Declining but Pronounced State-Level Disparities in Prescription Opioid Distribution in the United States.

The United States (US) opioid epidemic is a persistent and pervasive public health emergency that claims the lives of over 80,000 Americans per year as of 2021. There have been sustained efforts to reverse this crisis over the past decade, including a number of measures designed to decrease the use of prescription opioids for the treatment of pain. This study analyzed the changes in federal production quotas for prescription opioids and the distribution of prescription opioids for pain and identified state-level differences between 2010 and 2019. Data (in grams) on opioid production quotas and distribution (from manufacturer to hospitals, retail pharmacies, practitioners, and teaching institutions) of 10 prescription opioids (codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, and tapentadol) for 2010 to 2019 were obtained from the US Drug Enforcement Administration. Amounts of each opioid were converted from grams to morphine milligram equivalent (MME), and the per capita distribution by state was calculated using population estimates. Total opioid production quotas increased substantially from 2010 to 2013 before decreasing by 41.5% from 2013 (87.6 MME metric tons) to 2019 (51.3). The peak year for distribution of all 10 prescription opioids was between 2010 and 2013, except for codeine (2015). The largest quantities of opioid distribution were observed in Tennessee (520.70 MME per person) and Delaware (251.45) in 2011 and 2019. There was a 52.0% overall decrease in opioid distribution per capita from 2010 to 2019, with the largest decrease in Florida (-61.6%) and the smallest in Texas (-18.6%). Southern states had the highest per capita distribution for eight of the ten opioids in 2019. The highest to lowest state ratio of total opioid distribution, corrected for population, decreased from 5.25 in 2011 to 2.78 in 2019. The mean 95th/5th ratio was relatively consistent in 2011 (4.78 ± 0.70) relative to 2019 (5.64 ± 0.98). This study found a sustained decline in the distribution of ten prescription opioids during the last five years. Distribution was non-homogeneous at the state level. Analysis of state-level differences revealed a fivefold difference in the 95th:5th percentile ratio between states, which has remained unchanged over the past decade. Production quotas did not correspond with the distribution, particularly in the 2010-2016 period. Future research, focused on identifying factors contributing to the observed regional variability in opioid distribution, could prove valuable to understanding and potentially remediating the pronounced disparities in prescription opioid-related harms in the US.

Effects of Opioid Prescribing Cap Laws on Opioid and Other Pain Treatments Among Persons with Chronic Pain.

BACKGROUND: Many states have adopted laws that limit the amount or duration of opioid prescriptions. These limits often focus on prescriptions for acute pain, but there may be unintended consequences for those diagnosed with chronic pain, including reduced opioid prescribing without substitution of appropriate non-opioid treatments. OBJECTIVE: To evaluate the effects of state opioid prescribing cap laws on opioid and non-opioid treatment among those diagnosed with chronic pain. DESIGN: We used a difference-in-differences approach that accounts for staggered policy adoption. Treated states included 32 states that implemented a prescribing cap law between 2017 and 2019. POPULATION: A total of 480,856 adults in the USA who were continuously enrolled in medical and pharmacy coverage from 2013 to 2019 and diagnosed with a chronic pain condition between 2013 and 2016. MAIN MEASURES: Among individuals with chronic pain in each state: proportion with at least one opioid prescription and with prescriptions of a specific duration or dose, average number of opioid prescriptions, average opioid prescription duration and dose, proportion with at least one non-opioid chronic pain prescription, average number of such prescriptions, proportion with at least one chronic pain procedure, and average number of such procedures. KEY RESULTS: State laws limiting opioid prescriptions were not associated with changes in opioid prescribing, non-opioid medication prescribing, or non-opioid chronic pain procedures among patients with chronic pain diagnoses. CONCLUSIONS: These findings do not support an association between state opioid prescribing cap laws and changes in the treatment of chronic non-cancer pain.

Effects of state opioid prescribing cap laws on opioid prescribing after surgery.

