Population-Based Opioid Prescribing and Overdose Deaths in the USA: an Observational Study

Rising opioid-related death rates have prompted reductions of opioid prescribing, yet limited data exist on population-level associations between opioid prescribing and opioid-related deaths.

To evaluate population-level associations between five opioid prescribing measures and opioid-related deaths.

An ecological panel analysis was performed using linear regression models with year and commuting zone fixed effects.

People ≥10 years aggregated into 886 commuting zones, which are geographic regions collectively comprising the entire USA.

Annual opioid prescriptions were measured with IQVIA Real World Longitudinal Prescription Data including 76.5% (2009) to 90.0% (2017) of US prescriptions. Prescription measures included opioid prescriptions per capita, percent of population with ≥1 opioid prescription, percent with high-dose prescription, percent with long-term prescription, and percent with opioid prescriptions from ≥3 prescribers. Outcomes were age- and sex-standardized associations of change in opioid prescriptions with change in deaths involving any opioids, synthetics other than methadone, heroin but not synthetics or methadone, and prescription opioids, but not other opioids.

Change in total regional opioid-related deaths was positively correlated with change in regional opioid prescriptions per capita (β=.110, p<.001), percent with ≥1 opioid prescription (β=.100, p=.001), and percent with high-dose prescription (β=.081, p<.001). Change in total regional deaths involving prescription opioids was positively correlated with change in all five opioid prescribing measures. Conversely, change in total regional deaths involving synthetic opioids was negatively correlated with change in percent with long-term opioid prescriptions and percent with ≥3 prescribers, but not for persons ≥45 years. Change in total regional deaths in heroin was not associated with change in any prescription measure.

Regional decreases in opioid prescriptions were associated with declines in overdose deaths involving prescription opioids, but were also associated with increases in deaths involving synthetic opioids (primarily fentanyl). Individual-level inferences are limited by the ecological nature of the analysis.