Baseline- and treatment-associated pain in the X:BOT comparative effectiveness study of extended-release naltrexone versus buprenorphine-naloxone for OUD.

Chronic pain is highly prevalent among patients with opioid use disorder (OUD). However, little is known about how pharmacological treatments for OUD, for example, extended-release naltrexone (XR-NTX) and buprenorphine-naloxone (BUP-NX), affect pain. To begin addressing this question, we performed a secondary analysis of pain data on a large prospective 24-week, open-label, randomized-controlled comparative effectiveness trial of XR-NTX versus BUP-NX (X:BOT trial). Participants' pain status was measured by the EuroQol (EQ-5D). Based on their responses to the pain question at baseline, participants were dichotomized into "Pain" versus "No Pain" categories. Participant's pain status was evaluated every 4 weeks. A mixed effects longitudinal logistic regression model was fitted to examine the differential effect of XR-NTX versus BUP-NX on pain, modelling pain at all available follow-up assessments, adjusted for age, sex, and baseline pain. A total of 474 individuals who were successfully inducted onto their assigned medications were included in this analysis. Among participants endorsing pain at baseline, substantial reductions in pain were observed over the course of the study in both treatment groups. Howecver reduction in pain was slightly greater in the group treated with XR-NTX than the one treated with BUP-NX (OR = 1.60 [95% CI: 1.07-2.40], P = 0.023). Future research using instruments and design specifically focused on pain could extend the present observations and evaluate their clinical significance.

The Predictive Value of Degree of Preference for Extended-Release Naltrexone for Treatment Adherence, Opioid Use, and Relapse.

BACKGROUND: Extended-release naltrexone (XR-NTX) is effective for illicit opioid abstinence as an opioid maintenance treatment. To improve treatment outcomes, patient's preference for the modality of treatment is an important factor. OBJECTIVES: We aimed to test the relationship between baseline preference for XR-NTX and adherence to treatment, use of illicit opioids, and risk of relapse. METHODS: In an open-label, Norwegian clinical trial participants with opioid use disorder were randomized to either monthly injections with XR-NTX or daily sublingual buprenorphine-naloxone (BP-NLX) for 12 weeks. Subsequently, participants could continue with their preferred medication in a 36-week follow-up and in a prolonged period of 104 weeks. RESULTS: Of 153 participants who completed detoxification, 72% were men, with a mean age of 36 years. Preference levels were similar across the randomized groups, with no significant associations between preference and adherence to treatment, opioid use, or relapse. The BP-NLX group had a significantly higher risk of first relapse to opioids than the XR-NTX group for all levels of preference (p < 0.001) and a significantly higher number of days of illicit opioid use. In the follow-up period, the adherence rate was twice as high among participants with the highest preference compared to participants with the lowest preference, both among those who switched to XR-NTX and those who continued (hazard ratio 2.2; 1.2-4.0, p = 0.013). Opioid use was significantly higher among participants who switched to XR-NTX with the lowest preference than the medium (p = 0.003) or the highest (p = 0.001) preference. The risk of relapse to opioids, however, was significantly higher among XR-NTX continuing participants with the lowest (p = 0.002) or the medium (p = 0.043) preference than those with the highest preference. CONCLUSIONS: Individuals who matched with their preferred treatment used less illicit opioids than those who did not during short-term treatment. However, baseline preference for XR-NTX treatment primarily influenced longer term opioid use and treatment adherence.

Online Medication Assisted Treatment Education for Court Professionals: Need, Opportunities and Challenges.

