Discontinuation of medication treatment for opioid use disorder after a successful course: The discontinuation phase of the CTN-0100 (RDD) trial.

INTRODUCTION AND BACKGROUND: Buprenorphine, and extended-release naltrexone, are effective in decreasing opioid use, morbidity and mortality. The available evidence suggests that these medications should be used for long term treatment; however, patients often ask how long they need to be on medication, and whether it would be safe to discontinue. There are sparse data to guide us. The CTN-0100 trial will address this gap in our knowledge by studying participants who have decided to discontinue buprenorphine and extended-release naltrexone for OUD. RESEARCH DESIGN AND METHODS: The trial is a multicenter, randomized, non-blinded study. Participants are stable adult volunteers, on sublingual buprenorphine, extended-release buprenorphine, or extended-release naltrexone, expressing an interest in discontinuing medication. Participants on buprenorphine must be stable for at least 1 year and participants on extended-release naltrexone must be stable for at least 6 months. Participants are engaged in the study for up to 96 weeks, including a flexible taper period, and are then transitioned to follow-up within the trial. All participants are randomly assigned to the study Medical Management (MM) or to MM plus Connections (CHESS health) digital smartphone application aimed at recovery and abstinence (MMD). Sublingual Buprenorphine participants are also randomized (2 × 2 design) to a taper using either sublingual or extended-release buprenorphine. DISCUSSION/CONCLUSION: It is hoped that this trial will provide a rich source of data on management of patients discontinuing medication for opioid use disorder (MOUD) to inform future research and practice. The trial will shed light on which strategies are most likely to lead to long-term success (absence of relapse), and what participant characteristics distinguish those who can safely discontinue MOUD from those who remain at risk of relapse should they discontinue. CLINICALTRIALS: gov Identifier: NCT04464980.

Effects of Bundling Medication for Opioid Use Disorder With an mHealth Intervention Targeting Addiction: A Randomized Clinical Trial.

OBJECTIVE: Medication for opioid use disorder (MOUD) improves treatment retention and reduces illicit opioid use. A-CHESS is an evidence-based smartphone intervention shown to improve addiction-related behaviors. The authors tested the efficacy of MOUD alone versus MOUD plus A-CHESS to determine whether the combination further improved outcomes. METHODS: In an unblinded parallel-group randomized controlled trial, 414 participants recruited from outpatient programs were assigned in a 1:1 ratio to receive either MOUD alone or MOUD+A-CHESS for 16 months and were followed for an additional 8 months. All participants were on methadone, buprenorphine, or injectable naltrexone. The primary outcome was abstinence from illicit opioid use; secondary outcomes were treatment retention, health services use, other substance use, and quality of life; moderators were MOUD type, gender, withdrawal symptom severity, pain severity, and loneliness. Data sources were surveys comprising multiple validated scales, as well as urine screens, every 4 months. RESULTS: There was no difference in abstinence between participants in the MOUD+A-CHESS and MOUD-alone arms across time (odds ratio=1.10, 95% CI=0.90-1.33). However, abstinence was moderated by withdrawal symptom severity (odds ratio=0.95, 95% CI=0.91-1.00) and MOUD type (odds ratio=0.57, 95% CI=0.34-0.97). Among participants without withdrawal symptoms, abstinence rates were higher over time for those in the MOUD+A-CHESS arm than for those in the MOUD-alone arm (odds ratio=1.30, 95% CI=1.01-1.67). Among participants taking methadone, those in the MOUD+A-CHESS arm were more likely to be abstinent over time (b=0.28, SE=0.09) than those in the MOUD-alone arm (b=0.06, SE=0.08), although the two groups did not differ significantly from each other (∆b=0.22, SE=0.11). MOUD+A-CHESS was also associated with greater meeting attendance (odds ratio=1.25, 95% CI=1.05-1.49) and decreased emergency department and urgent care use (odds ratio=0.88, 95% CI=0.78-0.99). CONCLUSIONS: Overall, MOUD+A-CHESS did not improve abstinence relative to MOUD alone. However, MOUD+A-CHESS may provide benefits for subsets of patients and may impact treatment utilization.

