普拉克索治疗帕金森病的系统评价

目的 系统评价普拉克索治疗帕金森病(Pakinson's disease,PD)的临床疗效.方法 通过检索Pubmed、Embase、Cochrane Database及中国生物医学文献数据库,检索国内外2007年4月前已发表的普拉克索对照安慰剂治疗PD的临床研究.对所纳入的研究进行质量评价及meta分析.结果 共纳入10项随机对照试验(RCT)研究(纳入患者1738例),meta分析结果 显示:普拉克索可以降低PD患者统一PD评分量表(UPDRS)总分[加权均数差值(WMD)=-10.01,95%CI(-12.76～-7.26)]、UPDRSⅡ分值[WMD=-2.44,95%CI(-2.93～-1.95)]以及UPDRSⅢ分值[WMD=-6.61,95%C/(-8.38～-4.84)];普拉克索还可以降低晚期PD患者UPDRS Ⅳ分值[WMD=-0.73,95%CI(一1.16～-0.30)],以上结果 皆有统计学意义(P＜0.05).3项研究比较了普拉克索与安慰剂治疗震颤的疗效,研究间存在异质性,其中2项研究显示疗效差异有统计学意义.结论 普拉克索可以缓解患者的运动症状,改善生活质量.普拉克索具有改善治疗震颤的趋势,还需要更多的RCT研究进一步证实.     

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.     

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、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。     

普拉克索治疗帕金森病伴抑郁的临床疗效观察

目的：评价普拉克索治疗帕金森病（PD）伴抑郁的临床疗效。方法：采用随机对照研究,将68例PD伴抑郁患者随机分为对照组、帕罗西汀组和普拉克索组。冶疗12周后评价其疗效,评价指标包括Hamilton抑郁量表（HAM—D）、Zung抑郁自评量表和统一帕金森病评分量表（UPDRS）,观察各量表评分相对于基线值的变化情况。结果：普拉克索组HAM—D和Zung总评分第4周时与基线值相比已有下降趋势,而在第8周时与对照组相比差异有统计学意义（P〈0．05）,其作用与帕罗西汀组相比差异无统计学意义（P〉0．05）,而UPDRS评分均差异无统计学意义（P〉0．05）。结果：普拉克索具有抗抑郁作用,可能在治疗后4～8周时开始发挥比较明显的抗抑郁作用,治疗8周时其抗抑郁作用强度似平接近于帕罗西汀,抗抑郁作用可能小依赖于其对于运动症状的改善。     

普拉克索治疗帕金森病的多中心、随机、双盲、溴隐亭对照临床疗效和安全性研究

目的 评价普拉克索片剂治疗帕金森病患者的疗效和安全性。方法 随机、双盲、双模拟、普拉克索和溴隐亭平行分组多中心临床试验。208例帕金森病患者随机接受普拉克索（4．5mg／d）或溴隐亭（22．5mg／d）治疗，为期12周。疗效指标为统一帕金森病评定量表（UPDRS）各部分评分相对于基线的变化；左旋多巴每日剂量相对基线的变化；对合用左旋多巴出现“剂末现象”的患者，基于患者日记记录的“开”和“关”期时间的变化及临床疗效的整体评价。安全性指标为不良反应、血压、脉搏、实验室检查值和心电图。结果 意向性治疗人群中，治疗12周后与基线比较，普拉克索组和溴隐亭组的UPDRSⅢ总评分均值分别下降11．60分和10．01分；UPDRSⅡ总评分均值分别下降4．19分和3．27分；普拉克索非劣效于溴隐亭，两组之间也无优效关系。在UPDRSⅡ-Ⅳ总评分变化≥30％的受试者比例、研究者整体临床评价和药物的起效时间等方面，普拉克索均优于溴隐亭（P〈0．05）。普拉克索发生在5％以上的有关的不良反应有头晕、嗜睡、恶心、便秘、厌食、视觉异常、上腹部不适、体位性低血压等。普拉克索的不良反应发生频率与溴隐亭组间差异无统计学意义。结论 普拉克索用于治疗中国帕金森病患者是安全而有效的。     

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.     

