Faculty Bibliography

PURPOSE:Buprenorphine is an opioid partial agonist used to treat opioid use disorder. While several policy changes have attempted to increase buprenorphine availability, access remains well below optimal levels. This study characterized how buprenorphine utilization in the United States has changed over time and whether there are regional disparities in distribution of the medication. METHODS:The amount of buprenorphine distributed from 2007 to 2017 was obtained from the Drug Enforcement Administration's Automated Reports and Consolidated Ordering System. Data were expressed as the percent change and milligrams per person in each state. The formulations and cost for prescriptions covered by Medicaid (2008 to 2018) were also examined. RESULTS:Buprenorphine distributed to pharmacies increased about 7-fold (476.8 to 3179.9 kg) while the quantities distributed to hospitals grew 5-fold (18.6 to 97.6 kg) nationally from 2007 to 2017. Buprenorphine distribution per person was almost 20-fold higher in Vermont (40.4 mg/person) relative to South Dakota (2.1 mg/person). There was a strong association between the number of physicians authorized to prescribe buprenorphine and distribution per state (r[49] = +0.94, P < .0005). The buprenorphine/naloxone sublingual film (Suboxone) was the predominant formulation (92.6% of 0.31 million Medicaid prescriptions) in 2008 but accounted for less than three-fifth (57.3% of 6.56 million prescriptions) in 2018. CONCLUSIONS:Although buprenorphine availability has substantially increased over the last decade, distribution was very nonhomogeneous across the United States.

OBJECTIVE:To determine whether the adoption of laws that limit opioid prescribing or dispensing is associated with changes in the volume of opioids distributed in states. METHODS:State-level data on total prescription opioid distribution for 2015-2017 were obtained from the US Drug Enforcement Administration. We included in our analysis states that enacted an opioid prescribing law in either 2016 or 2017. We used as control states those that did not have an opioid prescribing law during the study period. To avoid confounding, we excluded from our analysis states that enacted or modified mandates to use prescription drug monitoring programs (PDMPs) during the study period. To estimate the effect of opioid prescription laws on opioid distribution, we ran ordinary least squares models with indicators for whether an opioid prescription law was in effect in a state-quarter. We included state and quarter fixed effects to control for time trends and time-invariant differences between states. RESULTS:With the exception of methadone and buprenorphine, the amount of opioids distributed in states fell during the study period. The adoption of opioid prescribing laws was not associated with additional decreases in opioids distributed. CONCLUSIONS:We did not detect an association between adoption of opioid prescribing laws and opioids distributed. States may instead wish to pursue evidence-based efforts to reduce opioid-related harm, with a particular focus on treatment access and harm reduction interventions.