Contingency Management and Pre-Exposure Prophylaxis Adherence Support Services (CoMPASS): A hybrid type 1 effectiveness-implementation study to promote HIV risk reduction among people who inject drugs.

BACKGROUND: HIV disproportionally affects persons who inject drugs (PWID), but engagement with HIV pre-exposure prophylaxis (PrEP) is low. We describe the rationale and study design for a new study, "Contingency Management and Pre-Exposure Prophylaxis (PrEP) Adherence Support Services (CoMPASS)," a hybrid type 1 effectiveness-implementation trial to promote HIV risk reduction among PWID. METHODS: In four community-based programs in the northeastern United States, PrEP-eligible PWID (target n = 526) are randomized to treatment as usual or Contingency Management (CM) and, as indicated, stepped up to PrEP Adherence Support Services (CoMPASS) over 24 weeks. During CM sessions, participants receive timely tangible rewards for verifiable activities demonstrating 1) PrEP initiation and adherence, and 2) engagement with medications for opioid use disorder (MOUD) and other OUD-related care. Participants who do not have high levels of biomarker-confirmed PrEP adherence at week 12 will be stepped up to receive PrEP Adherence Support Services (PASS) consisting of strengths-based case management over 12 weeks. Interventions are delivered by trained PrEP navigators, staff embedded within the respective sites. The primary outcome is sustained PrEP adherence by dried blood spot testing at 24 weeks. To inform future implementation, we are conducting implementation-focused process evaluations throughout the clinical trial. CONCLUSIONS: Results from this protocol are anticipated to yield novel findings regarding the impact and scalability of CoMPASS to promote HIV prevention among PWID in partnership with community-based organizations. http://ClinicalTrials.gov identifier: NCT04738825.

Retention in care for persons with opioid use disorder transitioning from sublingual to injectable buprenorphine.

INTRODUCTION: In the current overdose epidemic, effective treatments for opioid use disorders (OUD), including innovations in medication delivery such as extended-release formulations, have the potential to improve treatment access and reduce treatment discontinuation. This study assessed treatment retention in a primary care-based, extended-release buprenorphine program. METHODS: The study recruited individuals (n = 92) who transitioned from sublingual buprenorphine to extended-release buprenorphine (BUP-XR) in 2018-2019. The study defined the primary outcome, treatment retention, as three or more consecutive, monthly BUP-XR injections following the transition to BUP-XR in this retrospective chart review. RESULTS: Participants' mean age was 38 years old and 67% were male. The average duration of sublingual buprenorphine prior to transition was 17.1 (±28.1) months. Three months after transition, 48% of extended-release buprenorphine patients had discontinued BUP-XR treatment. Persons with chronic pain were more likely, and those who had used heroin in the past month less likely to continue BUP-XR. Mean months on sublingual buprenorphine prior to BUP-XR initiation was 24.3 (±32.5) months for people who received 3+ post-induction injections compared to only 8.9 (±19.5) months for those who did not (p = .009). CONCLUSIONS: Extended-release buprenorphine discontinuation was high in a real-world setting. Retention continues to represent a major obstacle to treatment effectiveness, and programs need interventions with even newer MOUD formulations.

Negative affect-associated drug refusal self-efficacy, illicit opioid use, and medication use following short-term inpatient opioid withdrawal management.

INTRODUCTION: Persons with opioid use disorder (OUD) are prone to frequent relapse following brief inpatient medically managed withdrawal. This longitudinal, naturalistic study examines associations among illicit opioid use, use of medication for opioid use disorder (MOUD), and one's confidence in the ability to resist drug use in the face of negative emotions (i.e., negative affect-associated drug refusal self-efficacy). METHOD: Participants were 220 adults with OUD who recently completed a short-term inpatient program and the study followed for 6 months. At baseline, participants reported demographics, illicit opioid use, recent engagement with MOUD, and negative affect-associated drug refusal self-efficacy. At follow-up (1 week and 1-, 3-, and 6-months following discharge), participants reported illicit opioid use and MOUD. RESULTS: Participants averaged 30.7 years of age, 63.2% were male, and 84.1% were white. Both illicit opioid use and rates of MOUD increased during the 6-month follow-up period, although only 34.1% received MOUD. At baseline, participants reported less than 50% self-confidence to resist using opioids during negative emotional states. Baseline negative affect-associated drug refusal self-efficacy inversely predicted illicit opioid use (p = .01) at follow-up but was not associated with follow-up MOUD. CONCLUSION: Among persons with OUD, lower confidence to resist using opioids in negative emotional states predicts greater use of illicit opioids in the months following medically managed withdrawal, even with receipt of MOUD.

