Novel Therapeutic and Program-Based Approaches to Opioid Use Disorders.

Opioid use disorder continues to drive overdose deaths in many countries, including the United States. Illicit fentanyl and its analogues have emerged as key contributors to the complications and mortality associated with opioid use disorder. Medications for opioid use disorder treatment, such as methadone and buprenorphine, are safe and substantially reduce opioid use, infectious complications, and mortality risk, but remain underutilized. Polysubstance use and emerging substances such as xylazine and designer benzodiazepines create additional treatment challenges. Recent clinical and policy innovations in treatment delivery, including telemedicine, bridge clinics, and expanded models for accessing methadone have the potential to increase access to life-saving care for people living with opioid use disorder.

Racial Inequality in Receipt of Medications for Opioid Use Disorder.

BACKGROUND: Since 2010, Black persons in the United States have had a greater increase in opioid overdose-related mortality than other groups, but national-level evidence characterizing racial and ethnic disparities in the use of medications for opioid use disorder (OUD) is limited. METHODS: We used Medicare claims data from the 2016-2019 period for a random 40% sample of fee-for-service beneficiaries who were Black, Hispanic, or White; were eligible for Medicare owing to disability; and had an index event related to OUD (nonfatal overdose treated in an emergency department or inpatient setting, hospitalization with injection drug use-related infection, or inpatient or residential rehabilitation or detoxification care). We measured the receipt of medications to treat OUD (buprenorphine, naltrexone, and naloxone), the receipt of high-risk medications (opioid analgesics and benzodiazepines), and health care utilization, all in the 180 days after the index event. We estimated differences in outcomes according to race and ethnic group with adjustment for beneficiary age, sex, index event, count of chronic coexisting conditions, and state of residence. RESULTS: We identified 25,904 OUD-related index events among 23,370 beneficiaries, with 3937 events (15.2%) occurring among Black patients, 2105 (8.1%) among Hispanic patients, and 19,862 (76.7%) among White patients. In the 180 days after the index event, patients received buprenorphine after 12.7% of events among Black patients, after 18.7% of those among Hispanic patients, and after 23.3% of those among White patients; patients received naloxone after 14.4%, 20.7%, and 22.9%, respectively; and patients received benzodiazepines after 23.4%, 29.6%, and 37.1%, respectively. Racial differences in the receipt of medications to treat OUD did not change appreciably from 2016 to 2019 (buprenorphine receipt: after 9.1% of index events among Black patients vs. 21.6% of those among White patients in 2016, and after 14.1% vs. 25.5% in 2019). In all study groups, patients had multiple ambulatory visits in the 180 days after the index event (mean number of visits, 6.6 after events among Black patients, 6.7 after events among Hispanic patients, and 7.6 after events among White patients). CONCLUSIONS: Racial and ethnic differences in the receipt of medications to treat OUD after an index event related to this disorder among patients with disability were substantial and did not change over time. The high incidence of ambulatory visits in all groups showed that disparities persisted despite frequent health care contact. (Funded by the National Institute on Drug Abuse and the National Institute on Aging.).

Buprenorphine versus Methadone for Opioid Use Disorder in Pregnancy.

BACKGROUND: Opioid agonist therapy is strongly recommended for pregnant persons with opioid use disorder. Buprenorphine may be associated with more favorable neonatal and maternal outcomes than methadone, but existing data are limited. METHODS: We conducted a cohort study involving pregnant persons who were enrolled in public insurance programs in the United States during the period from 2000 through 2018 in which we examined outcomes among those who received buprenorphine as compared with those who received methadone. Exposure to the two medications was assessed in early pregnancy (through gestational week 19), late pregnancy (gestational week 20 through the day before delivery), and the 30 days before delivery. Risk ratios for neonatal and maternal outcomes were adjusted for confounders with the use of propensity-score overlap weights. RESULTS: The data source for the study consisted of 2,548,372 pregnancies that ended in live births. In early pregnancy, 10,704 pregnant persons were exposed to buprenorphine and 4387 to methadone. In late pregnancy, 11,272 were exposed to buprenorphine and 5056 to methadone (9976 and 4597, respectively, in the 30 days before delivery). Neonatal abstinence syndrome occurred in 52.0% of the infants who were exposed to buprenorphine in the 30 days before delivery as compared with 69.2% of those exposed to methadone (adjusted relative risk, 0.73; 95% confidence interval [CI], 0.71 to 0.75). Preterm birth occurred in 14.4% of infants exposed to buprenorphine in early pregnancy and in 24.9% of those exposed to methadone (adjusted relative risk, 0.58; 95% CI, 0.53 to 0.62); small size for gestational age in 12.1% and 15.3%, respectively (adjusted relative risk, 0.72; 95% CI, 0.66 to 0.80); and low birth weight in 8.3% and 14.9% (adjusted relative risk, 0.56; 95% CI, 0.50 to 0.63). Delivery by cesarean section occurred in 33.6% of pregnant persons exposed to buprenorphine in early pregnancy and 33.1% of those exposed to methadone (adjusted relative risk, 1.02; 95% CI, 0.97 to 1.08), and severe maternal complications developed in 3.3% and 3.5%, respectively (adjusted relative risk, 0.91; 95% CI, 0.74 to 1.13). Results of exposure in late pregnancy were consistent with results of exposure in early pregnancy. CONCLUSIONS: The use of buprenorphine in pregnancy was associated with a lower risk of adverse neonatal outcomes than methadone use; however, the risk of adverse maternal outcomes was similar among persons who received buprenorphine and those who received methadone. (Funded by the National Institute on Drug Abuse.).

