Rapid Initiation of Injection Naltrexone for Opioid Use Disorder: A Stepped-Wedge Cluster Randomized Clinical Trial.

Importance: Injectable extended-release (XR)-naltrexone is an effective treatment option for opioid use disorder (OUD), but the need to withdraw patients from opioid treatment prior to initiation is a barrier to implementation. Objective: To compare the effectiveness of the standard procedure (SP) with the rapid procedure (RP) for XR-naltrexone initiation. Design, Setting, and Participants: The Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone study was an optimized stepped-wedge cluster randomized trial conducted at 6 community-based inpatient addiction treatment units. Units using the SP were randomly assigned at 14-week intervals to implement the RP. Participants admitted with OUD received the procedure the unit was delivering at the time of their admission. Participant recruitment took place between March 16, 2021, and July 18, 2022. The last visit was September 21, 2022. Interventions: Standard procedure, based on the XR-naltrexone package insert (approximately 5-day buprenorphine taper followed by a 7- to 10-day opioid-free period and RP, defined as 1 day of buprenorphine at minimum necessary dose, 1 opioid-free day, and ascending low doses of oral naltrexone and adjunctive medications (eg, clonidine, clonazepam, antiemetics) for opioid withdrawal. Main Outcomes and Measures: Receipt of XR-naltrexone injection prior to inpatient discharge (primary outcome). Secondary outcomes included opioid withdrawal scores and targeted safety events and serious adverse events. All analyses were intention-to-treat. Results: A total of 415 participants with OUD were enrolled (mean [SD] age, 33.6 [8.48] years; 205 [49.4%] identified sex as male); 54 [13.0%] individuals identified as Black, 91 [21.9%] as Hispanic, 290 [69.9%] as White, and 22 [5.3%] as multiracial. Rates of successful initiation of XR-naltrexone among the RP group (141 of 225 [62.7%]) were noninferior to those of the SP group (68 of 190 [35.8%]) (odds ratio [OR], 3.60; 95% CI, 2.12-6.10). Withdrawal did not differ significantly between conditions (proportion of days with a moderate or greater maximum Clinical Opiate Withdrawal Scale score (>12) for RP vs SP: OR, 1.25; 95% CI, 0.62-2.50). Targeted safety events (RP: 12 [5.3%]; SP: 4 [2.1%]) and serious adverse events (RP: 15 [6.7%]; SP: 3 [1.6%]) were infrequent but occurred more often with RP than SP. Conclusions and Relevance: In this trial, the RP of XR-naltrexone initiation was noninferior to the standard approach and saved time, although it required more intensive medical management and safety monitoring. The results of this trial suggest that rapid initiation could make XR-naltrexone a more viable treatment for patients with OUD. Trial Registration: ClinicalTrials.gov Identifier: NCT04762537.

Stress Exposure and PTSD in a Cross-Sectional Residential Substance Use Treatment Sample.

BACKGROUND: Aim 1 of this cross-sectional, observational study with people in residential treatment for substance use disorders (SUDs) was to document stress exposure. Aim 2 was to assess potential sociodemographic and health differences based on probable posttraumatic stress disorder (PTSD) status. Aim 3 was to assess relative contributions of Diagnostic and Statistical Manual (DSM)-congruent versus DSM-incongruent stressors (Criterion A vs non-Criterion A) to mental and physical health. We hypothesized that both types of stressors would significantly contribute to impairment across indicators and that DSM-congruent stressor exposure would be more strongly associated with impairment than DSM-incongruent exposure. METHODS: We assessed exposure to DSM-congruent traumatic stressors and DSM-incongruent life stressors, PTSD and depressive symptoms, emotion regulation difficulties, substance use recovery capital, and physical/mental health-related quality of life among 136 people in residential SUD treatment who were 64% men, 36% women; 49% white, 41% Black, 11% multiracial/another race; 18% lesbian, gay, or bisexual (LGB+); mean age = 39.82 (standard deviation = 12.24) years. RESULTS: Participants reported experiencing a mean of 9.76 (SD = 6.11) DSM-congruent events. Those with probable PTSD were younger and more likely to be LGB+ than those without probable PTSD (P < .05). Experiencing higher numbers of DSM-congruent events was associated with more severe PTSD and depressive symptoms, emotion regulation difficulties, and lower physical health-related quality of life (P < .05). DSM-incongruent stressor exposure was not independently associated with any indicators. Recovery capital was not associated with either type of stress exposure. CONCLUSIONS: Stressful event exposure among people in residential SUD treatment is very high. Those who are younger or LGB+ in residential SUD treatment may be at greater risk of developing PTSD. DSM-congruent stressors are more consistently associated with mental health indicators than are DSM-incongruent stressors. Prioritizing treatment targets and identifying implementable treatment strategies can be challenging with this complex population.

