Early piribedil monotherapy of Parkinson's disease: A planned seven-month report of the REGAIN study.

Piribedil is a D2 dopamine agonist, which has been shown to improve symptoms of Parkinson's disease (PD) when combined with L-dopa. The objective of this study was to compare the efficacy of piribedil monotherapy to placebo in patients with early PD over a 7-month period. Four hundred and five early PD patients were randomized (double-blind) to piribedil (150-300 mg/day) or placebo. L-dopa open-label supplementation was permitted. Unified Parkinson Disease Rating Scale part III (UPDRS III) score as the last observation on monotherapy over 7 months was the primary outcome measure. Secondary outcomes were proportion of responders (UPDRS III improvement > 30%), patients remaining on monotherapy after 7 months, UPDRS III subscores, and UPDRS II. UPDRS III improved on piribedil (-4.9 points) versus a worsening on placebo (2.6 points; estimated effect = 7.26 points; 95% CI = 5.38-9.14; P < 0.0001). The proportion of responders was significantly higher for piribedil (42%) than for placebo (14%) (OR = 4.69; 95% CI = 2.82-7.80; P < 0.001). Piribedil significantly improved several UPDRS III subscores. UPDRS II improved on piribedil by -1.2 points, while it deteriorated by 1.5 points on placebo (estimated effect = 2.71; 95% CI = 1.8-3.62; P < 0.0001). The proportion of patients remaining on monotherapy after 7 months was greater in the piribedil group (OR = 3.72; 95% CI = 2.26-6.11; P < 0.001). Safety was consistent with that reported for other dopamine agonists, gastrointestinal side effects being the most common (22% of patients in piribedil group vs. 14% on placebo). Piribedil is effective and safe as early PD therapy.     

The role of levodopa in the management of dementia with Lewy bodies

BACKGROUND: One of the core clinical features of dementia with Lewy bodies (DLB) is extrapyramidal syndrome (EPS). Levodopa is currently the gold standard oral therapy for Parkinson's disease (PD), but its use in DLB has been tempered by concerns of exacerbating neuropsychiatric symptoms. AIM: To assess the efficacy and tolerability of L-dopa in managing EPS in DLB and to compare the motor response with that seen in PD and PD with dementia (PDD). METHOD: EPS assessment consisted of the Unified Parkinson's Disease Rating Scale, motor subsection (UPDRS III), and finger tapping and walking tests. Patients with DLB were commenced on L-dopa. After 6 months, patients were examined in the "off" state, given L-dopa and assessed for motor responses. Identical assessments were performed in patients with PD and PDD also receiving L-dopa. RESULTS: Acute L-dopa challenge in 14 DLB patients yielded a mean 13.8% (p = 0.02) improvement in UPDRS III score, compared with 20.5% in PD (n = 28, p < 0.0001) and 23% in PDD (n = 30, p<0.0001) respectively. Finger tapping scores increased (12.3% v 20% and 23%), while walking test scores decreased (32% v 41% and 67%). Of the DLB patients, 36% were classified as "responders" on L-dopa challenge, compared with 70% of the PDD and 57% of the PD patients. Nineteen DLB patients were treated for 6 months with L-dopa (mean daily dose 323 mg). Two withdrew prematurely with gastrointestinal symptoms and two with worsening confusion. CONCLUSION: L-dopa was generally well tolerated in DLB but produced a significant motor response in only about one third of patients. Younger DLB cases were more likely to respond to dopaminergic treatment.     

End-of-dose akinesia after a single intravenous infusion of the dopaminergic agonist piribedil in Parkinson's disease patients: a pharmacokinetic/pharmacodynamic, randomized, double-blind study.