INTRODUCTION: Although medication-assisted treatment (MAT) effectively treats opioid use disorders (OUD), MAT access is restricted in criminal justice (CJ) settings. Previous studies have documented that stigma and limited knowledge about MAT are prevalent among CJ court personnel. We describe development and pilot testing of an eLearning intervention to improve MAT knowledge and increase MAT referrals in Ohio courts. Methods: Building upon a nationwide survey conducted in 2011 of drug courts and informed by MAT opinions from judges who supervised OUD clients, we developed two eLearning MAT modules. Judges completed a brief online MAT knowledge-attitude scale (K-A) before, after, and at 3 months. Judges were asked about MAT referrals pretest and 3 months later. Results: Sixty-three judges expressed interest in the study, 25 completed the pretest and viewed the modules, 11 completed a 3 month posttest. At pretest, K-A scores were significantly (p<.05) lower for agonist medications than for extended-release naltrexone (XR-NTX; Vivitrol). K-A scores improved at posttest for agonist medications (p<.05) but declined to pretest levels three months later. Three months after the pretest, buprenorphine referrals increased from 2.6% to 9.7% (p<.05). There was no significant difference on K-A scores for agonist medication between the Ohio sample (at pretest) and the 2011 sample. Conclusion: Although there is some indication that eLearning may have strengthened knowledge gains and increased buprenorphine referrals, a more robust eLearning intervention will likely be required to increase court personnel participation and sustain eLearning knowledge gains. Recruiting and sustaining judges' participation in the study represented a significant study limitation.

Gender differences among criminal justice-involved persons living with HIV interested in extended-release naltrexone treatment.

Background: Previous research has shown gender differences with respect to entry into medication treatment of substance use disorders (SUDs), yet few have examined gender differences among participants consented to be treated with extended-release naltrexone (XR-NTX). Understanding gender differences is critical to developing interventions to overcome barriers to initiation of and retention on medication treatment for SUDs. Methods: Data from two double-blind placebo-controlled trials of XR-NTX among persons with HIV and alcohol or opioid use disorders leaving the criminal justice system (CJS) were analyzed for gender differences among clinical characteristics, mental health, drug use severity, and other domains. The study that recruited persons with alcohol use disorder (AUD) was conducted from September 2010-February 2016 at two sites in Connecticut (CT), and the opioid use disorder (OUD) study was conducted from September 2010-March 2016 at three sites in CT and one site in Massachusetts. Results: Baseline data were analyzed from 193 participants consented to be randomized to XR-NTX or placebo; 40 women and 153 men. Women were younger, had worse mental health severity, and were more likely to be diagnosed with cocaine use disorder. There were no statistical differences between men and women in the prescription of antiretroviral therapy (ART) or ART adherence. Conclusions: Women had greater mental health severity and a higher prevalence of cocaine use as compared to men, both of which are known to be barriers to engagement and retention on medication treatment for alcohol and opioid use disorders. For women with CJS involvement and living with HIV and SUDs, understanding factors that may affect initiation and retention on medication treatment of SUDs are necessary to improve treatment outcomes in women.

Impact of extended release naltrexone on health-related quality of life in individuals with legal involvement and opioid use disorders.

Background: Understanding the impact of medications for opioid use disorder on health related quality of life (QOL) may help to explain why few individuals with legal involvement remain in treatment, specifically those receiving opioid antagonists. QOL is an established predictor of treatment retention and has been shown to improve with some treatment for opioid use disorder. Yet limited research has examined QOL with opioid antagonists. We examined the impact of extended release naltrexone (XR-NTX) on QOL and retention in treatment in a randomized, multi-site trial of individuals with legal involvement. Methods: The participants were 308 community-dwelling adults with current or recent legal involvement with opioid dependence at five site across United States. They were randomized to receive XR-NTX or treatment as usual for 6 months. QOL was measured every 2 weeks using Euro QOL individual items, summary index score, and health state today metric. Results: No significant difference in QOL scores were observed between the two groups at the completion of active treatment or on follow up at 52 and 78 weeks. There were no time effects of treatment on scores. Contrary to expectation, baseline and average QOL did not predict retention in treatment. Conclusion: In contrast to prior research, our findings did not demonstrate significant changes (improvements or decreases) in QOL associated with XR-NTX treatment. Clinicians may consider that individuals receiving XR-NTX may not experience changes in perceived well-being in response to treatment and consider discussing with patients that they may not necessarily perceive improvement in their QOL. This may help to ground patient's expectations about the effects of treatment and potentially reduce attrition from treatment with opioid antagonists.

