Donepezil, rivastigmine, galantamine and memantine for ...

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Clinical effectiveness
donepezil group and 24.3 (SEM 0.18) in the
placebo group. Those in the 10 mg donepezil
group (n = 91) demonstrated a mean change in
MMSE of 1.4 (SEM 0.33) and those in the placebo
group (n = 55) a mean change in MMSE of 0.1
(SEM 0.41). The study demonstrated a statistically
significant difference, p = 0.002.
SIB
One included trial 41 reports data on the Severe
Impairment Battery (SIB), which is a measure of
cognition where positive scores indicate clinical
improvement. In this 24-week trial cognition was
demonstrated to be improved compared with
baseline: the mean change from baseline was 1.4
in those treated with 10 mg donepezil and –3.0 in
those treated with placebo. This difference (4.4
points) was statistically significant at p < 0.01.
Computerised Memory Battery
One unpublished 24-week trial 55 reports on the
Computerised Memory Battery (CMB), which is
designed to simulate critical cognitive tasks of
everyday life. No details of the properties of this
scale were presented; however, from the results it
can be inferred that a positive score relates to
improvement. [Commercial/academic
TABLE 7 CGIC for donepezil
confidential information removed] CMB facial
recognition showed a mean change of 0.8 (SEM
0.64) and –1.6 (SEM 0.75) in the donepezil and
placebo groups, respectively, p = 0.007. The
methods in the report also suggest that other
components were tested (name–face association
total acquisition, house/object placement task
(total and first), telephone number recall, 10 and
seven digits), but data for these are not
presented.
Summary: treatment with donepezil appears to confer an
improvement on measures of cognition when compared
with placebo and this effect is mirrored in the metaanalysis.
Global outcomes
CIBIC-plus/CGIC
Four RCTs report the Clinician’s Interviews-based
Impression of Change-plus (CIBIC-plus) 41,50–52
and three trials report the Clinical Global
Impression of Change (CGIC) 44,53,54 (Homma and
colleagues 44 use a Japanese version) and can be
seen in Tables 7 and 8. The CIBIC-plus/CGIC use
a seven-point Likert-type scale where 1 = marked
improvement, 4 = no change and 7 = marked
worsening.
Homma et al., 200044 JCGIC
Donepezil 5 mg/day (n = 134)
(1 unassessable)
Placebo (n = 129) (1 unassessable) p-Value versus placebo
Improvement rates (% slightly improved or Improvement rates (% slightly improved or
better): 52% better): 22%
Aggravation rates (% slightly aggravated or Aggravation rates (% slightly aggravated or
worse): 17% worse): 43%
N, (%) change: N, (%) change:
Markedly improved: 1 (1) Markedly improved: 2 (2)
Improved: 21 (16) Improved: 13 (10)
Slightly improved: 42 (31) Slightly improved: 10 (8) p = 0.001
No change: 44 (33) No change: 49 (38)
Slightly aggravated: 19 (14) Slightly aggravated: 22 (17)
Aggravated: 6 (4) Aggravated: 25 (19)
Markedly aggravated: 0 (0) Markedly aggravated: 1 (1)
Greenberg et al., 200054 No. (%)
Donepezil 5 mg/day Placebo p-Value versus placebo
Improved/total 12/51 (24) Improved/total 12/53 (23) p = 0.34
Worsened/total 14/51 (27) Worsened/total 19/53 (36)
Rogers et al., 199653 CGIC at endpoint [success (5–7)/failure (1–4)]
1. Donepezil 2. Donepezil 3. Donepezil 4. Placebo p-Value versus placebo
1 mg/day 3 mg/day 5 mg/day (n = 40)
(n = 42) (n = 40) (n = 39)
34 (82%)/7 (18%) 33 (83%)/7 (18%) 34 (90%)/4 (11%) 32 (80%)/8 (20%) 3. p = 0.039