Importance/UNASSIGNED:The Patient Protection and Affordable Care Act (ACA) permits states to expand Medicaid coverage for most low-income adults to 138% of the federal poverty level and requires the provision of mental health and substance use disorder services on parity with other medical and surgical services. Uptake of substance use disorder services with medications for opioid use disorder has increased more in Medicaid expansion states than in nonexpansion states, but whether ACA-related Medicaid expansion is associated with county-level opioid overdose mortality has not been examined. Objective/UNASSIGNED:To examine whether Medicaid expansion is associated with county × year counts of opioid overdose deaths overall and by class of opioid. Design, Setting, and Participants/UNASSIGNED:This serial cross-sectional study used data from 3109 counties within 49 states and the District of Columbia from January 1, 2001, to December 31, 2017 (N = 3109 counties × 17 years = 52 853 county-years). Overdose deaths were modeled using hierarchical Bayesian Poisson models. Analyses were performed from April 1, 2018, to July 31, 2019. Exposures/UNASSIGNED:The primary exposure was state adoption of Medicaid expansion under the ACA, measured as the proportion of each calendar year during which a given state had Medicaid expansion in effect. By the end of study observation in 2017, a total of 32 states and the District of Columbia had expanded Medicaid eligibility. Main Outcomes and Measures/UNASSIGNED:The outcomes of interest were annual county-level mortality from overdoses involving any opioid, natural and semisynthetic opioids, methadone, heroin, and synthetic opioids other than methadone, derived from the National Vital Statistics System multiple-cause-of-death files. A secondary analysis examined fatal overdoses involving all drugs. Results/UNASSIGNED:There were 383 091 opioid overdose fatalities across observed US counties during the study period, with a mean (SD) of 7.25 (27.45) deaths per county (range, 0-1145 deaths per county). Adoption of Medicaid expansion was associated with a 6% lower rate of total opioid overdose deaths compared with the rate in nonexpansion states (relative rate [RR], 0.94; 95% credible interval [CrI], 0.91-0.98). Counties in expansion states had an 11% lower rate of death involving heroin (RR, 0.89; 95% CrI, 0.84-0.94) and a 10% lower rate of death involving synthetic opioids other than methadone (RR, 0.90; 95% CrI, 0.84-0.96) compared with counties in nonexpansion states. An 11% increase was observed in methadone-related overdose mortality in expansion states (RR, 1.11; 95% CrI, 1.04-1.19). An association between Medicaid expansion and deaths involving natural and semisynthetic opioids was not well supported (RR, 1.03; 95% CrI, 0.98-1.08). Conclusions and Relevance/UNASSIGNED:Medicaid expansion was associated with reductions in total opioid overdose deaths, particularly deaths involving heroin and synthetic opioids other than methadone, but increases in methadone-related mortality. As states invest more resources in addressing the opioid overdose epidemic, attention should be paid to the role that Medicaid expansion may play in reducing opioid overdose mortality, in part through greater access to medications for opioid use disorder.

BACKGROUND:Prescription drug monitoring programs (PDMPs) that collect and distribute information on dispensed controlled substances have been adopted by nearly all US states. We know little about program characteristics that modify PDMP impact on prescription opioid overdose deaths. METHODS:We measured associations between adoption of any PDMP and changes in fatal prescription opioid overdoses in 2002-2016 across 3,109 counties in 49 states. We then measured changes related to the adoption of "proactive PDMPs", which report outlying prescribing/dispensing patterns and provide broader access to PDMP data by law enforcement. Comparisons were made within three time intervals that broadly represent the evolution of PDMPs (2002-2004, 2005-2009, 2010-2016). We modeled overdoses using Bayesian space-time models. RESULTS:Adoption of electronic PDMP access was associated with 9% lower rates of fatal prescription opioid overdoses after three years (rate ratio [RR]=0.91, 95% credible interval [CI]: 0.88-0.93) with well-supported effects for methadone (RR=0.86, CI: 0.82-0.90) and other synthetic opioids (RR=0.82, CI: 0.77-0.86). Compared to states with no/weak PDMPs, proactive PDMPs were associated with fewer deaths attributed to natural/semi-synthetic opioids (2002-2004: RR=0.72 (0.66-0.78); 2005-2009: RR=0.93 (0.90-0.97); 2010-2016: 0.89 (0.86-0.92)) and methadone (2002-2004: RR=0.77 (0.69-0.85); 2010-2016: RR=0.90 (0.86-0.94)). Unintended effects were observed for synthetic opioids other than methadone (2005-2009: RR=1.29 (1.21-1.38); 2010-2016: RR=1.22 (1.16-1.29)). CONCLUSIONS:State adoption of PDMPs was associated with fewer prescription opioid deaths overall while proactive PDMPs alone were associated with fewer deaths related to natural/semi-synthetic opioids and methadone, the specific targets of these programs.

The United States continues to face a public health emergency of opioid-related harm, the effects of which could be dramatically reduced through increased access to the opioid antagonist naloxone. Unfortunately, naloxone is too often unavailable when and where it is most needed, partly due to its continued status as a prescription medication. Although states and the federal Food and Drug Administration (FDA) have acted to increase access to naloxone, these changes are insufficient to address this unprecedented crisis. In this Commentary, we argue that FDA can and should immediately reclassify naloxone from prescription-only to over-the-counter status, a change that could save hundreds if not thousands of lives in the United States every year.