Donepezil Helps Improves Cognition and Reduce Incidence of Dementia, Pitt Study Finds

Updated on January 3, 2011
Charles F. Reynolds III, MD

Donepezil, a medication used to treat dementia in Alzheimer’s patients, was found to enhance language, memory and executive functioning in older, depressed adults to a greater extent than was evident from the use of an antidepressant medication alone, according to a new study by the University of Pittsburgh School of Medicine. The study, which is published in the current issue of the Archives of General Psychiatry, is the first to provide scientifically rigorous evidence to guide clinical practice in older adults with both major depression and mild cognitive impairment.

“Cognitive impairment is a core feature of depression in older adults and may foreshadow the development of dementia,” said Charles F. Reynolds III, M.D., lead author of the study and UPMC Endowed Chair of Geriatric Psychiatry.

“While treatment of depression usually benefits associated cognitive impairment, it does not completely regulate cognitive impairment and may not delay the progression to dementia. So, even in remission, older adults with past depression may still show residual cognitive difficulties, such as slowing of information processing speed and impairments in executive or language function. Our study showed that by adding donepezil, cognition can be improved beyond that which is seen simply with the treatment of depression itself.”

For the study, researchers compared 130 depressed adults over the age of 65 – with 67 receiving donepezil, marketed under the trade name Aricept, and 63 receiving a placebo. The participants were followed for two years while researchers explored the effects of donepezil and placebo on five areas of neuropsychological functioning, including speed of information processing, memory, language, visuospatial functioning and executive functioning, or brain processes that are responsible for planning and abstract thinking.

The researchers noted two unexpected findings: donepezil seemed to delay the progression of mild cognitive impairment to frank dementia, and the use of the drug was associated with somewhat higher recurrence rates of clinical depression episodes, said Dr. Reynolds. “So, there was both a benefit and a risk to adding donepezil to antidepressant pharmacotherapy in older adults. Fortunately, the majority of recurrent depressive episodes could be treated to remission.”

Adding donepezil to maintenance antidepressant medication appears to be useful to the care of older, depressed patients with mild cognitive impairment but does not benefit those with normal cognition. The researchers stress that clinicians should watch for early signs of any depressive relapse and treat as needed.

Co-authors of the study include Meryl A. Butter, Ph.D., Mary Amanda Dew, Ph.D., Margo Holm, Ph.D., Joan C. Rogers, Ph.D., Jordan F. Karp, M.D., Mark D. Miller, M.D., Ellen M. Whyte, M.D., Ariel Gildengers, M.D., Katalin Szanto, M.D., Patricia R. Houck, M.S.H., Amy Begley, M.A., Jacqueline Stack, M.S.N., Salem Bensasi, B.A., all from the University of Pittsburgh School of Medicine’s Department of Psychiatry; Oscar Lopez, M.D., University of Pittsburgh Department of Neurology; Sati Mazumdar, Ph.D., and Stewart Anderson, Ph.D., University of Pittsburgh Department of  Biostatistics; M. Llyas Kamboh, Ph.D., University of Pittsburgh Graduate School of Public Health; Bruce G. Pollock, M.D., and Benoit H. Mulsant, M.D., University of Toronto Center for Addiction and Mental Health; Eric J. Lenze, M.D., Washington University, St. Louis Department of Psychiatry; Daniel I. Kaufer, M.D., University of North Carolina, Chapel Hill, Department of Neurology; and Steven T. DeKosky, M.D., University of Virginia School of Medicine.

This study was supported in part by the National Institutes of Health and by the UPMC Endowed Chair in Geriatric Psychiatry. This study was a unique collaboration between the National Institute of Mental Health-sponsored Late Life Depression Center and the Alzheimer’s Disease Research Center at UPMC. Fostering such collaboration is an important part of the mission of the Aging Institute at UPMC, which is directed by Dr. Reynolds.

Western Psychiatric Institute and Clinic (WPIC) is considered to be one of the nation’s foremost university-based psychiatric care facilities and one of the world’s leading centers for research and treatment of mental health disorders. WPIC houses the Department of Psychiatry of the University of Pittsburgh School of Medicine and is the flagship of UPMC Behavioral Health, the psychiatric specialty division of UPMC..

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