Buprenorphine

Opioid use disorder (OUD) is a major public health threat, contributing to morbidity and mortality from addiction, overdose, and related medical conditions. Despite our increasing knowledge about the pathophysiology and existing medical treatments of OUD, it has remained a relapsing and remitting disorder for decades, with rising deaths from overdoses, rather than declining. The COVID-19 pandemic has accelerated the increase in overall substance use and interrupted access to treatment. If increased naloxone access, more buprenorphine prescribers, greater access to treatment, enhanced reimbursement, less stigma and various harm reduction strategies were effective for OUD, overdose deaths would not be at an all-time high. Different prevention and treatment approaches are needed to reverse the concerning trend in OUD. This article will review the recent trends and limitations on existing medications for OUD and briefly review novel approaches to treatment that have the potential to be more durable and effective than existing medications. The focus will be on promising interventional treatments, psychedelics, neuroimmune, neutraceutical, and electromagnetic therapies. At different phases of investigation and FDA approval, these novel approaches have the potential to not just reduce overdoses and deaths, but attenuate OUD, as well as address existing comorbid disorders.

ImportanceHospitalizations related to opioid use disorder (OUD) represent an opportunity to initiate medication for OUD (MOUD).ObjectiveTo assess whether starting MOUD after a hospitalization or emergency department (ED) visit is associated with the odds of fatal and nonfatal opioid overdose at 6 and 12 months.Design, setting, and participantsThis population-based cohort study used data from the Oregon Comprehensive Opioid Risk Registry, which links all payer claims data to other administrative health datasets, for individuals aged 18 years or older who had diagnosis codes related to OUD recorded at an index ED visit or hospitalization from January 2017 to December 2019. Data were analyzed between May 2023 and January 2024.ExposuresReceipt of MOUD within the 7 days after an OUD-related hospital visit.Main outcomes and measuresThe primary outcome was fatal or nonfatal overdose at 6 and 12 months after discharge. Sample characteristics, including age, sex, insurance plan, number of comorbidities, and opioid-related overdose events, were stratified by receipt or nonreceipt of MOUD within 7 days after an OUD-related hospital visit. A logistic regression model was used to investigate the association between receipt of MOUD and having an opioid overdose event.ResultsThe study included 22 235 patients (53.1% female; 25.0% aged 25-39 years) who had an OUD-related hospital visit during the study period. Overall, 1184 patients (5.3%) received MOUD within 7 days of their ED visit or hospitalization. Of these patients, 683 (57.7%) received buprenorphine, 463 (39.1%) received methadone, and 46 (3.9%) received long-acting injectable naltrexone. Patients who received MOUD within 7 days after discharge had lower adjusted odds of fatal or nonfatal overdose at 6 months compared with those who did not (adjusted odds ratio [AOR], 0.63; 95% CI, 0.41-0.97). At 12 months, there was no difference in adjusted odds of fatal or nonfatal overdose between these groups (AOR, 0.79; 95% CI, 0.58-1.08). Patients had a lower risk of fatal or nonfatal overdose at 6 months associated with buprenorphine use (AOR, 0.50; 95% CI, 0.27-0.95) but not with methadone use (AOR, 0.57; 95% CI, 0.28-1.17).Conclusions and relevanceIn this cohort study of individuals with an OUD-related hospital visit, initiation of MOUD was associated with reduced odds of opioid-related overdose at 6 months. Hospitals should consider implementing programs and protocols to offer initiation of MOUD to patients with OUD who present for care.

