Search or browse years of Parkinsn Email list messages
Mail converted by MHonArc 2.6.10
 
Site Hosting donated by
&
Grant from The Parkinson Alliance

Parkinsn Current Topics

TITLE: The role of entacapone in the management of Parkinson's disease.
AUTHORS: Brooks DJ; Forsyth D; Playfer JR; Williams AC
AUTHOR AFFILIATION: Imperial College School of Medicine, Hammersmith Hospital, London.
SOURCE: Hosp Med 2000 Apr;61(4):267-71
CITATION IDS: PMID: 10858804 UI: 20316608
ABSTRACT: Catechol-O-methyltransferase (COMT) inhibition is an important advance in the treatment of Parkinson's disease. This consensus statement provides guidelines for the optimal use of the only currently available COMT inhibitor, entacapone (Comtess, Orion Pharma (UK) Ltd, Newbury, Berkshire).

2000/07
2000/15 11:00


--------------------------------------------------------------------------------


TITLE: The long-duration response to L-dopa in the treatment of early PD [see comments]
AUTHORS: Zappia M; Oliveri RL; Bosco D; Nicoletti G; Branca D; Caracciolo M; Napoli ID; Gambardella A; Quattrone A
AUTHOR AFFILIATION: Institute of Neurology, University of Catanzaro, Italy.
SOURCE: Neurology 2000 May 23;54(10):1910-5
CITATION IDS: PMID: 10822428 UI: 20284127
COMMENT: Comment in: Neurology 2000 May 23;54(10):1884-5
ABSTRACT: OBJECTIVE: To investigate the long-duration response (LDR) to L-dopa resulting from different regimens of L-dopa.

BACKGROUND: In clinical practice, L-dopa is usually administered without considering the LDR due to the drug. Moreover, it has not been established whether in early PD a multiple daily intake of small doses of L-dopa may induce a sustained LDR.

METHODS: Twenty-four patients with early PD underwent a double-blind, crossover trial, comparing three different 15-day treatment periods with L-dopa: treatment A (250 mg every 24 hours); treatment B (250 mg every 8 hours); and treatment C (125 mg every 8 hours). After completion, 20 patients underwent a subsequent open-label randomized trial with prolonged treatments (250 mg every 24 hours or 125 mg every 8 hours) up to 3 months. LDR was measured at the end of each treatment.

RESULTS: All patients achieved a sustained LDR after treatments A and B, whereas only 17% of patients reached a sustained LDR after treatment C. Overall, the LDRs resulting from treatments A and B had similar magnitude and were larger than the LDR deriving from treatment C. After 3 months of prolonged treatments, only three of 10 patients treated with 125 mg every 8 hours increased their LDR, whereas all 10 patients treated with 250 mg every 24 hours had a maximal and stable LDR.

CONCLUSIONS: Sustained LDR to L-dopa is dependent on the amount of the single doses of the drug. A regimen scheduling small, divided doses during the day, as done in clinical practice, is a questionable therapy for the achievement of a sustained LDR.

2000/06
2000/10 09:00


--------------------------------------------------------------------------------


TITLE: A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa. 056 Study Group.
AUTHORS: Rascol O; Brooks DJ; Korczyn AD; De Deyn PP; Clarke CE; Lang AE
AUTHOR AFFILIATION: Clinical Investigation Center, Neuropharmacology Unit, INSERM Unite 455, University Hospital, Toulouse, France. rascol@cict.fr
SOURCE: N Engl J Med 2000 May 18;342(20):1484-91
CITATION IDS: PMID: 10816186 UI: 20256707
ABSTRACT: BACKGROUND: There is debate about whether the initial treatment for patients with Parkinson's disease should be levodopa or a dopamine agonist.

METHODS: In this prospective, randomized, double-blind study, we compared the safety and efficacy of the dopamine D2-receptor agonist ropinirole with that of levodopa over a period of five years in 268 patients with early Parkinson's disease. If symptoms were not adequately controlled by the assigned study medication, patients could receive supplementary levodopa, administered in an open-label fashion. The primary outcome measure was the occurrence of dyskinesia.

