普拉克索治疗帕金森病有效性和安全性的meta分析

目的通过对普拉克索治疗帕金森病(PD)的临床随机对照研究进行Meta分析,探讨普拉克索的药效和安全性,为临床安全合理使用该药提供依据。方法计算机检索Ovid Medline(1966年~2009年3月),图书馆临床试验和专业资料库,Cochrane图书馆临床对照试验资料库(ACP Journal C1ub;Cochrane Central Register ofControlled Trials CENTRAL,2008年),中国生物医学文献数据库(1990~2008年),同时检索相关文献的参考文献。应用Cochrane协作网提供的Rev Man4.28软件系统评价,对普拉克索治疗PD的随机对照试验进行Meta分析。结果共纳入6个随机对照试验,包括普拉克索组898例患者,安慰剂对照组813例患者。Meta分析结果显示:(1)帕金森病评定量表(UPDRS)第Ⅱ部分评分相对基线的变化取加权均数差进行meta分析。普拉克索组和安慰剂组之间差异(WMD=-2.35,95%CI[-2.92,-1.79],P<0.01),差异有统计学意义。UPDRSⅢ评分相对基线的变化取加权均数差进行meta分析。普拉克索组和对照组之间...     

普拉克索治疗不宁腿综合征的Meta分析

目的 系统评价普拉克索治疗不宁腿综合征(restless legs syndrome,RLS)的疗效与安全性.方法 检索中国期刊全文数据库( CNKI)、美国国立医学生物信息中心PubMed数据库( PubMed)、荷兰医学文摘数据库(Embase)、Cochrane Library数据库关于普拉克索治疗RLS的随机、双盲、安慰剂对照研究.对符合条件的研究结果用RevMan 5.0软件进行Meta分析.以普拉克索组和安慰剂组在国际不宁腿研究组评分量表( International RLS Study Group rating scale,IRLS)评分变化方面的加权均数差(weighted mean difference,WMD)和普拉克索组相对于安慰剂组在临床疗效总评(clinical global impression-improvement,CGI-I)方面疗效显著率的相对危险度(relative risk,RR)为指标进行疗效评价,以其在不良事件方面的相对危险度为指标进行安全性评价.结果 共纳入5项研究,1776例患者被随机分配,其中普拉克索组945例,安慰剂组831例.Meta分析结果显示,普拉克索组相对于安慰剂组在IRLS评分变化方面的WMD=-6.34 (Z=12.76,P＜0.01),在CGI-I显著性评估方面的RR=1.65 (Z=10.39,P＜0.01);两组在不良事件方面的RR=1.14 (Z=1.87,P=0.06).结论 普拉克索是治疗RLS的有效且安全的药物.     

普拉克索、氟哌噻吨美利曲辛治疗帕金森病合并抑郁症的疗效

目的比较普拉克索、氟哌噻吨美利曲辛治疗帕金森病(PD)合并抑郁症的疗效。方法 102例PD合并抑郁症患者随机分为普拉克索治疗组和氟哌噻吨美利曲辛治疗组,治疗半年以上。用PD统一评分量表(UPDRS)评价PD症状改善情况,用汉密顿抑郁量表17项(HAMD)和抑郁自评量表(SDS)评价抑郁症状改善情况。结果 2组患者经过治疗后UP-DRS、HAMD和SDS均较治疗前有所改善,普拉克索组UPDRS评分高于氟哌噻吨美利曲辛治疗组,HAMD和SDS比较无明显差别。结论普拉克索和氟哌噻吨美利曲辛都能改善PD合并抑郁症患者症状,且普拉克索在改善帕金森症状方面优于氟哌噻吨美利曲辛。     

恩他卡朋添加治疗帕金森病症状波动的系统评价

目的 系统评价恩他卡朋治疗帕金森病(PD)症状波动的疗效.方法 采用Pubmed、Embase、Cochrane Database及其他互联网公共搜索引擎作为检索工具,检索国内外1966-2007年6月已发表的有关恩他卡朋对照、安慰剂治疗PD症状波动的临床研究资料.由2位研究者独立评价研究质量.使用Revman 4.2.10进行统计学处理.结果 共纳入10项随机对照临床试验(RCT)研究(共2212例患者),结果 表明恩他卡朋治疗PD伴症状波动的患者有延长"开"期、缩短"关"期、减少每日左旋多巴剂量(WMD=-1.41,95%CI-2.09～-0.72)和改善"开"期运动症状及生活质量的趋势,然而与安慰剂比,恩他卡朋可以增加异动症的发生率(OR=2.00,95%CI 1.55～2.58).结论恩他卡朋可以改善PD症状波动,同时也需要更多设有相同判效指标的大样本高质量RCT研究进一步证实.     