This randomized, double-blind trial was designed to define the possible relationship between piribedil plasma concentrations and the decrease of the Unified Parkinson's Disease Rating Scale (UPDRS) motor score or the switch from off to on state after single intravenous infusion. Ten fluctuating patients with idiopathic Parkinson's disease (PD) received escalating doses of piribedil (2-16 mg) and placebo. Starting from 2 mg, piribedil was effective in reducing the motor deficit (UPDRS, motor score) including akinesia at the first evaluation time point of 15 minutes, and in reversing off state of 7 of 10 patients. The doses were equally effective, although the effect was more sustained with the highest dose of 16 mg. Piribedil was well tolerated up to a 16-mg dose and pharmacokinetics were linear up to the 16-mg dose. Plasma levels of piribedil were not correlated to the motor score improvement or switch from off-->on. In conclusion, a short single infusion of piribedil at 2 to 16 mg was safe and effective in improving motor symptoms, including akinesia, of fluctuating PD patients.     

The Parkinson-Control study: a 1-year randomized, double-blind trial comparing piribedil (150 mg/day) with bromocriptine (25 mg/day) in early combination with levodopa in Parkinson's disease.

Dopamine agonists have been recommended as early treatment for Parkinson's disease (PD), alone or combined with levodopa. Piribedil is a non-ergot selective D(2)/D(3) agonist with alpha(2) antagonist properties shown to be effective in the treatment of PD. This 12-month international, randomized, double-blind trial aimed to assess the efficacy of piribedil 150 mg versus bromocriptine 25 mg, in early combination with levodopa in Stage I to III PD patients. Motor efficacy was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS III, Items 18-31) as improvement from baseline. Response rate was defined as a 30% improvement. Among the 425 randomly assigned patients, 178 were also included in a substudy on cognitive follow-up evaluated by a dysexecutive syndrome oriented battery. A relevant improvement in UPDRS III over the 12-month study duration was observed both in the piribedil and bromocriptine groups (-7.9 +/- 9.7 points from baseline versus -8.0 +/- 9.5; not significant [n.s.]) with a response rate of 58.4% and 55.3% (n.s.), respectively. Piribedil and bromocriptine resulted in similar improvement on all UPDRS III subscores. Piribedil patients required less levodopa dose increase than those on bromocriptine. Cognitive performance remained generally unchanged in both groups, with a significant effect of piribedil limited to the Wisconsin Card Sorting Test. An overall good tolerability of piribedil was observed. Early combination of piribedil 150 mg with levodopa resulted in significant long-term improvement of all motor symptoms in PD patients insufficiently controlled by levodopa alone. Taking into account both efficacy and acceptability in the long-term, piribedil proved in this bromocriptine controlled study to be an effective and safe treatment for PD.     

A randomized, double-blind study of a skin patch of a dopaminergic agonist, piribedil, in Parkinson's disease.

This randomized, double-blind trial was designed to evaluate the efficacy of a transdermal system of piribedil on the motor symptoms of Parkinson's disease during 3 weeks of treatment administered to three different groups: placebo, one piribedil patch (1 PP), and two (2 PP) piribedil patches. Twenty-seven patients with idiopathic Parkinson's disease, treated with L-dopa but not sufficiently controlled, were included in this trial. The test treatment did not demonstrate any clinical efficacy on either the main end point (Unified Parkinson's Disease Rating Scale motor score) or the secondary end points (rigidity, bradykinesia, postural, and resting tremor scores). The main adverse events were nausea (11%), vomiting (7.4%), and malaise (7.4%) mainly observed in the placebo group (four of seven patients). The local acceptability of the transdermal system was good. Plasma piribedil concentrations at the end of treatment were 6.74+/-1.10 and 9.31+/-3.33 ng/mL in the 1 PP and 2 PP groups, respectively. These plasma levels could account for the lack of clinical efficacy, because a previous pharmacokinetics-PD study conducted in parkinsonian patients and treated with the intravenous route demonstrated that the critical limits of activity on tremor were between 10 and 30 ng/mL.     

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.     

