Overdose responses among rural people who use drugs: A multi-regional qualitative study.

BACKGROUND: Efforts to distribute naloxone have equipped more people with the ability to reverse opioid overdoses but people who use drugs are often reluctant to call 911 due to concerns for legal repercussions. Rural communities face unique challenges in reducing overdose deaths compared to urban communities, including limited access to harm reduction services as well as greater concerns about stigma and privacy. METHODS: The Rural Opioid Initiative was funded in 2017 to better understand the health-related harms associated with the opioid crisis in rural US communities and consists of eight studies spanning ten states and 65 counties. Each study conducted semi-structured qualitative interviews with people who use drugs to understand contextual factors influencing drug use and health behaviors. We analyzed qualitative data from seven studies with data available at the time of analysis to understand peer response to overdose. RESULTS: Of the 304 participants interviewed, 55% were men, 70% were white, 80% reported current injection drug use, and 60% reported methamphetamine use. Similar to what has been found in studies focused on urban settings, people who use drugs in rural communities use a range of strategies to reverse overdoses, including non-evidence-based approaches. Several reported that multiple doses of naloxone are needed to reverse overdose. Three themes emerged around the willingness to call 911, including (1) hesitancy to call 911 for fear of legal consequences, (2) negative perceptions or experiences with law enforcement officers, and (3) efforts to obtain medical intervention while avoiding identification/law enforcement involvement. CONCLUSION: People who use drugs employ multiple strategies to attempt overdose reversal, including non-evidence-based approaches. Greater education about the most effective and least harmful strategies is needed. Reluctance to call 911 is rooted in concerns about potential legal consequences as well as perceptions about law enforcement officers, which may be heightened in rural communities where people who use drugs are more easily identified by law enforcement. People who use drugs will go to great strides to connect their peers to needed medical services, suggesting that comprehensive interventions to reduce interactions with law enforcement officers and eliminate legal consequences for reporting overdoses are critical.

Racial and Ethnic Disparities in Geographic Availability of Buprenorphine.

OBJECTIVES: Overdose mortality has risen most rapidly among racial and ethnic minority groups while buprenorphine prescribing has increased disproportionately in predominantly non-Hispanic White urban areas. To identify whether buprenorphine availability equitably meets the needs of diverse populations, we examined the differential geographic availability of buprenorphine in areas with greater concentrations of racial and ethnic minority groups. METHODS: Using IQVIA longitudinal prescription data, IQVIA OneKey data, and Microsoft Bing Maps, we calculated 2 outcome measures across the continental United States: the number of buprenorphine prescribers per 1000 residents within a 30-minute drive of a ZIP code, and the number of buprenorphine prescriptions dispensed per capita at retail pharmacies among nearby buprenorphine prescribers. We then estimated differences in these outcomes by ZIP codes' racial and ethnic minority composition and rurality with t tests. RESULTS: Buprenorphine prescribers per 1000 residents within a 30-minute drive decreased by 3.8 prescribers per 1000 residents in urban ZIP codes (95% confidence interval = -4.9 to -2.7) and 2.6 in rural ZIP codes (95% confidence interval = -3.0 to -2.2) whose populations consisted of ≥5% racial and ethnic minority groups. There were 45% to 55% fewer prescribers in urban areas and 62% to 79% fewer prescribers in rural areas as minority composition increased. Differences in dispensed buprenorphine per capita were similar but larger in magnitude. CONCLUSIONS: Achieving more equitable buprenorphine access requires not only increasing the number of buprenorphine-prescribing clinicians; in urban areas with higher racial and ethnic minority group populations, it also requires efforts to promote greater buprenorphine prescribing among already prescribing clinicians.

A case of naltrexone-induced acute eosinophilic pneumonia.

