恩他卡朋治疗帕金森病的多中心、随机、双盲、安慰剂对照临床研究

目的　研究恩他卡朋作为左旋多巴的辅助药物治疗帕金森病患者剂末现象的疗效和安全性。方法　帕金森病伴剂末现象患者 2 0 9例的 12周、多中心、随机、双盲、安慰剂、平行分组对照临床试验。根据患者日记记录的“开”和“关”期时间、统一帕金森病评定量表 (UPDRS)各部分评分、研究者总体评估变化量表和左旋多巴每日剂量评定疗效。结果　恩他卡朋治疗 12周时意向性治疗(ITT)人群“开”的时间自基线的 (7 4± 1 8)h/d延长至 (9 1± 2 5 )h/d ;“关”的时间自基线的 (6 8±2 2 )h/d缩短至 (5 2± 2 8)h/d ;UPDRS Ⅲ平均得分自基线的 36 7± 11 3减少至 30 0± 14 4 ;左旋多巴每日剂量 (mg/d)自基线的 5 89 2± 2 6 4 3减少至 4周的 5 6 1 5± 2 4 8 1;总体评估变化量表检查显示 6 9 9%的医生主观感觉到病情好转。与安慰剂组相比差异均有显著意义。常见的不良事件是多巴胺能反应 ,但是与安慰剂组相比差异均无显著意义。结论　恩他卡朋是有效而安全的治疗帕金森病伴剂末现象的辅助药物。     

恩他卡朋添加治疗症状波动的帕金森病的自身对照临床研究

目的:探讨添加恩他卡朋治疗帕金森病患者剂末现象的疗效及安全性。方法:17例伴有剂末现象的帕金森病患者进行添加服用恩他卡朋前后对照。根据患者日记记录的“开”“关”时间、UPDRSⅡ/Ⅲ评分、左旋多巴每天剂量来综合评估。结果:12周观察显示恩他卡朋添加治疗帕金森病剂末现象能够显著延长“开”时间、缩短“关”时间、降低UPDRSⅡ/Ⅲ评分,没有发现严重不良事件及实验室的异常改变。结论:帕金森病伴有剂末现象患者添加恩他卡朋治疗有效、安全。     

恩他卡朋对帕金森病大鼠的疗效

目的:观察恩他卡朋与左旋多巴/苄丝肼(美多芭)联用对帕金森病大鼠的治疗作用。方法:6-羟多巴(6-OHDA)毁损内侧前脑束(MFB)建立SD大鼠PD模型。成模大鼠腹腔注射不同剂量的美多芭与恩他卡朋,观测大鼠旋转圈数和持续时间。结果:单用恩他卡朋不能诱导PD大鼠旋转。采用美多芭(6.25、12.5mg·kg-1)和不同剂量的恩他卡朋(10、5、0mg·kg-1)联用的PD大鼠,旋转圈数明显增加、旋转时间也明显延长;恩他卡朋的剂量越大,旋转运动的持续时间越长,但出现旋转反应高峰的时间向后推迟。结论:足量的恩他卡朋可以加强左旋多巴的疗效,半量的恩他卡朋疗效欠佳。     

恩他卡朋治疗帕金森病的新进展

儿茶酚-氧位-甲基转移酶（COMT）抑制剂是继左旋多巴（L-dopa）和多巴胺受体激动剂之后推入临床的治疗帕金森病（PD）的一类新药，可抑制外周COMT活性，延长L-dopa的半衰期和药时曲线下面积（AUC），能延长和增加L-dopa的生物利用度，但不影响达峰时间（Tmax）及达峰浓度（Cmax），是长期L-dopa治疗后出现疗效减退和开关现象等并发症时重要的辅助药物。恩他卡Eq（entacapone）被认为是较安全的COMT抑制剂。近几年的研究结果显示，在出现运动波动的PD患者中，恩他卡朋可减少L-dopa剂量，延长“开”期，明显缩短“关”期，并改善UPDRS的运动评分，提高生活质量。     