RESULTS: Eighty-five of the 179 patients in the ropinirole group (47 percent) and 45 of the 89 patients in the levodopa group (51 percent) completed all five years of the study. In the ropinirole group 29 of the 85 patients (34 percent) received no levodopa supplementation. The analysis of the time to dyskinesia showed a significant difference in favor of ropinirole (hazard ratio for remaining free of dyskinesia, 2.82; 95 percent confidence interval, 1.78 to 4.44; P<0.001). At five years, the cumulative incidence of dyskinesia (excluding the three patients who had dyskinesia at base line), regardless of levodopa supplementation, was 20 percent (36 of 177 patients) in the ropinirole group and 45 percent (40 of 88 patients) in the levodopa group. There was no significant difference between the two groups in the mean change in scores for activities of daily living among those who completed the study. Adverse events led to the early withdrawal from the study of 48 of 179 patients in the ropinirole group (27 percent) and 29 of 89 patients in the levodopa group (33 percent). The mean (+/-SD) daily doses given by the end of the study were 16.5+/-6.6 mg of ropinirole (plus 427+/-221 mg of levodopa in patients who received supplementation) and 753+/-398 mg of levodopa (including supplements).

CONCLUSIONS: Early Parkinson's disease can be managed successfully for up to five years with a reduced risk of dyskinesia by initiating treatment with ropinirole alone and supplementing it with levodopa if necessary.

2000/05
2000/29 09:00


--------------------------------------------------------------------------------


TITLE: Levodopa-induced dyskinesias in Parkinson's disease: is sensitization reversible?
AUTHORS: Bejjani BP; Arnulf I; Demeret S; Damier P; Bonnet AM; Houeto JL; Agid Y
AUTHOR AFFILIATION: Centre d'Investigation Clinique, Federation de Neurologie and INSERM U289, Groupe-Hospitalier Pitie-Salpetriere, Paris, France.
SOURCE: Ann Neurol 2000 May;47(5):655-8
CITATION IDS: PMID: 10805339 UI: 20263089
ABSTRACT: Levodopa-induced dyskinesias (LIDs) in patients with Parkinson's disease are considered to result from the severity of dopaminergic denervation in the striatum, which is an irrevocable phenomenon, and sensitization induced by long-term intermittent administration of levodopa. Taking advantage of the 64% reduction of levodopa treatment allowed in 12 Parkinson's disease patients by continuous high-frequency stimulation of the subthalamic nucleus, we evaluated the severity of parkinsonian motor disability and LIDs during two levodopa challenges performed before the surgical implantation of the stimulation electrodes and after 8.8 months of continuous bilateral subthalamic nucleus stimulation that was interrupted 2 hours before the levodopa test. Motor disability during the "off" and "on" drug periods was unchanged. The severity of LIDs during the "on" period and dystonia during the "off" period decreased by 54% and 62%, respectively. The reduced severity of LIDs in the absence of subthalamic nucleus stimulation demonstrates that the sensitization phenomenon resulting from long-term intermittent levodopa administration is partially reversible.

2000/06
2000/03 09:00


--------------------------------------------------------------------------------


TITLE: Clinical, pharmacokinetic, and pharmacodynamic effects of tolcapone withdrawal in levodopa-treated patients with parkinsonism.
AUTHORS: Jorga KM; Davis TL; Kurth MC; Saint-Hilaire MH; LeWitt PA; Fotteler B; Zurcher G; Rabbia M
AUTHOR AFFILIATION: Department of Research and Development, F. Hoffmann-La Roche, Basel, Switzerland.
SOURCE: Clin Neuropharmacol 2000 Mar-Apr;23(2):98-105
CITATION IDS: PMID: 10803800 UI: 20260945
ABSTRACT: The effect and clinical significance of tolcapone withdrawal on erythrocyte catechol-O-methyltransferase (COMT) activity, levodopa pharmacokinetics, and levodopa requirements were investigated in 59 patients with fluctuating parkinsonism who were randomized to receive placebo or tolcapone 100 or 200 mg three times daily for 6 weeks. Tolcapone withdrawal caused a transient elevation in COMT activity by 64% in patients receiving 100 mg three times daily and by 128% in those receiving 200 mg three times daily at approximately 1-2 weeks after discontinuation of drug. Thereafter, COMT activity was declining but did not reach baseline values by the 12-week study endpoint. However, this had no effect on plasma levodopa and 3-O-methyldopa (3-OMD) concentrations or on levodopa requirements. During treatment, tolcapone increased "on" time and decreased "off" time; after discontinuation of study medication and levodopa dose adjustment, on and off times were similar to baseline. Withdrawal was generally well tolerated; no patients withdrew from the trial during the posttreatment period, and no serious adverse events were observed. In conclusion, the transient increase in erythrocyte COMT activity observed after discontinuation oftolcapone is not associated with changes in peripheral levodopa metabolism and therefore has no significant clinical consequences in terms of levodopa requirements, clinical symptoms, or adverse events.

