Edward V. Nunes

Objectives: Medically assisted withdrawal (MAW) for opioid use disorders (OUD) remains common. NIDA’s CTN-0051 (X:BOT) trial compared two OUD medications initiated during an acute inpatient MAW admission and continued postdischarge at 8 US sites. This ancillary observational follow-on study explored treatment-as-usual outcomes at 5 X:BOT sites. Methods: Adults admitted for OUD were conveniently and consecutively recruited to an 8-week, prospective, observational, noninterventional study targeting up to 300 participants. Withdrawal protocols and medications for OUD (MOUD) followed site usual practices. Baseline and postdischarge weeks 1, 4, and 8 measures were OUD severity, length-of-stay (LOS), urine samples, self-reported MOUD, nonprescribed opioid use, and overdoses. Data analyses were descriptive. Results: A total of N = 211 enrolled participants were primarily white men (74%) with daily heroin (87.2%) and intravenous (64.0%) use. About 41.7% (n = 88) reported MOUD treatment at discharge: extended-release naltrexone (n = 39), sublingual buprenorphine-naloxone (n = 38), methadone (n = 8), and oral naltrexone (n = 3). Self-reported MOUD use at week 8 was 28.0%, when 52.6% reported no regular use (<7 consecutive days) and 25.6% reported nonprescribed opioid abstinence. Negative urine rates for nonprescribed opioids ranged from 26.1% to 31.3%. One overdose death and 17 nonfatal opioid-related overdose events occurred in 15 participants. Conclusions: Return to nonprescribed opioid use, frequent overdose events, one death, and a relative lack of MOUD treatment uptake characterized this usual care cohort following inpatient OUD admissions. Scientific Significance: These findings underscore the urgent need for individuals and providers to prioritize linkage to evidence-based MOUD treatments following acute inpatient OUD-related admissions, given high rates of return to opioid use and overdose events.

Aim: We evaluated whether community‐level naloxone distribution, medication for opioid use disorder treatment and retention and incident high‐risk opioid prescribing rates were associated with opioid overdose death rates. Design: Observational cohort conducted using 2019 to 2023 community‐level data as an exploratory analysis of the HEALing (Helping to End Addiction Long‐term®) Communities Study (HCS). Exposures included: (1) community‐level naloxone distribution, past 12‐months, categorized as ≤1000 units per 100 000 population vs. 1001–3000 units per 100 000 population vs. >3000 units per 100 000 population; (2) individuals treated with buprenorphine per 100 000 adult population in the current quarter; (3) individuals retained on buprenorphine for ≥ 180 days per 100 000 adult population in the current quarter; and (4) incident high‐risk opioid prescribing per 100 000 adult population in the current quarter. Setting and participants: Population‐based study of 67 communities with 8.2 million adults in Kentucky, Massachusetts, New York and Ohio, USA, with required annual opioid overdose death rates of > 25 per 100 000 adult population and at least 30% rural. Across the 67 communities participating in the HCS, the adult population was 31% 18–34 years, 31% 35–54 years, 38% 55 years and over, 52% female, 73% non‐Hispanic White, 15% non‐Hispanic Black and 7.4% Hispanic. Measurements: Quarterly community‐level opioid overdose death rates from 2020 through 2023. Findings: The 2019 annual rates were 40.4 opioid overdose deaths, 1287 naloxone rescue units distributed, 977.7 people received buprenorphine treatment, 546.3 people retained for more than 180 days on buprenorphine and 1266.7 high‐risk opioid prescribing incidents per 100 000 population. In models adjusted for state, community age, sex, race/ethnicity, rurality, HCS intervention group assignment, 2019 rates of opioid overdose death, naloxone distribution, buprenorphine and high‐risk opioid prescribing, and the ratio of opioid overdose deaths involving fentanyl, an increase in 100 people treated with buprenorphine per 100 000 population was associated with a decrease of 0.92 [95% confidence interval (CI) = −1.30 to −0.55] in the quarterly opioid overdose death rate, while an increase of 100 people retained on buprenorphine for more than 180 days per 100 000 population was associated with a decrease of 1.3 (95% CI = −1.8 to −0. 76). There were no statistically significant associations between naloxone distribution or incident high‐risk opioid prescribing with change in quarterly opioid overdose death rates. Conclusions: In this exploratory analysis, increases in both buprenorphine treatment and retention were statistically significantly associated with decreases in opioid overdose death rates, after adjusting for baseline rates of buprenorphine treatment and retention.