Examining Overdose and Homelessness as Predictors of Willingness to Use Supervised Injection Facilities by Services Provided Among Persons Who Inject Drugs.

BACKGROUND AND OBJECTIVES: Internationally, supervised injection facilities (SIFs) have demonstrated efficacy in reducing rates of overdose and promoting entry into treatment among persons who inject drugs (PWID); however, they remain unavailable in the United States. Early findings examining American PWID illustrate high overall willingness to use SIFs. The current study expands upon this research by examining PWID's likelihood to use SIFs based on services offered (eg, provides clean needles, linkage to treatment programs) and whether known risk factors (prior overdose, homelessness) influence PWID's willingness to use a SIF. METHODS: Participants (n = 184) were patients entering short-term inpatient opioid withdrawal management in Massachusetts between May 2018 and February 2019 who reported injection drug use in the prior 30 days. We examined PWID's likelihood to use a SIF if eight unique services were available, and compared if this differed by overdose history and homelessness status using ordered logistic regression and Pearson's χ2 -tests of independence. RESULTS: Participants (34.2 [±8.3 SD] years of age, 68.5% male, 85.9% white, 8.2% Hispanic) reported being most likely to use SIFs that provided safety from police intervention (86.7%), entry into withdrawal management (85.9%), or clean needles (83.2%). Drug works disposal and safety from police were particularly important for PWID with a history of overdose. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Overall, treatment-seeking PWIDs reported greater willingness to utilize SIFs if particular services were provided. These findings point to features of SIFs that may enhance treatment-seeking PWID's amenability to utilizing these services if such sites open in the United States. (Am J Addict 2021;30:21-25).

Prescribed and non-prescribed gabapentin use among persons seeking inpatient opioid detoxification.

BACKGROUND: Persons with opioid use disorder (OUD) are at increased risk for gabapentin misuse. Rising rates of concomitant gabapentin-opioid use in the U.S. are concerning given heightened risk of fatal overdose. OBJECTIVE: To examine predictors of ever using gabapentin among persons seeking treatment for opioid use and to assess if reasons for gabapentin use differed by gender and how gabapentin was procured (prescribed, non-prescribed, or both). METHOD: Persons with OUD were recruited from a managed withdrawal program. t-Tests and Pearson χ2 tests of independence were used to compare reasons for gabapentin use by gender and source of acquisition. RESULTS: Among participants (n = 401; 69.1% male, 84.5% White, 86.8% sought treatment for heroin use, 90.0% insured), female gender, higher educational attainment, injection drug use (IDU), history of overdose, and chronic pain were associated with gabapentin use. Overall, reasons for use were similar across genders among those reporting a history of gabapentin use (65.8%), although males were more likely to use to get high than females. About half (47.0%) reported only using gabapentin that was not prescribed, 20.5% had only used prescribed gabapentin, and 32.5% reported prescribed and non-prescribed use. Persons prescribed gabapentin were most likely to use it to control pain (81.5%); for those using diverted gabapentin only and those reporting both prescribed and non-prescribed gabapentin use, the most common reasons for intake were to: get high, increase effects of heroin, substitute for opioids, and help with opioid withdrawal. CONCLUSIONS: In this sample of people with OUD entering inpatient detoxification program, a majority reported a history of gabapentin use, with most using diverted gabapentin. The range of reasons for gabapentin use point to the need to better understand why co-use is common.

Perceptions about fentanyl-adulterated heroin and overdose risk reduction behaviors among persons seeking treatment for heroin use.