Behavioral and Accumbal Responses During an Affective Go/No-Go Task Predict Adherence to Injectable Naltrexone Treatment in Opioid Use Disorder.

Adherence is a major factor in the effectiveness of the injectable extended-release naltrexone as a relapse prevention treatment in opioid use disorder. We examined the value of a variant of the Go/No-go paradigm in predicting extended-release naltrexone adherence in 27 detoxified opioid use disorder patients who were offered up to 3 monthly extended-release naltrexone injections. Before extended-release naltrexone, participants performed a Go/No-go task that comprised positively valenced Go trials and negatively valenced No-go trials during a functional magnetic resonance imaging scan. Errors of commission and neural responses to the No-go vs Go trials were independent variables. Adherence, operationalized as the completion of all 3 extended-release naltrexone injections, was the outcome variable. Fewer errors of commission and greater left accumbal response during the No-go vs Go trials predicted better adherence. These findings support the clinical potential of the behavioral and neurophysiological correlates of response inhibition in the prediction of extended-release naltrexone treatment outcomes in opioid use disorder.

Medications for Treatment of Opioid Use Disorder among Persons Living with HIV.

PURPOSE OF REVIEW: Recent HIV outbreaks have occurred as a result of the current US opioid epidemic. Providing medications for opioid use disorder (MOUD) with methadone, buprenorphine, and extended-release naltrexone is essential to achieving optimal HIV treatment outcomes including viral suppression and retention in treatment. This review describes the pharmacology of MOUD with specific attention to interactions with antiretroviral therapy, and to the effect of MOUD on HIV treatment outcomes. RECENT FINDINGS: Methadone and buprenorphine both improve HIV viral suppression, adherence to antiretroviral therapy, and overall mortality for persons with opioid use disorder (OUD). Extended-release naltrexone has been most extensively studied in persons with HIV leaving incarcerated settings, and improves HIV viral suppression in that context. Strategies that integrate MOUD and HIV treatment are crucial to optimize viral suppression. The differing pharmacokinetic and delivery characteristics of these MOUD offer diverse options. Given the chronic and relapsing nature of both HIV and OUD, long-term approaches are required.

Efficacy of Extended-Release Naltrexone on HIV-Related and Drinking Outcomes Among HIV-Positive Patients: A Randomized-Controlled Trial.

We sought to test the efficacy of extended-release naltrexone (XR-NTX) on HIV-related and drinking outcomes. From April 2011-February 2015, we conducted a 4-site randomized double-blind placebo controlled clinical trial involving 51 HIV-positive patients with heavy drinking and < 95% antiretroviral (ART) adherence. All participants received counseling. The primary outcome was proportion with ≥ 95% ART adherence. Secondary outcomes included HIV biomarkers, VACS Index score, and past 30-day heavy drinking days. Based on receipt of ≥ 5 injections, 23 participants were retained at 24 weeks. We did not detect an effect of XR-NTX on ART adherence (p = 0.38); undetectable HIV viral load (p = 0.26); CD4 cell count (p = 0.75) or VACS Index score (p = 0.70). XR-NTX was associated with fewer heavy drinking days (p = 0.03). While XR-NTX decreases heavy drinking days, we did not detect improvements in ART adherence or HIV outcomes. Strategies to improve retention in alcohol treatment and HIV-related outcomes among heavy drinking HIV-positive patients are needed.

Availability of Extended-Release Naltrexone May Increase the Number of Opioid-Dependent Individuals in Treatment: Extension of a Randomized Clinical Trial.