2000/07
2000/15 11:00

--------------------------------------------------------------------------------


TITLE: The effect of amantadine on levodopa-induced dyskinesias in Parkinson's disease: a double-blind, placebo-controlled study.
AUTHORS: Snow BJ; Macdonald L; Mcauley D; Wallis W
AUTHOR AFFILIATION: Department of Neurology, Auckland Hospital, New Zealand.
SOURCE: Clin Neuropharmacol 2000 Mar-Apr;23(2):82-5
CITATION IDS: PMID: 10803797 UI: 20260942
ABSTRACT: We performed a double-blind, placebo-controlled, crossover study to assess the effect of amantadine versus placebo on levodopa-induced dyskinesias in Parkinson's disease. We found a 24% reduction in the total dyskinesia score after amantadine administration (p = 0.004). This improvement was achieved without any influence on the severity of "on" period parkinsonism. The results confirm that amantadine reduces levodopa dyskinesias and support the hypothesis that dyskinesias can be reduced by blockade of excitatory pathways in the basal ganglia.

2000/07
2000/15 11:00


--------------------------------------------------------------------------------


TITLE: Lisuride for levodopa-induced complications in Parkinson's disease.
AUTHORS: Clarke CE; Speller JM
AUTHOR AFFILIATION: Department of Neurology, City Hospital NHS Trust, Dudley Road, Birmingham, West Midlands, United Kingdom, B18 7QH. c.e.clarke@bham.ac.uk
SOURCE: Cochrane Database Syst Rev 2000;(2):CD001515
CITATION IDS: PMID: 10796801 UI: 20257882
ABSTRACT: OBJECTIVES: To compare the efficacy and safety of adjuvant lisuride therapy versus placebo in patients with Parkinson's disease, already established on levodopa and suffering from motor complications.

SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Cambridge Laboratories and Roche Products Limited.

SELECTION CRITERIA: Randomised controlled trials of lisuride versus placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy.

DATA COLLECTION AND ANALYSIS: Data was to be abstracted independently by each author and differences settled by discussion.

MAIN RESULTS: No randomised controlled trials comparing lisuride with placebo in advanced Parkinson's disease with motor complications were found.

REVIEWER'S CONCLUSIONS: Well designed randomised controlled trials demonstrating efficacy and safety are required before the use of lisuride in later Parkinson's disease can be supported.

2000/07
2000/08 11:00


--------------------------------------------------------------------------------


TITLE: Lisuride versus bromocriptine for levodopa-induced complications in Parkinson's disease.
AUTHORS: Clarke CE; Speller JM
AUTHOR AFFILIATION: Department of Neurology, City Hospital NHS Trust, Dudley Road, Birmingham, West Midlands, United Kingdom, B18 7QH. c.e.clarke@bham.ac.uk
SOURCE: Cochrane Database Syst Rev 2000;(2):CD001514
CITATION IDS: PMID: 10796800 UI: 20257881
ABSTRACT: OBJECTIVES: To compare the efficacy and safety of adjunct lisuride therapy versus bromocriptine in patients with Parkinson's disease, already established on levodopa and suffering the long-term complications of therapy.

SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Cambridge Laboratories, Roche Products Limited and Sandoz Limited.

SELECTION CRITERIA: Randomised controlled trials of lisuride versus bromocriptine in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy.

