Donepezil Treatment and Alzheimer Disease: Can the Results of Randomized Clinical Trials Be Applied to Alzheimer Disease Patients in Clinical Practice?

• Published in: The American journal of geriatric psychiatry 2007-11, Vol.15 (11), p.953-960
• Main Authors: Tinklenberg, Jared R., M.D, Kraemer, Helena C., Ph.D, Yaffe, Kristine, M.D, Ross, Leslie, Ph.D, Sheikh, Javaid, M.D., M.B.A, Ashford, John W., M.D., Ph.D, Yesavage, Jerome A., M.D, Taylor, Joy L., Ph.D
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Alzheimer disease; Alzheimer Disease - diagnosis; Alzheimer Disease - drug therapy; Alzheimer Disease - psychology; California; Cholinesterase Inhibitors - therapeutic use; clinical practice; Clinical Protocols; donepezil effectiveness; Drug Prescriptions - statistics & numerical data; Drug Utilization; Female; Follow-Up Studies; Humans; Indans - therapeutic use; Internal Medicine; Longitudinal Studies; Male; Middle Aged; Multicenter Studies as Topic - statistics & numerical data; observational studies; Piperidines - therapeutic use; Practice Patterns, Physicians; Propensity analyses; Prospective Studies; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic - methods; Treatment Outcome
• ISSN: 1064-7481; 1545-7214
• DOI: 10.1097/JGP.0b013e3180986138

Objective To determine if results from randomized clinical trials of donepezil in Alzheimer disease (AD) patients can be applied to AD patients in clinical practice by comparing the findings from a Nordic one-year randomized AD donepezil trial with data from a one-year prospective, observational study of AD patients. Methods AD patients from a consortium of California sites were systematically followed for at least one year. Their treatment regimens, including prescription of donepezil, were determined by their individual physician according to his or her usual criteria. Results The 148 California patients treated with donepezil had a one-year decline of 1.3 (3.5 SD) points on the Mini-Mental State Exam compared to a decline of 3.3 (4.4 SD) in the 158 AD patients who received no anti-Alzheimer drugs. The Mini-Mental State Exam decline in Nordic sample was ∼0.25 points for the 91 patients receiving donepezil and ∼2.2 for the 98 placebo patients. The overall effect sizes were estimated at about 0.49 in both studies. The California data were further analyzed using propensity methods; after taking into account differences that could bias prescribing decisions, benefits associated with taking donepezil remained. Conclusion A comparison of a randomized clinical trial of donepezil in AD patients and this observational study indicates that if appropriate methodological and statistical precautions are undertaken, then results from randomized clinical trials can be predictive with AD patients in clinical practice. This California study supports the modest effectiveness of donepezil in AD patients having clinical characteristics similar to those of the Nordic study.