BACKGROUND: Fentanyl-adulterated heroin supply chains are increasing risks for fatal overdose in the U.S. OBJECTIVE: The current study examined the use of overdose risk reduction behaviors among persons seeking treatment for heroin use and whether perceptions about the presence of fentanyl in one's heroin are associated with overdose risk reduction behaviors. METHOD: We recruited persons with opioid use disorder entering a managed withdrawal program. We used multiple linear regression to estimate the adjusted associations of participant characteristics and perception of fentanyl exposure with the frequency of engaging in each of five overdose reduction behaviors. RESULTS: Participants (n = 239; 75.3% male, 81.2% White, 67% injectors) estimated that 69.2% of the heroin they use contains fentanyl, and 94.6% knew that fentanyl increases overdose risk. Approximately 30% of respondents reported usually or always making sure others are around when they use heroin, carrying naloxone, taking "tester" doses of heroin or intentionally using in reduced amounts. While a majority of the sample reported never carrying naloxone or taking tester doses, and 70.2% reported never making sure that others around them carry naloxone, 84.5% had implemented one or more behavior at least rarely. Past month injection drug use was associated with making sure others are around, but perceptions about fentanyl in one's heroin were not associated with use of harm reduction behaviors. CONCLUSIONS: In this sample of people who use heroin, although overdose risk reduction behaviors were not usually used, a majority had tried at least one behavior. That perceived exposure to fentanyl-adulterated heroin was not associated with the use of such behaviors provides important implications for public health education and intervention programming.

Long-term safety of a weekly and monthly subcutaneous buprenorphine depot (CAM2038) in the treatment of adult out-patients with opioid use disorder.

AIMS: To assess the long-term safety of subcutaneous buprenorphine (CAM2038) weekly and monthly depots. DESIGN: Phase 3, open-label, observational, multi-centre 48-week trial (ClinicalTrials.gov NCT02672111). SETTING: Twenty-six out-patient sites (United States, United Kingdom, Hungary, Denmark, Sweden, Germany, Australia) between 14 December 2015 and 12 April 2017. PARTICIPANTS: Two hundred and twenty-eight adults with opioid use disorder; 227 received CAM2038 (37 initiated onto CAM2038 and 190 converted from sublingual buprenorphine). INTERVENTIONS: CAM2038 weekly (8, 16, 24 or 32 mg) or monthly (64, 96, 128 or 160 mg) with flexible dosing and individualized titration utilizing multiple CAM2038 weekly and monthly doses. MEASUREMENTS: Safety variables, urine toxicology samples and self-reported illicit opioid use were collected at each visit. Participants were administered a patient satisfaction survey at months 6 and 12, completed by 162 of 227 (71.4%) participants. FINDINGS: The study treatment period was completed by 167 of 227 (73.6%) participants. At least one treatment-emergent adverse event (TEAE) was reported by 143 of 227 (63.0%) participants, of whom 60 of 227 (26.4%) reported as being drug-related. Most of the TEAEs, reported by 128 of 227 (56.4%) of participants, were mild or moderate in intensity. Injection-site reactions were reported by 46 of 227 (20.3%) participants, with most [45 of 46 (97.8%)] reported as mild to moderate. Five participants (2.2%) discontinued the study drug due to a TEAE, two cases (0.9%) of which were injection-site-related. No serious adverse events were attributed to the study drug. Among those remaining in the study, the percentage of opioid-negative urine tests combined with self-reports was 63.0% (17 of 27) in new-to-treatment participants and 82.8% (111 of 134) for those converted from sublingual buprenorphine. Participants reported high levels of satisfaction with CAM2038. CONCLUSIONS: Subcutaneous buprenorphine delivered weekly or monthly (CAM2038) was well tolerated, with a systemic safety profile consistent with the known profile of sublingual buprenorphine. CAM2038 weekly and monthly was associated with high retention rates and low levels of illicit opioid use throughout this study.

Worries About Discontinuing Buprenorphine Treatment: Scale Development and Clinical Correlates.

