Understanding the Rise in Overdose Deaths Involving Opioids and Non-Opioid Prescription Drugs in the United States

Background

Previous studies demonstrate that the reformulation of OxyContin in the U.S. in 2010 induced substitution to illicit opioids, causing illicit opioid markets to grow disproportionately fast in states more exposed to the reformulation. In this paper, we examine if this shift to the illicit market also led to a rise in polysubstance overdose deaths involving non-opioid prescription drugs, including gabapentinoids and "Z-drugs" and, separately, benzodiazepines.

Methods

Using a difference-in-differences framework, the relationship between exposure to reformulation and overdose death rates including specific substances was studied in each year from 1999 to 2020 while accounting for fixed differences across states, common nationwide shocks, and state-level differences in pain reliever misuse prior to reformulation. Exposure to reformulation was measured as the pre-reformulation rate of OxyContin misuse.

Results

Exposure to reformulation predicted growth in overdose deaths involving gabapentinoids and Z-drugs. There is less evidence that it predicted growth in overdose deaths involving benzodiazepines. However, for all substances, there is strong evidence that pre-reformulation OxyContin misuse rates predicted post-reformulation growth in overdose deaths concurrently involving synthetic opioids.

Discussion

The opioid crisis has changed in radical ways. This study links a major supply-side intervention to the increase in polysubstance overdose deaths involving non-opioid prescription drugs, specifically gabapentinoids and Z-drugs.