DATA COLLECTION AND ANALYSIS: Data was abstracted independently by each author and differences settled by discussion.

MAIN RESULTS: Only one randomised cross-over trial including 20 patients has compared lisuride with bromocriptine as adjunct therapy in Parkinson's disease. Both lisuride and bromocriptine improved motor fluctuations with no significant differences between the agonists. However, this conclusion is based on an unvalidated 4 point rating scale which could only record positive outcomes. This, combined with the small size of the trial, suggests that firm conclusions on motor fluctuations should not be drawn. Lisuride and bromocriptine produced similar benefits in parkinsonian impairments according to the Columbia Rating Scale. Adverse events were similar with the two agonists and no withdrawals were reported from either drug.

REVIEWER'S CONCLUSIONS: The small size of this study and other methodological problems do not allow any firm conclusions to be drawn regarding the efficacy and safety of lisuride compared with bromocriptine in advanced Parkinson's disease with motor complications.

2000/07
2000/08 11:00


--------------------------------------------------------------------------------


TITLE: Bromocriptine for levodopa-induced motor complications in Parkinson's disease.
AUTHORS: van Hilten JJ; Ramaker C; Van de Beek WJ; Finken MJ
AUTHOR AFFILIATION: Department of Neurology, Leiden University Medical Center, P.O. Box 9600, Leiden, The Netherlands, 2300 RC. jvhilten@neurology.azl.nl
SOURCE: Cochrane Database Syst Rev 2000;(2):CD001203
CITATION IDS: PMID: 10796755 UI: 20257835
ABSTRACT: OBJECTIVES: To assess the efficacy and safety of adjunct bromocriptine (BR) therapy compared to placebo in the treatment of Parkinson's disease (PD) patients with motor complications.

SEARCH STRATEGY: Sources including the Cochrane Library, a MEDLINE search-strategy, reference lists of the reviews found by the MEDLINE search-strategy, Sandoz (producer of BR), symposia reports, PD handbooks, SCISEARCH, contacts with colleagues who had co-ordinated trials on BR and reference lists of all included studies were used to identify randomized controlled trials (RCTs) of interest.

SELECTION CRITERIA: Randomized trials were eligible for inclusion if they evaluated the efficacy of BR as adjunctive to LD-therapy compared to placebo in PD patients with motor complications. Outcome measures that were evaluated, included occurrence and severity of motor complications, scores on impairment and disability, and the occurrence of side effects.

DATA COLLECTION AND ANALYSIS: Three reviewers independently reviewed the quality of identified trials. To determine the feasibility of a quantitative systematic review each eligible study was evaluated concerning the methodological quality.

MAIN RESULTS: This review identified important shortcomings regarding the methodological quality of eight trials. All studies failed to describe adequately their randomization procedure. Consultation with the trialists revealed that three trials adequately randomized their patients. Contrary to the information of the published report, one placebo-controlled trial appeared to be carried out as an open study and was therefore excluded. The remaining seven trials were reported to be carried out according to a double-blind design, although one was unblinded after five weeks. There was a conspicuous variability in the duration of trials: four to forty weeks (mean 14 weeks). None of the included trials was performed according to the intention-to-treat principle. With regard to the inclusion criteria, it frequently remained unclear if PD patients actually suffered from motor complications. Prominent differences between studies regarding the baseline characteristics and the rate by which BR was introduced during the titration phase were found. Major differences between studies emerged concerning the applied outcomes. The various methods used to evaluate the occurrence and/or severity of motor complications lacked a sound clinimetric basis. A great diversity of scales to evaluate impairment and disability was applied. None of the included trials reported whether scores on impairment and disability level referred to the "on"- or "off"-phase.

REVIEWER'S CONCLUSIONS: This review highlights major methodological problems and sources of heterogeneity that not only hamper the comparability of trials but also preclude a conclusion on the efficacy of BR in the adjunct treatment of PD patients with motor complications.

