Utilization and disparities in medication treatment for opioid use disorder among patients with comorbid opioid use disorder and chronic pain during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic's impact on utilization of medications for opioid use disorder (MOUD) among patients with opioid use disorder (OUD) and chronic pain is unclear. METHODS: We analyzed New York State (NYS) Medicaid claims from pre-pandemic (August 2019-February 2020) and pandemic (March 2020-December 2020) periods for beneficiaries with and without chronic pain. We calculated monthly proportions of patients with OUD diagnoses in 6-month-lookback windows utilizing MOUD and proportions of treatment-naïve patients initiating MOUD. We used interrupted time series to assess changes in MOUD utilization and initiation rates by medication type and by race/ethnicity. RESULTS: Among 20,785 patients with OUD and chronic pain, 49.3% utilized MOUD (versus 60.3% without chronic pain). The pandemic did not affect utilization in either group but briefly disrupted initiation among patients with chronic pain (ß=-0.009; 95% CI [-0.015, -0.002]). Overall MOUD utilization was not affected by the pandemic for any race/ethnicity but opioid treatment program (OTP) utilization was briefly disrupted for non-Hispanic Black individuals (ß=-0.007 [-0.013, -0.001]). The pandemic disrupted overall MOUD initiation in non-Hispanic Black (ß=-0.007 [-0.012, -0.002]) and Hispanic individuals (ß=-0.010 [-0.019, -0.001]). CONCLUSIONS: Adults with chronic pain who were enrolled in NYS Medicaid before the COVID-19 pandemic had lower MOUD utilization than those without chronic pain. MOUD initiation was briefly disrupted, with disparities especially in racial/ethnic minority groups. Flexible MOUD policy initiatives may have maintained overall treatment utilization, but disparities in initiation and care continuity remain for patients with chronic pain, and particularly for racial/ethnic minoritized subgroups.

Evaluating chronic pain as a risk factor for COVID-19 complications among New York State Medicaid beneficiaries: a retrospective claims analysis.

OBJECTIVE: To assess whether chronic pain increases the risk of COVID-19 complications and whether opioid use disorder (OUD) differentiates this risk among New York State Medicaid beneficiaries. DESIGN, SETTING, AND SUBJECTS: This was a retrospective cohort study of New York State Medicaid claims data. We evaluated Medicaid claims from March 2019 through December 2020 to determine whether chronic pain increased the risk of COVID-19 emergency department (ED) visits, hospitalizations, and complications and whether this relationship differed by OUD status. We included beneficiaries 18-64 years of age with 10 months of prior enrollment. Patients with chronic pain were propensity score-matched to those without chronic pain on demographics, utilization, and comorbidities to control for confounders and were stratified by OUD. Complementary log-log regressions estimated hazard ratios (HRs) of COVID-19 ED visits and hospitalizations; logistic regressions estimated odds ratios (ORs) of hospital complications and readmissions within 0-30, 31-60, and 61-90 days. RESULTS: Among 773 880 adults, chronic pain was associated with greater hazards of COVID-related ED visits (HR = 1.22 [95% CI: 1.16-1.29]) and hospitalizations (HR = 1.19 [95% CI: 1.12-1.27]). Patients with chronic pain and OUD had even greater hazards of hospitalization (HR = 1.25 [95% CI: 1.07-1.47]) and increased odds of hepatic- and cardiac-related events (OR = 1.74 [95% CI: 1.10-2.74]). CONCLUSIONS: Chronic pain increased the risk of COVID-19 ED visits and hospitalizations. Presence of OUD further increased the risk of COVID-19 hospitalizations and the odds of hepatic- and cardiac-related events. Results highlight intersecting risks among a vulnerable population and can inform tailored COVID-19 management.

Pathways to racial disparities in the effects of Good Samaritan Laws: A mixed methods pilot study.