Acute eosinophilic pneumonia (AEP) is a rare cause of acute respiratory failure. Clinical presentations can range from dyspnoea, fever and cough, to rapidly progressive and potentially fulminant respiratory failure. While its exact cause is often unknown, associations with inhalational injuries and exposures to new medications have been described.We report a case of a middle-aged, non-smoking man with a history of alcohol use disorder. He presented with 4 days of shortness of breath that started hours after taking injectable naltrexone (Vivitrol). The patient had rapidly worsening hypoxaemia, necessitating emergent bronchoscopy with transbronchial biopsies and bronchoalveolar lavage which showed 66% eosinophils. The patient was intubated for the procedure and unable to get extubated due to worsening hypoxaemic respiratory failure with high fractional inspired oxygen requirements. Chest radiograph showed worsening lung infiltrates and with a high index of suspicion for AEP, he was started empirically on methylprednisolone. He had rapid improvement in his respiratory status and was extubated on day 5 of admission then discharged on day 8. Histopathological examination confirmed acute/subacute eosinophilic pneumonia. A 3-week post-discharge follow-up chest radiograph confirmed the full resolution of pulmonary infiltrates.Naltrexone-induced AEP is rare, with only six other cases reported in the literature. Careful history taking and prompt evaluation for AEP are important given the potential for rapid progression to acute hypoxic respiratory failure and the excellent response to steroid treatment.

Effects of perioperative low-dose naloxone on the immune system in patients undergoing laparoscopic-assisted total gastrectomy: a randomized controlled trial.

BACKGROUND: Low immune function after laparoscopic total gastrectomy puts patients at risk of infection-related complications. Low-dose naloxone (LDN) can improve the prognosis of patients suffering from chronic inflammatory diseases or autoimmune diseases. The use of LDN during perioperative procedures may reduce perioperative complications. The purpose of this study was to examine the effects of LDN on endogenous immune function in gastric cancer patients and its specific mechanisms through a randomized controlled trial. METHODS: Fifty-five patients who underwent laparoscopic-assisted total gastrectomy were randomly assigned to either a naloxone group (n = 23) or a nonnaloxone group (n = 22). Patients in the naloxone group received 0.05 µg/kg-1.h- 1naloxone from 3 days before surgery to 5 days after surgery via a patient-controlled intravenous injection (PCIA) pump, and patients in the nonnaloxone group did not receive special treatment. The primary outcomes were the rates of postoperative complications and immune function assessed by NK cell, CD3+ T cell, CD4+ T cell, CD8+ T cell, WBC count, neutrophil percentage, and IL-6 and calcitonin levels. The secondary outcomes were the expression levels of TLR4 (Toll-like receptor), IL-6 and TNF-α in gastric cancer tissue. RESULTS: Compared with the nonnaloxone group, the naloxone group exhibited a lower incidence of infection (in the incision, abdomen, and lungs) (P < 0.05). The numbers of NK cells and CD8+ T cells in the naloxone group were significantly greater than those in the nonnaloxone group at 24 h after surgery (P < 0.05) and at 96 h after surgery (P < 0.05). Compared with those in the nonnaloxone group, the CD3 + T-cell (P < 0.05) and CD4 + T-cell (P < 0.01) counts were significantly lower in the naloxone group 24 h after surgery. At 24 h and 96 h after surgery, the WBC count (P < 0.05) and neutrophil percentage (P < 0.05) were significantly greater in the nonnaloxone group. The levels of IL-6 (P < 0.05) and calcitonin in the nonnaloxone group were significantly greater at 24 h after surgery. At 24 h following surgery, the nonnaloxone group had significantly greater levels of IL-6 (P < 0.05) and calcitonin than did the naloxone group. Compared with those in the naloxone group, the expression levels of TLR4 (P < 0.05) in gastric cancer tissue in the naloxone group were greater; however, the expression levels of IL-6 (P < 0.01) and TNF-α (P < 0.01) in the naloxone group were greater than those in the nonnaloxone group. CONCLUSION: Laparoscopic total gastrectomy patients can benefit from 0.05 ug/kg- 1. h- 1 naloxone by reducing their risk of infection. It is possible that LDN alters the number of cells in lymphocyte subpopulations, such as NK cells, CD3 + T cells, and CD4 + T cells, and the CD4+/CD8 + T-cell ratio or alters TLR4 receptor expression in immune cells, thereby altering immune cell activity. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry on 24/11/2023 (ChiCTR2300077948).

Implementation and Evaluation of a Bystander Naloxone Training Course.