恩他卡朋治疗帕金森病剂末现象的临床观察

目的探讨恩他卡朋对PD患者剂末现象影响。方法选择40例出现剂末现象的PD患者进行相关资料分析,根据不同治疗方案分为普拉克索组和恩他卡朋组,入选患者治疗8周,分析恩他卡朋对PD剂末现象的疗效。结果恩他卡朋组疗效(90%)高于普拉克索组(60%),UPDRSⅡ评分低于普拉克索组,关期时间短于普拉克索组;恩他卡朋组异动症时间(2.3±0.6)h,低于普拉克索组的(2.7±1.0)h,差异均有统计学意义(P0.05)。结论恩他卡朋能够延长患者开期时间,缩短关期时间,改善剂末现象开期运动症状。     

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。     

雷沙吉兰治疗帕金森病随机对照试验的 Meta 分析

目的：系统评价雷沙吉兰治疗帕金森病（PD）的疗效和安全性。方法通过计算机检索及手工检索,全面收集雷沙吉兰治疗帕金森病的符合纳入标准的随机对照试验,按 Cochrane 协作网 Meta 分析的方法进行评价。结果共纳入7个试验（3559例患者）,其中3个为雷沙吉兰与安慰剂对照研究,另外4个为早期启动的和延迟启动的雷沙吉兰对照研究。Meta 分析显示,雷沙吉兰1 mg/d、2 mg/d 治疗对于 PD 患者UPDRS 总分的改善均优于安慰剂（Z =7.99、8.30,P 〈0.00001）；早期启动的1 mg/d 雷沙吉兰治疗对于 PD患者 UPDRS 总分的改善优于延迟启动的1 mg/d 雷沙吉兰治疗（Z =2.18,P =0.03）；早期启动的2 mg/d 雷沙吉兰治疗对于 PD 患者 UPDRS 总分的改善与延迟启动的2 mg/d 雷沙吉兰治疗比较无明显差异（Z =0.63,P =0.53）,二者疗效相当。不良反应主要为晕厥、直立性低血压、跌倒、头晕、头痛、背痛、关节痛、肌肉痛、感染、嗜睡、恶心、疲劳等。不良反应发生率雷沙吉兰与安慰剂相当、早期启动雷沙吉兰治疗与延迟启动雷沙吉兰治疗相当（Z =0.49,P =0.63；Z =1.01,P =0.31）。退出试验患者比率雷沙吉兰与安慰剂相当（Z =1.13,P =0.26）；早期启动雷沙吉兰治疗退出率高于延迟启动雷沙吉兰治疗（Z =2.27,P =0.02）。结论雷沙吉兰治疗能使 PD 患者 UPDRS 总分得到改善,安全性较好。     

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.     

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.     

Randomized,double‐blind,multicenter evaluation of pramipexole extended release once daily in early Parkinson's disease

The objective of this study was to evaluate the efficacy and safety of pramipexole extended release (ER) administered once daily in early Parkinson's disease (PD). Pramipexole immediate release (IR) administered three times daily (TID) is an efficacious and generally well‐tolerated treatment for PD. A pramipexole ER formulation is now available. We performed a randomized, double‐blind, placebo and active comparator–controlled trial in subjects with early PD. The primary efficacy and safety evaluation of pramipexole ER compared with placebo took place at week 18. Two hundred fifty‐nine subjects were randomized 2:2:1 to treatment with pramipexole ER once daily, pramipexole IR TID, or placebo. Levodopa rescue was required by 7 subjects in the placebo group (14%), 3 subjects in the pramipexole ER group (2.9%, P = 0.0160), and 1 subject in the pramipexole IR group (1.0%, P = 0.0017). Adjusted mean [standard error (SE)] change in Unified Parkinson Disease Rating Scale (UPDRS) II [activities of daily living (ADL)] + III (motor) scores from baseline to week 18, including post‐levodopa rescue evaluations, was ?5.1 (1.3) in the placebo group, ?8.1 (1.1) in the pramipexole ER group (P = 0.0282), and ?8.4 (1.1) in the pramipexole IR group (P = 0.0153). Adjusted mean (SE) change in UPDRS ADL + motor scores, censoring post‐levodopa rescue data, was ?2.7 (1.3) in the placebo group, ?7.4 (1.1) in the pramipexole ER group (P = 0.0010), and ?7.5 (1.1) in the pramipexole IR group (P = 0.0006). Adverse events more common with pramipexole ER than placebo included somnolence, nausea, constipation, and fatigue. Pramipexole ER administered once daily was demonstrated to be efficacious compared with placebo and provided similar efficacy and tolerability as pramipexole IR administered TID. © 2010 Movement Disorder Society     

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.     

