People with mild, moderate or severe dementia due to Alzheimer's disease treated for periods of 12, 24 or 52 weeks with donepezil experienced benefits in cognitive function, activities of daily living and behaviour. Study clinicians rated global clinical state more positively in treated patients, and measured less decline in measures of global disease severity. There is some evidence that use of donepezil is neither more nor less expensive compared with placebo when assessing total health care resource costs. Benefits on the 10 mg/day dose were marginally larger than on the 5 mg/day dose. Taking into consideration the better tolerability of the 5 mg/day donepezil compared with the 10 mg/day dose, together with the lower cost, the lower dose may be the better option. The debate on whether donepezil is effective continues despite the evidence of efficacy from the clinical studies because the treatment effects are small and are not always apparent in practice.
Efficacy of donepezil on maintenance of activities of daily living in patients with moderate to severe Alzheimer's disease and the effect on caregiver burden.
This study investigated the efficacy of donepezil treatment on activities of daily living (ADLs) and social functioning in patients with moderate to severe Alzheimer's disease (AD) and the possible benefits of this treatment on caregiving time and stress levels.
                Randomized, double-blind, placebo-controlled, multinational study.
                Patients resided in the community or in assisted living facilities who did not require skilled 24-hour nursing care.
                Two hundred ninety patients with moderate to severe AD (baseline standardized Mini-Mental State Examination score of 5-17).
                Donepezil (5 mg/d for 4 weeks and 10 mg/d per clinician's judgment thereafter) or placebo for 24 weeks.
                ADLs were assessed using the Disability Assessment for Dementia (DAD), the modified instrumental activities of daily living (IADL) scale (IADL+), and the modified Physical Self Maintenance Scale (PSMS+). Caregiver time spent assisting patients with basic and instrumental ADLs was recorded as part of the IADL+ and PSMS+ scales. Patients' social behavior was evaluated through the use of a caregiver diary that captured observations of patients' motivation, interactions, and engagement. Caregivers were evaluated for their levels of caregiver stress with a modified, multiple-item Caregiver Stress Scale (CSS). For each outcome measure, the mean change from baseline at Week 24 using a last observation carried forward (LOCF) analysis was calculated.
                IADL+ and PSMS+ mean change from baseline scores for donepezil-treated patients showed a slower decline during the study than placebo-treated patients (Week 24 LOCF mean treatment differences: IADL+ = 6.83, P <.0001; PSMS+ = 1.32, P =.0015). Significant differences between the groups in favor of donepezil were observed on the DAD for instrumental and basic ADLs and on the three components required for the completion of each ADL: initiation, planning and organization, and effective performance. At baseline, caregivers of patients treated with donepezil (n = 141) did not differ significantly from caregivers of patients treated with placebo (n = 146) with respect to demographics or mean total scores on the CSS. At Week 24 LOCF, the overall distribution of caregiver ratings on each of the three caregiver diary items favored donepezil-treated patients over placebo-treated patients (P <.005). At Week 24 LOCF, mean change from baseline scores for CSS total and individual domain scores (all domains except caregiving competence, personal gain, and management of distress) were better for caregivers of donepezil-treated patients than for those of placebo-treated patients (CSS total, mean treatment difference = 1.82). Caregivers of donepezil-treated patients reported spending less time assisting with ADLs than caregivers of placebo-treated patients (mean difference = 52.4 min/d).
                Donepezil demonstrated a significantly slower decline than placebo in instrumental and basic ADLs in these patients with moderate to severe AD. The ADL benefits in AD patients treated with donepezil were associated with less caregiving time and lower levels of caregiver stress.