Orodispersible sublingual piribedil to abort OFF episodes: A single dose placebo‐controlled,randomized, double‐blind,cross‐over study

S90049, a novel sublingual formulation of the non‐ergoline D₂‐D₃ agonist piribedil, has a pharmacokinetic profile promising to provide rapid relief on motor signs in Parkinson's disease (PD). We assessed the efficacy and safety of S90049 in aborting OFF episodes responding to subcutaneous apomorphine in PD patients with motor fluctuations. This was a single‐dose double‐blind double‐placebo 3 × 3 cross‐over study. Optimal tested doses were determined during a previous open‐label titration phase (S90049 median dose: 60 mg, apomorphine: 5 mg). Primary endpoint was the maximal change versus baseline in UPDRS motor score (ΔUPDRS III) assessed after drug administration following an overnight withdrawal of antiparkinsonian medications. Thirty patients (age: 60 ± 8 years, PD duration: 12 ± 6 years, UPDRS III OFF: 37 ± 15) participated. S90049 wassuperior to placebo on ΔUPDRS III (?13 ± 12 versus ?7 ± 9 respectively; estimated difference ?5.2, 95% Confidence Interval (CI)[?10.4;0.05], P = 0.05). This was also true for secondary outcomes: number of patients switching from OFF to ON (17 on S90049 vs. 8 on placebo, P = 0.03), time to turn ON (P = 0.013) and duration of the ON phase (P = 0.03). In the 17 patients who switched ON on S90049, ΔUPDRS III was similar on S90049 (?21.2 ± 10.1) and apomorphine (?23.6 ± 14.1) (estimated difference: 4.0 95% CI [?2.9;10.9]). S90049 was well tolerated: no serious or unexpected adverse event occurred. A single dose of up to 60 mg of S90049 given sublingually was superior to placebo in improving UPDRS III and aborting a practical OFF in patients with advanced PD. Testing greater doses might improve response rate. © 2009 Movement Disorder Society     

Alpha-dihydroergocryptine in the treatment of de novo parkinsonian patients: results of a multicentre, randomized, double-blind, placebo-controlled study

INTRODUCTION: A multicentre, randomized, double-blind, placebo-controlled, parallel group study was carried out in 123 patients suffering from never treated (de novo) idiopathic Parkinson's disease (PD). The aim of the study was to confirm the efficiency and safety of alpha-dihydroergocryptine (alpha-DHEC) given as monotherapy in the symptomatic treatment of PD. The total score of the Unified Parkinson's Disease Rating Scale (UPDRS) was identified as the efficacy target variable. PATIENTS AND METHODS: Sixty-two patients (32 males, 30 females, mean age +/- SD 64 +/- 10) were randomized to alpha-dihydroergocryptine and 61 (30 males, 31 females, mean age 63.8 +/- 9.1) to placebo. According to the experimental design, a 18-month double-blind phase vs placebo was followed. Two interim analyses were planned both at the 3rd and 12th month of treatment, in order to avoid continuation on placebo, if clear differences between groups were found (stopping criterium: nominal significance level equal to 0.022 in the analysis of the target variable). Analysis of variance was performed both on the per protocol (PP) and intent-to-treat (ITT) sample. RESULTS: The results on the first interim analysis showed significant differences between treatment groups of the UPDRS total score both in the ITT (115 patients, alpha-DHEC: No. 56; placebo: No. 59; P=0.019) and PP (96 patients, alpha-DHEC: No. 46; placebo: No. 50; P=0.001) sample, why the trial was stopped. At the time of stopping the trial, 73 patients (alpha-DHEC: No. 37; placebo: No. 36) had reached the 6-month observation visit; the analysis carried out on this subset of patients confirmed the efficacy of alpha-dihydroergocryptine in early PD and the correctness of the decision to stop. The incidence of adverse drug reactions (ADR) did not differ between alpha-dihydroergocryptine and placebo recipients, gastrointestinal complaints being the most frequent. CONCLUSION: The results indicate that alpha-dihydroergocryptine is safe and effective in improving symptoms of de novo parkinsonian patients.     

