A Cochrane review [Abstract] 1 included 12 studies with a total of 2514 subjects. Eleven trials used selegiline, one lazabemide. The mean follow up was for 6 years. MAO-B inhibitors provided small benefits over control in impairment (WMD for change in motor UPDRS score was 3.79 points less with MAO-B inhibitors; 95% CI 2.27 to 5.30; 5 studies, n=1305) and disability (WMD for change in UPDRS ADL score was 1.49 less; 95% CI 0.49 to 2.49; 5 studies, n=1306) at one year which, although statistically significant, may not be clinically significant. There was a marked levodopa-sparing effect with MAO-B inhibitors which was associated with a significant reduction in motor fluctuations (OR 0.73; 95% CI 0.58 to 0.91; 6 studies, n=1461) but not dyskinesia (OR 0.96; 95% CI 0.76 to 1.22; 5 studies, n=1362). The reduction in motor fluctuations was, however, not robust in sensitivity analyses. Although adverse events were generally mild and infrequent, there was a trend to more withdrawals due to adverse events with MAO-B inhibitors (OR 1.72; 95% CI 0.98 to 3.01; 8 studies, n=1479). MAO-B inhibitors were not associated with a significant increase in deaths (OR 1.12; 95% CI 0.98 to 3.01; 12 studies, n=2430).
A topic in Clinical Evidence 2 summarizes the results of 9 RCTs. The first RCT (n=54) found that selegiline significantly delayed the need for levodopa compared with placebo (549 days with selegiline vs 312 days with placebo). The second RCT (n=800) found that selegiline significantly delayed the need for levodopa compared with placebo for 9 months (HR 0.50 for requiring levodopa in each time period, 95% CI 0.41 to 0.62). Four other RCTs came to the same conclusion. Three RCTs found that selegiline improved motor function compared to placebo. One large RCT (n=782) found no significant difference between selegiline and placebo in disability after 4 years. One non-systematic review (5 RCTs, n=589) found no significant difference in mortality between selegiline and placebo (15% vs 6%). One RCT found that selegiline significantly increased mortality at interim analysis after 5.6 years' follow-up (HR 1.57, 95% CI 1.07 to 2.31). Updated analysis found that the increase in mortality did not quite reach significance.
Comment: The quality of evidence is downgraded by study quality (inadequate allocation concealment).
Primary/Secondary Keywords