2000/07
2000/08 11:00


--------------------------------------------------------------------------------


TITLE: Pergolide versus bromocriptine for levodopa-induced motor complications in Parkinson's disease.
AUTHORS: Clarke C E; Speller J M
AUTHOR AFFILIATION: Department of Neurology, City Hospital NHS Trust, Dudley Road, Birmingham, West Midlands, United Kingdom, B18 7QH. c.e.clarke@bham.ac.uk
SOURCE: Cochrane Database Syst Rev 2000;(2):CD000236
CITATION IDS: PMID: 10796705 UI: 20257785
ABSTRACT: OBJECTIVES: To compare the efficacy and safety of adjunct pergolide therapy versus bromocriptine in patients with Parkinson's disease, already established on levodopa and suffering the long-term complications of therapy.

SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Eli Lilly Company and Sandoz Limited.

SELECTION CRITERIA: Randomised controlled trials of pergolide versus bromocriptine in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy.

DATA COLLECTION AND ANALYSIS: Data was abstracted independently by each author and differences settled by discussion.

MAIN RESULTS: Three short-term trials fulfilled the inclusion criteria for the review. Pergolide was superior to bromocriptine regarding UPDRS and NYPDS motor and NYPDS ADL scores in two trials. More patients recorded a 'marked' or 'moderate improvement' in clinician's global impression score with pergolide than bromocriptine in two studies. Insufficient evidence on fluctuations and dyskinesia was available to draw any conclusions. No significant differences between the agonists were seen in levodopa dose reduction, drop outs or adverse events.

REVIEWER'S CONCLUSIONS: Although pergolide is superior to bromocriptine in reducing motor impairments and disability, no firm conclusions regarding levodopa-induced motor complications can be reached. Levodopa dose reduction, adverse events and withdrawals from treatment are similar for the two agonists. The small advantage of pergolide in efficacy does not take into account its additional cost compared with bromocriptine.

2000/07
2000/08 11:00


--------------------------------------------------------------------------------


TITLE: Pergolide for levodopa-induced complications in Parkinson's disease.
AUTHORS: Clarke C E; Speller J M
AUTHOR AFFILIATION: Department of Neurology, City Hospital NHS Trust, Dudley Road, Birmingham, West Midlands, United Kingdom, B18 7QH. c.e.clarke@bham.ac.uk
SOURCE: Cochrane Database Syst Rev 2000;(2):CD000235
CITATION IDS: PMID: 10796704 UI: 20257784
ABSTRACT: OBJECTIVES: To compare the efficacy and safety of adjunct pergolide therapy versus placebo in patients with Parkinson's disease suffering from the complications of levodopa therapy.

SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Eli Lilly and Company Limited.

SELECTION CRITERIA: Randomised controlled trials of pergolide versus placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy.

DATA COLLECTION AND ANALYSIS: Data was abstracted independently by each author and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of drop outs and adverse events.

MAIN RESULTS: A large number of small RCTs were identified, but these were part of a large multicentre trial which was eventually published in full. The final publication was used as the only subject for this review. The time patients spent 'off' was reduced by 1.8 hours with pergolide compared with 0.2 hours with placebo (p < 0.001). Dyskinesia developed or deteriorated in 62% of pergolide-treated compared with 25% placebo-treated patients (p < 0. 05). The excess in dyskinesia prevalence and severity resolved by the end of the study with levodopa reduction. Levodopa dose was reduced more in those receiving pergolide (235 mg v 51 mg; p < 0. 001). Pergolide produced significant improvement in Hoehn and Yahr stage (p < 0.05) and both the motor and activities of daily living parts of a modified Columbia rating scale (both p < 0.001). Significantly more patients suffered nausea (24% v 13%; p < 0.001) and hallucinations (14% v 3%; p < 0.01) on pergolide. No difference was found in the numbers remaining on treatment at the end of the study (pergolide 84% v placebo 82%) but withdrawals due to adverse events were greater in those taking pergolide (10% v 4%).

REVIEWER'S CONCLUSIONS: Based on this single large multicentre study, pergolide reduces 'off' time and improves impairment and disability due to Parkinson's disease whilst allowing a reduction in levodopa dose. This is at the expense of dopaminergic adverse events. Further trials are required to compare pergolide with the newer dopamine agonists.

2000/07
2000/08 11:00



Return To Index of Current Parkinson's Topics