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.     

普拉克索添加治疗帕金森病的疗效观察

目的 观察添加普拉克索治疗帕金森病(PD)的疗效和安全性.方法 78例Hoehn-Yahr分级为Ⅱ～Ⅲ级的PD患者在接受左旋多巴达到剂量稳定≥30 d的基础上随机分为3组.A组添加普拉克索0.125 ng,每日2次,4周滴定至0.75 mg/d,维持8周.B组添加普拉克索0.125 mg,每日2次,6周滴定至1.5 mg/d,维持6周.C组不添加普拉克索.治疗前后应用统一PD评定量表(UPDRS)评分并评估疗效,观察不良反应.结果 与治疗前相比,治疗12周A组、B组的UPDRSⅡ、Ⅲ评分明显下降(均P＜0.05);B组显效率(21例,80.8%)显著高于A组(12例,46.2%)(P＜0.01).3组均未发生严重不良反应.B组2例出现轻度头晕、恶心,未影响治疗.结论 应用左旋多巴治疗的PD患者添加普拉克索可以有效缓解症状,改善生活质量;添加普拉克索1.5 mg/d的疗效优于0.75 mg/d.     

普拉克索治疗帕金森病运动并发症的临床研究

目的 探讨普拉克索对经复方左旋多巴治疗并且已经出现运动并发症的中晚期帕金森病(PD)患者的疗效和安全性.方法 42例PD患者在原有复方左旋多巴治疗的基础上加用普拉克索1.5～3.0mg/d,为期12周.疗效指标为治疗前后统一PD评定量表(Unified Parkinson's Disease Rating Scale,UPDRS)及汉密尔顿抑郁量表(Hamilton Depression Scale,HAMD)评分,其中UPDBS Ⅰ及HAMD用于评价精神、行为、情绪等非运动症状;UPDRS Ⅱ评价日常生活活动能力;UPDRS Ⅲ、Ⅳ及"开"期和"关"期时间的变化用于评价运动功能,并对患者的临床疗效进行整体评价.安全性指标为不良反应、血压、脉搏、实验室检查、心电图及对认知功能的影响.结果 治疗12周后,UPDRS各项评分均减少,差异具有统计学意义(UPDRS总分:52.05±7.69与39.26±7.64,t=25.378,P＜0.05).UPDRS运动评分改善22.61%,"开"期持续时间增加约1.64 h;复方左旋多巴用最平均减少129.46 mg/d;治疗并发症评分变化均值下降1.45分;HAMD评分均值下降6.14分.不良反应主要有头晕、嗜睡、恶心、便秘、厌食等.结论 普拉克索对运动症状和非运动症状均有较好的疗效,不良反应发生率低,中晚期PD患者加用普拉克索是安全而有效的.     