Introduction: Bystander provision of naloxone is a key modality to reduce opioid overdose-related death. Naloxone training courses are available, but no standardized program exists. As part of a bystander empowerment course, we created and evaluated a brief naloxone training module. Methods: This was a retrospective evaluation of a naloxone training course, which was paired with Stop the Bleed training for hemorrhage control and was offered to administrative staff in an office building. Participants worked in an organization related to healthcare, but none were clinicians. The curriculum included the following topics: 1) background about the opioid epidemic; 2) how to recognize the signs of an opioid overdose; 3) actions not to take when encountering an overdose victim; 4) the correct steps to take when encountering an overdose victim; 5) an overview of naloxone products; and 6) Good Samaritan protection laws. The 20-minute didactic section was followed by a hands-on session with nasal naloxone kits and a simulation mannequin. The course was evaluated with the Opioid Overdose Knowledge (OOKS) and Opioid Overdose Attitudes (OOAS) scales for take-home naloxone training evaluation. We used the paired Wilcoxon signed-rank test to compare scores pre- and post-course. Results: Twenty-eight participants completed the course. The OOKS, measuring objective knowledge about opioid overdose and naloxone, had improved scores from a median of 73.2% (interquartile range [IQR] 68.3%-79.9%) to 91.5% (IQR 85.4%-95.1%), P < 0.001. The three domains on the OOAS score also showed statistically significant results. Competency to manage an overdose improved on a five-point scale from a median of 2.5 (IQR 2.4-2.9) to a median of 3.7 (IQR 3.5-4.1), P < 0.001. Concerns about managing an overdose decreased (improved) from a median of 2.3 (IQR 1.9-2.6) to median 1.8 (IQR 1.5-2.1), P < 0.001. Readiness to intervene in an opioid overdose improved from a median of 4 (IQR 3.8-4.2) to a median of 4.2 (IQR 4-4.2), P < 0.001. Conclusion: A brief course designed to teach bystanders about opioid overdose and naloxone was feasible and effective. We encourage hospitals and other organizations to use and promulgate this model. Furthermore, we suggest the convening of a national consortium to achieve consensus on program content and delivery.

Addressing System and Clinician Barriers to Emergency Department-initiated Buprenorphine: An Evaluation of Post-intervention Physician Outcomes.

Introduction: Emergency departments (ED) are in the unique position to initiate buprenorphine, an evidence-based treatment for opioid use disorder (OUD). However, barriers at the system and clinician level limit its use. We describe a series of interventions that address these barriers to ED-initiated buprenorphine in one urban ED. We compare post-intervention physician outcomes between the study site and two affiliated sites without the interventions. Methods: This was a cross-sectional study conducted at three affiliated urban EDs where the intervention site implemented OUD-related electronic note templates, clinical protocols, a peer navigation program, education, and reminders. Post-intervention, we administered an anonymous, online survey to physicians at all three sites. Survey domains included demographics, buprenorphine experience and knowledge, comfort with addressing OUD, and attitudes toward OUD treatment. Physician outcomes were compared between the intervention site and the control sites with bivariate tests. We used logistic regression controlling for significant demographic differences to compare physicians' buprenorphine experience. Results: Of 113 (51%) eligible physicians, 58 completed the survey: 27 from the intervention site, and 31 from the control sites. Physicians at the intervention site were more likely to spend <75% of their work week in clinical practice and to be in medical practice for <7 years. Buprenorphine knowledge (including status of buprenorphine prescribing waiver), comfort with addressing OUD, and attitudes toward OUD treatment did not differ significantly between the sites. Physicians were 4.5 times more likely to have administered buprenorphine at the intervention site (odds ratio [OR] 4.5, 95% confidence interval 1.4-14.4, P = 0.01), which remained significant after adjusting for clinical time and years in practice, (OR 3.5 and 4.6, respectively). Conclusion: Physicians exposed to interventions addressing system- and clinician-level implementation barriers were at least three times as likely to have administered buprenorphine in the ED. Physicians' buprenorphine knowledge, comfort with addressing and attitudes toward OUD treatment did not differ significantly between sites. Our findings suggest that ED-initiated buprenorphine can be facilitated by addressing implementation barriers, while physician knowledge, comfort, and attitudes may be harder to improve.

Retrospective study investigating naloxone prescribing and cost in US Medicaid and Medicare patients.

