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.