罗匹尼罗治疗帕金森病有效性和安全性Meta分析

目的通过对罗匹尼罗治疗帕金森病(PD)的临床随机对照研究进行Meta分析,探讨罗匹尼罗的有效性和安全性,旨为临床安全合理用药提供理论依据。方法利用计算机检索美国国立医学图书馆(Pubmed)、考克兰图书馆(Cochrane Library)、荷兰医学文献数据库(Embase)、中国知网学术论文数据库(CNKI)、万方知识服务平台、维普期刊网,检索罗匹尼罗治疗帕金森病有效性及安全性的相关研究。提取研究中各组统一帕金森病评定量表第Ⅱ部分(UPDRSⅡ)评分、第III部分(UPDRSⅢ)评分以及各组不良事件发生率。采用Cochrane风险偏倚评估工具对纳入文献进行质量评价,采用Rev Man5. 3软件进行Meta分析。结果通过计算机检索数据库,共检出732篇文章,排除不符合要求的文献,最终纳入罗匹尼罗治疗PD有效性和安全性的RCT研究12篇,共3341例患者,其中试验组1855例,对照组1486例。Meta分析结果显示:在药物疗效方面,与安慰剂组相比,罗匹尼罗组治疗帕金森病UPDRSⅡ(MD-2. 23,95%CI-2. 82～-1. 64,P 0. 00001)及UPDRSⅢ(MD-4. 93,95%CI-5. 25～-4. 61,P 0. 00001)评分降低更明显。在不良反应发生率方面,罗匹尼罗组运动障碍(RR 3. 67,95%CI 2. 57～5. 24,P 0. 00001)、头晕(RR 1. 85,95%CI 1. 50～2. 28,P 0. 00001)、恶心(RR 2. 17,95%CI 1. 81～2. 59,P 0. 00001)、呕吐发生率(RR 2. 73,95%CI 1. 47～5. 09,P=0. 001)及嗜睡(RR 2. 19,95%CI 1. 39～3. 44,P=0. 0007)均高于安慰剂组,差异有统计学意义;而头痛(RR 1. 14,95%CI 0. 79～1. 65,P=0. 49)、失眠(RR 1. 06,95%CI 0. 72～1. 55,P=0. 17)、体位性低血压(RR 1. 35,95%CI 0. 81～2. 22,P=0. 25)及便秘(RR 1. 03,95%CI 0. 71～1. 50,P=0. 87)的发生率均低于安慰剂组,差异无统计学意义。结论本研究通过Meta分析的方法表明,罗匹尼罗治疗的PD患者在日常生活能力及运动功能评分方面的改善率明显高于接受安慰剂的患者,罗匹尼罗具有较好的耐受性和安全性,大多数不良反应与周围多巴胺能活动有关。     

多巴丝肼片合用多巴胺受体激动剂治疗帕金森病临床疗效观察

目的 研究多巴丝肼片合用普拉克索或吡贝地尔的疗效与安全性. 方法 选择自2008年8月至2010年1月在福建医科大学附属第一医院神经内科门诊接受治疗的40例PD患者,根据治疗药物的不同分为多巴丝肼片+普拉克索片组(普拉克索组)和多巴丝肼片+泰舒达组(泰舒达组),每组20例.经12周联合用药治疗后,以统一帕金森病评定量表(UPDRS)各部分评分相对于基线(治疗前评分)的变化为指标评估疗效.同时监测血压,观察患者不良反应,比较2组治疗方案的安全性. 结果 经12周治疗后2组UPDRS各项评分相对基线均有下降,差异有统计学意义(P＜0.05).普拉克索组UPDRS-Ⅰ(精神、行为和情感)评分、UPDRS-Ⅳ(治疗的并发症)评分较吡贝地尔组评分下降更多,差异有统计学意义(P＜0.05).普拉克索组临床总有效率为80％,泰舒达组临床总有效率为75％,差异无统计学意义(P＞0.05).2组药品不良反应发生率分别为55％和70％,差异无统计学意义(P＞0.05). 结论 普拉克索或吡贝地尔与多巴丝肼合用治疗PD可获得较显著的近期疗效;在改善PD患者精神、行为和情感及运动波动并发症方面的疗效,普拉克索优于吡贝地尔.     

普拉克索治疗帕金森病的临床疗效观察

目的 观察普拉克索治疗帕金森病的临床疗效.方法 对40例帕金森病病人进行统一评分量表(UPDRS)评分,其中6例病人未服用任何抗帕金森药物即予普拉克索治疗,其余病人在原药基础上加服普拉克索.用药12周后再次应用UDPRS量表进行评分.比较普拉克索治疗前后UDPRS量表分值的差异.部分帕金森病人采用2周,4周,8周,12周随访,对病情进行评分,来观察疗效.结果 40例病人经普拉克索治疗后,有效35例,有效率87.5%.治疗前后,大部分帕金森患者在UDPRS总评分、日常活动、运动功能、震颤、肌僵直、精神症状、开关现象等方面的评分改善均有统计学意义.而且对部分门诊病人的随访评分中发现,病人的各方面病情也有很大的好转.结论 普拉克索可有效改善帕金森病人的临床症状,是一种使用安全、疗效理想的抗帕金森病药物.     

