Donepezil, rivastigmine, galantamine and memantine for ...

TABLE 41 CIBIC-plus for memantine
group. At the endpoint, there was statistically
significantly less deterioration in the memantine
group than in the placebo group.
In the study by Tariot and colleagues, 71 analyses
using the LOCF approach showed a statistically
significant benefit of memantine versus treatment
with placebo. The mean change from baseline was
–2.0 for the memantine group and –3.4 in the
placebo group.
Both studies, therefore, showed less deterioration
in the memantine group than the placebo group,
although this was more evident in the Tariot and
colleagues study. 71 This variation may be
explained by the combined use of donepezil and
memantine by participants in this study. 71
Summary: less deterioration in functional outcome was
apparent in the memantine group compared with placebo
as measured by the ADCS/ADL.
Global outcomes
CIBIC-plus
Both studies report the CIBIC-plus as a test for
global outcomes and can be seen in Table 41. One
reported it as a primary outcome 72 and the other
as a secondary outcome. 71 The CIBIC-plus uses a
seven-point Likert-type scale ranging from 1
(= marked improvement) to 7 (= marked
worsening).
The mean change from baseline ranged from
4.41 71 to 4.5 72 in the memantine groups and from
4.66 71 to 4.8 72 in the placebo group. Scores
therefore were similar and the two studies
reported statistically significant improvement in
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Health Technology Assessment 2006; Vol. 10: No. 1
Reisberg et al. 72 Mean ± SD (n) change from baseline
Memantine 20 mg/day (n = 118) Placebo (n = 118) p-Value vs placebo
4.5 ± 1.12 4.8 ± 1.09 0.06
Tariot et al. 71 Mean (SE) change from baseline
Memantine 20 mg/day (n = 198) Placebo (n = 196) p-Value vs placebo
4.41 (0.074) 4.66 (0.075) 0.03
Distribution (% of participants) of CIBIC-plus ratings at endpoint
Memantine 20 mg/day (n = 198) Placebo (n = 196) p-Value vs placebo
1 = marked improvement 1% 1 = marked improvement 0%
p = 0.03 for the
2 = moderate improvement 4% 2 = moderate improvement 2%
comparison between the
3 = minimal improvement 8% 3 = minimal improvement 10%
distribution of values for
4 = no change 4% 4 = no change 33%
the memantine and
5 = minimal worsening 31% 5 = minimal worsening 32%
placebo groups
6 = moderate worsening 14% 6 = moderate worsening 20%
7 = marked worsening 1% 7 = marked worsening 3%
global measures using CIBIC-plus. In the study by
Reisberg and colleagues, the CIBIC-ratings at the
endpoint (mean difference between the groups
0.3l; p = 0.06) supported the effectiveness of
memantine.
The study by Tariot and colleagues 71 showed that
the mean CIBIC-plus score was statistically
significantly better for the memantine group
versus the placebo group using LOCF.
Furthermore, 55% of the memantine group was
rated as improved or unchanged versus 45% of
the placebo group at endpoint.
Summary: memantine appears to be more effective
than placebo in improving global function using the
CIBIC-plus.
Cognitive outcomes
SIB
The SIB is a test developed for the evaluation of
cognitive dysfunction in participants with more
severe AD. It assesses social interaction, memory,
language, visuo-spatial ability, attention, praxis
and construction. The SIB scores range from 0 to
100, with higher scores reflecting higher levels of
cognitive ability. Both studies report data using
the SIB, with one using it as a primary outcome 71
and the other as a secondary outcome. 72 Results
are shown in Table 42.
Statistically significant improvements were reported
in the SIB. The mean change from baseline scores
ranged from –4.0 to 0.9 in the memantine groups
and between –10.1 and –2.5 in the placebo groups.
In the Reisberg and colleagues study, 72 the SIB
showed statistically significant differences favouring
73