BACKGROUND AND OBJECTIVE: Opioid maintenance treatment (OMT) is highly available in Norway, but only 50% of opioid-dependent individuals are enrolled in such programs. This study was aimed at examining if availability of extended-release naltrexone (XR-NTX) could attract individuals who for different reasons were not enrolled in an OMT program. METHODS: In a Norwegian clinical study, n = 117 opioid-dependent adults volunteered to receive XR-NTX in a 9-month period, as an extension of a previous randomized clinical trial. RESULTS: Before study inclusion, 40.2% (n = 47) of the study participants were not enrolled in OMT while the remainder were recruited from OMT. Participants not enrolled in OMT displayed more ongoing severe addiction-related problems such as heroin use (p = 0.002), but displayed a higher retention in treatment in the 9-month extension study (p = 0.048 for log-rank test) than participants enrolled in OMT. CONCLUSION: Availability of XR-NTX attracted opioid-dependent individuals not previously enrolled in OMT. While OMT may be perceived as a burden with regard to daily intake and control measures, one-monthly injections with XR-NTX may be perceived favourable, offering more freedom to the patients, not having addictive properties, and potentially reducing heroin craving. We suggest that an introduction of XR-NTX in Europe may increase the number of opioid-dependent individuals in treatment.

Acceptability of Extended-Release Naltrexone by Heroin-Dependent Patients and Addiction Treatment Providers in the Netherlands.

BACKGROUND: Extended-release naltrexone (XRNT) was developed to overcome poor treatment compliance with oral naltrexone in alcohol and opioid-dependent patients. XRNT injections are registered in the United States and Russia, but not in The Netherlands. However, XRNT can be obtained for individual patients, but it is expensive and not reimbursed by the health insurance. OBJECTIVES: This study evaluates the support for abstinence oriented treatment among heroin-dependent patients and the acceptability of XRNT injections by heroin-dependent patients and treatment providers in The Netherlands. METHODS: A sample of 261 patients in methadone maintenance treatment or heroin assisted treatment and a sample of 188 addiction treatment providers completed specially designed questionnaires. RESULTS: The current study shows that many patients in opioid maintenance treatment (58%) report a desire to become abstinent from opioids and that 83% of the patients with a desire for abstinence are interested in XRNT. The majority of treatment providers (81%) are willing to support the prescription of XRNT injections in opioid-dependent patients to prevent relapse after detoxification. CONCLUSIONS: The current practice of automatic and indefinite continuation of opioid substitution should therefore be reconsidered. However, XRNT injections are very expensive and currently not reimbursed by the health insurance agencies in The Netherlands and thus not really available to most patients.

A delayed injection-site reaction in a patient receiving extended-release naltrexone.

BACKGROUND: Pharmacotherapy, such as oral naltrexone, has proven effective in treating alcohol use disorder, although medication adherence has presented challenges. Although a formulation of extended-release naltrexone for intramuscular injection has been developed to counter daily adherence issues, injection-site reactions can occur within days of depot injection. CASE: The authors report a case of an individual with alcohol use disorder who had a previously undescribed delayed injection-site reaction that occurred 11 days after injection. Subsequent challenge with the medication resulted in recurrence of the reaction. DISCUSSION: Although extended-release naltrexone is generally well tolerated, injection-site reactions can complicate treatment and can appear more than 10 days after medication administration.

Relapse prevention medications in community treatment for young adults with opioid addiction.

BACKGROUND: Despite the well-known effectiveness and widespread use of relapse prevention medications such as extended release naltrexone (XR-NTX) and buprenorphine for opioid addiction in adults, less is known about their use in younger populations. METHODS: This was a naturalistic study using retrospective chart review of N = 56 serial admissions into a specialty community treatment program that featured the use of relapse prevention medications for young adults (19-26 years old) with opioid use disorders. Treatment outcomes over 24 weeks included retention and weekly opioid-negative urine tests. RESULTS: Patients were of mean age 23.1, 70% male, 86% Caucasian, 82% with history of injection heroin use, and treated with either buprenorphine (77%) or XR-NTX (23%). The mean number of XR-NTX doses received was 4.1. Retention was approximately 65% at 12 weeks and 40% at 24 weeks, and rates of opioid-negative urine were 50% at 12 weeks and 39% at 24 weeks, with missing samples imputed as positive. There were no statistically significant differences in retention (t = 1.87, P = .06) or in rates of weekly opioid-negative urine tests (t = 1.96, P = .06) between medication groups, over the course of 24 weeks. The XR-NTX group had higher rates of weekly negative urine drug tests for other nonopioid substances (t = 2.83, P < .05) compared with the buprenorphine group. Males were retained in treatment longer and had higher rates of opioid-negative weeks compared with females. CONCLUSIONS: These results suggest that relapse prevention medications including both buprenorphine and XR-NTX can be effectively incorporated into standard community treatment for opioid addiction in young adults with good results. Specialty programming focused on opioid addiction in young adults may provide a promising model for further treatment development.

