普拉克索添加治疗帕金森病临床随机对照研究

目的 评价新型多巴胺受体激动剂普拉克索联合美多巴与单用美多巴治疗帕金森病(PD)患者的疗效及安全性. 方法 采用随机对照开放式研究,将70例PD患者按照随机数字表法分为普拉克索+美多巴组和美多巴组,每组各35例.治疗12周后判断其疗效及安全性.疗效判定的主要指标为统一PD评定量表第Ⅲ部分(UPDRSⅢ)的运动检查总评分相对患者基线的变化和第Ⅱ部分(UPDRS Ⅱ)的日常生活活动能力总评分相对患者基线的变化;次要指标为第Ⅰ部分(UPDRS Ⅰ)的精神、行为和情感总评分相对患者基线的变化和第Ⅳ部分(UPDRS Ⅳ)的治疗并发症总评分相对患者基线的变化和美多巴药物每日剂量相对基线的变化.安全性指标依据药物的不良反应来判定. 结果 普拉克索+美多巴组患者UPDRS Ⅲ总评分均值与基线相比下降了11.40分,高于美多巴组(9.26分),比较差异有统计学意义(P<0.05);UPDRS Ⅱ总评分均值与基线相比下降了4.57分,高于美多巴组(4.50分),比较差异无统计学意义(P<0.05);UPDRS Ⅰ总评分均值与基线相比下降了0.66分,低于美多巴组(1.14分),差异无统计学意义(P0.05);UPDRS Ⅳ总评分均值与基线相比下降了0.22分,美多巴组则升高了0.06分,差异有统计学意义(P<0.05).与基线相比,治疗后12周普拉克索+美多巴组美多巴的日用量下降了163.57 mg/d,美多巴组升高了8.57 mg/d,差异有统计学意义(P<0.05).普拉克索+美多巴组在治疗后12周发生疗效减退、症状波动、异动症的例数均低于美多巴组,差异有统计学意义(P<0.05).美多巴组出现了明显的疗效减退、症状波动、异动症,而普拉克索+美多巴组无明显的上述症状,但有2例出现突然入睡发作、1例嗜睡、1例直立性低血压. 结论 普拉克索+美多巴组在改善PD运动功能方面优于美多巴组,在日常活动,精神、行为和情绪方面疗效相似.同时服用普拉克索可以明显减少美多巴的用量及其治疗后所引起的并发症(疗效减退、症状波动及异动症)的发生率.普拉克索可引起突然入睡发作、嗜睡、直立性低血压等副作用.

Pramipexole combined with Madopar vs Madopar alone for treatment of Parkinson's disease: a randomized controlled clinical trial

Objective To assess the therapeutic effect and safety ofpramipexole combined with Madopar and Madopar alone in the treatment of Parkinson's disease (PD). Methods This randomized, controlled open-label trial involved 70 PD patients who were randomly assigned to receive pramipexole combined with Madopar (n=35) or Madopar alone (n=35) for 12 consecutive weeks. The therapeutic effect was assessed primarily by the Unified Parkinson's Disease Rating Scale (UPDRS). The main effect was motor symptoms of UPDRS Ⅲ and activities of daily living of UPDRS Ⅱ. The secondary effect was the changes relative to the baseline levels in the consciousness, behavior, and emotion of UPDRS Ⅰ, the complications of UPDRS Ⅳ and daily Madopar dosage. The safety of the drugs was evaluated according to the adverse reactions. Results Compared to the baseline levels, 12 weeks of treatment with pramipexole combined with Madopar resulted in significantly greater reduction in the total scores ofUPDRS Ⅲ than Madopar alone (11.40 vs 9.26, P<0.05), but the reduction in the total DOI: 10.3760/cma.j .issn. 1671.8925.2009.07.010scores of UPDRS Ⅱ and UPDRS Ⅰ was comparable between the two treatments (4.57 vs 4.50 and 0.66 vs 1.14, respectively, P>0.05). The combined treatment reduced the total score of UPDRS Ⅳ by 0.22 whereas Madopar alone increased the score by 0.06, showing significant difference between the two treatments (P<0.05). The daily Madopar dosage in the combined treatment group was decrease by 163.57 rag, but that in Medopar group increased by 8.57 rag (P<0.05). The frequencies of wearing-off, symptom fluctuation and movement disorder were significantly lower in combined treatment group than in Madopar group. Obvious wearing-off, symptom fluctuation and movement disorder occurred in Madopar group, which were not noted in the combined treatment group but two patients developed sudden sleep, one reported drowsiness, and another exhibited orthostatic hypotension. Conclusion Pramipexole combined with Madopar results in better improvement of the motor symptoms than Madopar alone in PD patients, but they show similar effect on the activities of daily living and consciousness, behavioral and emotional changes. Pramipexole can significantly decrease the daily dose of Madopar and help reduce the complications, suggesting its safety and effectiveness in the treatment of PD, but its adverse effects should be given due attention in clinical application.