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Effectiveness of Donepezil Therapy in Advanced Alzheimer’s Disease
Dementia [DAD], both instrumental and basic activities of daily Figure 3: Japanese Study
living (ADL) measures) and behaviour (NPI) compared with patients
In addition to the specific treatment effects for the patients, the
MSAD study further looked at the effect of treatment on carer
Carers completed a diary throughout the study recording
time spent caring and were assessed using a Caregiver Stress Scale.
At baseline, carer stress and time spent caring were similar between -2
the treatment groups. The level of decline in patients in both
instrumental and basic ADLs was significantly slower with donepezil
Mean SIB change from baseline
treatment compared with placebo in this study. After 24 weeks of
treatment, the overall carer ratings were significantly better for
Week 8 Week 16 Week 24 -FAS-LOCF
carers of donepezil-treated patients than for those caring
Placebo Donepezil 5mg/d Donepezil 10mg/d
for placebo patients. Carers of placebo patients spent almost one
hour more each day providing care than the carers of those
receiving donepezil. Therefore, treatment may also provide benefits B
to those caring for patients with severe AD.
In all four of these studies treatment with donepezil had a
consistently significant and positive effect on cognition. Where
global function was measured with the CIBIC-plus, again results
were positive in favour of donepezil. With the ADCS-ADL-sev, the
results were mixed, with a positive result from the Swedish study
and no significant difference from the multinational and Japanese
studies. MSAD measured function with DAD and, again, the result
was positive in favour of donepezil. Positive effects on measures of 0 10 20 30 40 50
behaviour were seen in MSAD trial, and there were trends for
possible effects in both the Swedish and multinational studies.
Placebo Donepezil 5mg/d Donepezil 10mg/d
These studies also showed that donepezil is safe and well tolerated
Effect of donepezil treatment on (A) Severe Impairment Battery (SIB) scores (data represent
in the severe AD population.
The safety and tolerability data
change from baseline at each time point using observed cases at weeks eight, 16 and 24,
from patients receiving donepezil in the cited studies were similar
and the full analysis set–last observation carried forward [FAS–LOCF] population at
end-point; error bars represent standard error of the mean; *p<0.001 versus placebo) and (B)
to those in patients receiving placebo and did not differ
Clinician’s Interview-Based Impression of Change-plus care-giver interview (CIBIC-plus)
substantially from data obtained in patients with mild to moderate
scores (three-category collapsed analysis) at end-point (FAS-LOCF); overall p=0.001 for
donepezil 10mg/day versus placebo.
AD. Side effects were typical of ChEI therapy (diarrhoea and
hallucinations), and were primarily transient and mild to moderate has found the combination therapy to be a cost-effective
in severity. therapy option.
Donepezil and Memantine in Combination Conclusions
The N-methyl-D-aspartate (NMDA) receptor antagonist memantine Studies of patients with severe AD have shown that, far from being a
is currently licensed for the treatment of MSAD. A number of stage at which all hope is lost, there are tangible benefits of treatment
published studies have shown that combination therapy to patients and carers. The initiation of treatment at the severe stage
(memantine plus donepezil) can be useful, particularly in the of the disease is worthwhile, and treatment that has shown benefits
advanced stages of the disease, with few additional tolerability seen throughout the course of the disease should be continued.
Guidelines advocate the treatment of patients with Donepezil has strong efficacy data in AD from the mild to the severe
severe AD (MMSE score <10) with memantine in combination stage
and has been shown to be effective for treating all
with a ChEI as required,
and a pharmacoeconomic evaluation domains of AD.
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