Background and aims: Clinicians have little guidance on the ideal length of time patients should remain on medication treatment for opioid use disorder (MOUD) before being able to safely discontinue MOUD. This study estimated how the risk of all‐cause mortality changes with the duration of MOUD, controlling for patient characteristics that change the risk profile independent of duration of therapy. Design, setting and participants: Retrospective cohort study using electronic health record data from the US Veterans Healthcare Administration. Veterans initiating MOUD with buprenorphine, methadone or extended‐release naltrexone from October 2010 to September 2020. Our analytic sample included 19 666 buprenorphine initiators, 8675 methadone initiators and 4007 extended‐release naltrexone initiators. Measurement: Duration of MOUD was measured in days. Discontinuation was defined as a gap in any MOUD coverage exceeding 28 days, regardless of MOUD type initiated. The primary outcome was all‐cause mortality. We estimated multistate survival models allowing for the modeling of multiple states (i.e. on and off MOUD, death) without having to consider censoring or competing events, while adjusting for sociodemographic, clinical, prescription and facility and provider characteristics. Findings: We observed approximately 226 000 person‐years of time at risk for discontinuation or pre‐discontinuation death, during which we observed 26 841 discontinuations (118.9 discontinuations per 1000 person‐years). We similarly observed a total of about 106 000 person‐years of post‐discontinuation follow‐up, during which we observed 3251 deaths (3.1 deaths per 1000 person‐years). We found the largest marginal gain in probability of 6‐year survival from an additional year on MOUD appears to occur around 2 years, as compared to 6 months on MOUD. Statistically significant gains continued through approximately 4–5 years of MOUD retention relative to 6‐month MOUD retention. After 4–5 years, the marginal gain from one additional year of MOUD was not statistically significant. Conclusions: Among US veterans, the benefit of retention on medication treatment for opioid use disorder (MOUD) towards overall survival continues through at least 4 years of MOUD treatment. Quality metrics based on 6‐month MOUD retention may be insufficient.

Background: Gabapentin may help manage opioid withdrawal symptoms, but its effectiveness during buprenorphine taper and transition to naltrexone is uncertain.Objectives: To assess gabapentin's efficacy in improving outcomes for lifetime prescription opioid use disorder (POUD) during outpatient buprenorphine taper and transition to extended-release naltrexone.Methods: This 12-week randomized, double-blind, placebo-controlled trial enrolled 117 (55% male) POUD participants. Weeks 1-3, participants attended clinic 5 days/week for medication, therapy, and assessments, including weekly craving and thrice-weekly opioid withdrawal and supervised urine screens. Participants were inducted onto buprenorphine (12 mg), randomized to receive either placebo or gabapentin (800 mg BID), and underwent a 10-day buprenorphine taper. In week 4, participants transitioned from oral to extended-release naltrexone. Chi-square and generalized estimating equation models assessed outcomes. A subset with baseline fentanyl tests was also examined for fentanyl's impact on outcomes.Results: Of 117 participants, 75 (64.1%) completed the buprenorphine taper (41 gabapentin, 34 placebo), and 24 (20.5%) transitioned to naltrexone (12 gabapentin, 12 placebo). No significant group differences were observed in taper completion, naltrexone transition, craving, withdrawal, or opioid use. Fentanyl-positive participants had lower taper completion (47.8% vs. 75.8%, OR = 0.286, p = .033) and more opioid-positive urines (z = -4.24, p < .0001). Fentanyl-positive participants on gabapentin had higher COWS (z = 3.70, p = .001) and SOWS (z = 3.73, p = .001) scores, while fentanyl-negative participants on gabapentin had lower SOWS scores than those on placebo (z = -3.52, p = .002).Conclusions: Fentanyl exposure impairs buprenorphine taper success and worsens withdrawal in the presence of gabapentin, underscoring the need to tailor OUD treatment in fentanyl-exposed patients. (Clinicialtrials.gov ID NCT02543944).

Improvement in depression accounted for approximately 25% of the treatment effect of naltrexone-bupropion on methamphetamine treatment response.

Background: Buprenorphine is a Food and Drug Administration–approved medication for opioid use disorder. However, individuals with opioid use disorder often report information needs regarding buprenorphine treatment on social media platforms such as Reddit. The field lacks a systematic approach to organizing these data and characterizing treatment information needs that may be unique and unavailable elsewhere. Objective: In this study, we curated and analyzed large-scale data from social media to characterize self-reported buprenorphine treatment information needs using a qualitative analysis. Methods: We collected 15,253 Reddit posts from the subreddit r/Suboxone. Following a standard protocol and guidance from clinical experts, we first identified 5 main themes from the data and then manually coded 6000 posts based on these themes. Finally, we determined the most frequently appearing topics within each theme by analyzing samples from each group. Results: Among the 6000 posts, 2417 (40.3%) contained a single theme, 2160 (36%) contained two themes, and 834 (13.9%) contained three themes. The most frequent topics found across these themes included reports of psychological and physical effects during recovery, complexities in accessing buprenorphine, and significant information gaps regarding medication administration, tapering, and substance use at different stages of recovery. Moreover, self-treatment strategies and peer-driven advice revealed potential rumors and misinformation. Conclusions: Our findings can guide the design of interventions to improve patient education and communication. They also help address knowledge gaps and misinformation related to treatment. Additionally, the results can support hypothesis generation for future clinical research on medication for opioid use disorder treatment.