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Patients with severe Alzheimer's disease who are living at home with family care givers and are treated with donepezil stabilise or decline more slowly than patients given placebo, according to a multinational, randomised, placebo controlled trial published in Neurology (2007;69:459-69).
Donepezil was approved by the US Food and Drug Administration last year for the treatment of severe Alzheimer's disease as well as mild to moderate forms. The Canadian authorities approved its use for severe forms of the disease in June 2007.
Sandra Black, of the University of Toronto and lead author of the paper, said that North American researchers were suspicious of the decision by the UK National Institute for Health and Clinical Excellence (NICE) not to fund donepezil for patients with mild Alzheimer's disease. She said that researchers thought it might slow decline in these patients. NICE only recommends its use in patients who have moderate Alzheimer's disease. And it recommends that the drug is stopped once the disease becomes severe.
The Neurology study shows that patients receiving donepezil maintained cognitive and global functions or declined more slowly than patients receiving placebo. These functions include memory; orientation; and day to day activities, such as dressing, bathing, and use of the toilet.
In the 24 week trial, 343 patients at 98 centres in the United States, Canada, France, the United Kingdom, and Australia were randomised to 10 mg of donepezil a day (176) or placebo (167). Patients were evaluated by testing functioning, cognition, and the burden on care givers at entry to the study and after 8, 16, and 24 weeks.
Dr Black told the BMJ that it was difficult to enrol patients because only about 10% of patients with severe Alzheimer's disease live in the community; most are in nursing homes. The study enrolled only patients who had never received memantine (Ebixa, Lundbeck), another drug used to treat Alzheimer's disease.
Because patients with Alzheimer's disease continue to decline—although more slowly with drug treatment—it was hard to keep patients and family members motivated to stay in the study, she said.
Many families wanted to keep the patient at home. Although the costs in care givers' time are high, costs for institutionalised patients with Alzheimer's disease are much higher. Many patients in the study were taking other drugs, such as risperidone (Risperdal, Janssen-Cilag), but the two groups were randomised, and both groups were similar in terms of drug prescriptions, Dr Black said.
She said that patients given donepezil showed significant improvement compared with patients given placebo in the “severe impairment battery test” and in the “clinician's interview based impression of change plus,” which includes care giver's input. These test patients' social interactions and include simple memory tests. The clinician's assessment was done by a doctor who saw the patients at checkpoints but was not otherwise involved with the study.
Dr Black acknowledged support from sponsors of the study, Pfizer and Eisai.