TY - JOUR
T1 - Dopamine agonist therapy in early Parkinson's disease
AU - Harrison, Rebecca
AU - Ives, Natalie
AU - Clarke, Carl
AU - Hawker, Robert
AU - Shah, Laila
AU - Wheatley, Keith
AU - Gray, Richard
PY - 2008/1/1
Y1 - 2008/1/1
N2 - 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.
AB - 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.
U2 - 10.1002/14651858.CD006564.pub2
DO - 10.1002/14651858.CD006564.pub2
M3 - Review article
C2 - 18425954
SN - 1469-493X
SN - 1465-1858
SP - CD006564
JO - Cochrane Database of Systematic Reviews
JF - Cochrane Database of Systematic Reviews
IS - 2
ER -