Pramipexole and pergolide in the treatment of depression in Parkinson''s disease: a national multicentre prospective randomized study

An 8-month multicentre prospective randomized study aimed at comparing the effects of dopamine receptor agonists pramipexole (PPX; Mirapexin) and pergolide (PRG; Permax) as add-on to L-dopa therapy on depression [Montgomery and Asberg Depression Rating Scale (MADRS)] in 41 non-demented patients (25 men, 16 women) suffering from both mild or moderate depression and advanced Parkinson's disease (PD). The assessment was performed by a blinded independent observer. Motor symptoms (UPDRS III), motor complications (UPDRS IV), activities of daily living (UPDRS II and VI) and depressive symptoms as measured by Self - Rating Depression Scale by Zung were evaluated in an open-label design. The average value of Zung scores decreased significantly in both groups with no statistical difference between both groups. A significant decrease in the average value of MADRS scores was present only in the PPX group. The average UPDRS scores decreased significantly with no statistical difference between both groups at the comparable average total daily dose of both preparations. In both cases, the total daily dose of L-dopa decreased significantly but the decrease was statistically more pronounced in the PRG group. Our results demonstrate the antidepressant effect of PPX in patients with PD while we can't make any conclusions with regard to antidepressant effect of PRG.     

SSRIs do not worsen Parkinson's disease: evidence from an open-label, prospective study

Selective serotonin reuptake inhibitors (SSRIs) have been reported to be useful in the treatment of depression in patients with Parkinson's disease (PD). However, a few reports have suggested that SSRIs may worsen parkinsonian motor symptomatology and extrapyramidal side effects have been reported in depressed patients treated with SSRIs. So far, no prospective trial comparing the effects of different SSRIs in depressed patients with PD has been performed. The aim of the present study was to assess the effects of four SSRIs (citalopram, fluoxetine, fluvoxamine, and sertraline) on motor performance and their efficacy on depression in a group of patients with PD. Sixty-two consecutive nondemented, nonfluctuating, depressed patients with PD were included in four treatment groups (15 patiens received citalopram, 16 fluoxetine, 16 fluvoxamine, and 15 sertraline). The evaluation of extrapyramidal and depressive symptomatology was performed with use of the Unified Parkinson's Disease Rating Scale (UPDRS), Beck Depression Inventory, and Hamilton Depression Rating Scale at baseline and after 1, 3, and 6 months. Fifty-two patients completed the study. UPDRS scores were not significantly modified by the add-on therapy with each of the SSRIs studied. A significant improvement in depressive symptoms from baseline to the end of the trial was obtained with all SSRIs (Beck and Hamilton scores improving; p < 0.05 according to an analysis of variance). Our findings suggest that SSRIs do not significantly worsen extrapyramidal symptomatology and may ameliorate depression in patients with PD.     

Deep-brain stimulation in the subthalamic nuclei improves balance performance in patients with Parkinson's disease, when tested without anti-parkinsonian medication

OBJECTIVE: To evaluate the effect of bilateral deep-brain stimulation (DBS) in the subthalamic nucleus (STN) on balance performance in patients with severe Parkinson's disease (PD), when tested without anti-parkinsonian medication. MATERIAL AND METHODS: Thirty-one patients (median age 65 years, range 50-77) were included. Assessments were made after 10-12 h withdrawal of medication, before and 6 and 12 months after surgery. Postoperative evaluations were performed with DBS on and off. Balance performance was evaluated with the Berg Balance Scale (BBS). Motor symptoms and postural stability (item 30) were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS III). RESULTS: DBS in STN improved balance performance as well as postural stability and motor symptoms significantly (P 相似文献   

Accuracy of acute levodopa challenge for clinical prediction of sustained long-term levodopa response as a major criterion for idiopathic Parkinson's disease diagnosis.