A pilot randomized controlled trial of medication adherence therapy: Psychosocial leverage using a significant other (MAT-PLUS) for individuals on extended-release naltrexone.

BACKGROUND: Extended-release naltrexone (XR-NTX) is an important treatment option for individuals with opioid use disorder (OUD) and/or alcohol use disorder (AUD). However, problems with retention are a major barrier to its overall effectiveness, and interventions to improve adherence are underdeveloped. The purpose of this study was to pilot test the MAT-PLUS intervention, which combines assertive outreach and involvement of a treatment significant other (TSO) to improve adherence to XR-NTX. METHODS: Adults (N = 41) seeking treatment for OUD and/or AUD with XR-NTX were recruited from an inpatient addiction treatment center and randomized to the MAT-PLUS intervention or treatment as usual (TAU) for 16-weeks. TSOs (N = 19) of individuals in the MAT-PLUS condition were also enrolled. The primary outcome was the number of XR-NTX doses received and relapse to regular heavy use (opioid or alcohol) was a secondary outcome. RESULTS: Participants in the MAT-PLUS group received 3.4 doses compared to 2.5 in TAU, which was significant after controlling for SUD diagnosis (p < 0.05). Rates of receipts of all prescribed doses were 61.1 % in MAT-PLUS compared to 30.4 % in TAU, giving an NNT of 3.3. Relapse rates and days of heavy use did not vary by treatment group. CONCLUSIONS: This study demonstrates preliminary efficacy of the MAT-PLUS intervention for XR-NTX adherence. This study was limited by its small sample size and future research should broaden the intervention to apply across medications for SUD in larger samples. Family support with an emphasis on medication adherence has strong potential for improving addiction treatment outcomes.

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.

Engagement, initiation, and retention in medication treatment for opioid use disorder among young adults: A narrative review of challenges and opportunities.

INTRODUCTION: Opioid Use Disorder (OUD) is a catastrophic public health problem for young adults (YAs) and their families. While medication for OUD (MOUD) is safe, effective, and recognized as the standard of care, its' uptake and success have been limited in YAs compared to older adults. METHODS: This narrative review summarizes the existing literature and highlights select studies regarding barriers to YA MOUD, potential explanations for those barriers, and strategies to overcome them. RESULTS: Barriers are prominent along the entire cascade of care, including: treatment engagement and entry, MOUD initiation, and MOUD retention. Hypothesized explanations for barriers include: developmental vulnerability, inadequate treatment system capacity, stigma against MOUD, among others. Interventions to address barriers include: promotion of family involvement, increasing provider capacity, integration of MOUD into primary care, assertive outreach, and others. CONCLUSIONS: Integrating an adapted version of family coaching from the Community Reinforcement Approach and Family Training (CRAFT) and other models into YA MOUD treatment serves as an example of an emerging novel practice that holds promise for broadening the funnel of engagement in treatment and initiation of MOUD, and enhancing treatment outcomes. This and other developmentally-informed approaches should be evaluated as part of a high-priority clinical and research agenda for improving OUD treatment for YAs.

Linkage facilitation services for opioid use disorder: Taxonomy of facilitation practitioners, goals, and activities.

INTRODUCTION: This article proposes a taxonomy of linkage facilitation services used to help persons with opioid use disorder access treatment and recovery resources. Linkage facilitation may be especially valuable for persons receiving medication for opioid use disorder (MOUD) given the considerable barriers to treatment access and initiation that have been identified. The science of linkage facilitation currently lacks both consistent communication about linkage facilitation practices and a conceptual framework for guiding research. METHODS: To address this gap, this article presents a taxonomy derived from expert consensus that organizes the array of practitioners, goals, and activities associated with linkage services for OUD and related needs. Expert panelists first independently reviewed research reports and policy guidelines summarizing the science and practice of linkage facilitation for substance use disorders generally and OUD specifically, then met several times to vet the conceptual scheme and content of the taxonomy until they reached a final consensus. RESULTS: The derived taxonomy contains eight domains: facilitator identity, facilitator lived experience, linkage client, facilitator-client relationship, linkage activity, linkage method, linkage connectivity, and linkage goal. For each domain, the article defines basic domain categories, highlights research and practice themes in substance use and OUD care, and introduces innovations in linkage facilitation being tested in one of two NIDA-funded research networks: Justice Community Opioid Innovation Network (JCOIN) or Consortium on Addiction Recovery Science (CoARS). CONCLUSIONS: To accelerate consistent application of this taxonomy to diverse research and practice settings, the article concludes by naming several considerations for linkage facilitation workforce training and implementation.