BACKGROUND AND OBJECTIVES: Despite the benefits of maintenance buprenorphine treatment for opioid use disorder (OUD), many individuals report an interest in discontinuing the medication, while also expressing worries about tapering. The purpose of this study was to develop a measure of worries about buprenorphine discontinuation ("Off Bupe") and determine the demographic and clinical characteristics associated with these worries. METHODS: Between May 2017 and May 2018, we surveyed adults in an outpatient primary care buprenorphine program (n = 138). Reliability and validity of the Off Bupe measure were examined. RESULTS: Participants averaged 39 years of age, 54% were male, average duration of buprenorphine was 189 weeks and 85.5% reported eventually wanting to discontinue buprenorphine, although fewer than 10% were actively tapering. We derived two scales, withdrawal symptom worry (10 items, ɑ = 0.94) and relapse worry (7 items, ɑ = 0.88). Worry about symptoms was positively associated with current buprenorphine dose (P = 0.016), physical discomfort avoidance (P < 0.001), and inversely associated with self-efficacy to quit buprenorphine (P < 0.001) and distress tolerance (P < 0.001). Worry about opioid relapse was associated positively with age (P = 0.019), current buprenorphine dose (P = 0.004), physical discomfort avoidance (P < 0.001), and impulsivity (P = 0.002), and inversely associated with self-efficacy to quit buprenorphine (P < 0.001). DISCUSSION AND CONCLUSIONS: Psychometric evaluation of the "Off Bupe" scale demonstrated its content and construct validity and internal reliability. SCIENTIFIC SIGNIFICANCE: The scale might help individuals with OUD and their providers identify concerns about discontinuing buprenorphine. (Am J Addict 2019;28:270-276).

A new brief opioid stigma scale to assess perceived public attitudes and internalized stigma: Evidence for construct validity.

One key strategy to improve treatment access for persons with opioid use disorder (OUD) is overcoming stigma that is internalized by such individuals. Because few theoretically-derived, multidimensional measures of substance abuse stigma exist, we contribute a brief, theoretically-based measure of opioid-related stigma (adapted from Corrigan's Self-Stigma of Mental Illness Scale) to assess perceived stigma and internalized stigma among individuals with OUD. This study presents initial validation of the newly-developed Brief Opioid Stigma Scale among 387 adults who entered an inpatient opioid managed-withdrawal program. The scale assesses: (1) Stereotype awareness ("Aware"), or the extent to which individuals who use opioids perceive community members to believe OUD-related stereotypes; (2) Stereotype agreement ("Agree"), or the endorsement of stigmatizing beliefs by individuals who use opioids; (3) Self-esteem decrement ("Harm"), or the diminution of self-esteem due to these negative stereotypes' impacts on self-worth. Psychosocial measures including self-esteem, depressive symptoms, mental and physical functioning, and desire for aftercare OUD medication treatment, were administered to assess construct validity. Results showed that greater endorsement of the "harm" stigma subscale was associated with greater depressive symptoms, lower self-esteem, and poorer mental and physical functioning. The "aware" stigma subscale displayed similar overall patterns of associations with self-esteem and depression but to a lesser magnitude. The "aware" stigma subscale was positively associated with desire for aftercare methadone and naltrexone treatment, and the "harm" subscale was positively associated with desire for aftercare buprenorphine treatment. Results indicated good initial construct validity. Tailored stigma interventions are recommended for specific aftercare OUD medication treatments.

Drug Use-Related Normative Misperceptions and Behaviors Among Persons Seeking Heroin Withdrawal Management.

OBJECTIVE: Normative perceptions about substance use are well-established predictors of substance use risk behaviors, yet no research to date has examined how people who use heroin perceive the drug use behaviors and their association with personal behaviors. In a sample of persons seeking heroin withdrawal, we compared normative beliefs (descriptive norms) about others' drug use behaviors, and examined the association between normative beliefs and behaviors. METHOD: Participants (n = 241) were patients undergoing short-term inpatient heroin withdrawal management in Massachusetts. t-Tests were used to compare participants' perceptions about various substance use behaviors among both US adults and persons seeking heroin withdrawal at the same site. We also examined associations between participants' normative beliefs and personal substance use behaviors. RESULTS: Participants significantly overestimated drug-related risk behaviors of adults nationally; overall, participants estimated that 44.7% had tried heroin, 37.6% had injected drugs in the past year, and 63.2% had smoked marijuana in the past month when actual national rates are 2.0%, 0.3%, and 5.5%, respectively. Participants also held significant misperceptions about contemporaneous patients in the heroin withdrawal program; behaviors about sharing works, diverting buprenorphine or methadone, and exchanging sex for drugs or money were most substantially overestimated. Normative perceptions were associated with a range of personal drug-using behaviors (eg, injection drug use, exchanging sex for drugs or money). CONCLUSIONS: Consistent with existing substance use norms research, participants in the current sample tended to overestimate others' engagement in risky substance use, and these normative perceptions were associated with increased personal risk. Leveraging norms in heroin harm reduction interventions may hold substantial promise.