左旋多巴联合恩他卡朋在帕金森病患者中的应用效果及安全性

目的 分析左旋多巴联合恩他卡朋在帕金森病患者中的应用效果及安全性。方法 选择2018—2019年在河南科技大学第二附属医院治疗的帕金森病患者78例,随机化原则分为2组,各39例。对照组给予左旋多巴治疗,观察组在对照组基础上加用恩他卡朋治疗,比较2组血清指标、帕金森评分量表-Ⅱ(UPDRS-Ⅱ)、UPDRS-Ⅲ评分及不良反应情况。结果 治疗后,观察组白细胞介素-1β(IL-1β)、IL-6、丙二醛(MDA)水平均明显低于对照组,超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSHPx)水平较高,差异有统计学意义(P0.05);与对照组治疗后比较,观察组UPDRS-Ⅱ、UPDRS-Ⅲ评分均较低,差异有统计学意义(P0.05);观察组不良反应发生率(10.25%)与对照组(15.38%)比较,差异无统计学意义(P0.05)。结论 左旋多巴联合恩他卡朋治疗帕金森病效果较好,可有效改善患者血清水平,提高帕金森量表评分,且未增加不良反应发生率。     

恩他卡朋添加治疗对药效减退的帕金森病患者的疗效观察

目的 探讨恩他卡朋添加治疗对药效减退的帕金森病(PD)患者的疗效及安全性.方法 对4l例服用美多芭疗效减退的PD患者添加恩他卡朋治疗.在添加恩他卡朋治疗前和治疗后第1个月、2个月、3个月分别进行"统一PD评定量表(UPDRS)"评分及运动诱发电位(MEP)检查,比较各时间点美多芭的每日服用总量,并观察其不良反应.结果 添加恩他卡朋治疗后第1个月、2个月、3个月UPDRSⅡ和UPDRSⅢ评分均较添加治疗前明显下降,差异有统计学意义(均P＜0.05),美多芭每日服用总量也明显减少,与添加治疗前比较有统计学意义(均P＜0.05);MEP静息阈值(RMT)在治疗后第3个月明显升高(P＜0.05),潜伏期(CL)及皮质静息期(CSP)明显延长(均P＜0.05);无严重不良反应.结论 恩他卡朋添加治疗能有效改善美多芭药效减退PD患者的运动功能,且安全.     

恩他卡朋治疗帕金森病的疗效及对患者抗氧化应激反应的影响

目的探讨左旋多巴联合恩他卡朋治疗帕金森病(PD)的临床疗效及对患者抗氧化应激反应的影响。方法选取本院在2015年11月至2017年3月收治的PD患者84例,按照随机数字表法分为观察组和对照组,各42例,对照组给予左旋多巴口服治疗,观察组在此基础上联合恩他卡朋口服治疗,12w 1个疗程;观察两组患者临床疗效、统一PD评定定量表(UPDRS)、日常生活能力表(ADL)、非运动症状评价表(NMSS)评分及抗氧化应激反应的影响。结果 (1)观察组临床总有效率95.24%,对照组临床总有效率为80.95%,差异有统计学意义(χ~2=4.086,P=0.043);(2)治疗后2组患者UPDRS、ADL、NMSS评分明显低于治疗前,且观察组UPDRS、ADL、NMSS评分明显低于对照组,差异有统计学意义(P0.05);治疗后2组患者UPDRS-I评分比较差异无统计学意义(P0.05),观察组UPDRS-II、UPDRS-III评分明显低于对照组,差异有统计学意义(P0.05);(3)治疗后观察组IL-1β、IL-6、丙二醛(MDA)水平低于对照组,超氧化物歧化酶(SOD)、还原型谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-PX)水平高于对照组,差异有统计学意义(P0.05);(4)治疗期间观察组不良反应发生率为11.90%,对照组不良反应发生率为30.95%,差异有统计学意义(χ~2=4.525,P=0.033)。结论左旋多巴联合恩他卡朋治疗PD临床疗效显著,可明显提高患者运动功能和日常生活能力,改善患者清除自由基的能力,延缓氧化应激的进展,且不良反应少,有临床应用价值。     

恩他卡朋治疗帕金森病的疗效观察

目的观察恩他卡朋辅助复方多巴制剂对帕金森病患者运动症状的影响。方法原发性帕金森病患者28例,均服用复方多巴制剂并在出现症状加重或运动波动时加用恩他卡朋。服药前、后定期行统一帕金森病评分量表(unified parkinson disease rating scale,UPDRS)Ⅱ与Ⅲ评分,观察其副作用,记录每剂复方多巴制剂的起效时间及药效维持时间。结果UPDRSⅡ与Ⅲ评分在服药前分别为15.1±5.1、22.2±8.1,服药1个月后(10.9±2.8;16.4±4.5)、服药3个月后(12.2±3.5;18.8±5.2)均降低(P<0.01)。服药后每剂药物起效时间不变,药效维持时间延长(1.3±0.6)h(P<0.05)。结论恩他卡朋可改善帕金森病患者的运动功能,副作用少,服用安全。     

