Donepezil, rivastigmine, galantamine and memantine for ...

Carer mental health and burden
One study measured the psychological well-being
of the principal caregiver, as measured by the
General Health Questionnaire 30 (GHQ-30). At
week 60 the change from baseline score for those
caring for people given donepezil (n = 151) was
–0.5 and in those caring for people given placebo
(n = 153) was similarly –0.5. These are estimated
figures.
[Commercial/academic confidential information
relating to Seltzer and colleagues 55 removed]
Summary: QoL results show varied results, but this may
be related to the measures used and the small number of
studies that examined QoL.
Behaviour and mood
The Neuropsychiatric Inventory (NPI) was
reported in four trials. 41,43,48,49 The NPI assesses
neuropsychiatric disturbances with a 12-item scale
based on information from the caregiver. The total
score ranges from 0 to 144; on the NPI a negative
score indicates clinical improvement. One trial 48
did not report full results on this outcome; the
treatment difference between those given 10 mg
donepezil compared with those given placebo,
after 12 weeks, was 3.16. This difference was
reported to be statistically significant at p < 0.05.
The mean change from baseline score at 24 weeks
of 10 mg donepezil in another trial 41 was –5.0 and
for placebo 0.92. This difference was statistically
significant, p < 0.01, suggesting improved
behaviour and mood. The trial also reports that
individual NPI item analysis at week 24 showed
benefit with donepezil compared with placebo on
all 12 items of the NPI, with statistically significant
differences for delusions (p = 0.0073), apathy
(p = 0.0131) and aberrant motor behaviour
(p = 0.0232). In another trial, 43 results at 60 weeks
showed an NPI change from baseline score of –3
in the 5/10 mg donepezil treatment group
(n = 149) compared with –4 in the placebo group
(n = 150). The study reports that these differences
are not statistically significant. Data have been
estimated from figures. One final trial 49
demonstrated a mean change on the NPI from
randomisation (after 12 weeks of open-label
donepezil) at 24 weeks of –2.9 (SEM 1.6) in the
10 mg donepezil group and 3.3 (SEM 2.1) in the
placebo groups. This was statistically significant at
p = 0.02. This study also reports data on the
Neuropsychiatric Inventory, Distress subscale
(NPI-D). Scores at randomisation point at week 12
compared with week 24 also showed improvement
(a decrease on the scale) in those treated with
10 mg donepezil compared with those treated with
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Health Technology Assessment 2006; Vol. 10: No. 1
placebo [–1.7 (SEM 0.7) vs 1.1 (SEM 1.1) in the
two groups, respectively]. Full details can be found
in Appendix 7.
Summary: better behaviour and mood, as assessed by the
NPI, are found in participants treated with donepezil
than placebo over short to medium durations of followup.
Over longer periods this difference may be reduced.
Compliance
Compliance was reported to be assessed in four of
the 12 published studies. Only one study
presented data relating to each study group rather
than the total population. In this study, Winblad
and colleagues 47 demonstrated a mean overall rate
of compliance for the donepezil group of 94.6%
and for the placebo group 94.9%. Greenberg and
colleagues 54 assessed compliance with dosing by
interview of caregivers and pill counts. Based on
pills returned, compliance was estimated to be
95.7% for the population evaluated. Homma and
colleagues 44 measured compliance by recovery of
residual drug from the caregiver on hospital visits
every 4 weeks and determining actual number of
tablets taken using caregivers’ diaries. They note
that 98% of the population evaluated reached the
specified compliance rate for the efficacy analysis.
Rogers and colleagues 52 also measured compliance
by counting returned tablets, but no data were
presented in the publication as to the rate of
compliance.
Compliance was also reported in one unpublished
trial. 55 The proportion was calculated by dividing
the number of doses by the number of treatment
days. In the 10 mg donepezil group the
proportion complying was 87.8% (SD 20.3%) and
in the placebo group 93.3% (SD 13.6%).
[Commercial/academic confidential information
removed]
Adverse events
Adverse events are especially important in trials
because:
● Any evidence of significant adverse events
should be taken into account when assessing
outcomes relating to treatment response. If
treatment response is shown to be beneficial but
there are significant adverse events, then the
overall benefit would need to be weighed
against these occurrences.
● In many cases adverse events are short-lived
and not particularly severe. Rare events, which
may be more severe, may not be detected in
clinical trials with a short duration of treatment.
However, all adverse events are recorded in
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