Pramipexole in patients with Parkinson's disease and marked drug resistant tremor: a randomised,double blind,placebo controlled multicentre study

OBJECTIVE: To compare the tremorlytic properties of pramipexole, a non-ergoline dopamine agonist to those of placebo as add on medication in patients with Parkinson's disease. METHODS: Eighty four patients with early or advanced Parkinson's disease and marked, drug resistant tremor under a stable and optimised antiparkinsonian medication were included in a double blind, randomised, placebo controlled, multicentre study and assigned to add on treatment (7 week dose titration interval, 4 week maintenance period) with either pramipexole (n=44) or placebo (n=40) as adjunct. The primary end point was the absolute change in tremor score, defined as the sum of tremor related items (16, 20, 21) of the unified Parkinson's disease rating scale (UPDRS) in "on" periods. Secondary end points included the percentage change in tremor score, the absolute and percentage changes in long term EMG tremor registration, and the change in tremor self rating scales. Safety and tolerability were assessed on the basis of adverse events, laboratory tests, ECG, and vital signs. RESULTS: Pramipexole was significantly superior to placebo with a difference between treatment groups in the mean absolute change in tremor score of -4.4 (95% confidence interval (95% CI) -6.2 to -2.5) (p<0.0001), corresponding to a difference in the mean percentage change of -34.7% in favour of pramipexole. The secondary end points were consistent with the significant change in tremor score and provided further evidence for the benefit of pramipexole compared with placebo. Long term EMG registration as an objective measure showed a difference in mean absolute change in tremor occurrence of -15.2% (95%CI -21.4 to -9.0) (p<0.0001), and a difference in the mean percentage change of -45.7% in favour of pramipexole. The treatment effects increased during dose titration and remained stable during the 4 week maintenance dose period until the end of the study. The average daily pramipexole dose during maintenance was 4.1 (SD 0.9) mg. Safety analysis showed an increased rate of fatigue, insomnia, nausea, abdominal pain, and headache under pramipexole, comparable with previous studies. CONCLUSION: Pramipexole proved to be an effective agent for patients with Parkinson's disease and drug resistant tremor.     

Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson's disease: a double blind, placebo controlled, randomised, multicentre study

OBJECTIVES: Pramipexole, a non-ergot dopamine D2/D3 receptor agonist, was investigated as an add on drug in advanced parkinsonian patients with motor fluctuations to assess efficacy, safety, and tolerance. METHODS: Seventy eight patients of either sex with advanced Parkinson's disease and treatment complications such as motor fluctuations were enrolled into a double blind, placebo controlled, randomised, multicentre study (phase II) and assigned to add on treatment with pramipexole (n=34) versus placebo (n=44) to a previously stabilised antiparkinsonian medication (7 week dose titration interval, 4 week maintenance period). The primary end point of efficacy was the change from baseline in the total score of the unified Parkinson's disease rating scale (UPDRS) in the on "period" (2 hours after intake of study medication). Safety and tolerability were assessed on the basis of adverse events, vital signs, laboratory measurements, and ECG recordings. RESULTS: There was a significant improvement of the pramipexole group in UPDRS total scores, subscores part II, III (activities of daily living and motor examination), and IV (complications of therapy). Mean UPDRS total score decreased by 37.3% under pramipexole compared with 12.2% under placebo (p<0.001). Patients under pramipexole reported an overall reduction in "off" periods of 12%--resulting in 1.7 more hours "on" time a day--compared with an increase in "off" periods of 2% under placebo. There were no unexpected safety results. The adverse event profile disclosed a high tolerability. The most important adverse events under pramipexole were fatigue, dyskinesia, and vivid dreams. CONCLUSION: Pramipexole administration is an efficacious and well tolerated add on therapy in patients with advanced Parkinson's disease with an improvement in activities of daily living, motor function, and treatment associated complications.     

