The Parkinson–Control study: A 1‐year randomized, double‐blind trial comparing piribedil (150 mg/day) with bromocriptine (25 mg/day) in early combination with levodopa in Parkinson's disease

Abstract

Dopamine agonists have been recommended as early treatment for Parkinson's disease (PD), alone or combined with levodopa. Piribedil is a non-ergot selective D(2)/D(3) agonist with alpha(2) antagonist properties shown to be effective in the treatment of PD. This 12-month international, randomized, double-blind trial aimed to assess the efficacy of piribedil 150 mg versus bromocriptine 25 mg, in early combination with levodopa in Stage I to III PD patients. Motor efficacy was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS III, Items 18-31) as improvement from baseline. Response rate was defined as a 30% improvement. Among the 425 randomly assigned patients, 178 were also included in a substudy on cognitive follow-up evaluated by a dysexecutive syndrome oriented battery. A relevant improvement in UPDRS III over the 12-month study duration was observed both in the piribedil and bromocriptine groups (-7.9 +/- 9.7 points from baseline versus -8.0 +/- 9.5; not significant [n.s.]) with a response rate of 58.4% and 55.3% (n.s.), respectively. Piribedil and bromocriptine resulted in similar improvement on all UPDRS III subscores. Piribedil patients required less levodopa dose increase than those on bromocriptine. Cognitive performance remained generally unchanged in both groups, with a significant effect of piribedil limited to the Wisconsin Card Sorting Test. An overall good tolerability of piribedil was observed. Early combination of piribedil 150 mg with levodopa resulted in significant long-term improvement of all motor symptoms in PD patients insufficiently controlled by levodopa alone. Taking into account both efficacy and acceptability in the long-term, piribedil proved in this bromocriptine controlled study to be an effective and safe treatment for PD.

Parkinsonian apathy responds to dopaminergic stimulation of D2/D3 receptors with piribedil

“…The present controlled study reinforces this treatment strategy with piribedil, another dopamine agonist. Although not marketed in several countries, piribedil was chosen in this study because of its broad use in France over several decades with well known safety profile and relatively low cost compared with more recent dopamine agonists, the fact that it is a non-ergot drug, its known efficacy on motor symptoms in Parkinson's disease but also based on early studies indicating a benefit on depression (Post et al, 1978;Castro-Caldas et al, 2006;Rascol et al, 2006Rascol et al, , 2010. Most importantly, in a previous study (Thobois et al, 2010) we had shown that dopamine withdrawal syndrome is related to mesolimbic dopaminergic denervation and we hypothesized that a D2/D3 agonist should be beneficial on non-motor psychic symptoms that we have classified as hypodopaminergic (Ardouin et al, 2009).…”

Piribedil for the Treatment of Motor and Non-motor Symptoms of Parkinson Disease

“…Dyskinesia was infrequently observed on piribedil over 1 year in patients with early PD (2.9 % of the patients) [66]. The same applied to bromocriptine (4.7 %), which was used as the active comparator in this study.…”

“…Castro-Caldas and colleagues compared the effects of piribedil and bromocriptine on cognitive function in a subset of 178/428 patients with early PD assessed primarily for motor response (see above) [66]. At both 6 and 12 months, there was a significant effect of piribedil on the Wisconsin Card Sorting Test in younger (aged \ 70 years) patients, with no effect of bromocriptine [0.2 points improvement on piribedil vs. 0.3 worsening on bromocriptine (p = 0.03)].…”

“…Piribedil efficacy has also been compared with bromocriptine in a third randomized study conducted in nonfluctuating patients insufficiently controlled with levodopa [66]. Follow-up was 12 months and piribedil and bromocriptine doses were 150 mg/day and 25 mg/day, respectively.…”

“…Nevertheless, in the same study, hallucinations were among the most common reasons for discontinuation in the active group (4 patients, 1 %) as compared with placebo (none). In a 12-month randomized double-blind trial aimed at assessing the efficacy of piribedil (150 mg/day) versus bromocriptine (25 mg/day) as early combination therapy with levodopa, the incidence of hallucinations was 8.1 % for piribedil and 2.8 % for bromocriptine, and treatment discontinuations because of hallucinations were 2.9 % for piribedil and 1.4 % for bromocriptine [66].…”