BACKGROUND: Opioid overdoses in the USA have increased to unprecedented levels. Administration of the opioid antagonist naloxone can prevent overdoses. OBJECTIVE: This study was conducted to reveal the pharmacoepidemiologic patterns in naloxone prescribing to Medicaid patients from 2018 to 2021 as well as Medicare in 2019. DESIGN: Observational pharmacoepidemiologic study SETTING: US Medicare and Medicaid naloxone claims INTERVENTION: The Medicaid State Drug Utilisation Data File was utilised to extract information on the number of prescriptions and the amount prescribed of naloxone at a national and state level. The Medicare Provider Utilisation and Payment was also utilised to analyse prescription data from 2019. OUTCOME MEASURES: States with naloxone prescription rates that were outliers of quartile analysis were noted. RESULTS: The number of generic naloxone prescriptions per 100 000 Medicaid enrollees decreased by 5.3%, whereas brand naloxone prescriptions increased by 245.1% from 2018 to 2021. There was a 33.1-fold difference in prescriptions between the highest (New Mexico=1809.5) and lowest (South Dakota=54.6) states in 2019. Medicare saw a 30.4-fold difference in prescriptions between the highest (New Mexico) and lowest states (also South Dakota) after correcting per 100 000 enrollees. CONCLUSIONS: This pronounced increase in the number of naloxone prescriptions to Medicaid patients from 2018 to 2021 indicates a national response to this widespread public health emergency. Further research into the origins of the pronounced state-level disparities is warranted.

Activation of Cardiac δ2-Opioid Receptors Increases Heart Tolerance to Reperfusion.

Coronary occlusion (45 min) and reperfusion (120 min) in male Wistar rats in vivo, as well as total ischemia (45 min) of an isolated rat heart followed by reperfusion (30 min) were reproduced. The selective δ2-opioid receptor agonist deltorphin II (0.12 mg/kg and 152 nmol/liter) was administered intravenously 5 min before reperfusion in vivo or added to the perfusion solution at the beginning of reperfusion of the isolated heart. The peripheral opioid receptor antagonist naloxone methiodide and δ2-opioid receptor antagonist naltriben were used in doses of 5 and 0.3 mg/kg, respectively. It was found that the infarct-limiting effect of deltorphin II is associated with the activation of δ2-opioid receptors. We have demonstrated that deltorphin II can improve the recovery of the contractility of the isolated heart after total ischemia.

Low-dose naltrexone for post-COVID fatigue syndrome: a study protocol for a double-blind, randomised trial in British Columbia.

INTRODUCTION: A significant proportion of individuals suffering from post COVID-19 condition (PCC, also known as long COVID) can present with persistent, disabling fatigue similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-viral fatigue syndromes. There remains no clear pharmacological therapy for patients with this subtype of PCC, which can be referred to as post-COVID fatigue syndrome (PCFS). A low dose of the opioid antagonist naltrexone (ie, low-dose naltrexone (LDN)) has emerged as an off-label treatment for treating fatigue and other symptoms in PCC. However, only small, non-controlled studies have assessed LDN in PCC, so randomised trials are urgently required. METHODS AND ANALYSIS: A prospective, randomised, double-blind, parallel arm, placebo-controlled phase II trial will be performed to assess the efficacy of LDN for improving fatigue in PCFS. The trial will be decentralised and open to eligible individuals throughout the Canadian province of British Columbia (BC). Participants will be recruited through the province-wide Post-COVID-19 Interdisciplinary Clinical Care Network (PC-ICCN) and research volunteer platform (REACH BC). Eligible participants will be 19-69 years old, have had a confirmed or physician-suspected SARS-CoV-2 infection at least 3 months prior and meet clinical criteria for PCFS adapted from the Institute of Medicine ME/CFS criteria. Individuals who are taking opioid medications, have a history of ME/CFS prior to COVID-19 or history of significant liver disease will be excluded. Participants will be randomised to an LDN intervention arm (n=80) or placebo arm (n=80). Participants in each arm will be prescribed identical capsules starting at 1 mg daily and follow a prespecified schedule for up-titration to 4.5 mg daily or the maximum tolerated dose. The trial will be conducted over 16 weeks, with assessments at baseline, 6, 12 and 16 weeks. The primary outcome will be fatigue severity at 16 weeks evaluated by the Fatigue Severity Scale. Secondary outcomes will include pain Visual Analogue Scale score, overall symptom severity as measured by the Patient Phenotyping Questionnaire Short Form, 7-day step count and health-related quality of life measured by the EuroQol 5-Dimension questionnaire. ETHICS AND DISSEMINATION: The trial has been authorised by Health Canada and approved by The University of British Columbia/Children's and Women's Health Centre of British Columbia Research Ethics Board. On completion, findings will be disseminated to patients, caregivers and clinicians through engagement activities within existing PCC and ME/CFS networks. Results will be published in academic journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT05430152.

