Donepezil, rivastigmine, galantamine and memantine for ...

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Clinical effectiveness
TABLE 3 Characteristics of included studies for donepezil
Study Methods Participants Outcomes
AD2000, 2004 43 Design: RCT, double-blind
multicentre
Interventions:
1. 5 or 10 mg/day donepezil
2. Placebo
Number of centres: 22
Duration of treatment: until judged
appropriate to stop, 60 weeks mainly
reported here as large dropout rate
after this time
Sponsor: NHS research funding
Burns et al.,
1999 50
Gauthier et al.,
2002 41
Greenberg et al.,
2000 54
Design: RCT, double-blind
multicentre
Interventions:
1. 5 mg/day donepezil
2. 10 mg/day donepezil (5 mg/day
for the first 7 days, then
10 mg/day for remainder)
3. Placebo
Number of centres: 82
Duration of treatment: 24 weeks
Sponsor: Eisai (USA) and Eisai (Japan)
Design: substudy of moderate
patients in Feldman 42 multicentre,
double-blind RCT
Interventions:
1. donepezil 5 mg/day for 28 days
(single dosage) followed by an
increase to 10 mg/day
2. placebo
Number of centres: 3
Duration of treatment: 24 weeks
Sponsor: Pfizer and Eisai
Design: two-centre, randomised,
placebo-controlled, double-blind,
crossover study
Interventions:
1. placebo followed by donepezil
5 mg/day
2. donepezil 5 mg/day followed by
placebo
Number of centres: 2
Duration of treatment: 24 weeks,
6 weeks of run-in followed by
18 weeks of treatment, washout and
a second treatment period.
Sponsor: National Institute of Aging
(through Massachusetts Alzheimer’s
Disease Research Center);
Massachusetts General Hospital;
Mallinckrodt General Clinical
Research Center
Inclusion criteria: AD diagnosed by
DSM-IV where there was
uncertainty about the benefits of
medication; MMSE 10–26 (1 had
MMSE 27 in donepezil group);
all were in a 12-week randomised
run-in period prior to
randomisation
Numbers: 486 randomised
1. 242 to donepezil
2. 244 to placebo
Median age (range):
1. 76 (54–93)
2. 75 (46–90)
Inclusion criteria: aged ≥ 50 years;
probable AD (DSM-III-R and
NINCDS-ADRDA); MMSE 10–26;
CDR 1 or 2
Numbers:
1. 271 to 5 mg/day
2. 273 to 10 mg/day
3. 274 to placebo
Mean age ± SE (range):
1. 72 ± 0.5 (51–91)
2. 72 ± 0.5 (53–93)
3. 71 ± 0.5 (50–90)
Inclusion criteria: subanalysis
patients met criteria for AD and
had MMSE scores of 10–17
Numbers:
1. 102 to donepezil
2. 105 to placebo
Mean age (range):
1. 74.3 (52–92)
2. 74.3 (48–90)
Inclusion criteria: diagnosis of
probable AD. Ability to undergo
cognitive testing (defined as an
information–memory–
concentration subscale score of
≤ 20) indicating mild to moderate
dementia.
Numbers: 60 randomised to a
crossover sequence, 30 in group
1 and 30 in group 2
Mean age ± SD:
1. 74.9 ± 10.1
2. 75.1 ± 9.0
Total 75.0 ± 9.5
Primary outcomes:
● Entry to institutional care
● Progression of disability
Secondary outcomes:
● BADLS
● MMSE
● NPI
● Carers’ GHQ
● Adverse events
Primary outcomes:
● ADAS-cog
● CIBIC-plus
Secondary outcomes:
● CDR-SB
● IDDD
● Patient-rated QoL
● Adverse events
Primary outcomes:
● CIBIC-plus
Secondary outcomes:
● sMMSE
● Severe Impairment Battery
(SIB)
● DAD
● IADL+
● Physical Self-maintenance
Scale (PSMS+)
● NPI
● Adverse events
Primary outcomes:
● ADAS-cog
Secondary outcomes:
● Explicit verbal recall
(assessed by NYU Stories
Test, delayed recognition
subscale)
● Verbal fluency
● Caregiver-rated global
impression of change
● Compliance
● Adverse events
continued