Faculty Bibliography

Despite its proven efficacy, buprenorphine remains dramatically underutilized for management of opioid use disorder largely due to onerous barriers to treatment initiation. During the COVID-19 pandemic, many substance use disorder treatment facilities have reduced their hours and services, exacerbating existing barriers. To this end, the U.S. Drug Enforcement Administration and Substance Abuse Mental Health Services Administration adjusted their guidelines to allow for new buprenorphine prescriptions following audio-only telehealth encounters, no longer requiring an in-person evaluation prior to treatment initiation. Under this new guidance, we established a 24/7 telephone hotline to function as a "tele-bridge" clinic where people with opioid use disorder can be linked with a buprenorphine prescriber in real-time for OUD assessment and unobserved buprenorphine initiation with connection to follow-up if appropriate. Additionally, we developed an ED callback protocol to reach patients recently seen for opioid overdose and facilitate their entry into care if interested. In this commentary we describe our hotline and ED callback protocols, discuss theoretical and anecdotal benefits to this approach, and advocate for continuation of current regulatory changes post-COVID-19 to maintain expanded access to novel treatment approaches.

BACKGROUND AND AIMS:Naloxone access laws (NALs) have been suggested to be an important strategy to reduce opioid-related harm. We describe the evolution of NALs across states and over time and review existing evidence of their overall association with naloxone distribution and opioid overdose as well as the potential effects of specific NAL components. METHODS:Descriptive analysis of temporal variation in US regional adoption of NAL components, accompanied by a systematic search of 13 databases for studies (published between 2005 and 20 December 2019) assessing the effects of NALs on naloxone distribution or opioid-related health outcomes. Eleven studies, all published since 2018, met inclusion criteria. Study time-frames spanned 1999-2017. Opioid-related overdose mortality, emergency department episodes and naloxone distribution were correlated with the presence of a NAL and, where data were available, NAL components. RESULTS:Existing evidence suggests mixed, but generally beneficial, effects for NALs. Nearly all studies show that NALs, particularly those that permit naloxone distribution without patient-specific prescriptions, are associated with increased naloxone access [incidence rate ratios (IRR) range from 1.40, 95% confidence interval (CI) = 1.15-1.66 to 7.75, 95% CI = 1.22-49.35] and increased opioid-related emergency department visits (IRR range from 1.14, 95% CI = 1.07-1.20 to 1.15, 95% CI = 1.02-1.29). Most studies show NALs are associated with reduced overdose mortality, although findings vary depending on the specific NAL components and time-period analyzed (IRR range from 0.66, 95% CI = 0.42-0.90 to 1.27, 95% CI = 1.27-1.27). Few studies account for the variation in opioid environments (i.e. illicit versus prescription) or other policy dimensions that may be correlated with outcomes. CONCLUSIONS:The existing literature on naloxone access laws in the United States supports beneficial effects for increased naloxone distribution, but provides inconclusive evidence for reduced fatal opioid overdose. Mixed findings may reflect variation in the laws' design and implementation, confounding effects of concurrent policy adoption, or differential effectiveness in light of changing opioid environments.

Pain management clinic (PMC) laws were enacted by 12 states to promote appropriate opioid prescribing, but their impact is inadequately understood. We analyzed county-level opioid overdose deaths (National Vital Statistics System) and patients filling long-duration (≥30 day) or high-dose (≥90 morphine milligram equivalents) opioid prescriptions (IQVIA, Inc) in the United States from 2010-2018. We fit Besag-York-Mollié spatiotemporal models to estimate annual relative rates (RR) of overdose and prevalence ratios (PR) of high-risk prescribing associated with any PMC law and three provisions: payment restrictions, site inspections, and criminal penalties. Laws with criminal penalties were significantly associated with reduced PRs of long-duration and high-dose opioid prescriptions (adjusted PR: 0.82, 95% credible interval (CrI) 0.92-0.83, and 0.73, and 0.73, 0.74 respectively), and reduced RRs of total and natural/semi-synthetic opioid overdoses (adjusted RR: 0.86, 95% CrI: 0.80, 0.92; and 0.84, and 0.77, 0.92, respectively). Conversely, PMC laws were associated with increased relative rates of synthetic opioid and heroin overdose deaths, especially criminal penalties (adjusted RR: 1.83, 95% CrI: 1.59, 2.11; and 2.59, and 2.22, 3.02, respectively). Findings suggest laws with criminal penalties were associated with intended reductions in high-risk opioid prescribing and some opioid overdoses, but raise concerns regarding unintended consequences on heroin/synthetic overdoses.

BACKGROUND AND AIMS:Opioid overdose is a public health emergency in the United States. In an attempt to reduce potentially inappropriate opioid prescribing, many US states have adopted legal restrictions on the ability of medical professionals to prescribe or dispense opioids for pain. This review describes the major elements of relevant US state laws and the ways in which they have changed over time. METHODS:Systematic legal review in which two trained legal researchers collected and reviewed all US state laws that limit the amount or duration of opioids that medical professionals may prescribe or dispense for pain. These laws were then coded on a set of pre-selected measures, including when the law was enacted, dosage and duration limits imposed, circumstances in which the restrictions do not apply and whether additional requirements or restrictions apply to prescriptions issued to minors. RESULTS:The number of US states with opioid limitation laws increased from 10 in 2016 to 39 by the end of 2019. The provisions of these laws vary between states and have shifted within states over time. At the end of 2019 the modal duration limit was 7 days, with a range of 3 to 31. Fourteen states imposed limits on the dosage of opioids that can be prescribed, ranging from 30 morphine milligram equivalents (MME) to a 120 MME daily maximum. In 16 states, different limits apply to prescriptions issued to minors. CONCLUSIONS:The number of US states with opioid limitation laws nearly quadrupled between 2016 and 2019, with a great amount of heterogeneity between state restrictions and changes over time.

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.

Treatment with buprenorphine significantly reduces both all-cause and overdose mortality among individuals with opioid use disorder. Offering buprenorphine treatment to individuals who experience a nonfatal opioid overdose represents an opportunity to reduce opioid overdose fatalities. Although some emergency departments (EDs) initiate buprenorphine treatment, many individuals who experience an overdose either refuse transport to the ED or are transported to an ED that does not offer buprenorphine. Emergency medical services (EMS) professionals can help address this treatment gap. In this Concepts article, we describe the federal legal landscape that governs the ability of EMS professionals to administer buprenorphine treatment, and discuss state and local regulatory considerations relevant to this promising and emerging practice.