BACKGROUND: Drug overdose deaths continue to rise, and considerable racial inequities have emerged. Overdose Good Samaritan laws (GSLs) are intended to encourage overdose witnesses to seek emergency assistance. However, evidence of their effectiveness is mixed, and little is known regarding racial disparities in their implementation. This study examined GSL impact by assessing racial differences in awareness of and trust in New York state's GSL. METHODS: Using a sequential mixed methods design, Black and white participants were recruited from an existing longitudinal cohort study of people who use illicit opioids in New York City to participate in a quantitative survey and qualitative interviews. Racially stratified survey responses were analyzed using chi-squared tests, Fisher exact tests, or t-tests. Qualitative interviews were analyzed using a hybrid inductive-deductive approach. RESULTS: Participants (n=128) were 56% male and predominantly aged 50 years or older. Most met criteria for severe opioid use disorder (81%). Fifty-seven percent reported that the New York GSL makes them more likely to call 911 even though 42% reported not trusting law enforcement to abide by the GSL; neither differed by race. Black people were less likely to have heard of the GSL (36.1% vs 60%) and were less likely to have accurate information regarding its protections (40.4% vs 49.6%). CONCLUSIONS: Though GSLs may reduce negative impacts of the criminalization of people who use drugs, their implementation may exacerbate existing racial disparities. Resources should be directed towards harm reduction strategies that do not rely on trust in law enforcement.

Racial/ethnic disparities in opioid overdose prevention: comparison of the naloxone care cascade in White, Latinx, and Black people who use opioids in New York City.

BACKGROUND: Drug overdose mortality is rising precipitously among Black people who use drugs. In NYC, the overdose mortality rate is now highest in Black (38.2 per 100,000) followed by the Latinx (33.6 per 100,000) and white (32.7 per 100,000) residents. Improved understanding of access to harm reduction including naloxone across racial/ethnic groups is warranted. METHODS: Using data from an ongoing study of people who use illicit opioids in NYC (N = 575), we quantified racial/ethnic differences in the naloxone care cascade. RESULTS: We observed gaps across the cascade overall in the cohort, including in naloxone training (66%), current possession (53%) daily access during using and non-using days (21%), 100% access during opioid use (20%), and complete protection (having naloxone and someone who could administer it present during 100% of opioid use events; 12%). Naloxone coverage was greater in white (training: 79%, possession: 62%, daily access: 33%, access during use: 27%, and complete protection: 13%, respectively) and Latinx (training: 67%, possession: 54%, daily access: 22%, access during use: 24%, and complete protection: 16%, respectively) versus Black (training: 59%, possession: 48%, daily access:13%, access during use: 12%, and complete protection: 8%, respectively) participants. Black participants, versus white participants, had disproportionately low odds of naloxone training (OR 0.40, 95% CI 0.22-0.72). Among participants aged 51 years or older, Black race (versus white, the referent) was strongly associated with lower levels of being trained in naloxone use (OR 0.20, 95% CI 0.07-0.63) and having 100% naloxone access during use (OR 0.34, 95% CI 0.13-0.91). Compared to white women, Black women had 0.27 times the odds of being trained in naloxone use (95% CI 0.10-0.72). CONCLUSIONS: There is insufficient protection by naloxone during opioid use, with disproportionately low access among Black people who use drugs, and a heightened disparity among older Black people and Black women.

I Don't Believe a Person Has to Die When Trying to Get High: Overdose Prevention and Response Strategies in Rural Illinois.

BACKGROUND: Overdose is a leading cause of morbidity and mortality among people who inject drugs. Illicitly manufactured fentanyl is now a major driver of opioid overdose deaths. METHODS: Semi-structured interviews were conducted with 23 participants (19 persons who inject drugs and 4 service providers) from rural southern Illinois. Data were analyzed using constant comparison and theoretical sampling methods. RESULTS: Participants were concerned about the growing presence of fentanyl in both opioids and stimulants, and many disclosed overdose experiences. Strategies participants reported using to lower overdose risk included purchasing drugs from trusted sellers and modifying drug use practices by partially injecting and/or changing the route of transmission. Approximately half of persons who inject drugs sampled had heard of fentanyl test strips, however fentanyl test strip use was low. To reverse overdoses, participants reported using cold water baths. Use of naloxone to reverse overdose was low. Barriers to naloxone access and use included fear of arrest and opioid withdrawal. CONCLUSIONS: People who inject drugs understood fentanyl to be a potential contaminant in their drug supply and actively engaged in harm reduction techniques to try to prevent overdose. Interventions to increase harm reduction education and information about and access to fentanyl test strips and naloxone would be beneficial.

Persistent Criminalization and Structural Racism in US Drug Policy: The Case of Overdose Good Samaritan Laws.

