Donepezil, rivastigmine, galantamine and memantine for ...

TABLE 32 Withdrawals due to adverse events for galantamine
[Commercial/academic confidential information removed]
Raskind et al. 61
were higher among galantamine participants
[range: 6% (8 mg/day)–44% (36 mg/day)] than
placebo (range 5–9%) (see Table 32).
Three trials 61,63,64 demonstrated differential
dropout rates between groups for reasons other
than adverse events. However, the pattern of the
proportion withdrawing was not consistent; in two
included trials the dropout rate was greater in the
treatment arms but in another study dropout rate
was greater in the placebo arm. In three published
trials [commercial/academic confidential
information removed] there appeared to be no
difference between groups. No statistical analyses
were undertaken by the trials. Very few deaths
were reported in any of the included studies. Data
relating to withdrawals and deaths for the
individual trials can be found in Appendix 9.
Summary
● Six published multicentre placebo-controlled
RCTs assessing doses ranging from 8 to
36 mg/day of galantamine over durations of
3–6 months met the inclusion criteria for the
systematic review. The methodological quality
and the quality of reporting in the studies were
variable. Of the six RCTs, three appeared to
limit selection bias, 62,64,65 three provided
adequate information to reduce the likelihood
of measurement bias 61,63,65 and one appeared to
guard against the effects of attrition bias. 64 Five
RCTs reported that they were sponsored by the
manufacturers.
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Health Technology Assessment 2006; Vol. 10: No. 1
Galantamine 24 mg/day (n = 212) Galantamine 32 mg/day (n = 211) Placebo (n = 213)
49/212 (23%) 67/211 (32%) 16/213 (8%)
Wilcock et al. 64
Galantamine 24 mg/day (n = 220) Galantamine 32 mg/day (n = 218) Placebo (n = 215)
31/220 (14%) 48/218 (22%) 19/215 (9%)
Tariot et al. 63
Galantamine Galantamine Galantamine Placebo (n = 286)
8 mg/day (n = 140) 16 mg/day (n = 279) 24 mg/day (n = 273)
9 19 27 20
Wilkinson and Murray65 Galantamine Galantamine Galantamine Placebo (n = 87)
18 mg/day (n = 88) 24 mg/day (n = 56) 36 mg/day (n = 54)
19 (21.6%) 10 (17.9%) 24 (44.4%) 8 (9.2%)
● [Commercial/academic confidential
information removed]
● Six published RCTs showed that galantamine
appears to confer a statistically significant
benefit to participants on the ADAS-cog scale
when compared with placebo, whether reducing
the deterioration or leading to some
improvement in their condition. The benefit
varies depending on the dose of galantamine.
The galantamine–placebo differences in ADAScog
for 8 mg/day was 1.3 points, 16 mg/day
3.1 points, 18 mg/day 1.7 points, 16 or
24 mg/day 2.5 to 2.8 points, 24–32 mg/day
1.7–3.4 points and 36 mg/day 2.3 points.
[Commercial/academic confidential
information removed] In addition, 14–17%
more of galantamine participants were classified
as responders (improving by ≥ 4 points on the
ADAS-cog) than those on placebo.
● Five published [commercial/academic
confidential information removed] RCTs
assessed the effect of galantamine compared
with placebo on the CIBIC-plus, individually
showing that higher proportions of participants
receiving galantamine experience improvement
in their condition compared with those on
placebo (0–6.5% more participants). In contrast,
a higher proportion of placebo participants
tend to deteriorate (4–18% more participants).
Also, a higher proportion of galantamine
compared with placebo participants were
considered to be responders to treatment with
differences of between 4% (8 mg/day) and 17%
65