Concomitant use of pre-emptive analgesia with local and general anesthesia in rat uterine pain surgical model.

Preemptive analgesia is used for postoperative pain management, providing pain relief with few adverse effects. In this study, the effect of a preemptive regime on rat behavior and c-fos expression in the spinal cord of the uterine surgical pain model was evaluated. It was a lab-based experimental study in which 60 female Sprague-Dawley rats; eight to 10 weeks old, weighing 150-300 gm were used. The rats were divided into two main groups: (i) superficial pain group (SG) (with skin incision only), (ii) deep pain group (with skin and uterine incisions). Each group was further divided into three subgroups based on the type of preemptive analgesia administered i.e., "tramadol, buprenorphine, and saline subgroups." Pain behavior was evaluated using the "Rat Grimace Scale" (RGS) at 2, 4, 6, 9 and 24 h post-surgery. Additionally, c-fos immunohistochemistry was performed on sections from spinal dorsal horn (T12-L2), and its expression was evaluated using optical density and mean cell count 2 hours postoperatively. Significant reduction in the RGS was noted in both the superficial and deep pain groups within the tramadol and buprenorphine subgroups when compared to the saline subgroup (p ≤ .05). There was a significant decrease in c-fos expression both in terms of number of c-fos positive cells and the optical density across the superficial laminae and lamina X of the spinal dorsal horn in both SD and DG (p ≤ .05). In contrast, the saline group exhibited c-fos expression primarily in laminae I-II and III-IV for both superficial and deep pain groups and lamina X in the deep pain group only (p ≤ .05). Hence, a preemptive regimen results in significant suppression of both superficial and deep components of pain transmission. These findings provide compelling evidence of the analgesic efficacy of preemptive treatment in alleviating pain response associated with uterine surgery.

Buprenorphine affects the initiation and severity of interleukin-induced acute pancreatitis in mice.

Acute pancreatitis (AP) is a common disease with no targeted therapy and has varied outcomes ranging from spontaneous resolution to being lethal. Although typically painful, AP can also be painless. Various agents, including opioids, are used for pain control in AP; the risks and benefits of which are often debated. As experimental AP in mice is used to study the efficacy of potential therapies, we studied the effect of a commonly used opioid, buprenorphine, on the initiation and progression of AP. For this, we administered extended-release buprenorphine subcutaneously before inducing the previously established severe AP model that uses interleukins 12 and 18 (IL12,18) in genetically obese (ob/ob) mice and compared this to mice with AP but without the drug. Mice were monitored over 3 days, and parameters of AP induction and progression were compared. Buprenorphine significantly reduced serum amylase, lipase, pancreatic necrosis, and AP-associated fat necrosis, which is ubiquitous in obese mice and humans. Buprenorphine delayed the AP-associated reduction of carotid artery pulse distention and the development of hypothermia, hastened renal injury, and muted the early increase in respiratory rate versus IL12,18 alone. The site of buprenorphine injection appeared erythematous, inflamed, and microscopically showed thinning, loss of epidermal layers that had increased apoptosis. In summary, subcutaneous extended-release buprenorphine interfered with the induction of AP by reducing serum amylase, lipase, pancreatic and fat necrosis, the worsening of AP by delaying hypotension, hypothermia, while hastening renal injury, respiratory depression, and causing cutaneous injury at the site of injection.NEW & NOTEWORTHY Extended-release buprenorphine interferes with the initiation and progression of acute pancreatitis at multiple levels.