Efficacy, safety, and tolerability of pramipexole in untreated and levodopa-treated patients with Parkinson's disease

OBJECTIVE: To evaluate the efficacy and safety of the non-ergot dopamine agonist pramipexole in untreated and levodopa-treated Chinese patients with early or advanced Parkinson's disease. METHODS: This randomized, double-blind, placebo-controlled, parallel-group study, which was conducted in Hong Kong and Taiwan, comprised a screening period of at least 1 week, a dose-escalation period of 7 weeks, and a maintenance period of 8 weeks (total duration of treatment: 15 weeks). During the dose-escalation period, the dose of pramipexole (or number of placebo tablets) was escalated in a blinded fashion according to a predetermined schedule to the optimum tolerated dose of pramipexole, administered three times a day (minimum dose=0.375 mg/day; maximum dose=4.5 mg/day). This dose was then maintained for the duration of the maintenance period. Efficacy was primarily assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). Safety and tolerability were evaluated by treatment-emergent adverse event reports, clinical laboratory test results (blood chemistry, hematology, and urinalysis), vital signs, and electrocardiograms. RESULTS: Pramipexole was significantly more effective than placebo in reducing the total scores of the UPDRS Part II, Part III, and Parts II and III combined. Approximately 70% of both the placebo- and pramipexole-treated patients evaluated in this analysis were on levodopa. Regardless of levodopa use, the mean UPDRS total scores showed a consistently greater improvement in pramipexole patients than in placebo patients. Mean scores for pramipexole patients not on levodopa showed a greater improvement than did pramipexole patients on levodopa. The mean improvement for the pramipexole/no levodopa group relative to the placebo/no levodopa group at week 15 was 10.93 points (i.e., -14.43 points minus -3.50 points). The mean improvement for the pramipexole/levodopa group relative to the placebo/levodopa group at week 15 was 9.04 points (i.e., -10.26 points minus -1.22 points). Pramipexole was also superior to placebo as measured by improvement in the modified Hoehn and Yahr Scale and a reduction in the number of "off" hours for patients on concomitant levodopa therapy. CONCLUSIONS: Pramipexole is an effective and well-tolerated therapy, with or without concomitant levodopa, for Chinese patients with Parkinson's disease.     

Randomized, double-blind, 3-month parallel study of the effects of pramipexole, pergolide, and placebo on Parkinsonian tremor.

We compared the antitremor effect of pramipexole, pergolide, or placebo in Parkinson's disease (PD). A double-blind, randomly controlled, parallel protocol was deployed to examine the effects of placebo, pergolide, and pramipexole [doses escalated to 1.5 mg three times daily (t.i.d.) over 3 months] on a compound Tremor Index (TI) and Unified Parkinson's Disease Rating Scale (UPDRS) part III. Thirty PD patients (19 men, 11 women; mean age 69 years, range 54-80 years; mean disease duration 3.9 years, range, 0.5-10 years) participated in the study, with 10 patients in each arm. Six subjects failed to complete the study (4 on pergolide and 2 on placebo). Analysis of covariance demonstrated strong evidence for a treatment effect on both TI and UPDRS III. There was no significant difference between the active treatments on either TI or UPDRS III. Both pergolide and pramipexole were significantly better than placebo. The results indicate that pergolide and pramipexole (1.5 mg t.i.d.) have similar anti-PD tremor and UPDRS III actions that are significantly superior to placebo. Patients on pergolide were more likely to drop out because of adverse events than those on pramipexole.     

Pramipexole in the treatment of advanced Parkinson's disease

Pramipexole is a novel nonergoline dopamine agonist with a preference for the dopamine D₃ receptor subtype. Its efficacy and safety in the treatment of advanced Parkinson's disease has been investigated in several clinical studies. This review provides a summary of the data currently available, particularly in reference to the recent results of the European clinical phase III study and the potential tremorlytic activity of pramipexole. Interim analysis of the open-label European clinical phase III study has provided evidence of long-term efficacy and safety of pramipexole. In another study pramipexole has been shown to be significantly superior to placebo with an improvement in tremor score by 48% (vs. 13% in the placebo group). In addition to its likely usefulness in the treatment of rest tremor in Parkinson's disease, data suggest that pramipexole is of interest due to its reported low frequency of cardiovascular and gastrointestinal side-effects. However, studies comparing pramipexole with other antiparkinsonian agents would be useful to further define its benefits in the treatment of tremor-dominant Parkinson's disease and to further document its favourable adverse event profile.     

Pramipexole, a nonergot dopamine agonist, is effective against rest tremor in intermediate to advanced Parkinson's disease.

