Donepezil, rivastigmine, galantamine and memantine for ...

26
Clinical effectiveness
Comparison:
Outcome:
Study
05 Donepezil: CIBIC change from baseline
01 Donepezil 5 mg
Treatment
n
Mean
(SD)
Control
n
01 at 24 weeks
Rogers 1998a don
Subtotal (95% CI)
Test for heterogeneity 2 149 4.15 (1.10) 152
149
152
= 0.0, df = 0
Test for overall effect z = 2.97, p = 0.003
02 at 12 weeks
Rogers 1998b don
Subtotal (95% CI)
Test for heterogeneity 2 156 3.90 (1.00) 150
156
150
= 0.0, df = 0
Test for overall effect z = 2.76, p = 0.006
of 5 mg donepezil; however, only those reporting
the CIBIC-plus (three trials 50–52 ) report data in
terms of mean change from baseline. Data on the
CGIC were reported in terms of proportions
responding and are discussed below. The mean
change from baseline CIBIC-plus score was
between 3.9 and 4.23 for the donepezil group and
between 4.2 and 4.52 for the placebo groups.
Despite variations between the study sample sizes,
the quality of the studies and the length of
duration of the studies, there is little variation in
the scores between studies. This is likely to reflect
the nature of the measure, which is nonparametric,
of a non-interval nature and has just
seven items on the scale. Overall, all three studies
found that CIBIC-plus scores were statistically
significantly lower (better) with 5 mg/day
donepezil than placebo.
Two of the three studies provided data (mean
change and SD) that allowed them to be combined
in a meta-analysis (Figure 5). Pooling the data
using a fixed-effect model showed an overall
improvement in CIBIC-plus with 5 mg/day
donepezil compared with placebo [WMD –0.33
(95% CI: –0.49 to –0.17)]. Heterogeneity was not
significant, p = 0.71. No difference was noted
using a random-effects model.
Donepezil 10 mg/day versus placebo. Four trials
included an intervention group with a daily dose
of 10 mg donepezil. The mean change from
4.51 (1.00) 44.6
44.6
4.20 (0.90) 55.4
55.4
–0.36 (–0.60 to –0.12)
–0.36 (–0.60 to –0.12)
–0.30 (–0.51 to –0.09)
–0.30 (–0.51 to –0.09)
Total (95% CI)
Test for heterogeneity 2 305 302 100.0 –0.33 (–0.49 to –0.17)
= 0.14, df = 1, p = 0.71
Test for overall effect z = 4.04, p = 0.00005
FIGURE 5 CIBIC-plus change from baseline with donepezil 5 mg
Mean
(SD)
WMD
(95% CI fixed)
Weight
%
–10 –5 0 5 10
Favours treatment Favours control
WMD
(95% CI fixed)
baseline CIBIC-plus score was between 3.8 and
4.13 for the donepezil group and between 4.2 and
4.52 for the placebo groups. Overall all four
studies found that CIBIC-plus scores were
statistically significantly lower (better) with
10 mg/day donepezil than placebo.
Two of the four trials provided data (mean change
and SD) that allowed them to be combined in a
meta-analysis (Figure 6). Pooling the data using a
fixed-effect model showed an overall improvement
in CIBIC-plus with 5 mg/day donepezil compared
with placebo [WMD –0.42 (95% CI: –0.57 to
–0.27)]. Heterogeneity was not statistically
significant, p = 0.8. No difference was noted using
a random-effects model.
CIBIC-plus/CGIC responders
Seven included trials report data on global
‘responders’, demonstrating clinical improvement
on the CIBIC-plus/CGIC. Three trials reporting
the CIBIC-plus and one reporting the CGIC
classify responders as those with scores of
≤ 3. 44,50–52 One trial reporting the CGIC 53 and one
trial reporting the CIBIC-plus rate treatment
success as scores 1–4 (which includes no change), 41
whereas one other does not report the definition
used. 54 Regardless of the definition used, in each
trial the proportion of responders was higher in
the treatment groups than the placebo groups, but
these differences were not tested for statistical
significance, except in two trials. 41,54 One of these