Donepezil, rivastigmine, galantamine and memantine for ...

● Rates of mild to moderate adverse events were
shown to be higher in the galantamine group
compared with the donepezil group; however,
rates of serious adverse events appeared to be
higher in the donepezil group. Higher
proportions of participants withdrew owing to
adverse events in the galantamine group than
the donepezil group.
Memantine
Quantity and quality of research
Two RCTs met the inclusion criteria for the review.
Details of the study characteristics are summarised
in Table 38 with further details in Appendix 11.
Both studies report data on participants with
moderately severe to severe AD, as measured by
the MMSE, although the range on the MMSE
score varies slightly between them, as can be seen
in Table 38.
TABLE 38 Characteristics of included studies for memantine
© Queen’s Printer and Controller of HMSO 2006. All rights reserved.
Health Technology Assessment 2006; Vol. 10: No. 1
Both studies compared one dose of memantine
(20 mg/day) versus placebo. In one study 71
treatment was titrated in 5-mg weekly increments
from a starting dose of 5 mg/day to the target of
20 mg/day at the beginning of week 4. All
participants receiving memantine were required to
receive the target dose of 20 mg/day by the end of
week 8, or else they were disenrolled. Both trials
were multicentred with sample size ranging from
252 72 to 404. 71 The sample size required was
calculated in just one of the studies. 71 The
duration of treatment was 24 weeks in one study 71
and 28 weeks in the other. 72 One major difference
exists between the two studies regarding drug
treatments. The participants in the study by Tariot
and colleagues 71 were included on the basis that
they had already been receiving donepezil for
more than 6 months before entrance into the trial
and at a stable dose (5–10 mg/day) for at least
3 months. These participants maintained stable
donepezil therapy at the entry dose as prescribed
Study Methods Participants Outcomes
Reisberg et al.,
2003 72
Tariot et al.,
2004 71
Design: RCT, multicentre, placebo
controlled, double-blind, parallel
group
Interventions:
1. Memantine 20 mg/day
2. Placebo
Number of centres: 32
Duration of treatment: 28 weeks
(mean ± SD duration of treatment
for both groups 24 ± 8 weeks)
Sponsor: Merz Pharmaceuticals
(Frankfurt, Germany) and National
Institute on Aging of the National
Institutes of Health
Design: RCT, multicentre, placebo
controlled, double-blind
Interventions:
1. Memantine 20 mg/day
2. Placebo
Number of centres: 37
Duration of treatment: 24 weeks
Sponsor: Forest Research Institute
(a division of Forest Laboratories)
Inclusion criteria: ≥ 50 years old;
probable AD (DSM-IV and
NINCDS-ADRDA); MMSE 3–14,
GDS stage 5 or 6, FAST stage
≥ 6a
Numbers: 252 randomised:
1. 126 to memantine 20 mg/day
2. 126 to placebo
Mean age: 76.1 ± 8.07
Inclusion criteria: probable AD
(NINCDS-ADRDA);
MMSE 5–14; ≥ 50 years; ongoing
cholinesterase inhibitor therapy
with donepezil 6 months before
study entrance and at steady dose
(5–10 mg/day) for at least
3 months
Numbers: 404 randomised:
1. 203 to memantine 20 mg/day
(reduced to 202 as 1 withdrew
consent before receiving
treatment)
2. 201 to placebo
Mean age:
1. 75.5 (8.45)
2. 75.5 (8.73)
Primary outcomes:
● CIBIC-plus
● ADCS/ADLsev
Secondary outcomes:
● SIB
● MMSE
● GDS
● FAST
● NPI
● Resource Utilisation in
Dementia instrument
● Adverse events
Primary outcomes:
● SIB
● ADCS/ADL
Secondary outcomes:
● CIBIC-plus
● NPI
● BGP
● Adverse effects
71