Extended-release naltrexone and harm reduction counseling for chronically homeless people with alcohol dependence.

BACKGROUND: Abstinence-based alcohol interventions are minimally desirable to and effective for chronically homeless individuals with alcohol dependence who have multimorbidity and high publicly funded service utilization and associated costs. Lower-barrier, patient-centered combined pharmacobehavioral interventions may more effectively treat this population. Harm reduction counseling involves a nonjudgmental, empathic style and patient-driven goal setting that requires neither abstinence nor use reduction. Extended-release naltrexone (XR-NTX), a monthly injectable formulation of an opioid receptor antagonist, reduces craving, is safe and effective for active drinkers, and may thereby support harm reduction goal setting. The aims of this 12-week, single-arm pilot were to initially document some aspects of feasibility, acceptability, and alcohol outcomes following XR-NTX administration and harm reduction counseling for chronically homeless individuals with alcohol dependence. METHODS: Participants were currently/formerly chronically homeless, alcohol-dependent individuals (N = 31) from 2 community-based agencies in the US Pacific Northwest. Measures included self-reported alcohol craving, quantity/frequency, problems, and biomarkers (ethyl glucuronide [EtG], liver transaminases). XR-NTX and harm reduction counseling were administered monthly over the 3-month treatment course. RESULTS: Of the 45 individuals approached, 43 were interested in participation. The first injection was received by 31 participants, and 24 complied with all study procedures. Participants reported the treatment was acceptable. Participants evinced decreases in alcohol craving (33%), typical (25%) and peak (34%) use, frequency (17%), problems (60%), and EtG from the baseline to the 12-week follow-up (Ps < .05). CONCLUSIONS: XR-NTX and harm reduction counseling are promising means of supporting reductions in alcohol use and alcohol-related harm among chronically homeless, alcohol-dependent individuals.

Associations between stimulant use and return to illicit opioid use following initiation onto medication for opioid use disorder.

AIM: The aim of this study was to estimate how ongoing stimulant use affects return to illicit opioid use after initiation onto medication for opioid use disorder (MOUD). DESIGN: This was a secondary analysis of pooled data from two clinical trials comparing buprenorphine (BUP-NX) and extended-release naltrexone (XR-NTX). SETTING: Thirteen opioid treatment programs and HIV clinics across 10 states in the United States from 2014 to 2019 took part in this study. PARTICIPANTS: A total of 528 participants who initiated MOUD as part of trial participation were included. Nearly half (49%) were between 30 and 49 years of age, 69% were male and 66% were non-Hispanic White. MEASUREMENTS: The primary outcome was first self-reported day of non-prescribed opioid use following MOUD initiation, and the exposure of interest was daily stimulant use (methamphetamine, amphetamines or cocaine). Both were defined using time-line follow-back. Among participants reporting at least 1 day of illicit opioid use, we also examined relapse to ongoing use, defined as (1) 7 days of continuous opioid use or (2) 4 consecutive weeks with self-reported opioid use, one or more positive urine drug screens (UDS) for opioids or one or more missing UDS. FINDINGS: Forty-seven per cent of participants reported stimulant use following MOUD initiation, 58% returned to illicit opioid use and 66% of those relapsed to ongoing use. Stimulant use was strongly associated with increased risk of misusing opioids after MOUD initiation when measured daily [adjusted hazard ratio (aHR) = 9.23, 95% confidence interval (CI) = 6.80-12.50, P < 0.001] and over a 7-day period (aHR = 1.27 for each additional day, CI = 1.18-1.37, P < 0.001). Using stimulants weekly or more often was associated with increased likelihood of relapse to ongoing opioid use compared with less than weekly or no stimulant use (adjusted odds ratio = 2.30, CI = 1.05-5.39, P = 0.044). CONCLUSIONS: People initiated on medication for opioid use disorder who subsequently use stimulants appear to be more likely to return to and continue using non-prescribed opioids compared with those without stimulant use. The association appears to be stronger among patients who initiate buprenorphine compared with those who initiate extended-release naltrexone.