OBJECTIVE: To evaluate the effects of state opioid prescribing cap laws on opioid prescribing after surgery. DATA SOURCES: OptumLabs Data Warehouse administrative claims data covering all 50 states from July 2012 through June 2019. STUDY DESIGN: We included individuals from 20 states that had implemented prescribing cap laws without exemptions for postsurgical pain by June 2019 and individuals from 16 control states plus the District of Columbia. We used a difference-in-differences approach accounting for differential timing in law implementation across states to estimate the effects of state prescribing cap laws on postsurgical prescribing of opioids. Outcome measures included filling an opioid prescription within 30 days after surgery; filling opioid prescriptions of specific doses or durations; and the number, days' supply, daily dose, and pill quantity of opioid prescriptions. To assess the validity of the parallel counterfactual trends assumption, we examined differences in outcome trends between law-implementing and control states in the years preceding law implementation using an equivalence testing framework. DATA COLLECTION/EXTRACTION METHODS: We included the first surgery in the study period for opioid-naïve individuals undergoing one of eight common surgical procedures. PRINCIPAL FINDINGS: State prescribing cap laws were associated with 0.109 lower days' supply of postsurgical opioids on the log scale (95% Confidence Interval [CI]: -0.139, -0.080) but were not associated with the number (Average treatment effect on the treated [ATT]: -0.011; 95% CI: -0.043, 0.021) or daily dose of postsurgical opioid prescriptions (ATT: -0.013; 95% CI: -0.030, 0.005). The negative association observed between prescribing cap laws and the probability of filling a postsurgical opioid prescription (ATT: -0.041; 95% CI: -0.054, -0.028) was likely spurious, given differences between law-implementing and control states in the pre-law period. CONCLUSIONS: Prescribing cap laws appear to have minimal effects on postsurgical opioid prescribing.

Systematic review of the emerging literature on the effectiveness of naloxone access laws in the United States.

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.

Laws limiting prescribing and dispensing of opioids in the United States, 1989-2019.

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.

Association of Pregnancy and Insurance Status With Treatment Access for Opioid Use Disorder.

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.

Opioid Policy Changes During the COVID-19 Pandemic - and Beyond.

: 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.

Rise and regional disparities in buprenorphine utilization in the United States.

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.

Association of Medicaid Expansion With Opioid Overdose Mortality in the United States.

Importance: 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: 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: 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: 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: 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: 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: 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.

Legal and policy changes urgently needed to increase access to opioid agonist therapy in the United States.

The United States continues to face a public health crisis of opioid-related harm, the effects of which could be dramatically reduced through increased access to opioid agonist therapy with the medications methadone and buprenorphine. Despite overwhelming evidence of their efficacy, unduly restrictive federal, state, and local regulation significantly impedes access to these life-saving medications. We outline immediate, concrete steps that federal, state, and local governments can take to change law from barrier to facilitator of evidence-based treatment for opioid use disorder. These include removing onerous restrictions on the prescription and dispensing of buprenorphine and methadone for opioid agonist therapy, requiring insurance coverage of these medications, and mandating that they be provided in correctional settings and promoted by drug courts. Finally, we argue that jurisdictions should proactively offer opioid agonist therapy to individuals at high risk of overdose, remove barriers to establishing methadone treatment facilities, and address underlying social determinants and barriers to treatment. These changes have the ability to save thousands of lives annually.

Laws limiting the prescribing or dispensing of opioids for acute pain in the United States: A national systematic legal review.

BACKGROUND: Opioid overdose is a continuing public health crisis. In response to an increasing recognition of the negative outcomes sometimes associated with the use of opioid analgesics, states have taken a number of steps attempting to reduce inappropriate prescribing of these medications. These include the imposition of strict legal limitations on the amount or duration that opioid analgesics may be prescribed or dispensed to patients with acute pain. METHODS: We conducted a systematic, multi-source legal review of state laws that impose mandatory limits on the ability of medical professionals to prescribe or dispense opioids for the treatment of acute pain. We also systematically searched for and examined publicly available documents on state legislative and regulatory bodies' websites. All relevant laws were downloaded and systematically coded. RESULTS: By the end of 2017, twenty-six states had passed laws that impose mandatory limits on the prescribing or dispensing of opioids for acute pain. The oldest of these laws became effective as early as 1989, but most are much newer: approximately 65% (17/26) were passed in 2017. There is wide variation in the characteristics of these laws. CONCLUSION: Just over half of all states have enacted laws that restrict the prescribing or dispensing of opioids for acute pain. To date, there is no data on whether and to what extent these laws mediate opioid-related morbidity and mortality, as well as whether they are associated with negative unintended outcomes. Research into these questions is urgently needed.

Perceived Unintended Consequences of Prescription Drug Monitoring Programs.

