Mortality among patients with long-term prescription opioid use in Norway: a nationwide registry-based cohort study

The aim was to estimate all-cause and cause-specific mortality in long-term prescription opioid users compared to the general population. This nationwide registry-based cohort study used data of patients aged 15 to 69 years with no previous cancer diagnosis and a recorded episode of long-term opioid analgesics use (anatomical therapeutic chemical [ATC] group N02A; N = 116,006) in Norway between 2011 and 2019. Sex-specific crude mortality rates (CMR) and age-standardized mortality ratios (SMRs) were calculated for all-cause and cause-specific mortality, ie, natural and unnatural causes for the whole study population and for different age groups (15-34, 35-54, and 55-69 years). Overall, 4.6% (2491/54,535) of men and 2.7% (1680/61,471) of women died during the follow-up period. Crude mortality rates for all-cause mortality were 1194 and 724 deaths per 100,000 person-years (PY) in men and women, respectively. Men had higher CMRs across all causes, particularly unnatural causes (221 and 101 deaths per 100,000 PY in men and women, respectively). Patients with long-term opioid use had a 4 times higher all-cause mortality (SMR = 3.8 [95% CI = 3.6-3.9] in men and 3.7 [3.5-3.9] in women aged 15-69 years) compared to the general Norwegian population of the same age. Excess mortality was observed across all causes, particularly suicide, accidents, and accidental poisoning. Standardized mortality ratios decreased with age and were highest for the youngest age group (15-34 years), particularly among men. Long-term prescription opioid use is associated with an increased risk of death. Clinicians should weigh the risks of long-term opioid use against the benefits.