Article type
Year
Abstract
Background: Theoretically, monoamine oxidase B (MAO-B) inhibitors could alter disease progression in Parkinson s disease (PD). Clinical trials have, however, produced conflicting results, including one that showed increased death rates with these agents.
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.
Methods: Selection criteria we sought to identify all unconfounded randomized controlled trials comparing MAO-B inhibitors with control (placebo or no treatment) in early PD (Hoehn & Yahr stage three or less). We excluded trials with treatment and follow-up less than one year.
Search strategy we searched the following electronic databases: Cochrane central register of controlled trials (The Cochrane Library Issue 4, 2003), MEDLINE (last searched 14th January 2004) and EMBASE (last searched 14th January 2004). We also hand-searched neurology and movement disorders conference proceedings, checked reference lists of relevant studies and contacted other researchers.
Data collection & analysis two reviewers independently selected trials for inclusion and assessed methodological quality. Data were extracted into the Cochrane Collaboration s Review Manager software, which was used to perform meta-analysis. We contacted authors of trials for missing information.
Results: We included 10 trials (2422 patients), nine using selegiline, one using lazabemide. Mean follow-up was 5.8 years. MAO-B inhibitors were not associated with an increase in deaths (odds ratio 1.15; 95% confidence interval 0.92 to 1.44; p = 0.21) and, although they were associated with statistically significant improvements in impairment and disability scores, these were too small to be clinically significant. However, there was a marked and sustained levodopa sparing effect with MAO-B inhibitors and significant reductions in motor fluctuations (odds ratio 0.75; 95% confidence interval 0.59 to 0.94, p= 0.01). Adverse events were, generally mild and infrequent, but withdrawals due to side-effects were increased (odds ratio 2.27; 95% confidence interval 1.14 to 4.49) with MAO-B inhibitors.
Conclusions: MAO-B inhibitors do not appear to significantly delay Parkinson s disease progression and do not reduce death rates. Whilst we cannot exclude a clinically significant increase in deaths with MAO-B inhibitors, the reduction in motor fluctuations is promising although not conclusive. Further research with randomized controlled trials should be carried out to clarify these issues and one such trial is underway.
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.
Methods: Selection criteria we sought to identify all unconfounded randomized controlled trials comparing MAO-B inhibitors with control (placebo or no treatment) in early PD (Hoehn & Yahr stage three or less). We excluded trials with treatment and follow-up less than one year.
Search strategy we searched the following electronic databases: Cochrane central register of controlled trials (The Cochrane Library Issue 4, 2003), MEDLINE (last searched 14th January 2004) and EMBASE (last searched 14th January 2004). We also hand-searched neurology and movement disorders conference proceedings, checked reference lists of relevant studies and contacted other researchers.
Data collection & analysis two reviewers independently selected trials for inclusion and assessed methodological quality. Data were extracted into the Cochrane Collaboration s Review Manager software, which was used to perform meta-analysis. We contacted authors of trials for missing information.
Results: We included 10 trials (2422 patients), nine using selegiline, one using lazabemide. Mean follow-up was 5.8 years. MAO-B inhibitors were not associated with an increase in deaths (odds ratio 1.15; 95% confidence interval 0.92 to 1.44; p = 0.21) and, although they were associated with statistically significant improvements in impairment and disability scores, these were too small to be clinically significant. However, there was a marked and sustained levodopa sparing effect with MAO-B inhibitors and significant reductions in motor fluctuations (odds ratio 0.75; 95% confidence interval 0.59 to 0.94, p= 0.01). Adverse events were, generally mild and infrequent, but withdrawals due to side-effects were increased (odds ratio 2.27; 95% confidence interval 1.14 to 4.49) with MAO-B inhibitors.
Conclusions: MAO-B inhibitors do not appear to significantly delay Parkinson s disease progression and do not reduce death rates. Whilst we cannot exclude a clinically significant increase in deaths with MAO-B inhibitors, the reduction in motor fluctuations is promising although not conclusive. Further research with randomized controlled trials should be carried out to clarify these issues and one such trial is underway.