Buprenorphine Versus Diclofenac for Pain Relief in Acute Pancreatitis: A Double-Blinded Randomized Controlled Trial.

BACKGROUND: Although both nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are used for analgesia in acute pancreatitis (AP), the analgesic of choice is not known. We compared buprenorphine, an opioid, and diclofenac, an NSAID, for analgesia in AP. METHODS: In a double-blind randomized controlled trial, AP patients were randomized to receive intravenous diclofenac or intravenous buprenorphine. Fentanyl was used as rescue analgesia, delivered through a patient-controlled analgesia pump. Primary outcome was the difference in the dose of rescue fentanyl required. Secondary outcomes were the number of effective and ineffective demands of rescue fentanyl, pain-free interval, reduction in visual analogue scale (VAS) score, adverse events, and organ failure development. RESULTS: Twenty-four patients were randomized to diclofenac and 24 to buprenorphine. The 2 groups were matched at baseline. The total amount of rescue fentanyl required was significantly lower in the buprenorphine group:130 µg, interquartile range (IQR), 80-255 vs 520 µg, IQR, 380-1065 (P < .001). The number of total demands was 32 (IQR, 21-69) in the diclofenac arm vs 8 (IQR, 4-15) in the buprenorphine arm (P < .001). The buprenorphine group had more prolonged pain-free interval (20 vs 4 hours; P < .001), with greater reduction in the VAS score at 24, 48, and 72 hours compared with the diclofenac group. These findings were confirmed in the subgroup of moderately severe/severe pancreatitis. Adverse events profile was similar in the 2 groups. CONCLUSIONS: Compared with diclofenac, buprenorphine appears to be more effective and equally safe for pain management in AP patients, even in the subcohort of moderately severe or severe pancreatitis (Trial Registration number: CTRI/2020/07/026914).

Sexually transmitted and blood-borne infection risk reduction with methadone and buprenorphine/naloxone among people with prescription-type opioid use disorder: Findings from a Canadian pragmatic randomized trial.

INTRODUCTION: People who use drugs are disproportionally affected by sexually transmitted and blood-borne infections (STBBIs). While the benefits of methadone in reducing injecting-risk behaviours are well documented, less is known on its impacts on sexual-related risks, as well as its comparative effectiveness to buprenorphine/naloxone, particularly in the context of highly potent opioids. The aim of this study was to estimate the relative effects of buprenorphine/naloxone and methadone on injecting and STBBI risks among people with prescription-type opioid use disorder (POUD). METHODS: Secondary analysis of a pan-Canadian pragmatic 24-week randomized clinical trial comparing methadone and buprenorphine/naloxone models of care among 272 people with POUD (including licit or illicit opioid analgesics, fentanyl). The Risk Behaviour Survey was used to collect injecting and sexual risks at baseline, and weeks 12 and 24. RESULTS: In total, 210 participants initiated treatment (103 buprenorphine/naloxone and 107 methadone). At baseline, 113/205 (55.1%) participants reported recently injecting drugs, 37/209 (17.7%) unsafe injection practices and 67/162 (41.4%) high-risk sex. Both methadone and buprenorphine/naloxone were associated with reductions in the prevalence of injection drug use and high-risk sex at weeks 12 and 24 with no interactions between treatment arm and time. CONCLUSION: Methadone and buprenorphine/naloxone were similarly effective in reducing injecting and sexual risk behaviours among people with POUD. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov NCT03033732.

Medications for Opioid Use Disorder and Mortality and Hospitalization Among People With Opioid Use-related Infections.

BACKGROUND: Severe skin and soft tissue infections related to injection drug use have increased in concordance with a shift to heroin and illicitly manufactured fentanyl. Opioid agonist therapy medications (methadone and buprenorphine) may improve long-term outcomes by reducing injection drug use. We aimed to examine the association of medication use with mortality among people with opioid use-related skin or soft tissue infections. METHODS: An observational cohort study of Medicaid enrollees aged 18 years or older following their first documented medical encounters for opioid use-related skin or soft tissue infections during 2007-2018 in North Carolina. The exposure was documented medication use (methadone or buprenorphine claim) in the first 30 days following initial infection compared with no medication claim. Using Kaplan-Meier estimators, we examined the difference in 3-year incidence of mortality by medication use, weighted for year, age, comorbidities, and length of hospital stay. RESULTS: In this sample, there were 13,286 people with opioid use-related skin or soft tissue infections. The median age was 37 years, 68% were women, and 78% were white. In Kaplan-Meier curves for the total study population, 12 of every 100 patients died during the first 3 years. In weighted models, for every 100 people who used medications, there were four fewer deaths over 3 years (95% confidence interval = 2, 6). CONCLUSION: In this study, people with opioid use-related skin and soft tissue infections had a high risk of mortality following their initial healthcare visit for infections. Methadone or buprenorphine use was associated with reductions in mortality.