Managing emergency department patients with opioid use disorder.

As the United States continues to grapple with the opioid crisis, emergency clinicians are on the front lines of managing patients with opioid use disorder. This issue reviews tools and best practices in emergency department management of patients with opioid overdose and opioid withdrawal, and how substance use history will inform treatment planning and disposition. As growing evidence shows that medications for opioid use disorder (MOUD)- buprenorphine, methadone, and naltrexone-can have lasting impacts on patients' addiction recovery, strategies for assessing patient readiness for MOUD and overcoming barriers to emergency department initiation of these medications are reviewed. Newer approaches to buprenorphine dosing (high-dose, low-dose, home induction, and long-acting injectable dosing) are also reviewed.

High-dose naloxone formulations are not as essential as we thought.

Naloxone is an effective FDA-approved opioid antagonist for reversing opioid overdoses. Naloxone is available to the public and can be administered through intramuscular (IM), intravenous (IV), and intranasal spray (IN) routes. Our literature review investigates the adequacy of two doses of standard IM or IN naloxone in reversing fentanyl overdoses compared to newer high-dose naloxone formulations. Moreover, our initiative incorporates the experiences of people who use drugs, enabling a more practical and contextually-grounded analysis. The evidence indicates that the vast majority of fentanyl overdoses can be successfully reversed using two standard IM or IN dosages. Exceptions include cases of carfentanil overdose, which necessitates ≥ 3 doses for reversal. Multiple studies documented the risk of precipitated withdrawal using ≥ 2 doses of naloxone, notably including the possibility of recurring overdose symptoms after resuscitation, contingent upon the half-life of the specific opioid involved. We recommend distributing multiple doses of standard IM or IN naloxone to bystanders and educating individuals on the adequacy of two doses in reversing fentanyl overdoses. Individuals should continue administration until the recipient is revived, ensuring appropriate intervals between each dose along with rescue breaths, and calling emergency medical services if the individual is unresponsive after two doses. We do not recommend high-dose naloxone formulations as a substitute for four doses of IM or IN naloxone due to the higher cost, risk of precipitated withdrawal, and limited evidence compared to standard doses. Future research must take into consideration lived and living experience, scientific evidence, conflicts of interest, and the bodily autonomy of people who use drugs.

Evaluation of Strategies to Enhance Community-Based Naloxone Distribution Supported by an Opioid Settlement.

Importance: Many US states are substantially increasing community-based naloxone distribution, supported in part through settlements from opioid manufacturers and distributors. Objectives: To evaluate the potential impact of increased naloxone availability on opioid overdose deaths (OODs) and explore strategies to enhance this impact by integrating interventions to address solitary drug use. Design, Setting, and Participants: This decision analytical modeling study used PROFOUND (Prevention and Rescue of Fentanyl and Other Opioid Overdoses Using Optimized Naloxone Distribution Strategies), a previously published simulation model, to forecast annual OODs between January 2023 and December 2025. The simulated study population included individuals from Rhode Island who misused opioids and stimulants and were at risk for opioid overdose. Exposures: The study modeled expanded naloxone distribution supported by the state's opioid settlement (50 000 naloxone nasal spray kits each year). Two approaches to expanding naloxone distribution were evaluated: one based on historical spatial patterns of naloxone distribution (supply-based approach) and one based on the spatial distribution of individuals at risk (demand-based approach). In addition, hypothetical interventions to enhance the likelihood of witnessed overdoses in private or semiprivate settings were considered. Main Outcomes and Measures: Annual number of OODs and ratio of fatal to nonfatal opioid overdoses. Results: Modeling results indicated that distributing more naloxone supported by the state's opioid settlement could reduce OODs by 6.3% (95% simulation interval [SI], 0.3%-13.7%) and 8.8% (95% SI, 1.8%-17.5%) in 2025 with the supply-based and demand-based approaches, respectively. However, increasing witnessed overdoses by 20% to 60% demonstrated greater potential for reducing OODs, ranging from 8.5% (95% SI, 0.0%-20.3%) to 24.1% (95% SI, 8.6%-39.3%). Notably, synergistic associations were observed when combining both interventions: increased naloxone distribution with the 2 approaches and a 60% increase in witnessed overdoses could reduce OODs in 2025 by 33.5% (95% SI, 17.1%-50.4%) and 37.4% (95% SI, 19.6%-56.3%), respectively. Conclusions and Relevance: These findings suggest that interventions to address solitary drug use are needed to maximize the impact of continued efforts to increase community-based naloxone distribution, which may be particularly important for jurisdictions that have strong community-based naloxone distribution programs.