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。     

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。     

Entacapone improves absorption of a coadministered salt in patients with Parkinson's disease

Entacapone (EN) improves the efficacy of levodopa/dopadecarboxylase inhibitor (LD/DDI) formulations by inhibition of the enzyme catechol‐O‐methyltransferase (COMT). COMT inhibition also promotes the synthesis of basic LD metabolites, whereas DDI support the composition of acidic LD derivatives. LD metabolism correlates to the one of ¹³C‐sodium‐octanoate, which is employed in breath tests to measure gastric emptying velocity. Objectives were to investigate the impact of COMT inhibition on the recovery rate of ¹³C‐sodium‐octanoate in parkinsonian patients, who received first 100 mg LD/Carbidopa (CD) and the next day 100 mg LD/CD/EN combined with ¹³C‐sodium‐octanoate in each case. The recovery rate of ¹³C‐sodium‐octanoate was significant higher during the LD/CD/EN–compared with the LD/CD condition. COMT inhibition combined with LD/DDI improves absorption of a co‐administered salt probably due to a COMT inhibition induced basic environment in gastrointestinal membranes. This improves dissolution and absorption of acids and salts. Thus it may enhance absorption of LD itself. © 2008 Movement Disorder Society     

Effects of Panax Ginseng Extract in Patients with Fibromyalgia: A 12-week,Randomized, Double-blind,Placebo-controlled Trial

The purpose of the study was to evaluate the efficacy of an extract of Panax ginseng in patients with fibromyalgia. A randomized, double-blind, controlled clinical trial was carried out over 12 weeks to compare the effects of P. ginseng (100 mg/d) with amitriptyline (25 mg/d) and placebo in 38 patients with fibromyalgia: 13 in Group I (amitriptyline), 13 in Group II (placebo), and 12 in Group III (P. ginseng). Ratings on the Visual Analogue Scale (VAS) revealed a reduction in pain in the P. ginseng group (p < .0001), an improvement in fatigue (p < .0001) and an improvement in sleep (p < .001), with respect to baseline characteristics, but there were no differences between the three groups. With respect to anxiety, improvements occurred in the P. ginseng group compared to baseline (p < .0001); however, amitriptyline treatment resulted in significantly greater improvements (p < .05).P. ginseng reduced the number of tender points and improved patients’ quality of life (using the Fibromyalgia Impact Questionnaire - FIQ); however, there were no differences between groups.The beneficial effects experienced by patients for all parameters suggest a need for further studies to be performed on the tolerability and efficacy of this phytotherapic as a complementary therapy for fibromyalgia.     

SELEDO: a 5-y-ear long-term trial on the effect of selegiline in early parkinsonian patients treated with levodopa

The SELEDO (from selegiline plus levodopa) study was carried out as a randomized, prospective, placebo-controlled, double- blind, multicenter long-term, 5-year trial to evaluate the possible advantages of combining selegiline and levodopa in the early treatment of Parkinson's disease. One-hundred-and-sixteen patients were randomized either to selegiline or placebo. Before starting the study medication, the levodopa dose was titrated to the individual requirements of each patient. The primary study end point (time when levodopa had to be increased by >50% of the titrated dose) was reached in 23 of 59 patients in the selegiline group and 26 of 48 patients in the placebo group. At the end of the 5 years' treatment period the rates derived from a life-table analysis were 50.4% in the selegiline group and 74.1% in the placebo group (P = 0.027, log-rank test). The median time to reach the primary end point was 4.9 years in the selegiline group and 2.6 years in the placebo group. In patients treated with selegiline, the mean levodopa dose changed only slightly over the 5 years of treatment compared to the initially titrated dose, but rose markedly in the placebo group, where the dose of levodopa had to be adjusted earlier than in the selegiline group. At the same time, the lower levodopa dosage in the selegiline group was accompanied by at least equal therapeutic efficacy (which is necessary for an unambiguous interpretation). Subgroup analyses showed greater benefit for selegiline treated) patients in the earlier stages. Long-term side effects appeared later in the selegiline group, although the difference was not significant. The early combination of selegiline and levodopa proved to be clearly superior to levodopa monotherapy.     