The US overdose crisis continues to worsen and is disproportionately harming Black and Hispanic/Latino people. Although the "War on Drugs" continues to shape drug policy-at the disproportionate expense of Black and Hispanic/Latino people-states have taken some steps to reduce War on Drugs-related harms and adopt a public health-centered approach. However, the rhetoric regarding these changes has, in many cases, outstripped reality. Using overdose Good Samaritan Laws (GSLs) as a case study, we argue that public health-oriented policy changes made in some states are undercut by the broader enduring environment of a structurally racist drug criminalization agenda that continues to permeate and constrict most attempts at change. Drawing from our collective experiences in public health research and practice, we describe 3 key barriers to GSL effectiveness: the narrow parameters within which they apply, the fact that they are subject to police discretion, and the passage of competing laws that further criminalize people who use illicit drugs. All reveal a persisting climate of drug criminalization that may reduce policy effectiveness and explain why current reforms may be destined for failure and further disadvantage Black and Hispanic/Latino people who use drugs. (Am J Public Health. 2023;113(S1):S43-S48. https://doi.org/10.2105/AJPH.2022.307037).

Cessation of self-reported opioid use and impacts on co-occurring health conditions.

BACKGROUND: Among veterans in care reporting opioid use, we investigated the association between ceasing opioid use on subsequent reduction in report of other substance use and improvements in pain, anxiety, and depression. METHODS: Using Veterans Aging Cohort Study survey data collected between 2003 and 2012, we emulated a hypothetical randomized trial (target trial) of ceasing self-reported use of prescription opioids and/or heroin, and outcomes including unhealthy alcohol use, smoking, cannabis use, cocaine use, pain, and anxiety and depressive symptoms. Among those with baseline opioid use, we compared participants who stopped reporting opioid use at the first follow-up (approximately 1 year after baseline) with those who did not. We fit logistic regression models to estimate associations with change in each outcome at the second follow-up (approximately 2 years after baseline) among participants with that condition at baseline. We examined two sets of adjusted models that varied temporality assumptions. RESULTS: Among 2473 participants reporting opioid use, 872 did not report use, 606 reported use, and 995 were missing data on use at the first follow-up. Ceasing opioid use was associated with no longer reporting cannabis (adjusted odds ratio [AOR]=1.82, 95% confidence interval [CI] 1.10, 3.03) and cocaine use (AOR=1.93, 95% CI 1.16, 3.20), and improvements in pain (AOR=1.53, 95% CI 1.05, 2.24) and anxiety (AOR=1.56, 95% CI 1.01, 2.41) symptoms. CONCLUSION: Cessation of opioid misuse may be associated with subsequent cessation of other substances and reduction in pain and anxiety symptoms, which supports efforts to screen and provide evidence-based intervention where appropriate.

Use of an Inverted Synthetic Control Method to Estimate Effects of Recent Drug Overdose Good Samaritan Laws, Overall and by Black/White Race/Ethnicity.

Overdose Good Samaritan laws (GSLs) aim to reduce mortality by providing limited legal protections when a bystander to a possible drug overdose summons help. Most research into the impact of these laws is dated or potentially confounded by coenacted naloxone access laws. Lack of awareness and trust in GSL protections, as well as fear of police involvement and legal repercussions, remain key deterrents to help-seeking. These barriers may be unequally distributed by race/ethnicity due to racist policing and drug policies, potentially producing racial/ethnic disparities in the effectiveness of GSLs for reducing overdose mortality. We used 2015-2019 vital statistics data to estimate the effect of recent GSLs on overdose mortality, overall (8 states) and by Black/White race/ethnicity (4 states). Given GSLs' near ubiquity, few unexposed states were available for comparison. Therefore, we generated an "inverted" synthetic control method (SCM) to compare overdose mortality in new-GSL states with that in states that had GSLs throughout the analytical period. The estimated relationships between GSLs and overdose mortality, both overall and stratified by Black/White race/ethnicity, were consistent with chance. An absence of effect could result from insufficient protection provided by the laws, insufficient awareness of them, and/or reticence to summon help not addressable by legal protections. The inverted SCM may be useful for evaluating other widespread policies.

Did prescribing laws disproportionately affect opioid dispensing to Black patients?