Patient and provider medication preferences affect treatment outcomes among adolescents and young adults with opioid use disorder.

BACKGROUND: The opioid epidemic in the United States has not spared youth or young adults, as evidenced by a six-fold increase in opioid use disorder (OUD) diagnoses in the last two decades. Given this dramatic rise, a call for greater uptake and accessibility of medications for opioid use disorder (MOUDs) among youth and young adults has ensued, resulting in an increasing number of MOUD treatment pathways for this vulnerable population. METHODS: This secondary data analysis seeks to characterize patient and provider preferences for MOUD treatment pathways, and test for associations between baseline MOUD treatment preferences and opioid use and treatment adherence outcomes. Participants included 288 youth and young adults (age 15-21 years), recruited from a residential treatment program in Maryland. The study assessed patient preferences at baseline (n = 253) and provider preferences at patient treatment discharge (n = 224). Mixed-effects negative binomial regression models were conducted for opioid use outcomes, and logistic regressions were conducted for treatment adherence outcomes. RESULTS: Results indicate that congruence of treatment with patients' (Incidence Rate Ratio [IRR] = 0.65) and providers' (IRR = 0.66) preferences was significantly associated with reduced self-reported days of opioid use in the past 90 days, but only for patients receiving extended-release naltrexone (XR-NTX). Results also indicated that patients were less likely to switch medication treatment pathways (e.g., from XR-NTX to buprenorphine, or vice versa) during follow-up if they received their preferred treatment at baseline, a finding which held true for both XR-NTX (Odds Ratio [OR] = 0.32) and buprenorphine (OR = 0.22). CONCLUSIONS: Receipt of MOUD congruent with patient and provider preferences was associated with reduced opioid use and greater treatment adherence in this sample of youth and young adults with OUD.

Comparative effectiveness of extended-release naltrexone and sublingual buprenorphine for treatment of opioid use disorder among Medicaid patients.

BACKGROUND AND AIMS: Extended-release naltrexone (XR-NTX) and sublingual buprenorphine (SL-BUP) are both approved for opioid use disorder (OUD) treatment in any medical setting. We aimed to compare the real-world effectiveness of XR-NTX and SL-BUP. DESIGN AND SETTING: This was an observational active comparator, new user cohort study of Medicaid claims records for patients in New Jersey and California, USA, 2016-19. PARTICIPANTS/CASES: The participants were adult Medicaid patients aged 18-64 years who initiated XR-NTX or SL-BUP for maintenance treatment of OUD and did not use medications for OUD in the 90 days before initiation. Our cohort included 1755 XR-NTX and 9886 SL-BUP patients. MEASUREMENTS: We examined two outcomes up to 180 days after medication initiation: (1) composite of medication discontinuation and death and (2) composite of overdose and death. FINDINGS: In adjusted analyses, treatment with XR-NTX was more likely to result in discontinuation or death by the end of follow-up than treatment with SL-BUP: cumulative risk 75.9% [95% confidence interval (CI) = 73.9%, 77.9%] versus 62.2% (95% CI = 61.2%, 63.2%), respectively (risk difference = 13.7 percentage points, 95% CI = 11.4, 16.0). There was minimal difference in the cumulative risk of overdose or death by the end of follow-up: XR-NTX 3.9% (95% CI = 3.0%, 4.8%) versus SL-BUP 3.3% (95% CI = 2.9%, 3.7%); risk difference = 0.5 percentage points, 95% CI = -0.4, 1.5. Results were consistent across sensitivity analyses. CONCLUSIONS: Medicaid patients in California and New Jersey, USA, receiving treatment for opioid use disorder stayed in treatment longer on sublingual buprenorphine than on extended-release naltrexone, but the risk of overdose was similar. Most patients in this study discontinued medication within 6 months, regardless of which medication was initiated.