Simulating the Simultaneous Impact of Medication for Opioid Use Disorder and Naloxone on Opioid Overdose Death in Eight New York Counties.

BACKGROUND: The United States is in the midst of an opioid overdose epidemic; 28.3 per 100,000 people died of opioid overdose in 2020. Simulation models can help understand and address this complex, dynamic, and nonlinear social phenomenon. Using the HEALing Communities Study, aimed at reducing opioid overdoses, and an agent-based model, Simulation of Community-Level Overdose Prevention Strategy, we simulated increases in buprenorphine initiation and retention and naloxone distribution aimed at reducing overdose deaths by 40% in New York Counties. METHODS: Our simulations covered 2020-2022. The eight counties contrasted urban or rural and high and low baseline rates of opioid use disorder treatment. The model calibrated agent characteristics for opioid use and use disorder, treatments and treatment access, and fatal and nonfatal overdose. Modeled interventions included increased buprenorphine initiation and retention, and naloxone distribution. We predicted a decrease in the rate of fatal opioid overdose 1 year after intervention, given various modeled intervention scenarios. RESULTS: Counties required unique combinations of modeled interventions to achieve a 40% reduction in overdose deaths. Assuming a 200% increase in naloxone from current levels, high baseline treatment counties achieved a 40% reduction in overdose deaths with a simultaneous 150% increase in buprenorphine initiation. In comparison, low baseline treatment counties required 250-300% increases in buprenorphine initiation coupled with 200-1000% increases in naloxone, depending on the county. CONCLUSIONS: Results demonstrate the need for tailored county-level interventions to increase service utilization and reduce overdose deaths, as the modeled impact of interventions depended on the county's experience with past and current interventions.

Development and Verification of a Full Physiologically Based Pharmacokinetic Model for Sublingual Buprenorphine in Healthy Adult Volunteers that Accounts for Nonlinear Bioavailability.

Sublingual buprenorphine is used for opioid use disorder and neonatal opioid withdrawal syndrome. The study aimed to develop a full physiologically based pharmacokinetic (PBPK) model that can adequately describe dose- and formulation-dependent bioavailability of buprenorphine. Simcyp (v21.0) was used for model construction. Four linear regression models (i.e., untransformed or log transformed for dose or proportion sublingually absorbed) were explored to describe sublingual absorption of buprenorphine across dose. Published clinical trial data not used in model development were used for verification. The PBPK model's predictive performance was deemed adequate if the geometric means of ratios between predicted and observed (P/O) area under the curve (AUC), peak concentration (Cmax), and time to reach Cmax (Tmax) fell within the 1.25-fold prediction error range. Sublingual buprenorphine absorption was best described by a regression model with logarithmically transformed dose. By integrating this nonlinear absorption profile, the PBPK model adequately predicted buprenorphine pharmacokinetics (PK) following administration of sublingual tablets and solution across a dose range of 2-32 mg, with geometric mean (95% confidence interval) P/O ratios for AUC and Cmax equaling 0.99 (0.86-1.12) and 1.24 (1.09-1.40), respectively, and median (5th to 95th percentile) for Tmax equaling 1.11 (0.69-1.57). A verified PBPK model was developed that adequately predicts dose- and formulation-dependent buprenorphine PK following sublingual administration. SIGNIFICANCE STATEMENT: The physiologically based pharmacokinetic (PBPK) model developed in this study is the first to adequately predict dose- and formulation-dependent sublingual buprenorphine pharmacokinetics. Accurate prediction was facilitated by the incorporation of a novel nonlinear absorption model. The developed model will serve as the foundation for maternal-fetal PBPK modeling to predict maternal and fetal buprenorphine exposures to optimize buprenorphine treatment for neonatal opioid withdrawal syndrome.

(RE-)AIMing for Rapid Uptake: Pilot Evaluation of a Modified Hub and Spoke Model of Medication for Opioid Use Disorder.