OBJECTIVE: To evaluate whether pain management clinic laws and prescription drug monitoring program (PDMP) prescriber check mandates, two state opioid policies with relatively rapid adoption across states, reduced opioid dispensing more or less in Black versus White patients. DATA SOURCES: Pharmacy claims data, US sample of commercially insured adults, 2007-2018. STUDY DESIGN: Stratifying by race, we used generalized estimating equations with an event-study specification to estimate time-varying effects of each policy on opioid dispensing, comparing to the four pre-policy quarters and states without the policy. Outcomes included high-dosage opioids, overlapping opioid prescriptions, concurrent opioid/benzodiazepines, opioids from >3 prescribers, opioids from >3 pharmacies. DATA EXTRACTION METHODS: We identified all prescription opioid dispensing to Black and White adults aged 18-64 without a palliative care or cancer diagnosis code. PRINCIPAL FINDINGS: Exactly 7,096,592 White and 1,167,310 Black individuals met inclusion criteria. Pain management clinic laws were associated with reductions in two outcomes; their association with high-dosage receipt was larger among White patients. In contrast, reductions due to PDMP mandates appeared limited to, or larger in, Black patients compared with White patients in four of five outcomes. For example, PDMP mandates reduced high-dosage receipt in Black patients by 0.7 percentage points (95% CI: 0.36-1.08 ppt.) over 4 years: an 8.4% decrease from baseline; there was no apparent effect in White patients. Similarly, while there was limited evidence that mandates reduced overlapping opioid receipt in White patients, they appeared to reduce overlapping opioid receipt in Black patients by 1.3 ppt. (95% CI: -1.66--1.01 ppt.) across post-policy years-a 14.4% decrease from baseline. CONCLUSIONS: PDMP prescriber check mandates but not pain management clinic laws appeared to reduce opioid dispensing more in Black patients than White patients. Future research should discern the mechanisms underlying these disparities and their consequences for pain management.

Racial/Ethnic and Geographic Trends in Combined Stimulant/Opioid Overdoses, 2007-2019.

In the United States, combined stimulant/opioid overdose mortality has risen dramatically over the last decade. These increases may particularly affect non-Hispanic Black and Hispanic populations. We used death certificate data from the US National Center for Health Statistics (2007-2019) to compare state-level trends in overdose mortality due to opioids in combination with 1) cocaine and 2) methamphetamine and other stimulants (MOS) across racial/ethnic groups (non-Hispanic White, non-Hispanic Black, Hispanic, and non-Hispanic Asian American/Pacific Islander). To avoid unstable estimates from small samples, we employed principles of small area estimation and a Bayesian hierarchical model, enabling information-sharing across groups. Black Americans experienced severe and worsening mortality due to opioids in combination with both cocaine and MOS, particularly in eastern states. Cocaine/opioid mortality increased 575% among Black people versus 184% in White people (Black, 0.60 to 4.05 per 100,000; White, 0.49 to 1.39 per 100,000). MOS/opioid mortality rose 16,200% in Black people versus 3,200% in White people (Black, 0.01 to 1.63 per 100,000; White, 0.09 to 2.97 per 100,000). Cocaine/opioid overdose mortality rose sharply among Hispanic and Asian Americans. State-group heterogeneity highlighted the importance of data disaggregation and methods to address small sample sizes. Research to understand the drivers of these trends and expanded efforts to address them are needed, particularly in minoritized groups.

Has Declining Opioid Dispensing to Cancer Patients Been Tailored to Risk of Opioid Harms?

CONTEXT: Opioid prescribing to cancer patients is declining, but it is unknown whether reductions have been tailored to those at highest risk of opioid-related harms. OBJECTIVES: Examine whether declines in opioid dispensing to patients receiving active cancer treatment are sharper in patients with substance use disorder (SUD) or mental health diagnoses. METHODS: We used 2008-2018 national, commercial healthcare claims data to examine adjusted and unadjusted trends in opioid dispensing (receipt of ≥1 fill; average daily dosage; receipt of high-dose opioids; receipt of concurrent opioids and benzodiazepines) to patients ages ≥18 receiving treatment for one of four cancer types (breast; colorectal; head and neck; sarcoma; N = 324,789 patients). To compare declines across subgroups with varying risk of opioid-related harms, we stratified by SUD and mental health diagnosis. To address potential confounding, we estimated subgroup-specific trends using generalized estimating equations, adjusting for covariates. RESULTS: Across groups, rate of ≥1 opioid fill per quarter fell 32.5% (95% CI: 31.8%-33.2%) from 2008 to 2018; daily dose among those receiving opioids fell 37.6% (95% CI: 36.7%-38.6%). In most cases, these declines were not sharper in subgroups at greater risk of opioid-related harms. For example, patients with opioid use disorder experienced the smallest declines in dispensing frequency, and there was no evidence that declines were sharper in patients with mental health diagnoses. CONCLUSION: Sharp declines in opioid prescribing during the drug overdose crisis have affected a wide range of patients undergoing cancer treatment and may not have been sufficiently tailored to patient characteristics. Research on implications for opioid-related harms and pain management is needed.

