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Correspondence
February 2003

Donepezil Use in the Treatment of Dementia Associated With Down Syndrome

Arch Neurol. 2003;60(2):292. doi:10.1001/archneur.60.2.292-a

In their recent ARCHIVES article, Lott et al1 presented the results of a nonrandomized controlled trial on the effect of donepezil treatment in a small sample of patients with Down syndrome (DS) who developed dementia, demonstrating a significant improvement in dementia scores. The use of acetylcholinesterase inhibitors in these patients is based on the well-known neurochemical and neuropathological similarities between DS and Alzheimer disease (AD).2 Our opinion is that many questions remain unresolved. First of all, the safety of donepezil treatment in DS is not well established, and the article by Lott and colleagues completely omits any information about the adverse effects of this treatment. Furthermore, the few case reports described in the literature do not demonstrate any clinical benefit of donepezil use and highlight the frequent adverse effects related to acetylcholinesterase inhibitors.3 On the other hand, a recent article by Prasher et al4 (the first randomized, double-blind placebo-controlled study on the efficacy and safety of donepezil as a treatment for dementia in patients with DS) concluded that donepezil could be a safe treatment in these patients, minimizing the high frequency of adverse effects. We made similar observations in our clinical experience with 3 patients with DS who developed dementia (a 58-year-old woman, a 50-year-old woman, and a 44-year-old man). All were treated with donepezil. In the first case, therapy lasted only 2 months (5 mg/d) and was then stopped because of the persistence of severe adverse events (abdominal pain and vomiting); the second case was similar (donepezil treatment at 5 mg/d was continued for 6 weeks and stopped because of abdominal pain and diarrhea). The third patient tolerated a 6-month course of treatment (after 3 months, the dosage was increased to 10 mg/d) without any cognitive or functional improvement.

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