BACKGROUND: Opioid-related injuries and deaths continue to present challenges for public health practitioners. Prescription Drug Monitoring Programs (PDMPs) are a prevalent policy option intended to address problematic opioid pain reliever (OPR) prescribing, but previous research has not thoroughly characterized their unintended consequences. OBJECTIVES: To examine state actors' perceptions of the unintended consequences of PDMPs. METHODS: We conducted 37 interviews with PDMP staff, law enforcement officials, and administrative agency employees in Florida, Kentucky, New Jersey, and Ohio from May 2015 to June 2016. RESULTS: We identified six themes from the interviews. Perceived negative unintended consequences included: access barriers for those with medical needs, heroin use as OPR substitute and related deaths, and need for adequate PDMP security infrastructure and management. Perceived positive unintended consequences were: community formation and problem awareness, proactive population-level OPR monitoring, and increased knowledge about population-level drug diversion. Conclusions/Importance: State actors perceive a range of both negative and positive unintended consequences of PDMPs. Our findings suggest that there may be unintended risks of PDMPs that states should address, but also opportunities to maximize certain benefits.

Do naloxone access laws increase outpatient naloxone prescriptions? Evidence from Medicaid.

BACKGROUND: Naloxone is a prescription medication that can quickly and effectively reverse opioid overdose. Medicaid is a major payer of substance use disorder services, and Medicaid beneficiaries experience especially high rates of opioid overdose. As opioid overdose rates have risen sharply, every state has modified its laws to make naloxone easier to access. The aim of this paper is to determine whether implementation of different provisions of naloxone access laws led to increased naloxone dispensing financed by Medicaid. METHODS: We reviewed naloxone legislation passed by every state between 2007 and 2016. We used the Medicaid State Drug Utilization dataset to examine the effect of different types of state naloxone access law provisions, separately and as a whole, on the number of outpatient naloxone prescriptions reimbursed by Medicaid from 2007 to 2016. We included state-level covariates in our models that may be correlated with naloxone utilization in Medicaid and passage of naloxone access laws. RESULTS: We found that the presence of any naloxone law was significantly associated with increases in outpatient naloxone reimbursed through Medicaid. Laws containing standing order provisions were most consistently associated with increases in naloxone dispensing across models. Standing order provisions led on average to an increase of approximately 33 naloxone prescriptions per state-quarter, which is equivalent to 74% of the average number of naloxone prescriptions per state-quarter. CONCLUSIONS: Naloxone access laws, particularly those with standing order provisions, appear to be an effective policy approach to increasing naloxone access among Medicaid beneficiaries.

State naloxone access laws are associated with an increase in the number of naloxone prescriptions dispensed in retail pharmacies.

BACKGROUND: In response to the ongoing opioid overdose epidemic, many states have enacted laws increasing naloxone access by lay people, such as friends and family members of people who use drugs (PWUD), as well as PWUD themselves. METHOD: We utilized Symphony Health Solutions' PHAST Prescription data from 2007 to 2016 to investigate whether naloxone access laws were associated with an increase in naloxone dispensed from retail pharmacies in the United States. RESULT: Using a negative binomial regression, we found that naloxone access laws were associated with an average increase of 78 prescriptions dispensed per state per quarter. This represents an average 79% increase in naloxone dispensed from U.S. retail pharmacies, compared with states where there were no such laws. CONCLUSION: Our study suggests that naloxone access laws can increase the availability and accessibility of naloxone.

Opioid-overdose laws association with opioid use and overdose mortality.

INTRODUCTION: Since the 1990's, governmental and non-governmental organizations have adopted several measures to increase access to the opioid overdose reversal medication naloxone. These include the implementation of laws that increase layperson naloxone access and overdose-specific Good Samaritan laws that protect those reporting overdoses from criminal sanction. The association of these legal changes with overdose mortality and non-medical opioid use is unknown. We assess the relationship of (1) naloxone access laws and (2) overdose Good Samaritan laws with opioid-overdose mortality and non-medical opioid use in the United States. METHODS: We used 2000-2014 National Vital Statistics System data, 2002-2014 National Survey on Drug Use and Health data, and primary datasets of the location and timing of naloxone access laws and overdose Good Samaritan laws. RESULTS: By 2014, 30 states had a naloxone access and/or Good Samaritan law. States with naloxone access laws or Good Samaritan laws had a 14% (p = 0.033) and 15% (p = 0.050) lower incidence of opioid-overdose mortality, respectively. Both law types exhibit differential association with opioid-overdose mortality by race and age. No significant relationships were observed between any of the examined laws and non-medical opioid use. CONCLUSIONS: Laws designed to increase layperson engagement in opioid-overdose reversal were associated with reduced opioid-overdose mortality. We found no evidence that these measures were associated with increased non-medical opioid use.