Rapid Initiation of Injection Naltrexone for Opioid Use Disorder: A Stepped-Wedge Cluster Randomized Clinical Trial.

Importance: Injectable extended-release (XR)-naltrexone is an effective treatment option for opioid use disorder (OUD), but the need to withdraw patients from opioid treatment prior to initiation is a barrier to implementation. Objective: To compare the effectiveness of the standard procedure (SP) with the rapid procedure (RP) for XR-naltrexone initiation. Design, Setting, and Participants: The Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone study was an optimized stepped-wedge cluster randomized trial conducted at 6 community-based inpatient addiction treatment units. Units using the SP were randomly assigned at 14-week intervals to implement the RP. Participants admitted with OUD received the procedure the unit was delivering at the time of their admission. Participant recruitment took place between March 16, 2021, and July 18, 2022. The last visit was September 21, 2022. Interventions: Standard procedure, based on the XR-naltrexone package insert (approximately 5-day buprenorphine taper followed by a 7- to 10-day opioid-free period and RP, defined as 1 day of buprenorphine at minimum necessary dose, 1 opioid-free day, and ascending low doses of oral naltrexone and adjunctive medications (eg, clonidine, clonazepam, antiemetics) for opioid withdrawal. Main Outcomes and Measures: Receipt of XR-naltrexone injection prior to inpatient discharge (primary outcome). Secondary outcomes included opioid withdrawal scores and targeted safety events and serious adverse events. All analyses were intention-to-treat. Results: A total of 415 participants with OUD were enrolled (mean [SD] age, 33.6 [8.48] years; 205 [49.4%] identified sex as male); 54 [13.0%] individuals identified as Black, 91 [21.9%] as Hispanic, 290 [69.9%] as White, and 22 [5.3%] as multiracial. Rates of successful initiation of XR-naltrexone among the RP group (141 of 225 [62.7%]) were noninferior to those of the SP group (68 of 190 [35.8%]) (odds ratio [OR], 3.60; 95% CI, 2.12-6.10). Withdrawal did not differ significantly between conditions (proportion of days with a moderate or greater maximum Clinical Opiate Withdrawal Scale score (>12) for RP vs SP: OR, 1.25; 95% CI, 0.62-2.50). Targeted safety events (RP: 12 [5.3%]; SP: 4 [2.1%]) and serious adverse events (RP: 15 [6.7%]; SP: 3 [1.6%]) were infrequent but occurred more often with RP than SP. Conclusions and Relevance: In this trial, the RP of XR-naltrexone initiation was noninferior to the standard approach and saved time, although it required more intensive medical management and safety monitoring. The results of this trial suggest that rapid initiation could make XR-naltrexone a more viable treatment for patients with OUD. Trial Registration: ClinicalTrials.gov Identifier: NCT04762537.

Buprenorphine Prescribing and Challenges Faced Among National Health Service Corps Clinicians.

