No evidence of benefit of selegiline for Alzheimer's disease

Birks J, Flicker L

Published Online:

July 16, 2008

Despite its initial promise, i.e. the potential neuroprotective properties, and its role in the treatment of Parkinson's disease, selegiline for Alzheimer's disease has proved disappointing. Although there is no evidence of a significant adverse event profile, there is also no evidence of a clinically meaningful benefit for people with Alzheimer's disease. There would seem to be no justification, therefore, to use it for Alzheimer's disease, nor for any further studies of its efficacy in Alzheimer's disease.

Abstract (click to read)

Background:

Alzheimer's disease is the most common cause of dementia in older people accounting for some 60% of cases with late-onset cognitive deterioration. It is now thought that several neurotransmitter dysfunctions are involved from an early stage in the pathogenesis of Alzheimer's disease-associated cognitive decline.

The efficacy of selegiline for symptoms of Alzheimer's disease remains controversial and is reflected by its low rate of prescription and the lack of approval by several regulatory authorities in Europe and elsewhere. Reasons for this uncertainty involve the modest overall effects observed in some trials, the lack of benefit observed in several trials, the use of cross-over designs which harbour methodological problems in a disease like dementia and the difficulty in interpreting results from trials when a variety of measurement scales are used to assess outcomes.

Objectives:

The objective of this review is to assess whether or not selegiline improves the well-being of patients with Alzheimer's disease.

Search strategy:

The Cochrane Dementia and Cognitive Impairment Group Register of Clinical Trials, was searched using the terms 'selegiline', 'l-deprenyl', ''eldepryl" and "monamine oxidase inhibitor-B" on 9 October 2002. This Register contains records from all major health care databases and many trials databases and is updated regularly.

Selection criteria:

All unconfounded, double-blind, randomized controlled trials in which treatment with selegiline was administered for more than a day and compared to placebo in patients with dementia.

Data collection and analysis:

An individual patient data meta-analysis of selegiline, Wilcock 2002 provides much of the data that are available for this review. Seven studies provided individual patient data and this was pooled with summary statistics from the published papers of the other nine studies. Where possible, intention-to-treat data were used but usually the meta analyses were restricted to completers' data (data on people who completed the study).

Main results:

There are 17 included trials. There were very few significant treatment effects and these were all in favour of selegiline; cognition at 4-6 weeks and 8-17 weeks, and activities of daily living at 4-6 weeks .

There is little evidence of adverse effects caused by selegiline, and few withdrew from trials, apart from the Sano trial. The analyses were conducted on data available. There was no attempt to correct for missing patients because there were so few and withdrawal was probably unconnected with treatment.

All trials examined the cognitive effects of selegiline, and in addition 12 trials examined the behavioural and mood effects.

The meta-analysis revealed benefits on memory function, shown by improvement in the memory tests from several cognitive tests. The combined memory tests, and overall the combined cognitive tests, analysed using standardised mean differences, showed an improvement due to selegiline compared with placebo at 4-6 weeks and 8-17 weeks.
The meta-analyses of emotional state show no treatment effects.

Several studies assessed activities of daily living using several different scales. The combined tests, analysed using the standardised mean difference, showed an improvement due to selegiline at 4-6 weeks.

The global rating scales analysed using standardised mean differences showed no effect of selegiline.

A variety of adverse effects were recorded, but very few patients left a trial as a direct result. The meta-analyses of the numbers suffering adverse effects, and of the numbers of withdrawals before the end of the trial show no difference between control and selegiline.

Authors' conclusions:

Despite its initial promise, i.e. the potential neuroprotective properties, and its role in the treatment of Parkinson's disease sufferers, selegiline for Alzheimer's disease has proved disappointing. Although there is no evidence of a significant adverse event profile, there is also no evidence of a clinically meaningful benefit for Alzheimer's disease sufferers. This is true irrespective of the outcome measure evaluated, i.e. cognition, emotional state, activities of daily living, and global assessment, whether in the short, or longer term (up to 69 weeks), where this has been assessed. There would seem to be no justification, therefore, to use it in the treatment of people with Alzheimer's disease, nor for any further studies of its efficacy in Alzheimer's disease.

This record should be cited as:

Birks J, Flicker L. Selegiline for Alzheimer's disease. Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD000442. DOI: 10.1002/14651858.CD000442

Assessed as up to date:

April 28, 2008

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Primary Review Group:

Dementia and Cognitive Improvement Group

Health topics:

Mental health > Dementia & cognition > Interventions aimed at interrupting disease processes

Neurology > Dementia & cognition > Interventions aimed at interrupting disease processes

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

No evidence of benefit of selegiline for Alzheimer's disease

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