We evaluated the efficacy of the nonergot dopamine receptor agonist pramipexole in 16 patients with advanced Parkinson's disease and marked rest tremor during an "on" period. The patients were drawn from a larger placebo-controlled, double-blind, randomized trial, which was not originally designed to investigate the effect of pramipexole on tremor. Eleven patients received pramipexole. The first effects were seen with a pramipexole dose of 0.75 mg/d with a reduction of the tremor item A of Unified Parkinson's Disease Rating Scale (UPDRS III, "on" state) by 25% and of rigidity and akinesia by 22%. Under the highest dose, 4.5 mg/d, the tremor score was improved by 61% over baseline (p < 0.0056, Wilcoxon signed rank) and the sum of rigidity and akinesia items by 66% (p < 0.0038, Wilcoxon signed rank). Five patients received placebo and did not improve. Based on this sample of patients, the nonergot dopamine receptor agonist pramipexole appears to have a potent anti-rest tremor action while being effective against akinesia and rigidity.     

Double-blind, single-dose, cross-over study of the effects of pramipexole, pergolide, and placebo on rest tremor and UPDRS part III in Parkinson's disease.

Tremor is one of the cardinal signs of Parkinson's disease (PD) but its response to antiparkinsonian medication is variable. It has been postulated that pramipexole may have a stronger antiparkinsonian tremor effect than pergolide, another direct acting dopamine agonist medication, possibly because the former has preferential affinity for the dopamine D3 receptor. The purpose of this pilot study was to compare the effects of a single oral dose of either pramipexole (Pr) or pergolide (Pe) or placebo (Pl) on parkinsonian tremor and the motor (part III) subsection of the UPDRS. Ten patients (6 men, 4 women), mean age 65.3 years, mean duration from diagnosis of 2.6 years, with tremor dominant PD were recruited. On three separate occasions a single dose of pramipexole (salt) 500 microg, pergolide 500 microg or placebo were administered in random order to each patient, who were pretreated with domperidone and had their antiparkinsonian medication withheld from midnight before study. After each medication patients were assessed at baseline and then every 30 min for 4 hr using a 0 to 10 tremor rating scale and the UPDRS (part III) in a double-blind protocol. Adverse effects were systematically recorded. The results demonstrate that 500 microg of either pramipexole or pergolide reduced PD rest tremor scores to a similar degree, which at peak effect was significantly greater than placebo (respectively Pe v Pl: P < 0.006, Pr v Pl: P < 0.033). The two active drugs also had weaker beneficial effects on the UPDRS part III. Pergolide, however, was significantly more likely than pramipexole to cause nausea (P = 0.005) or vomiting (P = 0.014).     

Pramipexole in Parkinson disease. Results of a treatment observation

Pramipexole is a novel, internationally available selective nonergot D2 dopamine agonist. The effectiveness, tolerability, and safety of pramipexole have been extensively proven in controlled trials in patients in the early and advanced stage of Parkinson's disease as monotherapy and in combination with L dopa. These trials indicated specific activity against tremor, anhedonia, and depression. Therefore, the present prospective, multicenter postmarketing surveillance study evaluated for the first time to what extent the results from the controlled pramipexole trials could be replicated under routine conditions in neurological practice and clinics. Modern scales were applied for the assessment of tremor and mood, i.e., the Short Parkinson's Evaluation Scale (SPES), the Tremor Impact Scale (TIS), and the German version of the Snaith-Hamilton Pleasure Scale (SHAPS-D). In 298 German Centers, 657 Parkinson's patients (365 men, 292 women) in advanced disease stages were treated with pramipexole in combination with levodopa. The average ages (+/- SD) were 67 (+/- 8.9) years for men and 69 (+/- 9.4) years for females. Motor functioning, especially tremor, motor complications, depression, and activities of daily living improved highly significantly (P < 0.0005), including self-rating by the patients. The dosage of levodopa could be reduced on average by 8% (P < 0.0001). This might contribute to a slowing of the disease progression in the long run. Dropouts due to side effects were observed only in 3.5% of the patients. Using new assessment scales suitable for routine application allowed confirmation of the results from controlled clinical trials with regard to tremor, anhedonia, and depression. The average daily dosage of pramipexole prescribed was 1.05 mg and thus was definitely lower than the average daily dosages of 2.35-2.66 mg used in controlled trials. This signifies that the option to adjust dosage according to effectiveness and tolerability under routine conditions yields a considerably lower incidence of adverse effects.