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Monoamine oxidase B inhibitors for early Parkinson's disease.

Abstract

BACKGROUND

It has been postulated that monoamine oxidase B (MAO-B) inhibitors alter disease progression in Parkinson's disease (PD). Clinical trials have produced conflicting results.

OBJECTIVES

To assess the evidence from randomized controlled trials for the effectiveness and safety of long-term use of MAO-B inhibitors in early PD.

SEARCH STRATEGY

We searched the following electronic databases: Cochrane Central Register of Controlled trials (CENTRAL) (The Cochrane Library Issue 2, 2004), MEDLINE (last searched 18th August 2004) and EMBASE (last searched 18th August 2004). We also handsearched neurology and movement disorders conference proceedings, checked reference lists of relevant studies and contacted other researchers.

SELECTION CRITERIA

We sought to include all unconfounded randomized 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 and 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. A small amount of additional data was provided by the original authors. Random-effects models were used to analyse results, where appropriate.

MAIN RESULTS

Ten trials were included (a total of 2422 patients), nine using selegiline, one using lazabemide. The methodological quality was reasonable although concealment of allocation was definitely adequate in only four trials. The mean follow up was for 5.8 years. MAO-B inhibitors were not associated with a significant increase in deaths (odds ratio (OR) 1.15; 95% confidence interval (CI) 0.92 to 1.44). They provided small benefits over control in impairment (weighted mean difference (WMD) for change in motor UPDRS score was 3.81 points less with MAO-B inhibitors; 95% CI 2.27 to 5.36) and disability (WMD for change in UPDRS ADL score was 1.50 less; 95% CI 0.48 to 2.53) at one year which, although statistically significant, were not clinically significant. There was a marked levodopa-sparing effect with MAO-B inhibitors which was associated with a significant reduction in motor fluctuations (OR 0.75; 95% CI 0.59 to 0.94) but not dyskinesia (OR 0.97; 95% CI 0.76 to 1.25). The reduction in motor fluctuations was, however, not robust in sensitivity analyses. Although adverse events were generally mild and infrequent, withdrawals due to side-effects were higher (OR 2.36; 95% CI 1.32 to 4.20) with MAO-B inhibitors.

AUTHORS' CONCLUSIONS

MAO-B inhibitors do not appear to delay disease progression but may have a beneficial effect on motor fluctuations. There was no statistically significant effect on deaths although the confidence interval does not exclude a small increase with MAO-B inhibitors. At present we do not feel these drugs can be recommended for routine use in the treatment of early Parkinson's disease but further randomized controlled trials should be carried out to clarify, in particular, their effect on deaths and motor complications.

Authors

No 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

16034956

Citation

Macleod, A D., et al. "Monoamine Oxidase B Inhibitors for Early Parkinson's Disease." The Cochrane Database of Systematic Reviews, 2005, p. CD004898.
Macleod AD, Counsell CE, Ives N, et al. Monoamine oxidase B inhibitors for early Parkinson's disease. Cochrane Database Syst Rev. 2005.
Macleod, A. D., Counsell, C. E., Ives, N., & Stowe, R. (2005). Monoamine oxidase B inhibitors for early Parkinson's disease. The Cochrane Database of Systematic Reviews, (3), CD004898.
Macleod AD, et al. Monoamine Oxidase B Inhibitors for Early Parkinson's Disease. Cochrane Database Syst Rev. 2005 Jul 20;(3)CD004898. PubMed PMID: 16034956.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Monoamine oxidase B inhibitors for early Parkinson's disease. AU - Macleod,A D, AU - Counsell,C E, AU - Ives,N, AU - Stowe,R, Y1 - 2005/07/20/ PY - 2005/7/22/pubmed PY - 2005/12/13/medline PY - 2005/7/22/entrez SP - CD004898 EP - CD004898 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 3 N2 - BACKGROUND: It has been postulated that monoamine oxidase B (MAO-B) inhibitors alter disease progression in Parkinson's disease (PD). Clinical trials have produced conflicting results. OBJECTIVES: To assess the evidence from randomized controlled trials for the effectiveness and safety of long-term use of MAO-B inhibitors in early PD. SEARCH STRATEGY: We searched the following electronic databases: Cochrane Central Register of Controlled trials (CENTRAL) (The Cochrane Library Issue 2, 2004), MEDLINE (last searched 18th August 2004) and EMBASE (last searched 18th August 2004). We also handsearched neurology and movement disorders conference proceedings, checked reference lists of relevant studies and contacted other researchers. SELECTION CRITERIA: We sought to include all unconfounded randomized 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 and 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. A small amount of additional data was provided by the original authors. Random-effects models were used to analyse results, where appropriate. MAIN RESULTS: Ten trials were included (a total of 2422 patients), nine using selegiline, one using lazabemide. The methodological quality was reasonable although concealment of allocation was definitely adequate in only four trials. The mean follow up was for 5.8 years. MAO-B inhibitors were not associated with a significant increase in deaths (odds ratio (OR) 1.15; 95% confidence interval (CI) 0.92 to 1.44). They provided small benefits over control in impairment (weighted mean difference (WMD) for change in motor UPDRS score was 3.81 points less with MAO-B inhibitors; 95% CI 2.27 to 5.36) and disability (WMD for change in UPDRS ADL score was 1.50 less; 95% CI 0.48 to 2.53) at one year which, although statistically significant, were not clinically significant. There was a marked levodopa-sparing effect with MAO-B inhibitors which was associated with a significant reduction in motor fluctuations (OR 0.75; 95% CI 0.59 to 0.94) but not dyskinesia (OR 0.97; 95% CI 0.76 to 1.25). The reduction in motor fluctuations was, however, not robust in sensitivity analyses. Although adverse events were generally mild and infrequent, withdrawals due to side-effects were higher (OR 2.36; 95% CI 1.32 to 4.20) with MAO-B inhibitors. AUTHORS' CONCLUSIONS: MAO-B inhibitors do not appear to delay disease progression but may have a beneficial effect on motor fluctuations. There was no statistically significant effect on deaths although the confidence interval does not exclude a small increase with MAO-B inhibitors. At present we do not feel these drugs can be recommended for routine use in the treatment of early Parkinson's disease but further randomized controlled trials should be carried out to clarify, in particular, their effect on deaths and motor complications. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/16034956/Monoamine_oxidase_B_inhibitors_for_early_Parkinson's_disease_ L2 - https://doi.org/10.1002/14651858.CD004898.pub2 DB - PRIME DP - Unbound Medicine ER -