Mortality Risk Significantly Increased With New Opioid Use in Older Adults With Dementia

Christina Jensen-Dahm, MD, PhD

Among older patients with dementia, findings from a Danish nationwide study suggest that new opioid use is associated with excess mortality, with a nearly 11-fold increase observed for all opioids within the first few weeks. 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, presented at the 2023 Alzheimer’s Association International Conference (AAIC), held June 16-20, in Amsterdam, Netherlands, included 75,471 Danish residents aged 65 years and older diagnosed with dementia, 42% (n = 31,619) of which redeemed a prescription for an opioid after their diagnosis. Led by Christina Jensen-Dahm, MD, PhD, research assistant at the University of Copenhagen, exposed participants were matched with up to 2 unexposed individuals based on age and sex (n = 63,235). Mortality risk was assessed within 180 days after the initiation of opioid treatment.

Among those exposed to opioids, 33.7% (n = 10,642) died within 180 days after initiating their first opioid prescription compared with 6.4% (n = 3980) of those unexposed, yielding a 4-fold increased excess mortality risk (HR, 4.13; 95% CI, 3.98-4.30). Strong opioids used in the study included morphine, oxycodone, ketobemidone, hydromorphone, pethidine, buprenorphine, and fentanyl. These medications were associated with a 6-fold increased mortality risk (HR, 6.34; 95% CI, 6.00-6.69) whereas the risk was lower for weak opioids (HR, 2.52; 95% CI, 2.38-2.67).

"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."

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To compare rates of death within 180 days after opioids, investigators used Cox proportional hazards models adjusted for potential confounders such as time since diagnosis, nursing home residency, comorbidity, admission within 30 days, and number of medications. Among those who had redeemed transdermal fentanyl as their first prescription, 65.3% died within the first 180 days compared with 6.7% of those unexposed, equating to a risk of 8.03 (95% CI, 7.02-9.18). Mortality for all opioid use was greatest within the first 14 days (HR, 10.95; 95% CI, 9.87-12.15), but there was still a 2-fold increased risk after 90 days (HR, 2.36; 95% CI, 2.21-2.52).

"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."

In 2022, the Centers for Disease Control and Prevention (CDC) announced clinical practice guidelines for prescribing opioids for pain, stating that opioids should only be considered for pain if benefits are anticipated to outweigh risks to the patient. It did not support rapid dosage tapering, patient abandonment, or abrupt discontinuation of opioids.

Opioids, similar to atypical antipsychotics, may pose as a risk for older individuals with dementia. Antipsychotic medications, which are commonly used to treat neuropsychiatric symptoms of depression, including aggression, agitation, and delusions, have been associated with significantly increased risk of death, even in short periods of less than 8 to 12 weeks. Clinicians have often noted that these therapies should only be used in individual situations where there is an identifiable risk of harm and when alternate therapies have failed.

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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
3. Summary of the 2022 Clinical Practice Guideline for Prescribing Opioids for Pain. Centers for Disease Control and Prevention. July 18, 2023. Accessed July 18, 2023. https://www.cdc.gov/opioids/patients/guideline.html
4. Stulberg DL. Increased mortality with atypical antipsychotics for dementia. Am Fam Physician. 2006;73(4):693-694.