New Use of Opioids Increases Risk of Death Elevenfold in Older Adults with Dementia

• Older adults who start on opioids after a dementia diagnosis face heightened risk of death, especially in the first two weeks of opioid use.
• A study of everyone diagnosed with Alzheimer’s disease in Denmark in a 10-year period found one-third died within 180 days after their first opioid dose, five times as many as those with the disease who didn’t take opioids.
• Among those who used fentanyl patches as their first prescription, nearly two-thirds died within the first 180 days.

AMSTERDAM, JULY 18, 2023 — New opioid use in older adults with dementia is associated with a significantly increased risk of death, including an elevenfold increase in the first two weeks, according to research first reported today at the Alzheimer’s Association International Conference^® (AAIC^®) 2023, in Amsterdam, Netherlands, and online.

The study population included everyone in Denmark aged 65 and older diagnosed with dementia between Jan. 1, 2008 and Dec. 31, 2018 (n=75,471), including both home-living and nursing home residents. Of that group, 42% (31,619) of those diagnosed with dementia redeemed a prescription for an opioid at a pharmacy.

The researchers followed study participants for 180 days after their first opioid prescription. They also followed a group of older adults with dementia who did not receive an opioid prescription and compared risk of death between the two groups.

• 10,474 (33.1%) study participants died within 180 days after initiating their first opioid prescription, compared with 3,980 (6.4%) of the unexposed. After adjusting for potential differences between groups, researchers found a fourfold increased excess mortality risk.
• The risk was greatest in the first 14 days, where mortality for all opioids was increased elevenfold.
• Strong opioids were associated with a sixfold increased mortality risk.
• Among those who used fentanyl patches as their first prescription, 64.4% died within the first 180 days compared with 6.4% in the unexposed (an eightfold increased risk of dying).

The researchers defined strong opioids as morphine, oxycodone, ketobemidone, hydromorphone, pethidine, buprenorphine and fentanyl. Strong opioids are used to relieve pain when non-opioid and mild opioid medicines are not effective.

“In our study, starting on an opioid after getting a dementia diagnosis was frequent and associated with a markedly increased risk of death, which is worrisome,” said Christina Jensen-Dahm, M.D., Ph.D., of the Neurology Department, Danish Dementia Research Centre, Copenhagen University Hospital — Rigshospitalet, Denmark. “The use of strong opioids has increased considerably over the past decade among older people with dementia. Our study shows the importance of careful evaluation of risk and benefits to the patient when considering initiating opioid therapy among elderly individuals with dementia.”

“Opioids are very powerful drugs, and while we need to see additional research in more diverse populations, these initial findings indicate they may put older adults with dementia at much higher risk of death,” said Nicole Purcell, D.O., M.S., neurologist and Alzheimer’s Association senior director, clinical practice.

“Pain should not go undiagnosed or untreated, in particular in people living with dementia who may not be able to effectively articulate the location and severity of the pain,” Purcell added. “These new findings further emphasize the need for discussion between the patient, family and physician. Decisions about prescribing pain medication should be thought through carefully, and, if used, there needs to be careful monitoring of the patient.”

As stated in CDC’s guideline from 2022, opioid therapy should only be considered for pain if benefits are anticipated to outweigh risks to the patient. "This is particularly important for older individuals with dementia," Jensen-Dahm said. "Opioids are known to have significant side-effects including sedation, confusion, respiratory depression and falls. Older adults with dementia have a severe brain disorder and are often frail. We suspect this is why they can not tolerate opioids, but we do not know for certain and need to do more research to answer these questions.”

This is not the first time that drugs have been found to be excessively risky for older people with dementia. A group of drugs used to treat psychiatric conditions, known as atypical antipsychotics, have consistently been found to nearly double the risk of death in this population.

About the Alzheimer's Association International Conference^® (AAIC^®)
The Alzheimer’s Association International Conference (AAIC) is the world’s largest gathering of researchers from around the world focused on Alzheimer’s and other dementias. As a part of the Alzheimer’s Association’s research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.
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About the Alzheimer's Association^®
The Alzheimer’s Association is the leading voluntary health organization in Alzheimer's care, support and research. Our mission is to lead the way to end Alzheimer's and all other dementia — by accelerating global research, driving risk reduction and early detection, and maximizing quality care and support. Visit alz.org or call +1 800.272.3900.

Media Contacts: 
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