OBJECTIVE: Medication for opioid use disorder (MOUD) is an effective, evidence-based treatment, but significant gaps in implementation remain. We evaluate one novel approach to address this gap: a Hub and Spoke model to increase buprenorphine access and management. METHODS: This outcome evaluation was guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework using secondary data analysis of clinical and administrative data to characterize program outcomes for program Reach, Effectiveness, Adoption, and Maintenance. Implementation was assessed through a chart review of provider progress notes and through key informant interviews with program staff to understand why this site was able to introduce a novel approach to MOUD. RESULTS: Nearly half of patients with opioid use disorder (45.48%, n=156) were reached by the program over 2 years. Of those, 91.67% had 1 or more program visits after an initial intake appointment, and 78.85% had a buprenorphine prescription. Patients in the program were 2.44 times more likely to have a buprenorphine prescription than those in comparator site that did not have a Hub and Spoke program (95% CI: 1.77-3.37; P <0.001). There was significantly greater program reach in year 1 than year 2, suggesting rapid initial uptake followed by modest program growth. Key informant interviews illustrated several themes regrading program implementation, including the importance of process champions, the beneficial impact of MOUD for patients, and addressing facility performance metrics. A supportive organizational culture and a receptive climate were also key factors for implementation. CONCLUSIONS: This program led to rapid improvement in MOUD uptake across the facility. Future efforts should focus on improving program maintenance, including supporting the exchange of patients from the hub to appropriate spokes.

Telehealth Initiation of Buprenorphine for Opioid Use Disorder: Patient Characteristics and Outcomes.

BACKGROUND: The COVID-19 pandemic exacerbated access barriers for patients with opioid use disorder. Telehealth presents an opportunity to improve access, treatment quality, and patient outcomes. OBJECTIVE: To determine patient characteristics associated with initiating buprenorphine treatment via telehealth and to examine how telehealth initiation is associated with access, treatment quality, and health outcomes. DESIGN AND PARTICIPANTS: This cross-sectional study used deidentified insurance claims to identify opioid use disorder adult patients initiating buprenorphine treatment between March 1, 2020, and November 30, 2021. Multivariable logistic regression assessed determinants of telehealth initiation. Propensity score matching addressed observed differences between in-person and telehealth initiators. MAIN MEASURES: Treatment quality outcomes included initiation within 14 days of diagnosis, engagement (at least 2 opioid use disorder-related visits), and any buprenorphine refill during the study period. Health outcomes included opioid overdose and opioid use disorder-related emergency department and inpatient visits. KEY RESULTS: We identified 23,565 adult buprenorphine initiators, including 3314 (14.1%) patients using telehealth. Younger patients (OR 0.91 to 0.77), females (OR 1.18), South (OR 1.63) and Midwest (OR 1.27) regions, rural area (OR 1.12), and higher-income (OR 1.16) neighborhood residents were more likely to use telehealth. Telehealth patients were more likely than in-person patients (54.5% vs. 48.4%; adjusted odds ratio (AOR), 1.29; 95% CI, 1.19-1.40) to stay engaged with opioid use disorder treatment, and more likely to refill buprenorphine during the study period (83.6% vs. 79.0%, AOR 1.37; 95% CI, 1.23-1.52). Telehealth initiation of buprenorphine was associated with 36% lower overdose rate than in-person initiation (adjusted incidence rate ratio 0.64; 95% CI, 0.45-0.94). The two groups evidenced no significant differences in opioid use disorder-related ED visit and hospitalization. CONCLUSIONS: Our findings suggest that telehealth-initiated buprenorphine treatment is associated with reduced opioid overdose rate and improved patient engagement. Our findings strengthen the case for extending telehealth exemptions and prescribing flexibilities for treatment.

Continuation of Buprenorphine During Hospitalization and Subsequent Retention in Therapy: an Observational Study in Veterans Administration Hospitals.