Expectations about alcohol, cocaine, and benzodiazepine abstinence following inpatient heroin withdrawal management.

BACKGROUND AND OBJECTIVES: Polysubstance use is associated with relapse and poor treatment outcomes among people dependent on heroin. Despite the high prevalence of polysubstance use among patients detoxifying from heroin, little is known about patients' expectations to abstain or use non-opiate substances. The current study examined factors associated with expectations about abstaining from alcohol, cocaine, and benzodiazepines (BZDs) following heroin withdrawal management. METHODS: Between May and December of 2015, we surveyed 417 patients (71.9% male, 31.7 [±8.39] mean years old) initiating short-term inpatient heroin withdrawal management who reported alcohol, cocaine, or BZD use in the past 30 days. We used logistic regression to evaluate the adjusted associations of background characteristics with expectations about using each substance following discharge. RESULTS: Approximately half of respondents reported past month alcohol (52%), cocaine (47.0%), or BZD (47.0%) use, and 25.9% reported using all three substances. Approximately half of those reporting drinking, 6.6% reporting cocaine use, and 27% of reporting BZD use expected to abstain from using that substance following heroin withdrawal. Prior opioid withdrawal was associated with a lower likelihood of expecting to stop using alcohol and BZDs, and more days of BZD use was associated with a greater likelihood of expecting to abstain from BZDs following discharge. CONCLUSION: Persons with opioid use disorder often do not expect to stop using other substances following withdrawal management, with very few planning cocaine cessation. SCIENTIFIC SIGNIFICANCE: Inpatient heroin withdrawal programs need to address and educate patients about how polysubstance use complicates recovery from heroin use. (Am J Addict 2019;28:36-42).

Buprenorphine treatment formulations: Preferences among persons in opioid withdrawal management.

BACKGROUND: In the current study, we examined factors predicting willingness to receive buprenorphine treatment and preferences for various buprenorphine formulations (oral, injection, implant) among persons in opioid withdrawal management. METHODS: Participants were three hundred thirty-eight persons entering brief inpatient opioid withdrawal management programs at two sites. We used t-tests and Pearson χ2 - tests of independence to compare participants willing and unwilling to be prescribed buprenorphine in the future. Among persons willing to receive buprenorphine, we used multinomial logistic regression to estimate the adjusted effects of potential correlates of type of buprenorphine formulation preferred. RESULTS: Participants averaged 33.9 (±9.5) years of age, 70.4% were male, 82.8% were White, and 11.0% were Latino/a. In all, 55.6% of participants had been prescribed buprenorphine in the past, and 54.7% were willing to use prescribed buprenorphine in the future. Those reporting past month illicit buprenorphine use and prior overdose were more willing to use prescribed buprenorphine. Of these (n = 180), most preferred daily buprenorphine formulations (tablet or film) (48.6%) over a weekly or monthly injection (23.1%) or bi-annual implant (28.3%). CONCLUSIONS: Past buprenorphine prescription does not predict future willingness to restart. Among those willing to use buprenorphine, newer formulations of buprenorphine appealed to more than half of the participants.

Weekly and Monthly Subcutaneous Buprenorphine Depot Formulations vs Daily Sublingual Buprenorphine With Naloxone for Treatment of Opioid Use Disorder: A Randomized Clinical Trial.

