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.     

金刚烷胺治疗帕金森病异动症的疗效观察

目的探讨金刚烷胺治疗帕金森病(PD)左旋多巴诱导异动症(LID)的临床疗效。方法将42例帕金森病患者随机分为金刚烷胺组与恩托卡朋组,每组21例,每组均应用美多巴和普拉克索作为帕金森病基础治疗。经12 w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,比较两组治疗方案的安全性。结果经12 w治疗后金刚烷胺组UPDRS.IV(治疗的并发症)评分相对基线有显著下降.差异有统计学意义(P<0.05)。金刚烷胺组UPDRS.IV(治疗的并发症)评分较恩托卡朋组评分下降更多,差异有统计学意义(P<0.05)。金刚烷胺组临床总有效率为86%,恩托卡朋组临床总有效率为32%,差异有显著统计学意义(P<0.05)。两组药品不良反应发生率分别为19%和23%。差异无统计学意义(P>0.05)。结论金刚烷胺治疗左旋多巴诱导的帕金森病异动症可获得较显著的近期疗效。     

普拉克索治疗帕金森病运动并发症的临床疗效观察

目的 评估普拉克索治疗帕金森病运动并发症的临床疗效及安全性.方法 收集92例晚期帕金森病患者并随机分为治疗组和对照组,每组46例.对照组给予多巴丝肼治疗,治疗组在对照组的基础上给予普拉克索,疗程均为12周.两组患者于治疗前后分时间点进行统一帕金森病评定量表修正(UPDRSⅣ-)的评分、不良反应的记录,疗程结束后评估疗效.结果 治疗后对照组和治疗组UPDRSⅣ-评分与基线比较均有下降,治疗组下降更显著,两组比较差异有统计学意义(P＜0.01).治疗组第12周剂末现象(93.75％vs 70.59％)、开关现象(91.67％ vs 63.64％)以及异动症(84.62％ vs48.00％)的总有效率优于对照组,差异均有统计学意义(P＜0.05).两组不良反应发生率差异无统计学意义(P＞0.05).结论 普拉克索治疗帕金森病运动并发症有效,安全性好.     

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。     

美多巴联合盐酸普拉克索对帕金森病患者运动功能的影响

目的评定美多巴联合盐酸普拉克索在改善帕金森病患者运动功能中的疗效及安全性。方法选取帕金森病患者84例,随机分为联合用药组(试验组)42例,单纯用药组(对照组)42例,试验组在服用美多巴的基础上加服盐酸普拉克索,对照组仅服用美多巴,观察治疗后的疗效及安全性。结果试验组治疗总有效率和临床受益率均高于对照组(P<0.05);在治疗12周时,试验组患者运动功能UPDRS评分改善情况优于对照组,生活质量评分高于对照组;同时2组患者不良事件发生率相比差异无统计学意义(P>0.05)。结论美多巴联合盐酸普拉克索治疗方案优于单一用药,在帕金森病治疗中具有重要的临床价值,值得推广应用。     

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.     

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、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.     

美多芭联合恩他卡朋治疗对帕金森病患者血浆同型半胱氨酸水平的影响

目的探讨美多芭联合恩他卡朋治疗对帕金森病(PD)患者血浆同型半胱氨酸(Hcy)水平的影响。方法选取30名健康体检者作为对照组,20例未服用过左旋多巴(LD)制剂的PD患者为未服药组,63例美多芭治疗的PD患者为美多芭组,49例美多芭联合恩他卡朋治疗的PD患者为联合组。检测患者外周血中的LD稳态峰浓度并进行统一PD评分量表Ⅲ(UPDRSⅢ)的评分。检测所有研究对象的血浆Hcy水平。结果联合组患者LD血浆浓度明显高于美多芭组(P0.05)。美多芭组及联合组患者UPDRSⅢ评分均明显低于未服药组(均P0.05)。与对照组比较,未服药组、美多芭组及联合组患者血浆Hcy水平均明显升高(均P0.05);且美多芭组患者血浆Hcy水平明显高于未服药组及联合组(均P0.05)。结论美多芭联合恩他卡朋能显著降低PD患者血浆Hcy水平,对PD治疗有积极意义。     

Increase in body weight after pramipexole treatment in Parkinson's disease.

Body weight changes occur during the clinical course of Parkinson's disease (PD) and with surgical treatment, but the effect of dopaminergic treatment on weight is unknown. Body mass index (BMI), Hamilton depression scale score (HDS), and Unified Parkinson's Disease Rating Scale III (UPRS-III) were measured before and 3 months after starting pramipexole in 28 PD patients. Pramipexole produced a significant weight increase, as well as motor and mood improvement (P <0.001). HDS and BMI changes were mildly related (P = 0.05). A direct effect of pramipexole on limbic D(3) receptors involved in the control of feeding may be responsible for weight gain in PD.     

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.