Clinical idiopathic Parkinson's disease (PD) diagnosis requires following strict clinical criteria. Final definitive diagnosis can only be made after pathological confirmation and, despite following clinical criteria, several cases are misdiagnosed. We assessed sensitivity and specificity of acute challenge with levodopa (L-dopa) to predict sustained long-term L-dopa responsiveness as a major criterion for clinical diagnosis of PD. A consecutive series of 82 patients first seen at a movement disorders clinic with a parkinsonian syndrome without specific diagnosis was included. A second examiner, blind to the presumptive diagnosis, performed in each patient an acute challenge with 250/50 mg of L-dopa-carbidopa and rated the test as positive or negative according to whether values reached a minimal 30% of improvement on UPDRS scores. Positive tests were considered supportive of presumptive clinical diagnosis of Parkinson's disease. Blind to test results and according to clinical presumption, the first examiner started patient treatment with the necessary L-dopa dose or, alternatively, until reaching 1 g for 1 month in those who failed to display a positive test response. At 24 month follow-up, they were re-tested with 1 g for 1 month when required. At this point, clinical criteria of the U.K. Parkinson's Disease Society Brain Bank were applied and definitive clinical diagnosis of PD was made. Sensitivity, specificity, and positive predictive ratio for acute challenge were calculated. Overall sensitivity and specificity of acute L-dopa challenge to predict clinical diagnosis of PD was 70.9% and 81.4%, respectively; positive predictive ratio was 88.6%. When patients were divided into three groups according to their UPDRS motor section score at initial examination, sensitivity and specificity varied: Group I (or=21), 36.4% and 87%, respectively. Positive predictive ratio increased to 100% in Group I and to 87.5% in Group III. The positive result of initial acute L-dopa challenge predicts chronic L-dopa responsiveness as major criterion of PD in all patients with UPDRS motor scores lower than 10.     

A comparison of sumanirole versus placebo or ropinirole for the treatment of patients with early Parkinson's disease.

To assess the safety and efficacy of sumanirole, a highly selective dopamine agonist, versus placebo and demonstrate its noninferiority to ropinirole, 614 patients with early Parkinson's disease (PD) were treated with sumanirole, 1 to 16 mg/day; ropinirole, 0.75 to 24 mg/day; or placebo. Primary end point in this flexible-dose, double-blind, double-dummy, parallel-group study of 40 weeks was the change in total sum of the United Parkinson's Disease Rating Scale (UPDRS) Parts II + III scores from baseline to end of maintenance. Approximately half the subjects in the sumanirole and placebo groups withdrew early from the study, most (51.8% and 68.5%, respectively) due to lack of efficacy. Of the ropinirole subjects who withdrew (50.5%), most discontinued because of adverse events. In sumanirole and ropinirole groups, mean changes from baseline of -2.48 and -5.20 in UPDRS II + III mean scores were significant versus 0.38 in the placebo group (P 相似文献   

Bilateral effects of unilateral subthalamic nucleus deep brain stimulation in advanced Parkinson's disease

To investigate the bilateral effects of unilateral subthalamic nucleus deep brain stimulation (STN-DBS), we prospectively studied 9 consecutive advanced Parkinson's disease (PD) patients (2 men and 7 women) who underwent unilateral STN-DBS. Patients were evaluated preoperatively and at 3 and 6 months postoperatively with and without dopaminergic medications ('on' and 'off' medication, respectively). Postoperatively, patients were assessed with and without stimulation. We found that, when compared with baseline, the 'off' medication scores of the Unified Parkinson's Disease Rating Scale motor part (UPDRS III) and activities of daily living (UPDRS II) were improved by 37% (p = 0.028) and 50% (p = 0.046) at 6 months after surgery, respectively. Stimulation while 'off' medication improved the total UPDRS score by 42% (p = 0.028) at 6 months. At 6 months after surgery, the subscore of UPDRS III of body parts contralateral to the DBS implantation had improved by 48% (p = 0.028), and the ipsilateral subscore of UPDRS III and the axial subscore of UPDRS III had improved by 20% (p = 0.027) and 39% (p = 0.028), respectively. Daily dosage of levodopa was reduced by 15% at 6 months. No patient exhibited permanent side effects. These findings indicate that unilateral STN-DBS may be a reasonable surgical procedure for selected PD patients who have markedly asymmetric parkinsonism.     

