Opioid Initiation in Dementia Tied to an 11-Fold Increased Risk of Death

Megan Brooks

July 18, 2023

Opioid initiation for older adults with dementia is linked to a significantly increased risk of death, especially in the first 2 weeks, when the risk is elevated 11-fold, new research shows.

"We expected that opioids would be associated with an increased risk of death, but we are surprised by the magnitude," study investigator Christina Jensen-Dahm, MD, PhD, with the Danish Dementia Research Centre, Copenhagen University Hospital, Rigshospitalet, Denmark, told Medscape Medical News.

"It's important that physicians carefully evaluate the risk and benefits if considering initiating an opioid, and this is particularly important in elderly with dementia," Jensen-Dahm added.

The findings were presented at the Alzheimer's Association International Conference (AAIC) 2023.

Risky Business

Using Danish nationwide registries, the researchers analyzed data on all 75,471 adults in Denmark who were aged 65 and older and had been diagnosed with dementia between 2008 and 2018. A total of 31,619 individuals (42%) filled a prescription for an opioid. These "exposed" individuals were matched to 63,235 unexposed individuals.

Among the exposed group, 10,474 (33%) died within 180 days after starting opioid therapy, compared with 3980 (6.4%) in the unexposed group.

After adjusting for potential differences between groups, new use of an opioid was associated with a greater than fourfold excess mortality risk (adjusted hazard ratio [aHR], 4.16; 95% CI, 4.00 – 4.33).

New use of a strong opioid ― defined as morphine, oxycodone, ketobemidone, hydromorphone, pethidine, buprenorphine, and fentanyl ― was associated with a greater than sixfold increase in mortality risk (aHR, 6.42; 95% CI, 6.08 – 6.79).

Among those who used fentanyl patches as their first opioid, 65% died within the first 180 days, compared with 6.7% in the unexposed ― an eightfold increased mortality risk (aHR, 8.04; 95% CI, 7.01 – 9.22).

For all opioids, the risk was greatest in the first 14 days, with a nearly 11-fold increased risk of mortality (aHR, 10.8; 95% CI, 9.74 – 11.99). However, there remained a twofold increase in risk after taking opioids for 90 days (aHR, 2.32; 95% CI, 2.17 – 2.48).

"Opioids are associated with severe and well-known side effects, such as sedation, confusion, respiratory depression, falls, and in the most severe cases, death. In the general population, opioids have been associated with an increased risk of death, and similar to ours, greatest in the first 14 days," said Jensen-Dahm.

Need to Weigh Risks, Benefits

Commenting on the study, Percy Griffin, PhD, director of scientific engagement at the Alzheimer's Association, told Medscape Medical News that the use of strong opioids has "increased considerably over the past decade among older people with dementia. Opioid therapy should only be considered for pain if the benefits are anticipated to outweigh the risks in individuals who are living 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," Nicole Purcell, DO, neurologist and senior director of clinical practice at the Alzheimer's Association, added in a conference statement.

"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 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, said Purcell.

The study was supported by a grant from the Capital Region of Denmark. Jensen-Dahm, Griffin, and Purcell have no relevant disclosures.

Alzheimer's Association International Conference (AAIC) 2023: Abstract 77103. Presented July 18, 2023.

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