Donepezil in Alzheimer's disease: eighteen month results from Southampton Memory Clinic

Abstract

The objective of this study was to assess the efficacy of donepezil in patients with mild to moderate Alzheimer's disease (AD) in clinical practice. This was an open‐label study in which patients were referred to an elderly mental health clinic in Southampton, UK. Eighty patients with mild to moderate AD received 5 mg/day donepezil for the first 4 weeks, after which, if tolerated, the dose was increased to 10 mg/day. Efficacy and safety assessments were carried out every 3 months. Efficacy was assessed by the Alzheimer's Disease Assessment Scale‐cognitive subscale (ADAS‐cog), Mini‐Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Neuropsychiatric Inventory‐carer Distress Scale (NPI‐D). Mean improvements from baseline were observed at the 3‐month assessment on all four efficacy measures. At 3 months, 39% of patients showed an improvement of at least 4 points on the ADAS‐cog, and 37% of patients had improved by 4 points or more on the NPI. In those patients who showed improvement and were maintained on donepezil, improvements were sustained for 18 months on the MMSE and NPI, 15 months on the NPI‐D, and for 6 months on the ADAS‐cog. Six per cent of patients discontinued medication due to adverse events. In a typical clinical practice setting, patients with mild to moderate AD tolerated donepezil well. Clinically meaningful improvements in cognitive function and a reduction in neuropsychiatric symptoms were demonstrated in nearly 40% of patients with associated reduction in carer distress. Continued benefit was seen for up to 18 months in the selected group of patients who initially responded in treatment. Copyright © 2000 John Wiley & Sons, Ltd.

Effectiveness of treatment with donepezil hydrochloride and changes in regional cerebral blood flow in patients with Alzheimer's disease

“…The existence of donepezil responders and nonresponders has been noted for some time [18,19]. This study showed an increase in the total cerebral blood fl ow after 1 month of treatment in responders and a decrease in nonresponders.…”

Stroke, dementia, and drug delivery

“…Whilst a meta-analysis of donepezil concluded that the drug did produce modest benefits in cognition and a physicians' rated global clinical assessment [45], the review also concluded that there had been no improvements in patients' self-assessed quality of life and the practical importance of these changes remained unclear. In UK clinical practice openlabel prescription of donepezil to patients referred to a Memory clinic improved cognitive function in >50% patients at 3 months and almost 50% of patients showed a reduction in neuropsychiatric symptoms [46]. In this group of patients 50% of carers also showed an improvement in carer distress, maintained over time if the patient continued donepezil.…”

“…Failing cholinergic function correlates with failing cognition in AD. Therefore fMRI could be used as a tool to assess drug responsiveness in AD, as only about 50% of patients have a meaningful response to anticholinesterases and at present there is no way of identifying responders prior to treatment [46]. In two clinical responders to donepezil fMRI showed increased visual cortex activation during a passive visual paradigm, findings which need replication in larger numbers [85].…”

Diagnosis and treatment of psychiatric and behavioral disturbances in alzheimer disease: A review of recent literature

“…Although the cognitive effects of these agents have been the primary focus of investigations, a number of studies [19,[47][48][49][50] have demonstrated the ability of cholinesterase inhibitors to improve psychiatric symptoms associated with dementia, especially in patients with more advanced disease requiring institutionalization or hospitalization. These studies support the continued use of cholinesterase inhibitors in AD, agents that are generally already prescribed in the presence of mild to moderate disease.…”