Importance: Buprenorphine treatment for opioid use disorder may be improved by sustained-release formulations. Objective: To determine whether treatment involving novel weekly and monthly subcutaneous (SC) buprenorphine depot formulations is noninferior to a daily sublingual (SL) combination of buprenorphine hydrochloride and naloxone hydrochloride in the treatment of opioid use disorder. Design, Setting, and Participants: This outpatient, double-blind, double-dummy randomized clinical trial was conducted at 35 sites in the United States from December 29, 2015, through October 19, 2016. Participants were treatment-seeking adults with moderate-to-severe opioid use disorder. Interventions: Randomization to daily SL placebo and weekly (first 12 weeks; phase 1) and monthly (last 12 weeks; phase 2) SC buprenorphine (SC-BPN group) or to daily SL buprenorphine with naloxone (24 weeks) with matched weekly and monthly SC placebo injections (SL-BPN/NX group). Main Outcomes and Measures: Primary end points tested for noninferiority were response rate (10% margin) and the mean proportion of opioid-negative urine samples for 24 weeks (11% margin). Responder status was defined as having no evidence of illicit opioid use for at least 8 of 10 prespecified points during weeks 9 to 24, with 2 of these at week 12 and during month 6 (weeks 21-24). The mean proportion of samples with no evidence of illicit opioid use (weeks 4-24) evaluated by a cumulative distribution function (CDF) was an a priori secondary outcome with planned superiority testing if the response rate demonstrated noninferiority. Results: A total of 428 participants (263 men [61.4%] and 165 women [38.6%]; mean [SD] age, 38.4 [11.0] years) were randomized to the SL-BPN/NX group (n = 215) or the SC-BPN group (n = 213). The response rates were 31 of 215 (14.4%) for the SL-BPN/NX group and 37 of 213 (17.4%) for the SC-BPN group, a 3.0% difference (95% CI, -4.0% to 9.9%; P < .001). The proportion of opioid-negative urine samples was 1099 of 3870 (28.4%) for the SL-BPN/NX group and 1347 of 3834 (35.1%) for the SC-BPN group, a 6.7% difference (95% CI, -0.1% to 13.6%; P < .001). The CDF for the SC-BPN group (26.7%) was statistically superior to the CDF for the SL-BPN/NX group (0; P = .004). Injection site adverse events (none severe) occurred in 48 participants (22.3%) in the SL-BPN/NX group and 40 (18.8%) in the SC-BPN group. Conclusions and Relevance: Compared with SL buprenorphine, depot buprenorphine did not result in an inferior likelihood of being a responder or having urine test results negative for opioids and produced superior results on the CDF of no illicit opioid use. These data suggest that depot buprenorphine is efficacious and may have advantages. Trial Registration: ClinicalTrials.gov Identifier: NCT02651584.

Loaded: Gun involvement among opioid users.

INTRODUCTION: Despite ample research examining how alcohol use relates to gun involvement, little is known about the relationship between opioids and gun involvement. In the current study, we examined correlates of gun possession, accessibility, and related behaviors in an opioid dependent sample. METHODS: Between October 2016 and April 2017, we surveyed persons entering a brief, inpatient opioid detoxification (n = 386) and 51 contemporaneous persons seeking alcohol detoxification at the same facility in Massachusetts and recorded their lifetime experiences with gun involvement. RESULTS: Participants averaged 33 years of age, 74% were male, 83% were White, and 64% had a history of incarceration. Opioid users had significantly higher rates of gun involvement than persons in alcohol detoxification; for example, 31.3% (vs. 3.9%) had carried a gun for protection, 45.1% (vs. 25.5%) had been threatened with a gun, and 13.8% (vs. 2.0%) had shot at another person. Among persons misusing opioids, male and non-White respondents, and those with a history of incarceration or poorer self-control reported greater gun involvement. CONCLUSIONS: Opioid users, both men and women, lead gun-involved lives.

Expected and actual fentanyl exposure among persons seeking opioid withdrawal management.