帕金森病患者自主神经功能障碍评估

目的：评估帕金森病（PD）患者中自主神经功能障碍症状发生比例、各症状分布的差异，及其与PD临床特点之间的关系。方法：应用SCOPA-AUT量表、统一帕金森病评分量表（UPDRS）、日常生活能力量表（ADL）、Hamilton抑郁量表和简易智能量表（MMSE）对116例原发性PD患者进行评估。结果：SCOPA-AUT总分和消化系统（GI）症状、排尿（UR）症状、体温调节（TH）症状、性功能（SX）症状评分均高于对照组，差异有极显著统计学意义（P=0．0001）。SCOPA-AUT总分与UPDRS评分、Hamilton抑郁量表评分呈正相关（P〈0．001），与生活质量ADL评分呈负相关（P〈0．001）。结论：自主神经功能障碍在PD早期就会出现，并随着疾病进展而加重，影响患者的生活质量。     

Efficacy of combining levodopa with entacapone on quality of life and activities of daily living in patients experiencing wearing-off type fluctuations

OBJECTIVES: To compare the efficacy of levodopa/dopa decarboxylase inhibitor (DDCI) plus entacapone with levodopa/DDCI plus placebo on measures of parkinsonian disability and health-related quality of life (QoL) in subjects with Parkinson's disease (PD) experiencing motor fluctuations. MATERIALS AND METHODS: A double-blind, placebo-controlled phase IV study was performed in 270 PD patients randomized to receive either entacapone 200 mg or placebo with each dose of their current levodopa regimen. The primary variables were the Unified Parkinson's Disease Rating Scale (UPDRS) part II activities of daily living (ADL) and the Parkinson's Disease Questionnaire (PDQ)-39 summary index. UPDRS parts I, III-VI, Global Assessment of Change, PDQ-39 subscores, and the Short-Form (SF)-36 and the European Quality of Life five-dimension questionnaire (EQ-5D) were included as secondary variables. RESULTS: There was a significant improvement in ADL scores with levodopa/DDCI/entacapone compared with levodopa/DDCI/placebo at 5 and 13 weeks (-2.3 vs -0.7, respectively; P = 0.0001). However, no significant differences were observed between treatments using the PDQ-39 summary index. UPDRS part III (motor) scores significantly decreased in the levodopa/DDCI/entacapone group compared with the levodopa/DDCI/placebo group (-5.0 vs -2.9, respectively; P = 0.03). Similarly, the change in the investigators Global Assessment was significantly greater (P = 0.004) in the levodopa/DDCI/entacapone group. There were no significant differences between treatments for any of the PDQ-39 subscores, the SF-36 variables or the EQ-5D utility score. CONCLUSIONS: Levodopa combined with entacapone demonstrated good efficacy in terms of ADL, global function, motor performance and was well tolerated. However, this short-term study did not generate significant improvements in QoL.     

Pergolide monotherapy in the treatment of early PD: a randomized, controlled study. Pergolide Monotherapy Study Group.

