The effect of selegiline in the treatment of people with Alzheimer's disease: a meta-analysis of published trials

Objective To evaluate the effect of selegiline in the treatment of patients with Alzheimer's disease, in terms of cognitive performance, functional ability, emotional state (including behaviour and mood) and global response. Data Sources The Cochrane database of trials, Embase, Medline and Psychlit. Study Selection Unconfounded, double-blind, randomised trials of selegiline compared with placebo reported before 31 December 1998. Data Extraction The reviewers selected trials for inclusion. Individual patient data were sought, but when these could not be retrieved summary data were extracted from published papers. Results Of 27 identified trials, 14 met the inclusion criteria. Individual patient data were retrieved from eight trials on 821 patients. Summary data were extracted from five trials on 240 patients. No data were available from one trial on. 12 patients, which was therefore excluded from the meta-analysis. Fixed and random effects meta-analyses were performed on standardised mean differences. For cognition there was a statistically significant difference between selegiline and placebo at 4-6 weeks and 8-17 weeks after randomisation (at 8-17 weeks: smd = 0.45 [95% confidence interval 0.03 to 0.88]), but this disappeared at later assessments. The size of the treatment difference was considered unlikely to be of clinical importance. Although there was a statistically significant difference at 4-6 weeks for activities of daily living, this disappeared at later assessments (at 8-17 weeks: smd = 0.33 [ - 0.33, 0.69]). There were no statistically significant differences or clinically relevant differences between selegiline and placebo in terms of emotional state or global response. Conclusion Although there was some evidence of improvement with selegiline in the short term in cognition and activities of daily living, the magnitude of the effect did not reach clinical importance. There was no evidence of long term effects. Copyright (C) 2002 John Wiley Sons, Ltd.