Use of Donepezil With an Antidepressant Cuts Incidence of Dementia in Older Adults, Reynolds-Led Study Finds

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, published in 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, 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 older than 65—with 67 of the adults 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: 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, Reynolds said. “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 in 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.

The study was supported in part by the National Institutes of Health and by the UPMC Endowed Chair in Geriatric Psychiatry. It was also a unique collaboration between the National Institute of Mental Health-sponsored Late Life Depression Center and UPMC’s Alzheimer’s Disease Research Center.