BACKGROUND: Dopamine agonists are being used increasingly as first line treatment for Parkinson's disease, but there remains uncertainty about their clinical and cost-effectiveness relative to levodopa.
OBJECTIVES: This meta-analysis aims to quantify more reliably the benefits and risks of dopamine agonists compared to placebo or levodopa in early Parkinson's disease.
SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, PubMed, LILACS and Web of Science, plus major journals in the field, abstract books, conference proceedings and reference lists of retrieved publications.
SELECTION CRITERIA: Randomised trials comparing an orally administered dopamine agonist (with or without levodopa) versus placebo or levodopa or both placebo and levodopa in participants with early Parkinson's disease.
DATA COLLECTION AND ANALYSIS: Two authors independently extracted data on clinician-rated disability, motor complications, other side-effects, treatment concordance, levodopa dose and mortality.
MAIN RESULTS: Twenty-nine eligible trials, involving 5247 participants, were identified. Participants randomised to a dopamine agonist were less likely to develop dyskinesia (odds ratio (OR) 0.51, 95% confidence interval (CI) 0.43 to 0.59; P < 0.00001), dystonia (OR 0.64, 95% CI 0.51 to 0.81; P = 0.0002) and motor fluctuations (OR 0.75, 95% CI 0.63 to 0.90; P = 0.002) than levodopa-treated participants. However, various 'non-motor' side-effects, including oedema (OR 3.68, 95% CI 2.62 to 5.18; P < 0.00001), somnolence (OR 1.49, 95% CI 1.12 to 2.00; P = 0.007), constipation (OR 1.59, 95% CI 1.11 to 2.28; P = 0.01), dizziness (OR 1.45, 95% CI 1.09 to 1.92; P = 0.01), hallucinations (OR 1.69, 95% CI 1.13 to 2.52; P = 0.01) and nausea (OR 1.32, 95% CI 1.05 to 1.66; P = 0.02) were all increased in agonist-treated participants (compared with levodopa-treated participants). Agonist-treated participants were also significantly more likely to discontinue treatment due to adverse events (OR 2.49, 95% CI 2.08 to 2.98; P < 0.00001). Finally symptomatic control of Parkinson's disease was better with levodopa than with agonists, but data were reported too inconsistently and incompletely to meta-analyse.
AUTHORS' CONCLUSIONS: This meta-analysis confirms that motor complications are reduced with dopamine agonists compared to levodopa, but also establishes that other important side-effects are increased and symptom control is poorer with agonists. Larger, long-term comparative trials assessing patient-rated quality of life are needed to assess more reliably the balance of benefits and risks of dopamine agonists compared to levodopa.
BACKGROUND: Drugs that mimic dopamine as bromocriptine were introduced as monotherapy or in combination with LD in the hope that this approach would prevent or delay the onset of motor complications in patients with Parkinson's disease (PD). However, hitherto, the role of bromocriptine (BR) in this issue has remained controversial.
OBJECTIVES: To assess the efficacy and safety of bromocriptine (BR) monotherapy for delaying the onset of motor complications associated with levodopa (LD) therapy in patients with PD.
SEARCH STRATEGY: We searched the Movement Disorders Group trials register which includes MEDLINE and EMBASE; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); handsearched appropriate neurology journals and reference lists of reviews found by the search-strategy. We also contacted Sandoz -now Novartis- (manufacturer of BR) and contacted colleagues who had co-ordinated trials on BR.
SELECTION CRITERIA: Randomised trials evaluating the efficacy of BR monotherapy for delaying the onset of motor complications compared to LD therapy alone in PD patients.
DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated the methodological quality of identified trials and extracted the data from the trials.
MAIN RESULTS: Six trials with 850 participants were included. The trials were of low methodological quality and were heterogeneous so we were unable to perform a meta-analysis. The occurrence of dyskinesias in three short trials was too low to draw any conclusion. The results of the longer trials indicate a lower occurrence of dyskinesias in the BR tier. In five trials that evaluated dystonia, this motor complication occurred less frequently in the BR tier. However, for both dyskinesias and dystonia a statistically significant difference in favour of BR emerged only in the largest trial. There was a trend for wearing-off and on-off fluctuations to occur less frequently in the BR group. Although all trials evaluated participants at the impairment level, only the largest trial reported a significantly larger improvement for the LD tier during the first year of therapy. Concerning disability, which was evaluated by five trials no statistically significant differences were found. Overall, a statistically larger number of dropouts occurred in the BR group because of an inadequate therapeutic response or intolerable side effects.
AUTHORS' CONCLUSIONS: Based on a qualitative review of the available data we conclude that in the treatment of early Parkinson's disease, bromocriptine may be beneficial in delaying motor complications and dyskinesias with comparable effects on impairment and disability in those patients that tolerate the drug.
BACKGROUND: Monoamine oxidase B (MAO-B) inhibitors slow disease progression in Parkinson's disease (PD) but clinical trials have produced conflicting results.