BACKGROUND: Inpatient hospitalization has the potential to disrupt buprenorphine therapy. OBJECTIVE: Among patients receiving outpatient buprenorphine prior to admission, we determined the rate of discontinuation during medical and surgical admissions to VA hospitals and its association with subsequent post-discharge continuation of buprenorphine therapy. DESIGN AND MAIN MEASURES: We conducted an observational study using Veterans Administration data from 10/1/2018 to 3/31/2020 for all medical and surgical admissions where Veterans had active buprenorphine prescriptions at the time of admission. Pre-admission buprenorphine prescriptions were categorized as either sublingual (presumed indication for opioid use disorder (OUD)) or buccal/topical (presumed indication for pain). The primary measure of post-discharge buprenorphine receipt was any outpatient buprenorphine prescription dispensed between 1 day prior to discharge and 60 days following discharge. KEY RESULTS: A total of 830 unique inpatient hospitalizations to medical or surgical services occurred among Veterans receiving sublingual (48.3%) or buccal/topical (51.7%) buprenorphine prior to admission. Fewer than half (43.9%) of these patients received buprenorphine at some point during the medical or surgical portion of their hospital stay. Among the 766 patients discharged from a medical or surgical unit, 74.3% received an outpatient buprenorphine prescription within the 60 days following discharge (80.2% sublingual and 69.1% buccal/topical). Among patients who had received buprenorphine during the final 36 h prior to discharge, subsequent outpatient buprenorphine receipt was observed in 94.0%, compared to only 63.7% among those not receiving buprenorphine during the final 36 h (χ2 = 83.5, p < 0.001). CONCLUSION: Inpatient buprenorphine administrations near the time of discharge were highly predictive of continued outpatient therapy and a significant subset of patients did not continue or reinitiate buprenorphine therapy following discharge. As recommendations for perioperative and inpatient management of buprenorphine coalescence around continuation, efforts are needed to optimize hospital-based buprenorphine practices.

Integrating Buprenorphine for Opioid Use Disorder into Rural, Primary Care Settings.

BACKGROUND: Medications for opioid use disorder (MOUD) including buprenorphine are effective, but underutilized. Rural patients experience pronounced disparities in access. To reach rural patients, the US Department of Veterans Affairs (VA) has sought to expand buprenorphine prescribing beyond specialty settings and into primary care. OBJECTIVE: Although challenges remain, some rural VA health care systems have begun offering opioid use disorder (OUD) treatment with buprenorphine in primary care. We conducted interviews with clinicians, leaders, and staff within these systems to understand how this outcome had been achieved. DESIGN: Using administrative data from the VA Corporate Data Warehouse (CDW), we identified rural VA health care systems that had improved their rate of primary care-based buprenorphine prescribing over the period 2015-2020. We conducted qualitative interviews (n = 30) with staff involved in implementing or prescribing buprenorphine in these systems to understand the processes that had facilitated implementation. PARTICIPANTS: Clinicians, staff, and leaders embedded within rural VA health care systems located in the Northwest, West, Midwest (2), South, and Northeast. APPROACH: Qualitative interviews were analyzed using a mixed inductive/deductive approach. KEY RESULTS: Interviews revealed the processes through which buprenorphine was integrated into primary care, as well as processes insufficient to enact change. Implementation was often initially catalyzed through a targeted hire. Champions then engaged clinicians and leaders one-on-one to "pitch" the case, describe concordance between buprenorphine prescribing and existing goals, and delineate the supportive role that they could provide. Sites were prepared for implementation by developing new clinical teams and redesigning clinical processes. Each of these processes was made possible with the active, instrumental support of leadership. CONCLUSIONS: Results suggest that rural systems seeking to improve buprenorphine accessibility in primary care may need to alter primary care structures to accommodate buprenorphine prescribing, whether through new hires, team development, or clinical redesign.

Pregnancy Rates Among Women Treated with Medication for Opioid Use Disorder.

BACKGROUND: Treatment-seeking people with opioid use disorder (OUD) who are capable of pregnancy need accurate information about the potential impact of medication to treat OUD (MOUD) on fertility to make informed choices about treatment that are consistent with their reproductive wishes. There is a dearth of research on fertility associated with MOUD receipt in birthing people with OUD. OBJECTIVE: To estimate the association between treatment with MOUD and odds of conception among birthing people using national administrative claims. DESIGN: Retrospective case-crossover study using multi-state US administrative data (2006-2016). Dates of conception were estimated from delivery dates and served as "case" days for which MOUD exposures were compared to those on all other ("control") days of insurance enrollment. PARTICIPANTS: Treatment-seeking people with OUD with a delivery during the observation period. MAIN MEASURES: Odds ratios for conception from within-person fixed effects models were modeled as a function of exposure to MOUD (buprenorphine, methadone, extended-release depot naltrexone, or oral naltrexone) using conditional logistic regression. KEY RESULTS: A total of 21,928 births among 19,133 people with OUD were identified. In the sample, 5873 people received buprenorphine, 1825 methadone, 486 extended-release naltrexone, and 714 oral naltrexone. Participants could receive more than one type of MOUD. Mean age was 28.2 years (SD = 2.2; range = 16-45), with 76.2% having Medicaid. vs. commercial insurance. Compared to no MOUD, periods of methadone (aOR = 0.55 [95% CI = 0.48-0.63]) or buprenorphine receipt (aOR = 0.84 [0.77-0.91]) were associated with fewer conceptions. Treatment periods with extended-release depot naltrexone compared to no medication were associated with higher odds of conception (aOR = 1.75 [1.22-2.50]) and there was no significant difference in conception with oral naltrexone (aOR = 1.02 [0.67-1.54]). CONCLUSIONS: The association between MOUD and odds of conception among birthing people varied by type of MOUD, with extended-release naltrexone associated with higher odds of conceiving compared to no treatment. Clinical studies are urgently needed to investigate these findings further.

