First Opioid Use in Older Adults with Dementia Significantly Increased Mortality Risk

Among older patients with dementia in Denmark, a nationwide study found a first prescription for an opioid significantly increased risk of death, including an observed 11-fold increase in mortality within the first 2 weeks of opioid use.¹

_{Christina Jensen-Dahm, MD, PhD}

The study, which followed all Danish residents diagnosed with Alzheimer disease over a 10-year period, revealed that approximately 33% died within 180 days of a first opioid dose, a proportion 5 times greater than of those with the diagnosis who were not prescribed opioids.

Investigators called for additional research to identify subgroups of patients with the highest excess mortality risk in efforts to ultimately create guidelines for appropriate prescription.

The study, led by Christina Jensen-Dahm, MD, PhD, of the Neurology Department, Danish Dementia Research Centre, Copenhagen University Hospital — Rigshospitalet, Denmark, and presented in June at the 2023 Alzheimer’s Association International Conference, included 75 471 Danish residents aged 65 years and older diagnosed with dementia between January 1, 2008, and December 31, 2018. Among them, 42% (n=31 619) filled a prescription for an opioid after their diagnosis.

Jensen-Dahm and colleagues matched study participants exposed to opioid treatment with 2 unexposed individuals from the study population, based on age and sex (n=63 235). They assessed mortality risk in both groups within 180 days after the initiation of opioid treatment using Cox proportional hazards models adjusted for potential confounders such as time since diagnosis, nursing home residency, comorbidity, admission within 30 days, and number of concomitant medications.

Investigators reported that among those exposed to opioids, 33.7% (n=10 642) died within 180 days of a first opioid prescription compared with 6.4% (n=3980) of those unexposed. Within that 6-month period, they calculated the excess mortality risk at 4-fold (HR, 4.13; 95% CI, 3.98-4.30) after adjusting for potential differences between the study groups. Mortality risk was greatest within the first 14 days of an opioid prescription when Jensen-Dahm et al reported an 11-fold increase in risk of death (HR, 10.95; 95% CI, 9.87-12.15). Even at 90 days however, a more than 2-fold increased risk persisted (HR, 2.36; 95% CI, 2.21-2.52).

The strong opioids identified during the study, morphine, oxycodone, ketobemidone, hydromorphone, pethidine, buprenorphine, and fentanyl, were associated with a more than 6-fold increased risk of mortality (HR, 6.34; 95% CI, 6.00-6.69) compared with a 2-fold increase in risk associated with weak opioids (HR, 2.52; 95% CI, 2.38-2.67). Among study participants whose first opioid prescription was for fentanyl, 65.3% died within the first 180 days compared with 6.7% of those unexposed, a risk calculated to be 8.03 (95% CI, 7.02-9.18).

"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," Jensen-Dahm said in a statement. "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,” Nicole Purcell, DO, MS, neurologist, and senior director of the Alzheimer’s Association, said in a statement. "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."

REFERENCES
1. New use of opioids increases risk of death elevenfold in older adults with dementia. News release. Alzheimer’s Association. July 18, 2023. Accessed July 18, 2023. https://www.prnewswire.com/news-releases/new-use-of-opioids-increases-risk-of-death-elevenfold-in-older-adults-with-dementia-301879360.html
2. Jensen-Dahm C, Janbek J, Gasse C, et al. Excessive mortality risk associated with new opioids use in older people with dementia. Presented at: AAIC 2023; June 16-20; Amsterdam, Netherlands. Abstract 77103