Donepezil, rivastigmine, galantamine and memantine for ...

Comparison:
Outcome:
Study
05 Donepezil: CIBIC change from baseline
02 Donepezil 10 mg
Treatment
n
Mean
(SD)
Control
n
01 at 24 weeks
Rogers 1998a don
Subtotal (95% CI)
Test for heterogeneity 2 149 4.07 (0.90) 152
149
152
= 0.00, df = 0, p = 1
Test for overall effect z = 4.01, p = 0.00006
02 at 12 weeks
Rogers 1998b don
Subtotal (95% CI)
Test for heterogeneity 2 155 3.80 (1.00) 150
155
150
= 0.00, df = 0, p = 1
Test for overall effect z = 3.67, p = 0.0002
demonstrated a statistically significant
difference, 41 whereas the other demonstrated no
statistically significant difference. 54 The
proportion showing clinical improvement in the
studies using the conventional cut-off ≤ 3 ranged
from 21 to 32% in the 5 mg donepezil groups, 25
to 38% in the 10 mg donepezil groups and 11 to
24% in the placebo groups. One study 53 reporting
treatment success (scores 1–4) demonstrated a 90%
success rate in their 5 mg donepezil treatment
group compared with an 80% success rate in the
placebo group. The remaining study 41 reporting
treatment success as scores 1–4 demonstrated a
70% success rate in their 10 mg donepezil-treated
group compared with a 47% success rate in the
placebo group. All but two of these studies were of
24 weeks’ duration; the study of Rogers and
colleagues 52,53 were of 12 weeks’ duration.
Three studies provided data for 5 mg/day
donepezil compared with placebo that allowed
them to be combined in a meta-analysis (Figure 7).
Pooling the data using a fixed-effect model
showed an overall improvement in CIBIC-plus
responders with donepezil compared with placebo
[odds ratio (OR) 2.83 (95% CI: 2.04 to 3.93)].
Heterogeneity was not statistically significant,
p = 0.35. No difference was noted using a
random-effects model.
Two studies provided data for 10 mg/day
donepezil compared with placebo that allowed
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Health Technology Assessment 2006; Vol. 10: No. 1
4.51 (1.00) 49.7
49.7
4.20 (0.90) 50.3
50.3
–0.44 (–0.65 to –0.23)
–0.44 (–0.65 to –0.23)
–0.40 (–0.61 to –0.19)
–0.40 (–0.61 to –0.19)
Total (95% CI)
Test for heterogeneity 2 304 302 100.0 –0.42 (–0.57 to –0.27)
= 0.07, df = 1, p = 0.8
Test for overall effect z = 5.44, p < 0.00001
FIGURE 6 CIBIC-plus change from baseline with donepezil 10 mg
Mean
(SD)
WMD
(95% CI fixed)
Weight
%
–10 –5 0 5 10
Favours treatment Favours control
WMD
(95% CI fixed)
them to be combined in a meta-analysis (Figure 8).
Pooling the data using a fixed-effect model
showed an overall improvement in CIBIC-plus
responders with donepezil compared with placebo
[OR 2.72 (95% CI: 1.82 to 4.08)]. Heterogeneity
was not statistically significant, p = 0.88. No
difference was noted using a random-effects
model.
CDR-SB
Five trials included the CDR-SB and the results are
given in Table 9. On the CDR-SB a negative score
indicates clinical improvement.
One trial was a two-arm comparison, three were
three-arm trials and one was a four-arm trial.
Changes from baseline scores for each individual
trial can be seen in Table 9. The summary that
follows will predominantly discuss comparisons
between 5 mg donepezil and placebo and between
10 mg donepezil and placebo, regardless of the
number of arms in the individual trial.
Donepezil 5 mg/day versus placebo. Four trials
included an intervention group with a daily dose
of 5 mg donepezil. The mean change from
baseline CDR-SB score was between –0.11 and
0.06 for the donepezil group and between –0.14
and 0.75 for the placebo groups. Overall changes
from baseline were small, which is likely to be
related to the scoring of the scale. The differences
between donepezil and placebo groups were
27