Importance: The National Health Service Corps (NHSC) Loan Repayment Program (LRP) expansion in fiscal year (FY) 2019 intended to improve access to medication for opioid use disorder (MOUD) by adding more clinicians who could prescribe buprenorphine. However, some clinicians still face barriers to prescribing, which may vary between rural and nonrural areas. Objective: To examine the growth in buprenorphine prescribing by NHSC clinicians for Medicaid beneficiaries during the NHSC LRP expansion and describe the challenges to prescribing that persist in rural and nonrural areas. Design, Setting, and Participants: This cross-sectional study analyzed preexpansion and postexpansion Medicaid claims data to evaluate the percentage of prescriptions of buprenorphine filled during FY 2017 through 2021. This study also analyzed challenges and barriers to prescribing MOUD between rural and urban areas, using results from annual surveys conducted with NHSC clinicians and sites from FY 2019 through FY 2021. Exposure: Prescribing of buprenorphine by NHSC clinicians. Main Outcomes and Measures: The main outcomes were the percentage and number of Medicaid beneficiaries with opioid use disorder (OUD) who filled a prescription for buprenorphine before and after the LRP expansion and the challenges NHSC clinicians and sites faced in providing substance use disorder and OUD services. Survey results were analyzed using descriptive statistics. Results: During FYs 2017 through 2021, 7828 NHSC clinicians prescribed buprenorphine (standard LRP: mean [SD] age, 38.1 [8.4] years and 4807 females [78.9%]; expansion LRPs: mean [SD] age, 39.4 [8.1] years and 1307 females [75.0%]). A total of 3297 NHSC clinicians and 4732 NHSC sites responded to at least 1 survey question to the 3 surveys. The overall percentage of Medicaid beneficiaries with OUD who filled a prescription for buprenorphine during the first 2.5 years post expansion increased significantly from 18.9% before to 43.7% after expansion (an increase of 123 422 beneficiaries; P < .001). The percentage more than doubled among beneficiaries living in areas with a high Social Vulnerability Index score (from 17.0% to 36.7%; an increase of 31 964) and among beneficiaries living in rural areas (from 20.8% to 55.7%; an increase of 45 523). However, 773 of 2140 clinicians (36.1%; 95% CI, 33.6%-38.6%) reported a lack of mental health services to complement medication for OUD treatment, and 290 of 1032 clinicians (28.1%; 95% CI, 24.7%-31.7%) reported that they did not prescribe buprenorphine due to a lack of supervision, mentorship, or peer consultation. Conclusions and Relevance: These findings suggest that although the X-waiver requirement has been removed and Substance Abuse and Mental Health Services Administration guidelines encourage all eligible clinicians to screen and offer patients with OUD buprenorphine, as permissible by state law, more trained health care workers and improved care coordination for counseling and referral services are needed to support comprehensive OUD treatment.

Barriers to Buprenorphine Dispensing by Medicaid-Participating Community Retail Pharmacies.

Importance: Controlled substances have regulatory requirements under the US Federal Controlled Substance Act that must be met before pharmacies can stock and dispense them. However, emerging evidence suggests there are pharmacy-level barriers in access to buprenorphine for treatment for opioid use disorder even among pharmacies that dispense other opioids. Objective: To estimate the proportion of Medicaid-participating community retail pharmacies that dispense buprenorphine, out of Medicaid-participating community retail pharmacies that dispense other opioids and assess if the proportion dispensing buprenorphine varies by Medicaid patient volume or rural-urban location. Design, Setting, and Participants: This serial cross-sectional study included Medicaid pharmacy claims (2016-2019) data from 6 states (Kentucky, Maine, North Carolina, Pennsylvania, Virginia, West Virginia) participating in the Medicaid Outcomes Distributed Research Network (MODRN). Community retail pharmacies serving Medicaid-enrolled patients were included, mail-order pharmacies were excluded. Analyses were conducted from September 2022 to August 2023. Main Outcomes and Measures: The proportion of pharmacies dispensing buprenorphine approved for opioid use disorder among pharmacies dispensing an opioid analgesic or buprenorphine prescription to at least 1 Medicaid enrollee in each state. Pharmacies were categorized by median Medicaid patient volume (by state and year) and rurality (urban vs rural location according to zip code). Results: In 2016, 72.0% (95% CI, 70.9%-73.0%) of the 7038 pharmacies that dispensed opioids also dispensed buprenorphine to Medicaid enrollees, increasing to 80.4% (95% CI, 79.5%-81.3%) of 7437 pharmacies in 2019. States varied in the percent of pharmacies dispensing buprenorphine in Medicaid (range, 73.8%-96.4%), with significant differences between several states found in 2019 (χ2 P < .05), when states were most similar in the percent of pharmacies dispensing buprenorphine. A lower percent of pharmacies with Medicaid patient volume below the median dispensed buprenorphine (69.1% vs 91.7% in 2019), compared with pharmacies with above-median patient volume (χ2 P < .001). Conclusions and Relevance: In this serial cross-sectional study of Medicaid-participating pharmacies, buprenorphine was not accessible in up to 20% of community retail pharmacies, presenting pharmacy-level barriers to patients with Medicaid seeking buprenorphine treatment. That some pharmacies dispensed opioid analgesics but not buprenorphine suggests that factors other than compliance with the Controlled Substance Act influence pharmacy dispensing decisions.

