Project description:BackgroundOpioid 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.MethodsWe 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.ResultsThe 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.ConclusionsThe 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.).

Project description:ObjectiveAlthough buprenorphine treatment reduces risk of overdose and death in opioid use disorder, most patients discontinue treatment within a few weeks or months. Adverse health outcomes following buprenorphine discontinuation were compared among patients who were successfully retained beyond 6 months of continuous treatment, a minimum treatment duration recently endorsed by the National Quality Forum.MethodsA retrospective longitudinal cohort analysis was performed using the MarketScan multistate Medicaid claims database (2013-2017), covering 12 million beneficiaries annually. The sample included adults (18-64 years of age) who received buprenorphine continuously for ≥180 days by cohorts retained for 6-9 months, 9-12 months, 12-15 months, and 15-18 months. For outcome assessment in the postdiscontinuation period, patients had to be continuously enrolled in Medicaid for 6 months after buprenorphine discontinuation. Primary adverse outcomes included all-cause emergency department visits, all-cause inpatient hospitalizations, opioid prescriptions, and drug overdose (opioid or non-opioid).ResultsAdverse events were common across all cohorts, and almost half of patients (42.1%-49.9%) were seen in the emergency department at least once. Compared with patients retained on buprenorphine for 6-9 months (N=4,126), those retained for 15-18 months (N=931) had significantly lower odds of emergency department visits (odds ratio=0.75, 95% CI=0.65-0.86), inpatient hospitalizations (odds ratio=0.79, 95% CI=0.64-0.99), and filling opioid prescriptions (odds ratio=0.67, 95% CI=0.56-0.80) in the 6 months following discontinuation. Approximately 5% of patients across all cohorts experienced one or more medically treated overdoses.ConclusionsRisk of acute care service use and overdose were high following buprenorphine discontinuation irrespective of treatment duration. Superior outcomes became significant with treatment duration beyond 15 months, although rates of the primary adverse outcomes remained high.

Project description:ImportanceAlthough substantial evidence supports buprenorphine for treatment of opioid use disorder (OUD) in controlled trials, prospective study of patient outcomes in clinical implementation of emergency department (ED) buprenorphine treatment is lacking.ObjectiveTo examine the association between buprenorphine treatment in the ED and follow-up engagement in OUD treatment 1 month later.Design, setting, and participantsThis multisite cohort study was conducted in 7 California EDs participating in a statewide implementation project to improve access to buprenorphine treatment. The study population included ED patients aged at least 18 years identified with OUD between April 1, 2021, and June 30, 2022. Data analysis was performed in October 2023.ExposureAll participants were offered buprenorphine treatment for OUD (either in ED administration, prescription, or both), the uptake of which was examined as the exposure of interest.Main outcomes and measuresThe primary outcome was engagement in OUD treatment 30 days after the ED visit, determined by patient report or clinical documentation. The association of ED buprenorphine treatment with subsequent OUD treatment engagement was estimated using hierarchical generalized linear models.ResultsThis analysis included 464 ED patients with OUD. Their median age was 36.0 (IQR, 29.0-38.7) years, and most were men (343 [73.9%]). With regard to race and ethnicity, 64 patients (13.8%) self-identified as non-Hispanic Black, 183 (39.4%) as Hispanic, and 185 as non-Hispanic White (39.9%). Most patients (396 [85.3%]) had Medicaid insurance, and more than half (262 [57.8%]) had unstable housing. Self-reported fentanyl use (242 [52.2%]) and a comorbid mental health condition (328 [71.5%]) were common. Interest in buprenorphine treatment was high: 398 patients (85.8%) received buprenorphine treatment; 269 (58.0%) were administered buprenorphine in the ED and 339 (73.1%) were prescribed buprenorphine. With regard to OUD treatment engagement at 30 days after the ED visit, 198 participants (49.7%) who received ED buprenorphine treatment remained engaged compared with 15 participants (22.7%) who did not receive ED buprenorphine treatment. An association of ED buprenorphine treatment with subsequent OUD treatment engagement at 30 days was observed (adjusted risk ratio, 1.97 [95% CI, 1.27-3.07]).Conclusions and relevanceThe findings of this cohort study suggest that among patients with OUD presenting to EDs implementing low-threshold access to medications for OUD, buprenorphine treatment was associated with a substantially higher likelihood of follow-up treatment engagement 1 month later. Future research should investigate techniques to optimize both the uptake and effectiveness of buprenorphine initiation in low-threshold settings such as the ED.

