Faculty Bibliography

Since 1999, annual opioid-related overdose (ORO) mortality has increased more than six-fold. In response to this crisis, the US Department of Health and Human Services outlined a 5-point strategy to reduce ORO mortality which included the widespread distribution of naloxone, an opioid antagonist that can rapidly reverse an opioid overdose. Increased distribution has been facilitated by the implementation of naloxone access laws in each US state aimed at increasing community access to naloxone. While these laws differ from state-to-state, most contain mechanisms to enable pharmacists to dispense naloxone without a patient-specific prescription. These laws have enhanced community naloxone distribution, both from pharmacies and overdose education and naloxone distribution programs, and produced positive effects on ORO mortality. However, a growing body of evidence has revealed that significant barriers to naloxone access from pharmacies remain, and annual ORO deaths have continued to climb. Given these concerns, there has been a push among some clinicians and policymakers for the US Food and Drug Administration to re-classify naloxone as an over-the-counter (OTC) medication as a means to further increase its accessibility. If an OTC transition occurs, educational outreach and funding for clinical innovations will continue to be crucial given the important role of health professionals in recommending naloxone to people at risk for experiencing or witnessing an ORO. Recognizing the severity of the ORO public health crisis, we believe transitioning formulations of naloxone approved for layperson use to OTC status would result in a net benefit through increased access. However, such a change should be combined with measures to ensure affordability.

Importance:Medications for opioid use disorder, including buprenorphine hydrochloride and methadone hydrochloride, are highly effective at improving outcomes for individuals with the disorder. For pregnant women, use of these medications also improves pregnancy outcomes, including the risk of preterm birth. Despite the known benefits of medications for opioid use disorder, many pregnant and nonpregnant women with the disorder are not receiving them. Objective:To determine whether pregnancy and insurance status are associated with a woman's ability to obtain an appointment with an opioid use disorder treatment clinician. Design, Setting, and Participants:In this cross-sectional study with random assignment of clinicians and simulated-patient callers (performed in "secret shopper" format), outpatient clinics that provide buprenorphine and methadone were randomly selected from publicly available treatment lists in 10 US states (selected for variability in opioid-related outcomes and policies) from March 7 to September 5, 2019. Pregnant vs nonpregnant woman and private vs public insurance assigned randomly to callers to create unique patient profiles. Simulated patients called the clinics posing as pregnant or nonpregnant women to obtain an initial appointment with a clinician. Main Outcomes and Measures:Appointment scheduling, wait time, and out-of-pocket costs. Results:A total of 10 871 unique patient profiles were assigned to 6324 clinicians. Among all women, 2312 of 3420 (67.6%) received an appointment with a clinician who prescribed buprenorphine, with lower rates among pregnant vs nonpregnant callers (1055 of 1718 [61.4%] vs 1257 of 1702 [73.9%]; relative risk, 0.83; 95% CI, 0.79-0.87). For clinicians who prescribed methadone, there was no difference in appointment access for pregnant vs nonpregnant callers (240 of 271 [88.6%] vs 237 of 265 [89.4%]; relative risk, 0.99; 95% CI, 0.93-1.05). Insurance was frequently not accepted, with 894 of 3420 buprenorphine-waivered prescribers (26.1%) and 174 of 536 opioid treatment programs (32.5%) granting appointments only when patients agreed to pay cash. Median wait times did not differ between pregnant and nonpregnant callers among buprenorphine prescribers (3 days [interquartile range, 1-7 days] vs 3 days [interquartile range, 1-7 days]; P = .43) but did differ among methadone prescribers (1 day [interquartile range, 1-4 days] vs 2 days [interquartile range, 1-6 days]; P = .049). For patients agreeing to pay cash, the median out-of-pocket costs for initial appointments were $250 (interquartile range, $155-$300) at buprenorphine prescribers and $34 (interquartile range, $15-$120) at methadone prescribers. Conclusions and Relevance:In this cross-sectional study with random assignment of clinicians and simulated-patient callers, many women, especially pregnant women, faced barriers to accessing treatment. Given the high out-of-pocket costs and lack of acceptance of insurance among many clinicians, access to affordable opioid use disorder treatment is a significant concern.

: The United States is currently in the midst of 2 public health emergencies: COVID-19 and the ongoing opioid crisis. In an attempt to reduce preventable harm to individuals with opioid use disorder (OUD), federal, state, and local governments have temporarily modified law and policy to increase access to OUD treatment and divert some individuals at high risk away from the correctional system. In this Commentary, we briefly describe how people with OUD are at increased risk for COVID-19, discuss existing policy barriers to evidence-based prevention and treatment for individuals with OUD, explain the temporary rollbacks of those barriers, and argue that these changes should be made permanent. We also suggest several additional steps that federal and state governments can urgently take to reduce barriers to care for individuals with OUD, both during the current crisis and beyond.

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.