ImportanceBuprenorphine treatment of opioid use disorder (OUD) is safe and effective, but opioid withdrawal during treatment initiation is associated with poor retention in care. As fentanyl has replaced heroin in the drug supply, case reports and surveys have indicated increased concern for buprenorphine-precipitated withdrawal (PW); however, some observational studies have found a low incidence of PW.ObjectiveTo estimate buprenorphine PW incidence and assess factors associated with PW among emergency department (ED) or hospitalized patients.Design, setting, and participantsThis retrospective cohort study at 3 academic hospitals in Philadelphia, Pennsylvania, included adults with OUD who underwent traditional or high-dose buprenorphine initiation between January 1, 2020, and December 31, 2021. Exclusion criteria included low-dose buprenorphine initiation and missing documentation of opioid withdrawal severity within 4 hours of receiving buprenorphine.ExposureBuprenorphine initiation with an initial dose of at least 2 mg of sublingual buprenorphine after a Clinical Opiate Withdrawal Scale (COWS) score of 8 or higher. Additional exposures included 4 predefined factors potentially associated with PW: severity of opioid withdrawal before buprenorphine (COWS score of 8-12 vs ≥13), initial buprenorphine dose (2 vs 4 or ≥8 mg), body mass index (BMI) (Main outcome and measuresThe main outcome was PW incidence, defined as a 5-point or greater increase in COWS score from immediately before to within 4 hours after buprenorphine initiation. Logistic regression was used to estimate the odds of PW associated with the 4 aforementioned predefined factors.ResultsThe cohort included 226 patients (150 [66.4%] male; mean [SD] age, 38.6 [10.8] years). Overall, 26 patients (11.5%) met criteria for PW. Among patients with PW, median change in COWS score was 9 points (IQR, 6-13 points). Of 123 patients with confirmed fentanyl use, 20 (16.3%) had PW. In unadjusted and adjusted models, BMI of 30 or greater compared with less than 25 (adjusted odds ratio [AOR], 5.12; 95% CI, 1.31-19.92) and urine fentanyl concentration of 200 ng/mL or greater compared with less than 20 ng/mL (AOR, 8.37; 95% CI, 1.60-43.89) were associated with PW.Conclusions and relevanceIn this retrospective cohort study, 11.5% of patients developed PW after buprenorphine initiation in ED or hospital settings. Future studies should confirm the rate of PW and assess whether bioaccumulated fentanyl is a risk factor for PW.

ImportanceTreating opioid use disorder (OUD) in pregnancy with sublingual buprenorphine is an evidence-based practice, but it has disadvantages that could be addressed with an extended-release formulation.ObjectiveTo evaluate the effectiveness and safety of extended-release buprenorphine vs sublingual buprenorphine for OUD in pregnancy through 12 months post partum.Design, setting, and participantsThis 2-group, open-label, noninferiority, randomized clinical trial was conducted between July 2, 2020, and October 30, 2024, among adults with OUD and a singleton pregnancy of 6 to 30 weeks' gestational age at 13 outpatient cross-disciplinary peripartum OUD treatment sites.InterventionsRandomization to sublingual or extended-release buprenorphine (weekly formulation during pregnancy, monthly formulation optional post partum if not breastfeeding).Main outcomes and measuresThe primary and key secondary outcomes were illicit opioid abstinence during pregnancy and the postpartum period, respectively, defined as the proportion of weekly collected urine samples negative for illicit opioids. If noninferiority was demonstrated at a margin of 0.15, testing for superiority was planned. Key secondary infant outcomes from medical records were opioid treatment for neonatal opioid withdrawal syndrome (NOWS; yes or no) and number of opioid treatment days for NOWS.ResultsAmong 140 randomized participants, the mean (SD) age was 31.2 (4.6) years. There were 10 Black participants (7.1%), 10 Hispanic participants (7.1%), 116 (82.9%) White participants, and 14 participants (10.0%) who belonged to additional groups. All but 2 were already prescribed sublingual buprenorphine. Study completion was 98% through pregnancy (137 participants) and 81% through 12 months post partum (114 participants). Illicit opioid abstinence was higher during pregnancy for participants receiving extended-release vs sublingual buprenorphine (82.5% vs 72.6%; mean difference, 9.84 [95% CI, 1.72 to 17.95] percentage points; P = .009). Postpartum abstinence rates declined and were similar in both groups (60.2% vs 59.5%; mean difference, 0.65 [98% CI, -12.72 to 14.02] percentage points; P = .45). Those receiving extended-release buprenorphine experienced fewer serious adverse events during pregnancy (8.7% vs 26.8%; P = .007) and post partum (6.0% vs 18.6%; P = .04). Nonserious adverse events rates did not differ between groups, but more were deemed medication-related for extended-release participants during pregnancy (26.1% vs 7.0%; P = .003). Infants exposed to extended-release vs sublingual buprenorphine did not differ in need for opioid treatment (30.2% vs 26.5%; relative risk, 1.14 [98% CI, 0.54 to 1.99]; P = .64) or mean (SE) treatment days (10.9 [2.2] vs 14.8 [3.0] days; relative risk, 0.73 [98% CI, 0.36 to 1.51]; P = .28). At birth, extended-release-exposed neonates had larger mean (SE) head circumferences than those exposed to sublingual buprenorphine (34.0 [0.2] vs 33.4 [0.2] cm; mean difference, 0.63 [95% CI, -0.00 to 1.26] cm; P = .049).Conclusions and relevanceThe findings of this randomized clinical trial support weekly extended-release buprenorphine for OUD treatment during pregnancy.Trial registrationClinicalTrials.gov Identifier: NCT03918850.