Long-term opioid therapy and risk of opioid overdose by derived clinical
indication in North Carolina, 2006-2018
Abstract
Purpose: Long-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. Methods: Data 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
subdistribution 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.
Results: We identified 491,369 patients, and 1.7% were exposed
to LTOT. The three-year risk of opioid overdose was 0.3 percentage
points (RD w= 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 (HR w 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.
Conclusions: Exposure 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.