Long-term effect of donepezil for Alzheimer's disease: Retrospective clinical evaluation of drug efficacy in Japanese patients


Dr Ryo Kumagai, MD, Department of Psychiatry, Juntendo Tokyo Koto Geriatric Medical Center, 3-3-20 Shinsuna, Koto-ku, Tokyo 136-0075, Japan. Email: ykumagai@juntendo.gmc.ac.jp


Background:  Alzheimer's disease (AD) is common in the Japanese population. In 1999, donepezil was authorized in Japan for the treatment of AD. However, because the time since donepezil was authorized is relatively short, there are few reports regarding the long-term effects of donepezil in Japanese AD patients.

Methods:  In the present study, the clinical features of 72 AD patients treated at Juntendo University Urayasu Hospital were examined retrospectively in order to examine the long-term effects of donepezil. Sixty-two AD patients had been administrated donepezil. The effect of donepezil was evaluated using the Revised Hasegawa Dementia Scale (HDS-R). In patients with increased points on the HDS-R after 6 months, treatment was regarded as effective, whereas patients in whom there was no change in points on the HDS-R were classified as ‘no change’; finally, in patients with decreased points on the HDS-R after 6 months, treatment was regarded as non-effective.

Results:  The duration of medication was divided into four groups: (i) 6 months (16 cases; 26%); (ii) 1 year (16 cases; 26%); (iii) 2 years (13 cases; 21%); and (iv) more than 3 years (11 cases; 18%). Donepezil treatment was stopped in six patients (10%) because of adverse effects. Thus, the 56 patients who continued with donepezil treatment were categorized as follows: treatment was effective in 27 cases (48%), no change was found in five cases (9%) and, in 24 cases (43%), donepezil treatment was found to be non-effective. Differences in treatment efficacy were not related to sex, apolipoprotein E genotype or medical history. Comparative studies for the age of onset of AD and points of the HDS-R before administration of donepezil suggest that donepezil tended to be effective in patients in whom AD developed at 71–80 years of age and with 16–20 points of the HDS-R. In patients in whom donepezil was effective, cognition returned to the state before treatment 2 years later. However, the marked degradation of points on the HDS-R was not seen in these cases. Conversely, the long-term consequences for patients in whom donepezil was not effective after 6 months were similar to those for patients not treated with donepezil.

Conclusion:  Donepezil improved the dementia symptoms in patients in whom it was effective over the long term. We suggest that the presence of drug efficacy after 6 months is an indicator that long-term treatment with donepezil is warranted. In particular, donepezil was effective in cases with mild to moderate AD.