Project description:ImportanceAgonist medications for opioid use disorder (MOUD), buprenorphine and methadone, in carceral settings might reduce the risk of postrelease opioid overdose but are uncommonly offered. In April 2019, the Massachusetts Department of Correction (MADOC), the state prison system, provided buprenorphine for incarcerated individuals in addition to previously offered injectable naltrexone.ObjectiveTo evaluate postrelease outcomes after buprenorphine implementation.Design, setting, and participantsThis cohort study with interrupted time-series analysis used linked data across multiple statewide data sets in the Massachusetts Public Health Data Warehouse stratified by sex due to differences in carceral systems. Eligible participants were individuals sentenced and released from a MADOC facility to the community. The study period for the male sample was January 2014 to November 2020; for the female sample, January 2015 to October 2019. Data were analyzed between February 2022 and January 2024.ExposureApril 2019 implementation of buprenorphine during incarceration.Main outcomes and measuresReceipt of MOUD within 4 weeks after release, opioid overdose, and all-cause mortality within 8 weeks after release, each measured as a percentage of monthly releases who experienced the outcome. Segmented linear regression analyzed changes in outcome rates after implementation.ResultsA total of 15 225 individuals were included. In the male sample there were 14 582 releases among 12 688 individuals (mean [SD] age, 35.0 [10.8] years; 133 Asian and Pacific Islander [0.9%], 4079 Black [28.0%], 4208 Hispanic [28.9%], 6117 White [41.9%]), a rate of 175.7 releases per month; the female sample included 3269 releases among 2537 individuals (mean [SD] age, 34.9 [9.8] years; 328 Black [10.0%], 225 Hispanic [6.9%], 2545 White [77.9%]), a rate of 56.4 releases per month. Among male participants at 20 months postimplementation, the monthly rate of postrelease buprenorphine receipt was higher than would have been expected under baseline trends (21.2% vs 10.6% of monthly releases; 18.6 additional releases per month). Naltrexone receipt was lower than expected (1.0% vs 6.0%; 8.8 fewer releases per month). Monthly rates of methadone receipt (1.4%) and opioid overdose (1.8%) were not significantly different than expected. All-cause mortality was lower than expected (1.9% vs 2.8%; 1.5 fewer deaths per month). Among female participants at 7 months postimplementation, buprenorphine receipt was higher than expected (31.6% vs 9.5%; 12.4 additional releases per month). Naltrexone receipt was lower than expected (3.4% vs 7.2%) but not statistically significantly different. Monthly rates of methadone receipt (1.1%), opioid overdose (4.8%), and all-cause mortality (1.6%) were not significantly different than expected.Conclusions and relevanceIn this cohort study of state prison releases, postrelease buprenorphine receipt increased and naltrexone receipt decreased after buprenorphine became available during incarceration.

Project description:ImportanceRetention in buprenorphine therapy is associated with a lower risk of opioid overdose. Nevertheless, many patients discontinue treatment, and there is limited evidence to guide buprenorphine tapering.ObjectiveTo understand what prescribing characteristics are associated with opioid overdose following buprenorphine taper.Design, setting, and participantsThis is a population-based, retrospective, cohort study of adults who were maintained on buprenorphine for at least 60 days and underwent a buprenorphine taper. The study was conducted in the Canadian province of Ontario, using linked administrative health data. New buprenorphine treatment episodes were accrued between January 1, 2013, and January 1, 2019, and the maximum follow-up was April 30, 2020. Data analysis was performed from December 2020 to August 2022.ExposuresThe primary exposure of interest was time to taper initiation (≤1 year vs >1 year). Secondary exposures included mean rate of taper, percentage days during which the dose was decreasing, and taper duration.Main outcomes and measuresThe primary outcome measure was time to fatal or nonfatal opioid overdose within 18 months following treatment discontinuation.ResultsAmong 5774 individuals, the median (IQR) age at index date was 34 (28-44) years, and 3462 individuals (60.0%) were male. Time to taper initiation longer than 1 year vs 1 year or less (6.73 vs 10.35 overdoses per 100 person-years; adjusted hazard ratio [aHR], 0.69; 95% CI, 0.48-0.997), a lower mean rate of taper (≤2 mg per month, 6.95 overdoses per 100 person-years; >2 to ≤4 mg per month, 11.48 overdoses per 100 person-years; >4 mg per month, 17.27 overdoses per 100 person-years; ≤2 mg per month vs >4 mg per month, aHR, 0.65; 95% CI, 0.46-0.91; >2 to ≤4 mg per month vs >4 mg per month, aHR, 0.69; 95% CI, 0.51-0.93), and dose decreases in 1.75% or less of days vs more than 3.50% of days during the taper period (5.87 vs 13.87 overdoses per 100 person-years; aHR, 0.64; 95% CI, 0.43-0.93) were associated with reduced risk of opioid overdose; however, taper duration was not.Conclusions and relevanceIn this retrospective cohort study, buprenorphine tapers undertaken after at least 1 year of therapy, a slower rate of taper, and a lower percentage of days during which the dose was decreasing were associated with a significantly lower risk of opioid overdose, regardless of taper duration. These findings underscore the importance of a carefully planned taper and could contribute to reduction in opioid-related overdose death.

