A Gateway to Misuse? Synthetic Opioid Mortality and the Rescheduling of Hydrocodone in the United States

Opioid-related overdose mortality in the United States continues to rise, with opioid mortality reaching an all-time high in 2022 with more than 110,000 drug poisonings. To address the continuing opioid crisis, a variety of policies have been implemented in the United States aimed at decreasing opioid prescribing and reducing opioid-related mortality, including the rescheduling of hydrocodone from a schedule III to a schedule II narcotic in 2014. Previous studies find that the rescheduling of hydrocodone in the United States is associated with a decrease in hydrocodone-related overdose mortality but an increase or no change in mortality related to other opioids such as oxycodone and tramadol. However, these studies only examine opioid-related mortality in the year following the rescheduling of hydrocodone. <br><br>This study explores additional longer-term mechanisms through which the rescheduling of hydrocodone may be associated with decreases in opioid-related mortality as the opioid epidemic continues to evolve in the United States. We used the county-specific pre-scheduling exposure to hydrocodone from the pharmacy level Drug Enforcement Administration's ARCOS dataset to identify counties that are disproportionately affected by the policy using a difference-indifferences research design. County-level mortality data were taken from the Centers for Disease Control and Prevention's Vital Statistics. We follow data from 2003 to 2019. We found that in the five years following the rescheduling of hydrocodone, those counties mostly exposed did not experienced as many as 3.15 deaths from drug poisonings per year in comparison to the rest of the country (and up to 6.7 if compared to the least exposed set of counties). The leading individual cause explaining the phenomenon stemmed from synthetic opioids poisoning deaths (i.e. fentanyl, tramadol). Treated counties disproportionately exposed to hydrocodone prior to the rescheduling experienced on average 3.7 fewer deaths from synthetic opioids per 100,000 persons (and up to 8 deaths), each year after the rescheduling from 2014 to 2019. Our results suggest that the rescheduling of hydrocodone in the United States not only reduced overall drug poisoning related mortality from but in the long-run, it may also be associated with a reduction in synthetic opioid misuse serving.