The COVID-19 pandemic and the health of people who use illicit opioids in New York City, the first 12 months.

BACKGROUND: Concurrent opioid-related overdose and COVID-19 crises in the U.S. have imposed unprecedented challenges on people who use illicit opioids. METHODS: Using the experiences of 324 people who use illicit opioids between April 2020 and March 2021, we examined four domains of health and well-being potentially impacted by COVID-19: drug risks and responses, healthcare and related services, material hardship, and mental health. Data were drawn from participants' completed monthly survey assessments which were grouped into four periods of interest for the unfolding pandemic: April-June 2020, July-October 2020, November-January 2021, and February-March 2021. RESULTS: A majority of measures in our four domains showed early COVID-19 related impacts, which quickly diminished as people and agencies responded to the pandemic. Difficulty obtaining food was the most frequently reported material hardship and appeared worst in April-June 2020. Over half of the population reported depression in April-June 2020, but this declined over the study period. Some participants reported changes to the heroin supply, including higher prices, lower quality, difficulty finding the drug, and fentanyl contamination. There was no discernable temporal shift in the frequency of use of each substance or the frequency of withdrawal symptoms. Over the study period, the mean number of overdoses per month decreased while the percent of opioid use events at which both a witness and naloxone were present (i.e., protected events) increased. Most participants receiving MOUD experienced an increase in take-home doses. CONCLUSIONS: Findings speak to the resilience of people who use drugs as a population with disproportionate experience of trauma and crisis and also to the rapid response of NYC health agencies and service providers working with this population. Despite evident signs of adaptability and resilience, the COVID-19 pandemic has highlighted some of the unique vulnerabilities of people who use illicit opioids and the need for greater rates of "protected" opioid use and greater availability of wrap-around services to efficiently address the safety, food security, mental health, and treatment needs of the population.

CDC Guideline For Opioid Prescribing Associated With Reduced Dispensing To Certain Patients With Chronic Pain.

The Centers for Disease Control and Prevention's 2016 Guideline for Prescribing Opioids for Chronic Pain aimed to reduce unsafe opioid prescribing. It is unknown whether the guideline influenced prescribing in the target population: patients with chronic, noncancer pain, who may be at particular risk for opioid-related harms. To study this question, we used 2014-18 data from a commercial claims database to examine associations between the release of the guideline and opioid dispensing in a national cohort of more than 450,000 patients with four common chronic pain diagnoses. We also examined whether any reductions associated with the guideline were larger for diagnoses for which there existed stronger expert consensus against opioid prescribing. Overall, the guideline was associated with substantial reductions in dispensing opioids, including a reduction in patients' rate of receiving at least one opioid prescription by approximately 20 percentage points by December 2018 compared with the counterfactual, no-guideline scenario. However, the reductions in dispensing did not vary by the strength of expert consensus against opioid prescribing. These findings suggest that although voluntary guidelines can drive changes in prescribing, questions remain about how clinicians are tailoring opioid reductions to best benefit patients.

Big Events theory and measures may help explain emerging long-term effects of current crises.

Big Events are periods during which abnormal large-scale events like war, economic collapse, revolts, or pandemics disrupt daily life and expectations about the future. They can lead to rapid change in health-related norms, beliefs, social networks and behavioural practices. The world is undergoing such Big Events through the interaction of COVID-19, a large economic downturn, massive social unrest in many countries, and ever-worsening effects of global climate change. Previous research, mainly on HIV/AIDS, suggests that the health effects of Big Events can be profound, but are contingent: Sometimes Big Events led to enormous outbreaks of HIV and associated diseases and conditions such as injection drug use, sex trading, and tuberculosis, but in other circumstances, Big Events did not do so. This paper discusses and presents hypotheses about pathways through which the current Big Events might lead to better or worse short and long term outcomes for various health conditions and diseases; considers how pre-existing societal conditions and changing 'pathway' variables can influence the impact of Big Events; discusses how to measure these pathways; and suggests ways in which research and surveillance might be conducted to improve human capacity to prevent or mitigate the effects of Big Events on human health.

Pathways to Educational Disparities in Disability Incidence: The Contributions of Excess Body Mass Index, Smoking, and Manual Labor Involvement.

