Short-Term Mortality After Opioid Initiation Among Opioid-Naïve and Non-Naïve Patients with Dementia: A Retrospective Cohort Study

Despite the ongoing opioid epidemic, the mortality risk of opioid initiation in patients with dementia or mild cognitive impairment (MCI) remains understudied despite their vulnerability. This study evaluates mortality risks associated with opioid use in patients diagnosed with dementia or MCI by comparing outcomes between new and consistent users. We conducted a retrospective cohort study using data from Northern California academic healthcare system (2015/01/01-2024/07/31), including 27,757 patients aged 50–100 with dementia or MCI. Of these, 14,105 received opioids after diagnosis and were classified as new (opioid-naïve; n=9444) or consistent (non-naïve; n=4663) users. Cox regression assessed 14-day mortality risk. Aalen’s additive model examined time-varying impact. Causes of death were extracted from clinical notes using GPT-3·5-Turbo. Findings were validated in community healthcare system cohort (n=207,873) across western U.S. states (2015/01/01-2023/05/31). In the primary cohort, 4.1% (572/14105) of patients died within 14 days of opioid exposure. New users had a significantly higher 14-day mortality risk than consistent users (adjusted hazard ratio [aHR], 2·00 [1·59–2·52]; P<0·0001). The validation cohort had a 14-day mortality rate of 6·2% (7022/113343) with a smaller difference between new (n=77,204) and consistent (n=36,194) users (aHR 1·20 [1·13–1·27]; P<0·0001). In both cohorts, elevated risk stabilized after day 30. In the primary cohort, respiratory conditions, particularly pneumonia, were more prevalent among new users who died early. Opioid initiation in these patients is associated with increased short-term mortality in new users, underscoring the need for cautious initiation and close monitoring during the first month. NIH