OBJECTIVE: Fentanyl-contaminated opioid supplies have led to rising overdose fatalities in recent years. We compared beliefs, behaviors, and risk perceptions related to fentanyl with actual toxicology reports among people who used opioids. METHOD: Participants (n=231) were patients undergoing short-term inpatient opioid withdrawal management in Fall River, Massachusetts. We compared persons testing positive and negative for fentanyl on urine toxicological testing at program entry. RESULTS: Nearly all (95.7%) participants believed that fentanyl increases risk for overdose/death, and 86.6% of participants tested positive for fentanyl. Positive fentanyl toxicology test results were associated with lower educational attainment, history of injection drug use, and self-reported lifetime use of fentanyl. Of those reporting they had never been exposed to fentanyl (intentionally or unintentionally) (n=33), two-thirds tested positive for fentanyl; among those believing their tests would be negative (n=49), 71.4% tested positive for fentanyl. Heroin use was associated with fentanyl exposure; persons who reported past month heroin use (n=213) were more likely to test positive for fentanyl (91.1%) than persons using non-heroin opioids (n=18; 33.3%). CONCLUSIONS: Nearly nine in ten participants tested positive for fentanyl, including participants who anticipated their tests would be negative. Leveraging toxicology results in opioid withdrawal settings may be helpful in educating patients about fentanyl exposure and risks.

Correlates of Stigma Severity Among Persons Seeking Opioid Detoxification.

INTRODUCTION: Among people with opioid use disorder (OUD), stigma is a known barrier to accessing treatment and has negative impacts on physical and mental health. The purpose of this study was to understand the factors associated with self-stigma and perceived stigma severity among people with OUD entering an inpatient detoxification program. METHODS: Between December 2015 and August 2016, consecutive persons seeking inpatient opioid detoxification were asked to complete a survey that included sociodemographic, drug use, treatment variables, an 8-item General Self-Stigma scale, and a 3-item Treatment Stigma scale. Correlates of stigma severity were estimated using ordinary least squares regression. RESULTS: The 407 participants had an average age of 32.4 (±8.79) years, with 72.2% male and 84.5% non-Hispanic White. Two-thirds had ever received medication-assisted treatment for OUD and 323 (79.4%) had ever been admitted to a detoxification program. Adjusted mean General Self-Stigma scores were positively and significantly associated with recent injection drug use (b = 0.262, P = 0.032), and having previously entered detoxification programs (b = 0.330, P = 0.016). Adjusted mean Treatment Stigma scores were positively and significantly associated with years of education (b = 0.142, P = 0.002), having ever been prescribed naltrexone (b = 0.277, P = 0.025) and having previously entered detoxification programs (b = 0.389, P = 0.007). CONCLUSION: People with OUD presenting for inpatient detoxification struggle with experiences of self and perceived stigma. Strikingly, people with previous detoxification program admission had higher levels of stigma on both scales. Our findings suggest an opportunity for targeted intervention in this group.

Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Extended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX. METHODS: We initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433. FINDINGS: Between Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10-1·68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0·44). Opioid-negative urine samples (p<0·0001) and opioid-abstinent days (p<0·0001) favoured BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0·0012), then converged by week 24 (p=0·20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group). INTERPRETATION: In this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications. FUNDING: NIDA Clinical Trials Network.

Factors associated with naloxone administration in an opioid dependent sample.

INTRODUCTION: Naloxone is a safe and effective antidote for reversing opioid overdose. Layperson administration of naloxone is increasingly common, yet little is known about demographic and clinical factors associated with opioid users' likelihood of having administered naloxone to another opioid user who had overdosed. We examined predictors of reported naloxone administration in the past year. METHODS: Four hundred and sixty-eight patients were interviewed upon admission to brief, inpatient opioid detoxification between May and December of 2015. Between group differences were tested using t-tests for differences in means and χ2-tests for differences in counts. RESULTS: Participants averaged 32years of age, 28.9% were female, and 86.8% were White. Most (86.8%) reported detoxifying from heroin, 69.0% had injected drugs in the last 30days. One sixth (n=68) of those detoxifying from heroin, but none of those detoxifying from other opioids (n=62) had administered naloxone in the past year. Among the small number of Black/African American participants (n=20), none had administered naloxone, although 90% were heroin users. Respondents were more likely to have administered naloxone if they reported recent injection drug use (IDU), had a history of overdose, or witnessed an overdose in the past year (ps<0.05), even though less than one-third of bystanders of overdose reported administering naloxone. CONCLUSIONS: Higher opioid-related mortality risk (heroin use, IDU, past overdose) was associated with greater likelihood of reported naloxone administration in the past year. The non-use of naloxone among certain groups-prescription pill users and Blacks-was unexpected.