Comparative effectiveness of extended release naltrexone and sublingual buprenorphine for treatment of opioid use disorder among Medicaid patients.

Aims: To compare the real-world effectiveness of extended release naltrexone (XR-NTX) and sublingual buprenorphine (SL-BUP) for the treatment of opioid use disorder (OUD). Design: An observational active comparator, new user cohort study. Setting: Medicaid claims records for patients in New Jersey and California, 2016-2019. Participants/Cases: Adult Medicaid patients aged 18-64 years who initiated XR-NTX or SL-BUP for maintenance treatment of OUD and did not use medications for OUD in the 90-days before initiation. Comparators: New initiation with XR-NTX versus SL-BUP for the treatment of OUD. Measurements: We examined two outcomes up to 180 days after medication initiation, 1) composite of medication discontinuation and death, and 2) composite of overdose and death. Findings: Our cohort included 1,755 XR-NTX and 9,886 SL-BUP patients. In adjusted analyses, treatment with XR-NTX was more likely to result in discontinuation or death by the end of follow-up than treatment with SL-BUP: cumulative risk 76% (95% confidence interval [CI] 75%, 78%) versus 62% (95% CI 61%, 63%), respectively (risk difference 14 percentage points, 95% CI 13, 16). There was minimal difference in the cumulative risk of overdose or death by the end of follow-up: XR-NTX 3.8% (95% CI 2.9%, 4.7%) versus SL-BUP 3.3% (95% 2.9%, 3.7%); risk difference 0.5 percentage points, 95%CI -0.5, 1.5. Results were consistent across sensitivity analyses. Conclusions: Longer medication retention is important because risks of negative outcomes are elevated after discontinuation. Our results support selection of SL-BUP over XR-NTX. However, most patients discontinued medication by 6 months indicating that more effective tools are needed to improve medication retention, particularly after initiation with XR-NTX, and to identify which patients do best on which medication.

Comparing outcomes of extended-release naltrexone in adolescents and young adults with opioid use disorder.

INTRODUCTION: Opioid use among youth is a public health concern in the United States, with >3300 overdose deaths occurring nationally each year. Unfortunately, youth in the United States are still prescribed medication for opioid use disorder (OUD) at a lower rate than their adult counterparts. METHODS: From 10/2013 to 01/2018, adolescents (ages 15-17; n = 25) and young adults (ages 18-21; n = 263) with moderate to severe OUD enrolled in the parent trial of extended-release naltrexone (XR-NTX; n = 82) versus treatment-as-usual (TAU; either buprenorphine maintenance [n = 94] or counseling without buprenorphine maintenance [n = 112]). The study assessed opioid use outcomes for adolescents vs. young adults using timeline follow-back self-report procedures at baseline and 3-/6-month follow-up assessments. Mixed-effects longitudinal and clustered panel regression models compared treatment effects over time of XR-NTX and TAU on opioid use outcomes in this secondary analysis. RESULTS: Though adolescent participants reported significantly less opioid use at baseline relative to their young adult counterparts (p < 0.05), the two age groups reported similar rates of opioid use throughout the intervention period. Additionally, both adolescents and young adults receiving XR-NTX evidenced lower rates of opioid use than those receiving TAU at all time points, and adolescents on XR-NTX were the only group who reduced their opioid use at all time points. Mixed-effects models indicated adolescents receiving XR-NTX demonstrated a 48 % lower rate of opioid use days [Incidence Rate Ratio (IRR) = 0.52; p = 0.020], while young adults receiving XR-NTX reported an estimated 26 % lower rate (IRR = 0.74; p = 0.009). CONCLUSIONS: Results indicate that adolescents respond favorably to XR-NTX relative to TAU for treatment of OUD, demonstrating similar outcomes to young adults.

Personal recovery among people with opioid use disorder during treatment with extended-release naltrexone.