Fentanyl-induced respiratory depression in rodents is inhibited by bioabsorbable, subcutaneous naltrexone implants at 3.5 months.

The aim of this study is to determine if extended-release, bioabsorbable, subcutaneous naltrexone (NTX) implants inhibit respiratory depression after an IV injection of fentanyl. Bioabsorbable implants fabricated from two different release-controlling polymers, poly-D-L-lactide (PDLLA) and polycaprolactone (PCL), alone (placebo) or containing NTX, were subcutaneously implanted in Sprague Dawley rats. After 3.5 months of implantation, the rodents were administered an IV bolus of fentanyl through the tail vein. The placebo implant rats received a dose of 4 micrograms (mcg) - (10 mcg/kg/dose), while the NTX implanted animals received a dose of 8 mcg (20 mcg/kg/dose). The minimum active dose of fentanyl that caused a > 50 ± 2% depression in the respiration rate in the placebo implanted rodents was 4 mcg. The respiration rate of the placebo implanted rats dropped from 208 ± 14 breaths/minute at predose, to 84 ± 12 breaths/minute (p = 0.0003) at 2 min. In contrast, all NTX implanted animals easily tolerated twice the dose of 8 mcg of fentanyl without any significant reduction in respiration rate. The mean respiration rate = increased from 164 ± 22 breaths/minute at predose to 178 ± 17 breaths/minute (p = 0.24) at 2 min. The mean plasma concentrations of NTX, 3.5 months after implantation, ranged from 7.4 (±1.1) ng/mL to 80.3 (±37.5) ng/mL. Bioabsorbable implants containing NTX effectively blocked fentanyl-induced respiratory depression in rodents as compared with placebo implants, 3.5 months after implantation.

Launching Relationship-Oriented Behavioral Services for Youth Opioid Use Disorder: Innovations in Medication Decision-Making and Adherence Planning.

This article presents behavioral interventions designed to enhance uptake and retention on medication for opioid use disorder (MOUD) among transition-age youth (16-25 years) enrolled in treatment services. The article describes three relationship-oriented interventions designed to address barriers to MOUD uptake, enhance MOUD adherence planning, and strengthen OUD recovery among youth: Relational Orientation; Medication Education and Decision-making Support, and Family Leadership and Ownership of Adherence to Treatment. These interventions are inter-connected can be delivered flexibly. The article concludes with three case examples that illustrate how these modular interventions can be tailored to meet the needs of diverse client profiles.

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.

Health care use and cost of treatment for adolescents and young adults with opioid use disorder.

BACKGROUND: Few studies have examined the cost of medication for opioid use disorder (MOUD) with counseling for the adolescent and young adult population. This study calculated the health care utilization and cost of MOUD treatment, other substance use disorder treatment, and general health care for adolescents and young adults receiving treatment for opioid use disorder. METHODS: The study randomized youth ages 15 to 21 (N = 288) equally into the two study conditions: extended-release naltrexone (XR-NTX) or treatment as usual (TAU). While participants committed to treatment based on randomization the study observed considerable nonadherence to both randomized conditions. Instead of using the randomly assigned study conditions, we present descriptive costs by the type of MOUD treatment received: XR-NTX only, buprenorphine only, any other combination of MOUD treatments, and no MOUD. Health care use was aggregated over the 6-month period for each participant, and we calculated average/participant utilization for each treatment group. To determine participant costs, we multiplied the unit costs of health care services obtained from the literature by the reported amount of health care utilization for each participant. We then calculated the mean, standard error, median and IQR for MOUD costs, other substance use disorder treatment costs and general healthcare cost from the health care sector perspective. RESULTS: On average, participants in the XR-NTX only group received 2.6 doses of XR-NTX (equivalent to approximately 78 days of treatment). The buprenorphine only group had an average of 97 days of buprenorphine treatment. The XR-NTX only group had higher/patient costs compared to participants in the buprenorphine only group ($10,491 vs. $8765) and higher XR-NTX utilization would further increase costs. Participants in the any other MOUD combination group had the highest total costs ($14,627) while participants in the no MOUD group at the lowest ($3453). DISCUSSION: Our cost analysis calculates the real-world cost of MOUD treatment and, while not generalizable, provides policy makers an estimate of costs for adolescents and young adults. We found that participants in the XR-NTX only group received fewer days of medication compared to the buprenorphine only group, but their medication costs were higher due to the cost of XR-NTX injections. While the buprenorphine only group had the highest number of days of medication utilization of all the groups, the average number of days of medication utilization was considerably shorter than the six-month treatment period.