吡贝地尔对早期帕金森病非运动症状的影响

目的:观察复方左旋多巴和吡贝地尔单用和联合应用对早期帕金森病(PD)患者非运动症状的影响。方法:早期PD患者67例,分为单用吡贝地尔组(25例),复方左旋多巴与吡贝地尔联合用药组(20例),单用复方左旋多巴组(22例)。采用UPDRS-Ⅰ、Ⅱ,PD生活质量评定量表,Hamilton抑郁量表和PD睡眠评分量表对患者进行基线评定,并在治疗后1、3和6个月进行跟踪随访。结果:联合用药组UPDRS-Ⅰ、Ⅱ、抑郁情绪评分、睡眠质量评分以及生活质量评分在各个随访点均较用药前有显著改善;吡贝地尔组Hamilton抑郁评分在各观察窗内均较用药前降低;复方左旋多巴组在第6个月出现睡眠状况的恶化。结论:吡贝地尔单用或联合复方旋多巴应用,吡贝地尔可以较好地改善早期PD患者的精神、情绪和睡眠等非运动症状;早期联合应用吡贝地尔可显著提高患者生活质量。     

One-Year Open-Label Study of Entacapone in Patients with Advanced Parkinson Disease

Background and purpose

A carboxy-O-methyl transferase inhibitor entacapone has been introduced as an adjuvant drug for Parkinson disease (PD) patients. Although clinical trials reported beneficial role of entacapone, a long-term trial over 3 years failed to show significant effect. The goals of this study were to evaluate the clinical benefit and the efficacy of entacapone in an open clinical practice.

Methods

After the completion of a double-blind placebo-controlled entacapone study, 149 patients from 4 centers were included. Antiparkinsonian medications were optimized by the judgment of the neurologists in charge. The clinical global impression (CGI) scale was obtained at 6 months and 1 year after the initiation of entacapone treatment.

Results

Of the 149 patients, 117 patients chose to try entacapone in an open-label fashion. Sixty-nine (59%) patients completed the 1-year trial. Twenty-nine patients discontinued entacpaone before 6 months, and 19 between 6 months and 1 year during trial. Twelve patients out of 48 patients discontinued entacapone because of its poor efficacy. The CGI scale was 3.9 (±1.5) at the beginning of the trial, 4.3 (±1.1) at 6 month, and 3.8 (±1.3) at 1 year, respectively. The CGI scale of those who discontinued between 6 month and 1 year was 3.4 (±1.7), which was worse, but insignificantly, than that of the continuer.

Conclusions

The dropout at 1 year of our study was very high at 41%. Even though entacapone is indicated for advanced PD patients with motor fluctuation, the fluctuators commonly have dyskinesia and mental symptoms, which can become more troublesome with entacapone. In the patients with advanced PD, the clinical efficacy and side effects should be carefully considered in a long-term use of entacapone.     

Effects of a Non-focal Plasticity Protocol on Apathy in Moderate Alzheimer's Disease: A Randomized,Double-blind,Sham-controlled Trial

BackgroundApathy is the most common neuropsychiatric symptom in Alzheimer's disease (AD) and it is associated with changes in prefrontal neural circuits involved with generation of voluntary actions. To date no effective treatment for apathy has been demonstrated.ObjectiveWe aimed to investigate the effects and safety of repetitive transcranial direct current stimulation (tDCS) on apathy in moderate AD patients.MethodsForty patients were randomized to receive either active or sham-tDCS over the left dorsolateral prefrontal cortex (DLPFC). Patients received six sessions of intervention during 2 weeks and were evaluated at baseline, at week 1 and 2, and after 1 week without intervention. Clinical raters, patients, and caregivers were blinded. The primary outcome was apathy. Global cognition and neuropsychiatric symptoms were examined as secondary outcomes.ResultsThe mean MMSE score at baseline was 15.2 ± 2.9 and the mean Apathy Scale score was 27.7 ± 6.7. Changes on apathy scores over time were not different between active and sham tDCS (P = 0.552 for repeated measures). Further analyses confirm that changes from baseline did not differ between groups after the sixth session (active tDCS −1.95 (95%CI −3.49, −0.41); sham-tDCS −2.05 (95%CI −3.68, −0.42); P = 0.989]. Similarly, tDCS had no effect on secondary outcomes (P > 0.40). tDCS was well tolerated and not associated with significant adverse effects.ConclusionIn this adequately powered study for minimal clinically significant difference, our findings show that using the parameters we chose for this study, repeated anodal tDCS over the left DLPFC had no effect on apathy in elderly patients with moderate AD.