Pramipexole extended release in Parkinson's disease

Pramipexole extended release (ER) is a new once-daily formulation of pramipexole, a nonergot dopamine agonist, which is available in five dosage strengths: 0.26 (0.375) mg, 0.52 (0.75) mg, 1.05 (1.5) mg, 2.1 (3) mg and 3.15 (4.5) mg (all doses are expressed in terms of pramipexole base and the corresponding dose strengths of pramipexole salt are given in brackets). Pramipexole ER is currently approved as monotherapy in early Parkinson's disease (PD), as well as an adjunct therapy to levodopa in advanced PD. Compared with the immediate release (IR) formulation, the ER formulation offers several advantages, including the potential for improved compliance owing to its simple once-daily dosing regimen and steadier plasma levels over 24 h. Double-blind, randomized, placebo and active comparator controlled trials in early, as well as advanced PD, established the superiority of both pramipexole ER and IR over placebo. The overnight switch from pramipexole IR three times a day to ER once-daily in early PD has been shown to be successful in more than 80% of patients. Pramipexole ER is well tolerated, with a similar adverse event profile to pramipexole IR. The aim of this article is to provide a short review of the most relevant pharmacological and clinical data on pramipexole ER.     

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.     

A double-blind, placebo-controlled, randomized, multi-center study of pramipexole in advanced Parkinson's disease

Pramipexole (SND 919), a potent non-ergot dopamine agonist, or placebo, was administered to 69 patients with advanced Parkinson's disease (33 received placebo, 36 received pramipexole) in a double-blind, randomized, multi-center study in which individually optimized doses of l -dopa plus a dopa decarboxylase inhibitor were associated with dyskinesia, "on–off" fluctuation, dystonia, akinesia, or end-of-dose deterioration. Study medication was titrated over 7 weeks to the maximal tolerated dose or to the maximal dose allowed by the study (5 mg/day in four divided doses). Dosing was maintained for 4 weeks and then tapered during the final week. Total score on the Unified Parkinson's Disease Rating Scale (UPDRS) for the intent-to-treat population was significantly improved in the pramipexole-treated group compared with the placebo-treated group (16.9 ± 14.9 vs 9.0 ± 16.1; p = 0.0184). By the end of maintenance, the mean reduction in l -dopa requirement was −150.7 mg for pramipexole-treated patients compared to −10.6 for placebo-treated patients. The most common adverse events (> 10%) were dizziness, insomnia, nausea, and postural hypotension. Aggravated parkinsonism occurred only after withdrawal of the study medication. Treatment with pramipexole in doses up to 5 mg/day was safe and well tolerated by patients with advanced Parkinson's disease.     

Pramipexole-induced somnolence and episodes of daytime sleep.

Pramipexole is a non-ergot dopamine agonist used to treat Parkinson's disease (PD). Because of concern regarding driving safety, we evaluated the incidence and nature of somnolence experienced by patients receiving pramipexole in clinical trials at our center. A retrospective chart review was performed and structured interviews were conducted with patients who had reported moderate or severe somnolence. In addition, two patients underwent polysomnography (PSG) and multiple sleep latency tests (MSLT) while on and 2 weeks after discontinuation of pramipexole. Forty patients with PD participating in pramipexole clinical trials were identified. In the double-blind phases of the studies, 22 patients were randomized to pramipexole and 18 were randomized to placebo. Six patients assigned to pramipexole reported somnolence as an adverse event (1 moderate, 5 mild) compared with two patients assigned to placebo (1 severe, 1 moderate; p = 0.19, one-tailed Fisher's exact test). Thirty-seven patients participated in open-label extension studies. Twenty-one (57%) reported somnolence as an adverse event. Eleven (30%) patients reported moderate somnolence and three (8%) patients reported severe somnolence. For patients with moderate or severe somnolence, the onset of worst-reported somnolence occurred at a mean (+/- standard error) pramipexole dose of 4.0 +/- 0.4 mg (range, 0.75-4.5 mg) per day. Patients had been taking pramipexole for a total of 10.0 +/- 1.5 months (range, .03-22 mos) and at their maximal dose for 6.7 +/- 1.5 months (range, .03-20 mos). During structured interviews with 12 of the 14 patients reporting moderate or severe somnolence, seven reported falling asleep while driving and two reported minor motor vehicle accidents caused by falling asleep. Most patients reported relatively continuous drowsiness that led to falling asleep without acute warning during periods of inactivity. Three patients reported discreet waves of irresistible sleepiness heralded by prodromal symptoms occurring against a background of normal wakefulness. MSLT in two of these patients revealed decreased latency to sleep without early onset of rapid eye movements. Sleep latency normalized after withdrawal of pramipexole. Intensive patient education is necessary to prevent motor vehicle accidents in patients taking pramipexole. We recommend that patients who are experiencing generalized drowsiness and falling asleep during periods of inactivity be instructed not to drive because these patients do fall asleep without acute warning. Somnolence usually resolves with pramipexole dose reduction or discontinuation. Patients should also be alerted to pull over and stop driving immediately if they feel a wave of sleepiness coming on. Patient education and compliance are critical to maximize safety.     

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.