JAMA. 1997 Jul 9;278(2):125-30. doi: 10.1001/jama.1997.03550020057038.
Monotherapy with dopamine agonists may be useful in early Parkinson disease.
To evaluate dose-response relationships for tolerability, safety, and efficacy of the synthetic dopamine agonist pramipexole.
Multicenter, multidosage, parallel-group, double-blind, placebo-controlled, randomized clinical trial.
University or academically based movement disorder clinics.
A total of 264 patients with early Parkinson disease (PD) who were not requiring or receiving levodopa or other dopamine agonists were enrolled.
Subjects were randomized to 1 of 5 treatment groups: pramipexole doses of 1.5 mg/d, 3.0 mg/d, 4.5 mg/d, and 6.0 mg/d, or matching placebo. A 6-week dosage escalation period was followed by a 4-week maintenance period and a 1-week period during which active treatment was withdrawn.
The primary measure of tolerability was the proportion of subjects completing the study on the assigned treatment. The primary measure of efficacy was the change from baseline to 10 weeks in the total score on the Unified Parkinson's Disease Rating Scale (UPDRS).
Pramipexole was generally safe and well tolerated in this 10-week study. The proportion of subjects completing the study on the originally assigned dosage was 98% for placebo and 81% for the 1.5-mg/d, 92% for the 3.0-mg/d, 78% for the 4.5-mg/d, and 67% for the 6.0-mg/d treatment groups. There was a trend toward increased frequency of adverse experiences, particularly somnolence, in the 6.0-mg/d group. After 10 weeks of treatment, pramipexole-treated subjects showed a 20% improvement in total UPDRS scores, with mean improvements in scores ranging from 5.9 to 7.0 units among active treatment groups, compared with 0.9 units for the placebo group (P<.005 for each comparison with placebo). There was also evidence that the treatment effects were more pronounced in subjects with worse UPDRS scores at baseline.
Pramipexole is safe and effective as short-term monotherapy in patients with early PD who are not receiving levodopa. Further study is warranted to determine the long-term impact of pramipexole on the progression of disability in PD and its value in comparison with levodopa therapy and other dopamine agonists.
多巴胺激动剂单药治疗可能对早期帕金森病有用。
评估合成多巴胺激动剂普拉克索在耐受性、安全性和疗效方面的剂量反应关系。
多中心、多剂量、平行组、双盲、安慰剂对照、随机临床试验。
大学或基于学术机构的运动障碍诊所。
共纳入264例早期帕金森病（PD）患者，这些患者未需要或正在接受左旋多巴或其他多巴胺激动剂治疗。
受试者被随机分配到5个治疗组中的1组：普拉克索剂量为1.5mg/d、3.0mg/d、4.5mg/d和6.0mg/d，或匹配的安慰剂。6周的剂量递增期后是4周的维持期和1周的停药期。
耐受性的主要指标是在指定治疗方案下完成研究的受试者比例。疗效的主要指标是统一帕金森病评定量表（UPDRS）总分从基线到10周的变化。
在这项为期10周的研究中，普拉克索总体上安全且耐受性良好。在最初指定剂量下完成研究的受试者比例，安慰剂组为98%，1.5mg/d组为81%，3.0mg/d组为92%，4.5mg/d组为78%，6.0mg/d治疗组为67%。6.0mg/d组不良事件发生率有增加趋势，尤其是嗜睡。治疗10周后，普拉克索治疗的受试者UPDRS总分改善了20%，活性治疗组的分数平均改善5.9至7.0个单位，而安慰剂组为0.9个单位（与安慰剂组的每次比较P<0.005）。也有证据表明，在基线时UPDRS评分较差的受试者中，治疗效果更明显。
对于未接受左旋多巴治疗的早期PD患者，普拉克索作为短期单药治疗是安全有效的。有必要进一步研究以确定普拉克索对PD患者残疾进展的长期影响及其与左旋多巴治疗和其他多巴胺激动剂相比的价值。