Association Between Cost-Sharing and Buprenorphine Prescription Abandonment.

BACKGROUND: Prior studies suggest cost-sharing decreases buprenorphine dispensing. However, these studies used databases that only report prescriptions filled by patients, not those that were "abandoned." Consequently, the studies could not calculate the probability of buprenorphine prescription abandonment or evaluate whether cost-sharing is associated with abandonment. OBJECTIVE: To evaluate the association between cost-sharing and buprenorphine prescription abandonment. DESIGN: Cross-sectional analysis of the IQVIA Formulary Impact Analyzer, a pharmacy transaction database representing 63% of U.S. retail pharmacies. The database includes transaction records ("claims") for prescriptions even if they are not filled. PARTICIPANTS: Buprenorphine claims in 2022 among commercially insured and Medicare patients. MAIN MEASURES: We evaluated the association between cost-sharing per 30-day supply and abandonment using logistic regression, controlling for patient characteristics, product type, and buprenorphine use in the prior 180 days. We assessed for effect modification by prior buprenorphine use. KEY RESULTS: Analyses included 2,346,994 and 1,242,596 buprenorphine prescription claims for commercially insured and Medicare patients, respectively. Among these claims, mean (SD) cost-sharing per 30-day supply was $28.1 (46.4) and $8.4 (20.2), and 1.5% and 1.2% were abandoned. Each $10 increase in cost-sharing per 30-day supply was associated with a 0.09 (95% CI: 0.09, 0.10) and 0.09 (95% CI: 0.08, 0.10) percentage-point increase in abandonment among commercially insured and Medicare patients. Among commercially insured and Medicare patients without prior buprenorphine use, respectively, a $10 increase in cost-sharing per 30-day supply was associated with a 0.12 (95% CI: 0.11, 0.14) and 0.13 (95% CI: 0.07, 0.18) percentage-point higher increase in the probability of abandonment compared with patients with > 90 days of prior buprenorphine use. CONCLUSIONS: Among commercially insured and Medicare patients, buprenorphine prescription abandonment is rare and only minimally associated with cost-sharing. Findings suggest elimination of buprenorphine cost-sharing should only be one component of a larger, multi-faceted campaign to increase buprenorphine dispensing.

Prescribing and Acceptance of Medications for Opioid Use Disorder in VA Primary Care: Veteran and Provider Perspectives.

BACKGROUND: Medications to treat opioid use disorder (MOUD) such as buprenorphine/naloxone can effectively treat OUD and reduce opioid-related mortality, but they remain underutilized, especially in non-substance use disorder settings such as primary care (PC). OBJECTIVE: To uncover the factors that can facilitate successful prescribing of MOUD and uptake/acceptance of MOUD by patients in PC settings in the Veterans Health Administration. DESIGN: Semi-structured qualitative telephone interviews with 77 providers (e.g., primary care providers, hospitalists, nurses, addiction psychiatrists) and 22 Veteran patients with experience taking MOUD. Interviews were recorded, transcribed, and analyzed thematically using a combination a priori/inductive approach. KEY RESULTS: Providers and patients shared their general perceptions and experiences with MOUD, including high satisfaction with buprenorphine/naloxone with few side effects and caveats, although some patients reported drawbacks to methadone. Both providers and patients supported the idea of prescribing MOUD in PC settings to prioritize patient comfort and convenience. Providers described individual-level barriers (e.g., time, stigma, perceptions of difficulty level), structural-level barriers (e.g., pharmacy not having medications ready, space for inductions), and organizational-level barriers (e.g., inadequate staff support, lack of nursing protocols) to PC providers prescribing MOUD. Facilitators centered on education and knowledge enhancement, workflow and practice support, patient engagement and patient-provider communication, and leadership and organizational support. The most common barrier faced by patients to starting MOUD was apprehensions about pain, while facilitators focused on personal motivation, encouragement from others, education about MOUD, and optimally timed provider communication strategies. CONCLUSIONS: These findings can help improve provider-, clinic-, and system-level supports for MOUD prescribing across multiple settings, as well as foster communication strategies that can increase patient acceptance of MOUD. They also point to how interprofessional collaboration across service lines and leadership support can facilitate MOUD prescribing among non-addiction providers.

