Donepezil, rivastigmine, galantamine and memantine for ...

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Evidence from systematic reviews
improvement was also demonstrated on the PDS
in the rivastigmine group compared with the
placebo groups. Benefits on a global measure, the
CIBIC-plus, were also shown in the meta-analysis.
Wolfson and colleagues 74,78
This review did not include mild to moderate
severity as an inclusion criterion. However, all
studies reviewed included participants with mild to
moderately severe AD and so it is presented here.
This review also reports data for a number of
other drugs including donepezil (see above),
metrifonate and Ginkgo Biloba; however, the last
two do not meet the inclusion criteria of the
present review and are not discussed here.
Two studies were included in the review for
rivastigmine, both of which are included in the
present review. The review reports that the
disparate methods of reporting within the
included trials made it difficult to compare the
magnitude of the results. However, the in-depth
review revealed a moderate benefit on both
cognition and global clinical status from high-dose
treatment with rivastigmine.
Livingstone and Katona 75
Although the review did not include mild to
moderate severity as an inclusion criterion, all
studies reviewed included participants with mild to
moderately severe AD and so it is presented here
to provide a comparison for the results of the
current review. This review also report trials on
donepezil (above), tacrine and huperzine-A, the
last two of which were not included in the present
review. Three studies on rivastigmine met the
inclusion criteria of the review and were also
included in the present review. The review
presents an NNT analysis and concludes that
higher doses of rivastigmine (6–12 mg) are
associated with lower NNTs.
Galantamine
One systematic review met the inclusion criteria
for this review. 79 Although the review did not
include mild to moderate severity as an inclusion
criterion, all studies reviewed included
participants with mild to moderately severe AD
and so it is presented here. Seven studies were
included in the review, of which six provided
sufficient outcome data for analysis. The
remaining study was published as an abstract, and
did not meet the inclusion criteria for the present
review. Meta-analyses were carried out and a
summary of results is given here to provide a
comparison for the results of the present review.
Overall, galantamine showed statistically
significant treatment effects at daily doses of
16–32 mg/day for trials of 3–6 months’ duration.
All six included trials provided global ratings.
Trials of 3 months’ duration with doses of 24–32
and 36 mg/day were statistically significant in
favour of treatment. For trials of 6 months’
duration the pattern was the same except with
doses of 8 mg/day. Five trials report cognitive
function as measured by the ADAS-cog and all
daily doses gave statistically significant results at
6 months with the effect size increasing with dose.
Results also favoured galantamine on the DAD
scale, although only two trials reported this
outcome.
Memantine
One systematic review was identified on
memantine for dementia. 80 However, it did not
meet our inclusion criteria as it consisted of any
type of dementia, and not predominantly AD.
However, the review does report separately the
results for the effect of memantine in participants
with moderately severe to severe AD, where only
one study, namely that by Reisberg and
colleagues, 72 is included.
The review reports that analysis of change from
baseline at 28 weeks gave statistically significant
results in favour of memantine for 20 mg/day on
cognition (6.1, 95% CI: 2.99 to 9.21, p = 0.0001),
activities of daily living (2.10, 95% CI: 0.46 to
3.74, p = 0.01) and in the global clinical
impression of change measured by the CIBIC-plus
at 28 weeks (0.30, 95% CI: –0.58 to –0.02,
p = 0.04). In all cases the analysis was an ITT
LOCF population. There were no statistically
significant differences between memantine and
placebo for the number of dropouts and total
number of adverse events, but a statistically
significant difference in favour of memantine for
the number who suffer agitation. The authors
conclude that there is a beneficial effect of
memantine (20 mg/day) for participants with
moderately severe to severe AD on cognition and
functional decline but not in the clinical
impression of change.