OBJECTIVES: In the United States, educational disparities in disability are large and increasing, but the mechanisms underlying them are not well understood. We estimate the proportion of population-level educational disparities in disability incidence explained by excess body mass index (BMI), smoking, and manual labor. METHOD: We use waves 2003-2015 of the nationally representative Panel Study of Income Dynamics to calculate observed disability incidence and counterfactual incidence absent the key mediators (3,129 individuals; 13,168 observations). We take advantage of earlier-life measures, including childhood socioeconomic status, 1986 BMI, and occupational history between 1968 and 2001. To account for distinct processes in women and men at middle versus older ages, we stratify by gender and at age 65. RESULTS: Educational disparities in disability incidence were evident in women and men at younger and older ages, and were largest among older women. Together, the mediators of interest were estimated to explain roughly 60% of disparities in younger women, 65%-70% in younger men, 40% in older women, and 20%-60% in older men. The main contributors to disparities appeared to be excess BMI and smoking in younger women; manual labor and smoking in younger men; excess BMI in older women; and smoking in older men. DISCUSSION: These mediators explain much of disparities in earlier-age disability; successful interventions to address these factors may substantially reduce them. However, a considerable proportion of disparities remained unexplained, particularly at older ages, reflecting the myriad pathways by which educational attainment can influence disability status.

Contributions of obesity and cigarette smoking to incident disability: A longitudinal analysis.

Downward trends in U.S. disability levels are stagnating. Assessing the key contributors to U.S. disability incidence is critical to improving the functional status of the U.S. population. Using longitudinal, nationally representative data from waves 2003-2015 of the Panel Study of Income Dynamics (PSID), we estimated age-specific U.S. disability incidence and quantified the individual and joint contributions of obesity (contemporaneous and earlier-life; BMI ≥ 30) and cigarette smoking to disability incidence. Participants were adults ages 33-96 who participated in PSID in 1986 and at least two consecutive waves 2003-2015 (N = 3247). We conducted age-stratified logistic regressions to predict incident disability at middle and older ages (33-69 years, 70-96 years). Next, counterfactual scenarios were used to estimate the contributions of each risk factor to incident disability. Disability incidence was greater in women than men (5.8 and 4.5 cases per 100 person-years, respectively) and increased with age. Obesity and cigarette smoking jointly explained 17-38% of disability incidence; each factor contributed roughly equal amounts in all groups but older men, for whom smoking history appeared more important. Obesity and smoking appeared to explain more of disability at younger ages (women: 33.1%, 95% CI: 25.1 to 41.0%; men: 37.6%, 95% CI: 28.8 to 46.5%) than at older ages (women: 16.5%, 95% CI: 8.2 to 24.9%; men: 24.5.%, 95% CI: 12.7 to 36.3%). This study provides a benchmark for monitoring trends in U.S. disability incidence. Obesity and smoking are key contributors to disability, accounting for 17-38% of incident disability in U.S. adults.

Cost-effectiveness analysis of alternative naloxone distribution strategies: First responder and lay distribution in the United States.

BACKGROUND: The U.S. is facing an unprecedented number of opioid-related overdose deaths, and an array of other countries have experienced increases in opioid-related fatalities. In the U.S., naloxone is increasingly distributed to first responders to improve early administration to overdose victims, but its cost-effectiveness has not been studied. Lay distribution, in contrast, has been found to be cost-effective, but rising naloxone prices and increased mortality due to synthetic opioids may reduce cost-effectiveness. We evaluate the cost-effectiveness of increased naloxone distribution to (a) people likely to witness or experience overdose ("laypeople"); (b) police and firefighters; (c) emergency medical services (EMS) personnel; and (d) combinations of these groups. METHODS: We use a decision-analytic model to analyze the cost-effectiveness of eight naloxone distribution strategies. We use a lifetime horizon and conduct both a societal analysis (accounting for productivity and criminal justice system costs) and a health sector analysis. We calculate: the ranking of strategies by net monetary benefit; incremental cost-effectiveness ratios; and number of fatal overdoses. RESULTS: High distribution to all three groups maximized net monetary benefit and minimized fatal overdoses; it averted 21% of overdose deaths compared to minimum distribution. High distribution to laypeople and one of the other groups comprised the second and third best strategies. The majority of health gains resulted from increased lay distribution. In the societal analysis, every strategy was cost-saving compared to its next-best alternative; cost savings were greatest in the maximum distribution strategy. In the health sector analysis, all undominated strategies were cost-effective. Results were highly robust to deterministic and probabilistic sensitivity analysis. CONCLUSIONS: Increasing naloxone distribution to laypeople and first responder groups would maximize health gains and be cost-effective. If feasible, communities should distribute naloxone to all groups; otherwise, distribution to laypeople and one of the first responder groups should be emphasized.