of adjunct bromocriptine (BR) therapy compared to placebo in the treatment of Parkinson's disease (PD) patients with motor complications.
Sources including the Cochrane Library, a MEDLINE search-strategy, reference lists of the reviews found by the MEDLINE search-strategy, Sandoz (producer of BR), symposia reports, PD handbooks, SCISEARCH, contacts with colleagues who had co-ordinated trials on BR and reference lists of all included studies were used to identify randomized controlled trials (RCTs) of interest.
Randomized trials were eligible for inclusion if they evaluated the efficacy of BR as adjunctive to LD-therapy compared to placebo in PD patients with motor complications. Outcome measures that were evaluated, included occurrence and severity of motor complications, scores on impairment and disability, and the occurrence of side effects.
Three reviewers independently reviewed the quality of identified trials. To determine the feasibility of a quantitative systematic review each eligible study was evaluated concerning the methodological quality.
This review identified important shortcomings regarding the methodological quality of eight trials. All studies failed to describe adequately their randomization procedure. Consultation with the trialists revealed that three trials adequately randomized their patients. Contrary to the information of the published report, one placebo-controlled trial appeared to be carried out as an open study and was therefore excluded. The remaining seven trials were reported to be carried out according to a double-blind design, although one was unblinded after five weeks. There was a conspicuous variability in the duration of trials: four to forty weeks (mean 14 weeks). None of the included trials was performed according to the intention-to-treat principle. With regard to the inclusion criteria, it frequently remained unclear if PD patients actually suffered from motor complications. Prominent differences between studies regarding the baseline characteristics and the rate by which BR was introduced during the titration phase were found. Major differences between studies emerged concerning the applied outcomes. The various methods used to evaluate the occurrence and/or severity of motor complications lacked a sound clinimetric basis. A great diversity of scales to evaluate impairment and disability was applied. None of the included trials reported whether scores on impairment and disability level referred to the "on"- or "off"-phase.