Reducing overdose deaths among persons with opioid use disorder in connecticut.

BACKGROUND: People in Connecticut are now more likely to die of a drug-related overdose than a traffic accident. While Connecticut has had some success in slowing the rise in overdose death rates, substantial additional progress is necessary. METHODS: We developed, verified, and calibrated a mechanistic simulation of alternative overdose prevention policy options, including scaling up naloxone (NLX) distribution in the community and medications for opioid use disorder (OUD) among people who are incarcerated (MOUD-INC) and in the community (MOUD-COM) in a simulated cohort of people with OUD in Connecticut. We estimated how maximally scaling up each option individually and in combinations would impact 5-year overdose deaths, life-years, and quality-adjusted life-years. All costs were assessed in 2021 USD, employing a health sector perspective in base-case analyses and a societal perspective in sensitivity analyses, using a 3% discount rate and 5-year and lifetime time horizons. RESULTS: Maximally scaling NLX alone reduces overdose deaths 20% in the next 5 years at a favorable incremental cost-effectiveness ratio (ICER); if injectable rather than intranasal NLX was distributed, 240 additional overdose deaths could be prevented. Maximally scaling MOUD-COM and MOUD-INC alone reduce overdose deaths by 14% and 6% respectively at favorable ICERS. Considering all permutations of scaling up policies, scaling NLX and MOUD-COM together is the cost-effective choice, reducing overdose deaths 32% at ICER $19,000/QALY. In sensitivity analyses using a societal perspective, all policy options were cost saving and overdose deaths reduced 33% over 5 years while saving society $338,000 per capita over the simulated cohort lifetime. CONCLUSIONS: Maximally scaling access to naloxone and MOUD in the community can reduce 5-year overdose deaths by 32% among people with OUD in Connecticut under realistic budget scenarios. If societal cost savings due to increased productivity and reduced crime costs are considered, one-third of overdose deaths can be reduced by maximally scaling all three policy options, while saving money.

Topiramate Versus Naltrexone for Alcohol Use Disorder: A Genotype-Stratified Double-Blind Randomized Controlled Trial.

OBJECTIVE: There have been no well-controlled and well-powered comparative trials of topiramate with other pharmacotherapies for alcohol use disorder (AUD), such as naltrexone. Moreover, the literature is mixed on the effects of two polymorphisms-rs2832407 (in GRIK1) and rs1799971 (in OPRM1)-on response to topiramate and naltrexone, respectively. The authors sought to examine the comparative effectiveness of topiramate and naltrexone in improving outcomes in AUD and to examine the role of the rs2832407 and rs1799971 polymorphisms, respectively, on response to these medications. METHODS: In a 12-week, double-blind, placebo-controlled, randomized, multisite, genotype-stratified (rs2832407 and rs1799971) clinical trial comparing topiramate and naltrexone in treating AUD, 147 patients with AUD were randomly assigned to treatment with topiramate or naltrexone, stratified by genotype (rs2832407*CC and *AC/AA genotypes and rs1799971*AA and *AG/GG genotypes). The predefined primary outcome was number of heavy drinking days per week. Predefined secondary outcomes included standard drinks per drinking day per week, body mass index (BMI), craving, markers of liver injury, mood, and adverse events. RESULTS: For the number of heavy drinking days per week, there was a near-significant time-by-treatment interaction. For the number of standard drinks per drinking day per week, there was a significant time-by-treatment interaction, which favored topiramate. There were significant time-by-treatment effects, with greater reductions observed with topiramate than naltrexone for BMI, craving, and gamma-glutamyltransferase level. Withdrawal due to side effects occurred in 8% and 5% of the topiramate and naltrexone groups, respectively. Neither polymorphism showed an effect on treatment response. CONCLUSIONS: Topiramate is at least as effective and safe as the first-line medication, naltrexone, in reducing heavy alcohol consumption, and superior in reducing some clinical outcomes. Neither rs2832407 nor rs1799971 had effects on topiramate and naltrexone treatments, respectively.