Background and aims: Recovery from substance use disorders (SUD) has traditionally been equated with abstinence. "Personal recovery" however emphasizes recovery as a unique and personal process, supported by changes in connectedness, hope, identity, meaning and empowerment. This study aimed to examine personal recovery in people receiving extended-release naltrexone (XR-NTX); specifically investigate changes in personal recovery during treatment, identify groups of participants following distinct trajectories of recovery, and characteristics predicting group-belonging. Methods: Overall change in recovery (Questionnaire about the Process of Recovery, QPR) score was assessed by linear mixed model in a subsample of 135 people with opioid use disorder (OUD) participating in a 24 + 28-week trial of XR-NTX. Growth mixture model was used to identify potential groups of people following distinct trajectories of personal recovery. Results: Overall, there was a significant change in QPR score during treatment. Four groups with distinct recovery trajectories were identified: "initially low- increase" (G1), "initially average- no change" (G2), "initially high- no change" (G3) and "initially high- increase" (G4). The groups were different with regards to level of psychological distress, social support, and the use of benzodiazepines. In addition, previous participation in opioid agonist treatment programs, current pain, life satisfaction, employment, heroin craving and previous use of heroin also differed between groups. Conclusions: Personal recovery among people receiving XR-NTX follows different trajectories, and various factors are associated with personal recovery. Particular attention regarding psychological distress, social support and heroin use among patients commencing XR-NTX treatment is important to facilitate successful recovery trajectories.

Estimating the impact of stimulant use on initiation of buprenorphine and extended-release naltrexone in two clinical trials and real-world populations.

BACKGROUND: Co-use of stimulants and opioids is rapidly increasing. Randomized clinical trials (RCTs) have established the efficacy of medications for opioid use disorder (MOUD), but stimulant use may decrease the likelihood of initiating MOUD treatment. Furthermore, trial participants may not represent "real-world" populations who would benefit from treatment. METHODS: We conducted a two-stage analysis. First, associations between stimulant use (time-varying urine drug screens for cocaine, methamphetamine, or amphetamines) and initiation of buprenorphine or extended-release naltrexone (XR-NTX) were estimated across two RCTs (CTN-0051 X:BOT and CTN-0067 CHOICES) using adjusted Cox regression models. Second, results were generalized to three target populations who would benefit from MOUD: Housed adults identifying the need for OUD treatment, as characterized by the National Survey on Drug Use and Health (NSDUH); adults entering OUD treatment, as characterized by Treatment Episodes Dataset (TEDS); and adults living in rural regions of the U.S. with high rates of injection drug use, as characterized by the Rural Opioids Initiative (ROI). Generalizability analyses adjusted for differences in demographic characteristics, substance use, housing status, and depression between RCT and target populations using inverse probability of selection weighting. RESULTS: Analyses included 673 clinical trial participants, 139 NSDUH respondents (weighted to represent 661,650 people), 71,751 TEDS treatment episodes, and 1,933 ROI participants. The majority were aged 30-49 years, male, and non-Hispanic White. In RCTs, stimulant use reduced the likelihood of MOUD initiation by 32% (adjusted HR [aHR] = 0.68, 95% CI 0.49-0.94, p = 0.019). Stimulant use associations were slightly attenuated and non-significant among housed adults needing treatment (25% reduction, aHR = 0.75, 0.48-1.18, p = 0.215) and adults entering OUD treatment (28% reduction, aHR = 0.72, 0.51-1.01, p = 0.061). The association was more pronounced, but still non-significant among rural people injecting drugs (39% reduction, aHR = 0.61, 0.35-1.06, p = 0.081). Stimulant use had a larger negative impact on XR-NTX initiation compared to buprenorphine, especially in the rural population (76% reduction, aHR = 0.24, 0.08-0.69, p = 0.008). CONCLUSIONS: Stimulant use is a barrier to buprenorphine or XR-NTX initiation in clinical trials and real-world populations that would benefit from OUD treatment. Interventions to address stimulant use among patients with OUD are urgently needed, especially among rural people injecting drugs, who already suffer from limited access to MOUD.