August 1, 2018
Results from a clinical trial conducted by Columbia University Irving Medical Center and Duke University Health System suggest that donepezil—an Alzheimer’s drug—may not improve cognitive performance in people at risk for Alzheimer’s disease who also had depression.
The study’s findings were published in the July 2018 issue of the American Journal of Geriatric Psychiatry, the medical journal of the American Association for Geriatric Psychiatry.
More than 5 million Americans and 40 million people worldwide have mild cognitive impairment. Studies have shown that about 30 percent of people with mild cognitive impairment also have clinical depression.
"Both late-life depression and mild memory loss are established risk factors for dementia, and when they co-occur, the risk for future dementia is even higher. That is why it is critical to find effective therapies for this population," said study author Devangere Devanand, MD, professor of psychiatry and neurology and director of geriatric psychiatry at Columbia University Vagelos College of Physicians and Surgeons.
Co-author Murali Doraiswamy, MD, professor of psychiatry and medicine at Duke University Health System added, "There are no FDA-approved therapies for preventing dementia in at-risk people with both mild cognitive impairment and depression. Cholinesterase inhibitors used to treat Alzheiemer’s, such as donepezil, and a variety of supplements are often used in clinical practice to treat such patients, but their efficacy in this population isn’t proven."
The study enrolled 79 people who were experiencing both mild cognitive impairment and major depression. Participants were first given standard antidepressant treatment for 16 weeks. During this time, 64 percent of the group had an improvement in their depression symptoms. Subjects were then randomly assigned either to additional daily treatment by donepezil or placebo for another 62 weeks. Compared with placebo, donezepil did not produce a significant improvement in cognitive performance, daily functioning, or slowing of the progression to dementia. In addition, patients who were treated with donepezil experienced more adverse effects than those on placebo.
Dr. Devanand noted that implications of these results run counter to the common practice of treating people who have both depression and cognitive impairment with cholinesterase inhibitors. Dr. Doraiswamy emphasized that their findings highlight the need to prioritize discovery of novel Alzheimer’s treatments for people who also have depression.
The study is titled, "Donepezil Treatment in Patients With Depression and Cognitive Impairment on Stable Antidepressant Treatment: A Randomized Controlled Trial."
The other authors of this paper are Gregory H. Pelton, MD, Kristina D'Antonio, MSW, Adam Ciarleglio, PhD, Jennifer Scodes, MS, Howard Andrews, PhD, Julia Lunsford, MD, John L. Beyer, MD, Jeffrey R. Petrella, MD, Joel Sneed, PhD, and Michaela Ciovacco, BA.
This study was supported by the National Institute on Aging NCT01658228.
Dr. Devanand has served as an advisor to pharmaceutical companies and Dr. Doraiswamy has also served as an advisor to pharmaceutical companies and advocacy groups for other projects. [read more CUIMC news]