The Efficacy and Safety of Piribedil Relative to Pramipexole for the Treatment of Early Parkinson Disease: A Systematic Literature Review and Network Meta-Analysis

Abstract

Objectives Patients with early Parkinson disease (PD) frequently defer initiation of levodopa treatment to minimize long-term complications. Nonergoline dopamine agonists, such as pramipexole and piribedil, are frequent first-line therapies for early PD patients, yet limited head-to-head randomized controlled trial (RCT) evidence exists for dopamine agonists in this population. We therefore conducted a systematic literature review and network meta-analysis. Methods MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were systematically searched (until January 7, 2020), identifying RCTs assessing the efficacy of piribedil or pramipexole in early PD. Eligible trial data were incorporated into fixed- and random-effects Bayesian network meta-analyses. Results No RCTs were identified directly comparing piribedil with pramipexole, but 6 trials provided data for pramipexole versus placebo and 2 compared piribedil versus placebo, facilitating indirect comparisons. Across all time points assessed, no significant differences were found between pramipexole and piribedil for change in the Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline. Piribedil and pramipexole demonstrated superiority relative to placebo for UPDRS II/III change at weeks 22 to 30. No significant differences were noted between the treatments at weeks 20 to 35 for anxiety, constipation, hypotension, nausea, and somnolence. Sensitivity analyses on adjustment for dose titration periods and baseline risk yielded the same pattern of results. Conclusions No significant differences were found for pramipexole versus piribedil in the UPDRS II/III scores from baseline in early PD, with similar safety profiles.

Comparison of the effectiveness, safety, and costs of anti‐Parkinson drugs: A multiple‐center retrospective study

“…Additionally, for interclass comparison of efficacy, consistent with our research, a Cochrane meta‐analysis including 44 trials involving 8436 participants has also revealed that as adjuvant treatments to levodopa therapy, dopamine agonists were more efficacious in PD patients with UPDRS score improvements, off‐time, and levodopa dose reduction than MAOBIs and COMTIs 14 . While for the intraclass comparison between dopamine agonists, several network meta‐analyses have reported that pramipexole and piribedil had no significant differences in improving non‐motor symptoms with similar UPDRS II and UPDRS III scores in early Parkinson's disease, 26,27 which was not in line with our study. Meanwhile, pramipexole was likely superior to selegiline in effectiveness as monotherapy, which turned out to be the opposite when used in combination with levodopa 28 .…”

Terazosin Analogs Targeting Pgk1 as Neuroprotective Agents: Design, Synthesis, and Evaluation

“…The introduction of active fragments is a common strategy for drug development. Similar in structure to terazosin, Piribedil also has a pyrimidine-2-piperazine group and has been shown to exert anti-PD effects by affecting energy metabolism ( Chen et al, 2020 ). We developed compound 7c by introducing its unique piperonyl group.…”

A Systematic Review and Meta-Analysis of the Efficacy and Safety of Rasagiline or Pramipexole in the Treatment of Early Parkinson’s Disease

“…When compared to rasagiline, fewer systematic reviews and meta-analyses are available for pramipexole and PD patients. A recent systematic review by Chen et al [ 44 ] identified six trials that compared the efficacy of pramipexole versus placebo in patients with early PD as defined by a Hoehn and Yahr score of <3. This study showed no benefit of pramipexole at 22 to 30 weeks after initiation of therapy on the change in either UPDRS Part II (mean difference = 0.02, 95% confidence interval: −1.15 to 1.12) or Part III (mean difference = 0.32, 95% confidence interval: −8.22 to 7.95) scores.…”

“…This study showed no benefit of pramipexole at 22 to 30 weeks after initiation of therapy on the change in either UPDRS Part II (mean difference = 0.02, 95% confidence interval: −1.15 to 1.12) or Part III (mean difference = 0.32, 95% confidence interval: −8.22 to 7.95) scores. Evaluation of safety data showed that pramipexole demonstrated significantly higher event rates for nausea than placebo [ 44 ]. A systematic review by Ji et al [ 45 ] including 23 randomized clinical trials showed pramipexole was effective in lowering the Hamilton Depression Rating Scale (HAM-D) score in PD patients with anxiety or depression.…”