OBJECTIVES: To assess the evidence from randomised controlled trials for the effectiveness and safety of long-term use of MAO-B inhibitors in early PD.
SEARCH METHODS: We searched the following electronic databases: Cochrane Central Register of Controlled trials (CENTRAL) (The Cochrane Library Issue 11, 2011), MEDLINE (last searched 8th November 2011) and EMBASE (last searched 8th November 2011); and handsearched neurology and movement disorders conference proceedings, checked reference lists of relevant studies and contacted other researchers.
SELECTION CRITERIA: We included all unconfounded randomised controlled trials that compared a MAO-B inhibitor with control, in the presence or absence of levodopa or dopamine agonists, in patients with early PD where treatment and follow up lasted at least one year.
DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed the methodological quality, and extracted the data. Some additional data were provided by the original authors. Random-effects models were used to analyse results, where appropriate.
MAIN RESULTS: Twelve trials were included (2514 patients, average follow-up six years), 11 using selegiline. The methodological quality was reasonable although concealment of allocation was definitely adequate in only five trials. MAO-B inhibitors were not associated with a significant increase in deaths (odds ratio (OR) 1.12; 95% confidence interval (CI) 0.90 to 1.41). They provided small benefits over control in impairment (weighted mean difference (WMD) for change in motor UPDRS score 3.79 points less with MAO-B inhibitors; 95% CI 2.27 to 5.30) and disability (WMD for change in UPDRS ADL score 1.49 less; 95% CI 0.49 to 2.49) at one year which may not be clinically significant. There was a levodopa-sparing effect with MAO-B inhibitors, which was associated with a significant reduction in motor fluctuations (OR 0.73; 95% CI 0.58 to 0.91) but not dyskinesia (OR 0.96; 95% CI 0.76 to 1.22). The reduction in motor fluctuations was, however, not robust in sensitivity analyses. There was a trend to more withdrawals due to adverse events with MAO-B inhibitors (OR 1.72; 95% CI 0.98 to 3.01).
AUTHORS' CONCLUSIONS: MAO-B inhibitors (more specifically selegiline which contributes most of the data) do not appear to delay disease progression in terms of improved survival but may reduce later motor fluctuations. At present, we do not feel these drugs can be recommended for routine use in the treatment of early Parkinson's disease.
Dopamine agonists are being used increasingly as first line treatment for Parkinson's disease, but there remains uncertainty about their clinical and cost-effectiveness relative to levodopa.
OBJECTIVES:
This meta-analysis aims to quantify more reliably the benefits and risks of dopamine agonists compared to placebo or levodopa in early Parkinson's disease.
SEARCH STRATEGY:
We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, PubMed, LILACS and Web of Science, plus major journals in the field, abstract books, conference proceedings and reference lists of retrieved publications.
SELECTION CRITERIA:
Randomised trials comparing an orally administered dopamine agonist (with or without levodopa) versus placebo or levodopa or both placebo and levodopa in participants with early Parkinson's disease.
DATA COLLECTION AND ANALYSIS:
Two authors independently extracted data on clinician-rated disability, motor complications, other side-effects, treatment concordance, levodopa dose and mortality.
MAIN RESULTS:
Twenty-nine eligible trials, involving 5247 participants, were identified. Participants randomised to a dopamine agonist were less likely to develop dyskinesia (odds ratio (OR) 0.51, 95% confidence interval (CI) 0.43 to 0.59; P < 0.00001), dystonia (OR 0.64, 95% CI 0.51 to 0.81; P = 0.0002) and motor fluctuations (OR 0.75, 95% CI 0.63 to 0.90; P = 0.002) than levodopa-treated participants. However, various 'non-motor' side-effects, including oedema (OR 3.68, 95% CI 2.62 to 5.18; P < 0.00001), somnolence (OR 1.49, 95% CI 1.12 to 2.00; P = 0.007), constipation (OR 1.59, 95% CI 1.11 to 2.28; P = 0.01), dizziness (OR 1.45, 95% CI 1.09 to 1.92; P = 0.01), hallucinations (OR 1.69, 95% CI 1.13 to 2.52; P = 0.01) and nausea (OR 1.32, 95% CI 1.05 to 1.66; P = 0.02) were all increased in agonist-treated participants (compared with levodopa-treated participants). Agonist-treated participants were also significantly more likely to discontinue treatment due to adverse events (OR 2.49, 95% CI 2.08 to 2.98; P < 0.00001). Finally symptomatic control of Parkinson's disease was better with levodopa than with agonists, but data were reported too inconsistently and incompletely to meta-analyse.
AUTHORS' CONCLUSIONS:
This meta-analysis confirms that motor complications are reduced with dopamine agonists compared to levodopa, but also establishes that other important side-effects are increased and symptom control is poorer with agonists. Larger, long-term comparative trials assessing patient-rated quality of life are needed to assess more reliably the balance of benefits and risks of dopamine agonists compared to levodopa.
Systematic Review Question»Systematic review of interventions
