Long-term opioid use and mortality in patients with chronic non-cancer pain: Ten-year follow-up study in South Korea from 2010 through 2019

Background: We aimed to investigate the prevalence and factors associated with long-term opioid use among patients with chronic non-cancer pain (CNCP). Methods: We extracted data from the National Health Insurance Service (NHIS) database in South Korea. As a nationwide database, the NHIS database contains information regarding all disease diagnoses and prescriptions for any drug and/or procedures. A total of 2.5% of adult patients (≥20 years of age) who were diagnosed with musculoskeletal diseases and CNCP from 2010 to 2019 were selected using a stratified random sampling technique and included in the analysis. Patients who were prescribed opioids continuously for ≥90 days were classified as long-term opioid users. Findings: A total of 19,645,161 patients with CNCP were included in the final analysis. The prevalence of long-term opioid use was 0.47% (95% confidence interval [CI]: 0.46%, 0.48%; 8421/1,808,043) in 2010, which gradually increased to 2.63% (95% CI: 2.61%, 2.66%; 49,846/1,892,913) in 2019. Among the 2010 cohort (n = 1,804,019), in multivariable logistic regression: old age, underlying disability, increased Charlson comorbidity index, use of benzodiazepine or Z-drug, rheumatoid arthritis, osteoarthritis, and low back pain were associated with an increased prevalence of long-term opioid use among patients with CNCP. In a multivariable Cox regression, the 10-year all-cause mortality in long-term opioid users was found to be 1·21-fold (hazard ratio: 1.21, 95% CI: 1.13, 1.31; P<0·001) higher than that in opioid-naive patients with CNCP. Interpretation: Long-term opioid use increased in patients with CNCP in South Korea from 2010 to 2019. Certain factors were potential risk factors for long-term opioid use. Moreover, long-term opioid use was associated with increased 10-year all-cause mortality among patients with CNCP. Funding: None.