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Drugs Aging. 2010 Nov 1;27(11):903-13. doi: 10.2165/11584290-000000000-00000.

Use of antipsychotic drugs in patients with Alzheimer's disease treated with rivastigmine versus donepezil: a retrospective, parallel-cohort, hypothesis-generating study.

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Department of Neurology, Ohio State University, Columbus, Ohio 43210, USA.



Rivastigmine and donepezil are two cholinesterase inhibitors (ChEIs) indicated for the treatment of mild-to-moderate Alzheimer's disease. Dementia-related behavioural issues are typically managed by environmental modification and the use of psychotropics including antipsychotic medications. However, ChEIs have also been associated with reductions in behavioural symptoms in Alzheimer's disease patients. This retrospective, parallel-cohort, hypothesis-generating study investigated whether treatment with rivastigmine is associated with reduced prescription of antipsychotic medications compared with treatment with donepezil.


A combined analysis of two claims databases was conducted. Patients were included if they had a diagnosis of Alzheimer's disease and were newly initiated on either rivastigmine or donepezil. Patients with prior use of memantine and/or antipsychotics were excluded. Kaplan-Meier and Cox analyses were conducted to compare the rate of antipsychotic drug use between the rivastigmine and donepezil groups.


A total of 956 patients receiving rivastigmine and 12 778 patients receiving donepezil formed the study population. Analysis revealed that 64 (6.7%) rivastigmine and 989 (7.7%) donepezil recipients received antipsychotic medications (log-rank test from Kaplan-Meier analysis, p = 0.2289). The Cox regression analysis showed that rivastigmine was associated with a statistically significant reduction in the prescription of antipsychotic drugs relative to donepezil (hazard ratio 0.73; p = 0.044). Older age, longer time between Alzheimer's disease diagnosis and first ChEI dispensing, lower dose of ChEI at treatment initiation and the presence of baseline depression and neuropsychiatric symptoms were associated with a significantly increased likelihood of antipsychotic drug use.


In this retrospective analysis, Alzheimer's disease patients with no prior use of antipsychotics initiated on rivastigmine had a significantly lower rate of prescription of antipsychotic drugs than those treated with donepezil.

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