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Dopamine agonist therapy in early Parkinson's disease.

Abstract

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.

Authors+Show Affiliations

University of Birmingham Clinical Trials Unit, Division of Medical Sciences, Robert Aitken Institute, Edgbaston, Birmingham, UK, B15 2TT.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Review
Systematic Review

Language

eng

PubMed ID

18425954

Citation

Stowe, R L., et al. "Dopamine Agonist Therapy in Early Parkinson's Disease." The Cochrane Database of Systematic Reviews, 2008, p. CD006564.
Stowe RL, Ives NJ, Clarke C, et al. Dopamine agonist therapy in early Parkinson's disease. Cochrane Database Syst Rev. 2008.
Stowe, R. L., Ives, N. J., Clarke, C., van Hilten, J., Ferreira, J., Hawker, R. J., Shah, L., Wheatley, K., & Gray, R. (2008). Dopamine agonist therapy in early Parkinson's disease. The Cochrane Database of Systematic Reviews, (2), CD006564. https://doi.org/10.1002/14651858.CD006564.pub2
Stowe RL, et al. Dopamine Agonist Therapy in Early Parkinson's Disease. Cochrane Database Syst Rev. 2008 Apr 16;(2)CD006564. PubMed PMID: 18425954.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dopamine agonist therapy in early Parkinson's disease. AU - Stowe,R L, AU - Ives,N J, AU - Clarke,C, AU - van Hilten,J, AU - Ferreira,J, AU - Hawker,R J, AU - Shah,L, AU - Wheatley,K, AU - Gray,R, Y1 - 2008/04/16/ PY - 2008/4/22/pubmed PY - 2008/6/14/medline PY - 2008/4/22/entrez SP - CD006564 EP - CD006564 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 2 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. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/18425954/Dopamine_agonist_therapy_in_early_Parkinson's_disease_ L2 - https://doi.org/10.1002/14651858.CD006564.pub2 DB - PRIME DP - Unbound Medicine ER -