Neurocognitive Functions After 6-Month Buprenorphine (Naloxone)-Based Opioid Agonist Maintenance Treatment: A Controlled Prospective Study.

BACKGROUND: Medications for opioid use disorder (OUD) may influence neurocognitive functions. Inadequate power, confounders, and practice effects limit the validity of the existing research. We examined the change in cognitive functions in patients with OUD at 6-month buprenorphine (naloxone) posttreatment and compared the cognitive performance of the buprenorphine-treated group with control subjects. METHODS: We recruited 498 patients with OUD within a week of initiating buprenorphine. Assessments were done twice-at baseline and 6 months. Those abstinent from illicit opioids and adherent to treatment (n = 199) underwent follow-up assessments. Ninety-eight non-substance-using control subjects were recruited from the community. The neurocognitive assessments comprised the Wisconsin Card Sorting Test, Iowa Gambling Task, Trail-Making Tests A and B (TMT-A and TMT-B), and verbal and visual N-Back Test. We controlled for potential effect modifiers. RESULTS: Twenty-five of the 32 test parameters significantly improved with 6 months of buprenorphine treatment; 20 parameters withstood corrections for multiple comparisons (P < 0.001). The improved test domains spread across cognitive tests: Wisconsin Card Sorting Test (perseverative errors and response, categories completed, conceptual responses), TMTs (time to complete), verbal and visual N-Back Tests (hits, omission, and total errors). After treatment, OUD (vs control subjects) had less perseverative response and error (P < 0.001) and higher conceptual response (P = 0.004) and took lesser time to complete TMT-A (P < 0.001) and TMT-B (P = 0.005). The baseline neurocognitive functions did not differ between those who retained and those who discontinued the treatment. CONCLUSION: Cognitive functions improve in patients with OUD on buprenorphine. This improvement is unlikely to be accounted for by the practice effect, selective attrition, and potential confounders.

Federal Impacts on Buprenorphine Prescribing in Washington State, 2012 to 2022.

Objectives. To evaluate changes in monthly buprenorphine dispensation associated with federal prescribing policies in Washington State from 2012 to 2022. Methods. We conducted an interrupted time series analysis comparing monthly buprenorphine prescriptions dispensed per 1000 population after the Comprehensive Addiction and Recovery Act (CARA), Substance Use-Disorder Prevention That Promotes Opioid Recovery and Treatment for Patients and Communities Act (SUPPORT), and new prescribing rules during the COVID-19 pandemic. Buprenorphine formulated for opioid use disorder was included from the Washington State Prescription Monitoring Program. A log-linear autoregressive model measured linear trend changes. Results. Physician prescribing increased by 1.63% (95% confidence interval [CI] = 1.41%, 1.85%) per month after CARA with sustained declines after SUPPORT. Nurse practitioner (NP) prescribing increased by 19.48% (95% CI = 18.8%, 20.16%) per month after CARA with physician assistants (PAs) showing similar trends. Following the implementation of SUPPORT, NP and PA trends continued to increase at a reduced growth rate of 3.96% (95% CI = 2.01%, 5.94%) and 1.87% (95% CI = 0.56%, 3.19%), respectively. No prescribers experienced increases during the COVID-19 pandemic. Conclusions. CARA nearly tripled the buprenorphine prescribing rate. The SUPPORT Act initiated sustained declines for physician prescribing, and the COVID-19 period reversed gains for PAs and NPs. The current opioid crisis requires expanded efforts in Washington State. (Am J Public Health. 2024;114(7):696-704. https://doi.org/10.2105/AJPH.2024.307649).

Scaling Emergency Department Opioid Use Disorder Treatment Across California to Reduce Overdose Deaths, 2019-2023.

Since April 2019, CA Bridge has worked with emergency departments (EDs) in diverse geographic and emergency care settings across California to scale up low-threshold buprenorphine access, patient navigation programs, harm reduction services, and take-home naloxone. Between April 2019 and June 2023, 268 (81.0%) of 331 acute care hospitals in California received funding and technical assistance from CA Bridge and completed data reporting. These hospitals provided navigation services during 279 025 patient encounters and gave patients buprenorphine in 89 549 ED visits. (Am J Public Health. 2024;114(9):874-878. https://doi.org/10.2105/AJPH.2024.307710).