Long-Term Opioid Therapy and Risk of Opioid Overdose by Derived Clinical Indication in North Carolina, 2006-2018

PurposeLong-term opioid therapy (LTOT) has been shown to be associated with opioid overdose, but the definition of LTOT varies widely across studies. We use a rigorous LTOT definition to examine risk of opioid overdose by duration of treatment.MethodsData were from a large private health insurance provider in North Carolina linked to mortality records from 2006-2018. Eligible patients were adults (18-64) newly initiating opioid therapy after a pain diagnosis or surgery. We defined LTOT as >= 1 opioid prescription per month totaling >= 60 days' supply within 90 days. We used inverse probability (IP)-weighted cumulative incidence functions to estimate three-year risk of opioid overdose and IP-weighted Fine-Gray models to estimate sub-distribution hazard ratios, comparing LTOT to short- to medium-term opioid therapy (SMTOT). We also examined modification by derived indication of acute pain or surgery versus chronic pain.ResultsWe identified 491 369 patients, and 1.7% were exposed to LTOT. The three-year risk of opioid overdose was 0.3 percentage points (RDw = 0.003, 95% CI: 0.001, 0.005) higher in LTOT patients compared to patients with SMTOT. The weighted hazard of opioid overdose was 4.4 times as high (HRw 4.42, 95% CI 2.41, 8.11) among patients exposed to LTOT versus SMTOT. We did not find meaningful modification by clinical indication for opioid therapy.ConclusionsExposure to LTOT was associated with increased risk of opioid overdose in this population of privately insured patients using a rigorous definition of LTOT. These findings confirm the importance of guidelines to minimize duration of opioid therapy whenever possible.