OBJECTIVE: To determine whether pergolide monotherapy provides symptomatic relief in early PD. BACKGROUND: Early treatment with dopamine agonists may reduce the risk of motor fluctuations, which are most likely linked to levodopa therapy. Pergolide, a D1-D2 dopamine agonist, has been studied as "add on" therapy in PD, but no controlled clinical trial studying the efficacy of pergolide monotherapy is available. METHODS: The efficacy and tolerability of pergolide were evaluated in a multicenter, double-blind, randomized, parallel-group, 3-month trial versus placebo. Patients with a diagnosis of idiopathic PD, a modified Hoehn & Yahr score of 1 to 3, and a score greater than 14 points on the Unified Parkinson's Disease Rating Scale (UPDRS) part III at baseline were enrolled in the study (pergolide, n = 53; placebo, n = 52). RESULTS: Patient characteristics at study entry were comparable in the two study groups. The pergolide group showed a significantly greater percent of responders (defined as a -30% decrease in UPDRS part III score at end point) compared with placebo (57% versus 17%; p < 0.001). Pergolide-treated patients experienced a significantly greater improvement than placebo-treated patients (p < 0.001) in UPDRS (overall, part II, and part III) score, Schwab & England score, and Clinical Global Impression improvement score. By the study end the mean dose of pergolide was 2.06 mg/day. Six patients in the pergolide group versus two patients in the placebo group discontinued the study because of treatment emergent side effects. CONCLUSION: This study suggests that pergolide monotherapy may be an efficacious and well-tolerated first-line treatment in patients with early-stage PD.     

Long-term, open-label study of once-daily ropinirole prolonged release in early Parkinson's disease

Long-term safety and efficacy of once-daily ropinirole prolonged release (PR) were evaluated in subjects with early Parkinson's disease (PD). Subjects (n = 83) who completed one of two studies were enrolled in this open-label, multicenter, extension study, and followed for up to 78 months. Ropinirole PR was titrated/continued, and adjusted as appropriate during the maintenance phase (maximum 24 mg/day). L-dopa and other non-dopamine agonist PD medications were permitted. Safety outcomes included adverse events (AEs). Efficacy outcomes included Unified Parkinson's Disease Rating Scale (UPDRS) II and III scores, and Clinical Global Impression-Severity (CGI-S) and Improvement (CGI-I) scores. The median duration of ropinirole PR exposure was 1,069 days. Most subjects (97.6%) reported at least one AE, most commonly (≥ 30%) nausea (42.2%), dizziness (41.0%), peripheral edema (38.6%), back pain (33.7%), and headache (31.3%). Seventeen (20.5%) subjects discontinued due to an AE. UPDRS and CGI scores indicated that the clinical status of subjects was maintained throughout the treatment period. In patients with early PD, long-term treatment with once-daily ropinirole PR was not associated with any new safety concerns, and was effective in maintaining clinical status. These results support the extended use of ropinirole PR for treatment of PD.     

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).     

Long-term effectiveness and quality of life improvement in entacapone-treated Parkinson's disease patients: the effects of an early therapeutic intervention

To evaluate the long-term effects of entacapone on both mean daily 'on' time and health-related quality of life (QoL) in patients with Parkinson's disease (PD) experiencing 'end-of-dose' motor fluctuations and the benefits of an early therapeutic intervention. A prospective, multicenter, observational, 12-month study was performed with an initial 3-month intervention phase, consisting of a phone call to half of the patients from randomly selected investigators to assess if dose adjustment was necessary. Effectiveness was determined by home diaries ('on' time), subscales II and III of the Unified Parkinson's Disease Rating Scale (UPDRS), and the Parkinson's Disease Questionnaire (PDQ-8). After 3 months of treatment, 4.0% of the intervention group patients discontinued the study, versus 18.4% in the control group ( P  < 0.01). The improvement in 'on' time was significantly increased since the 3-month visit (21%, P  < 0.0001) until the end of the study (23% at 12 months, P  < 0.0001). Entacapone also induced significant reductions in the UPDRS scores for subscales II and III and in the PDQ-8 score. 11.2% of patients experienced at least one adverse reaction. This study confirms the effectiveness of entacapone in reducing motor fluctuations by increasing 'on' time, and in improving QoL of PD patients. An early adjustment of entacapone and levodopa doses reduces the number of treatment discontinuations during the first months of treatment.