Project description:BackgroundTwo phase I studies assessed the pharmacokinetics of buprenorphine, its metabolite norbuprenorphine, and naloxone following administration of buprenorphine/naloxone sublingual tablets in Chinese participants.MethodsIn the first phase I, open-label, single ascending-dose (SAD) study, 82 opioid-naïve volunteers received a single buprenorphine/naloxone dose ranging from 2 mg/0.5 mg to 24 mg/6 mg while under naltrexone block. In a second phase I, open-label, multiple ascending-dose (MAD) study, 27 patients with opioid dependence in withdrawal received buprenorphine/naloxone doses of either 16 mg/4 mg or 24 mg/6 mg for 9 consecutive days. Serial blood samples were collected after a single dose (SAD study) and at steady-state (MAD study). Pharmacokinetic parameters were calculated using non-compartmental analysis. Safety assessments included adverse events monitoring and laboratory tests.ResultsThe pharmacokinetic profiles of buprenorphine and naloxone were consistent between single- and multiple-dose studies. Peak plasma concentrations (Cmax) were reached early for buprenorphine (0.75-1.0 h) and naloxone (0.5 h), supporting rapid absorption. In the SAD study, increases in plasma exposures to buprenorphine and naloxone were less than dose proportional, in line with previous observations in Western populations. Buprenorphine-to-naloxone ratios for Cmax and area under the curve (AUC) were constant over the dose range investigated and also consistent with Western populations data. Steady state was reached within 7 days of daily dosing, with slight accumulation over repeated doses. No serious adverse events were observed.ConclusionsThe present data suggest that buprenorphine/naloxone pharmacokinetic profiles in Chinese participants are consistent, overall, with those in Western populations, supporting no differences in dosing.Clinical trial registrationThe protocols were registered on the official website of the China Food and Drug Administration (CFDA): http://www.chinadrugtrials.org.cn/ ; Registration numbers CTR20132963 (RB-CN-10-0012), CTR20140153 (RB-CN-10-0015).

Project description:ImportanceIn April 2021, the US Department of Health and Human Services (HHS) released practice guidelines exempting educational requirements to obtain a Drug Addiction Treatment Act (DATA) waiver to treat up to 30 patients with opioid use disorder with buprenorphine.ObjectiveTo compare demographic and practice characteristics of clinicians who received traditional DATA waivers before and after release of the education-exempted HHS practice guidelines and those who were approved under the guidelines.Design, setting, and participantsThis survey study was conducted electronically from February 1 to March 1, 2022. Eligible survey recipients were US clinicians who obtained an initial DATA waiver between April 2020 and November 2021.ExposureDATA waiver approval pathway.Main outcome and measuresThe outcomes were clinician demographic and practice characteristics, buprenorphine prescribing barriers, and strategies to treat patients with opioid use disorder, measured using χ2 tests and z tests to assess for differences among the waivered groups.ResultsOf 23 218 eligible clinicians, 4519 (19.5%) responded to the survey. This analysis was limited to 2736 respondents with a 30-patient limit at the time of survey administration who identified their DATA waiver approval pathway. Among these respondents, 1365 (49.9%; female, 831 [61.9%]; male, 512 [38.1%]) received their DATA waiver prior to the education-exempted practice guidelines (prior DATA waiver), 550 (20.1%; female, 343 [63.4%]; male, 198 [36.6%]) received their waiver after guidelines were released but met education requirements (concurrent DATA waiver), and 821 (30.0%; female, 396 [49.2%]; male, 409 [50.8%]) received the waiver under the education-exempted guidelines (practice guidelines). Among practice guidelines clinicians, 500 (60.9%) reported that traditional DATA waiver educational requirements were a reason for not previously obtaining a waiver. Demographic and practice characteristics differed by waiver approval type. Across all groups, a large minority had not prescribed buprenorphine since obtaining a waiver (prior DATA waiver, 483 [35.7%]; concurrent DATA waiver, 226 [41.2%]; practice guidelines, 359 [44.3%]; P < .001). Clinicians who prescribed buprenorphine in the past 6 months reported treating few patients in an average month: 27 practice guidelines clinicians (6.0%) prescribed to 0 patients and 338 (75.1%) to 1 to 4 patients compared with 16 (2.2%) and 435 (59.9%) for prior and 11 (3.6%) and 166 (55.0%) for concurrent DATA waiver clinicians, respectively (P < .001). Across waiver types, clinicians reported multiple challenges to buprenorphine prescribing.Conclusions and relevanceIn this survey of DATA-waivered clinicians, clinician- and systems-level challenges that limit buprenorphine prescribing were observed, even among clinicians approved under the education-exempted guidelines pathway. The findings suggest that as implementation of legislation removing the DATA waiver begins, addressing these barriers could be essential to increasing buprenorphine access.

Dataset Information

Buprenorphine uptake during pregnancy following the 2017 guidelines update on prenatal opioid use disorder.

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Buprenorphine uptake during pregnancy following the 2017 guidelines update on prenatal opioid use disorder.

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