Impact of Medication-Based Treatment on Health Care Utilization Among Individuals With Opioid Use Disorder.

OBJECTIVE: This study evaluated the association between medication for opioid use disorder (MOUD) and health care utilization over time among a sample of treatment-seeking individuals with opioid use disorder. In contrast to previous studies, this study used a novel measure of MOUD adherence, more comprehensive utilization data, and analyses that controlled for detailed individual and social determinants of health. METHODS: This study was a secondary analysis of a comparative effectiveness trial (N=570) of extended-release naltrexone versus buprenorphine-naloxone. The outcome of interest was usage of nonstudy acute care, inpatient and outpatient addiction services, and other outpatient services across 36 weeks of assessment. Adherence (percentage of days taking MOUD) was defined as low (<20%), medium (≥20% but <80%), or high (≥80%). A two-part model evaluated the probability of utilizing a resource and the quantity (utilization days) of the resource consumed. A time-varying approach was used to examine the effect of adherence in a given month on utilization in the same month, with analyses controlling for a wide range of person-level characteristics. RESULTS: Participants with high adherence (vs. low) were significantly less likely to use inpatient addiction (p<0.001) and acute care (p<0.001) services and significantly more likely to engage in outpatient addiction (p=0.045) and other outpatient (p=0.042) services. CONCLUSIONS: These findings reinforce the understanding that greater MOUD adherence is associated with reduced usage of high-cost health services and increased usage of outpatient care. The results further suggest the need for enhanced access to MOUD and for interventions that improve adherence.

A pilot test of Written Exposure Therapy for PTSD in residential substance use treatment.

BACKGROUND AND OBJECTIVES: Posttraumatic stress disorder (PTSD) is highly comorbid with substance use disorders (SUD) and can impede SUD recovery. Residential SUD treatment is a crucial opportunity to address PTSD. However, PTSD treatment is lacking in residential SUD care. METHODS: We conducted a nonrandomized feasibility study of Written Exposure Therapy (WET), a brief, evidence-based treatment for PTSD, with patients in residential SUD treatment. We assessed attitudes towards treatment (Credibility and Expectancy Questionnaire, Barriers to Treatment Participation Scale) and mental health indicators (PTSD Checklist for DSM-5, Trauma Coping Self-Efficacy, Difficulties in Emotion Regulation-Short Form, and Brief Assessment of Recovery Capital). RESULTS: Thirty of 49 eligible participants completed WET (61%) and 92% (n = 45) attended at least one WET session. Paired sample t-tests revealed significant posttreatment improvement across all mental health indicators, with medium to large effect sizes. DISCUSSION AND CONCLUSIONS: Attendance and completion rates compared favorably to prior exposure-based treatment for PTSD in SUD settings. Although causality cannot be inferred without a randomized controlled trial, mental health indicators, including PTSD, improved significantly following WET. SCIENTIFIC SIGNIFICANCE: These findings provide evidence that PTSD can be successfully treated in short-term residential care using brief exposure-based interventions, which is a crucial clinical need that has been minimally studied in the past.

Guidance for Handling the Increasing Prevalence of Drugs Adulterated or Laced With Fentanyl.

The use of fentanyl and its analogs is the primary driver of deaths related to the opioid overdose crisis. In fall 2021, the U.S. Drug Enforcement Administration issued its first public safety alert in 6 years to raise awareness of the escalating prevalence of fentanyl in counterfeit pills and in other opioids, such as heroin, and nonopioids, such as methamphetamine. In addition to increased public awareness, specific actions are needed to remediate the risk for fentanyl overdose. The authors endorse four principles to address the opioid overdose crisis and provide guidance for remediating its impacts: an incremental approach to behavior change or harm reduction; engagement strategies for individuals with substance use disorder; an integrated care approach to ensure better access to treatment programs and effective interventions; and vigilance among clinicians, program staff, and patients to the threat of fentanyl-adulterated drugs. The authors offer specific recommendations on how to apply these principles effectively within health care systems, communities, and law enforcement agencies across the United States.

Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone (SWIFT): A stepped wedge hybrid type 1 effectiveness-implementation study.

BACKGROUND: Extended-release injectable naltrexone (XR-NTX) is an effective treatment for opioid use disorder (OUD), but initiation remains a barrier to implementation. Standard practice requires a 10- to 15-day inpatient admission prior to XR-NTX initiation and involves a methadone or buprenorphine taper followed by a 7- to 10-day washout, as recommended in the Prescribing Information for XR-NTX. A 5- to 7-day rapid induction approach was developed that utilizes low-dose oral naltrexone and non-opioid medications. METHODS: The CTN-0097 Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone (SWIFT) study was a hybrid type I effectiveness-implementation trial that compared the effectiveness of the standard procedure (SP) to the rapid procedure (RP) for XR-NTX initiation across six community inpatient addiction treatment units, and evaluated the implementation process. Sites were randomized to RP every 14 weeks in an optimized stepped wedge design. Participants (target recruitment = 450) received the procedure (SP or RP) that the site was implementing at time of admission. The hypothesis was RP will be non-inferior to SP on proportion of inpatients who receive XR-NTX, with a shorter admission time for RP. Superiority testing of RP was planned if the null hypothesis of inferiority of RP to SP was rejected. DISCUSSION: If RP for XR-NTX initiation is shown to be effective, the shorter inpatient stay could make XR-NTX more feasible and have an important public health impact expanding access to OUD pharmacotherapy. Further, a better understanding of facilitators and barriers to RP implementation can help with future translatability and uptake to other community programs. TRIAL REGISTRATION: NCT04762537 Registered February 21, 2021.

Trajectories of depression among patients in treatment for opioid use disorder: A growth mixture model secondary analysis of the XBOT trial.

BACKGROUND AND OBJECTIVES: To inform clinical practice, we identified subgroups of adults based on levels of depression symptomatology over time during opioid use disorder (OUD) treatment. METHODS: Participants were 474 adults in a 24-week treatment trial for OUD. Depression symptoms were measured using the 17-item Hamilton Depression Rating Scale (HAM-D) at nine-time points. This was a secondary analysis of the Clinical Trials Network Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment (XBOT) trial using a growth mixture model. RESULTS: Three distinct depression trajectories were identified: Class 1 High Recurring-10% with high HAM-D with initial partial reductions (of HAM-D across time), Class 2 Persistently High-5% with persistently high HAM-D, and Class 3 Low Declining-85% of the participants, with low HAM-D with early sustained reductions. The majority (low declining) had levels of depression that improved in the first 4 weeks and then stabilized across the treatment period. In contrast, 15% (high recurring and persistently high) had high initial levels that were more variable across time. The persistently high class had higher rates of opioid relapse. DISCUSSION AND CONCLUSIONS: In this OUD sample, most depressive symptomatology was mild and improved after medication treatment for opioid use disorder (MOUD). Smaller subgroups had higher depressive symptoms that persisted or recurred after the initiation of MOUD. Depressive symptoms should be followed in patients initiating treatment for OUD, and when persistent, should prompt further evaluation and consideration of antidepressant treatment. SCIENTIFIC SIGNIFICANCE: This study is the first to identify three distinct depression trajectories among a large clinical sample of individuals in MOUD treatment.

Relationship-Oriented Recovery System for Youth (RORSY): Clinical Protocol for Transition-Age Youth with Opioid Use Disorders.

This article introduces the Relationship-Oriented Recovery System for Youth (RORSY) protocol, which is designed to increase uptake of Medications for Opioid Use Disorder (MOUD) and related services among adolescents and young adults. Youth exhibit alarmingly poor rates of MOUD initiation and adherence, OUD services involvement and long-term recovery success. RORSY attends to three developmentally unique recovery needs of this age group: assess and bolster youth recovery capital, prioritize involvement of concerned significant others, and use digital direct-to-consumer recovery supports. RORSY contains five evidence-informed intervention modules that can be flexibly tailored to meet the individual and relationship needs of a given youth: Relational Orientation, Youth Recovery Management Planning, Relational Recovery Management Planning, Relationship Skills Building, and Digital Recovery Support Planning. The article concludes with practice and policy recommendations for making relationship-building a top clinical priority for addressing youth OUD.

Buprenorphine & methadone dosing strategies to reduce risk of relapse in the treatment of opioid use disorder.

BACKGROUND: Although there is consensus that having a "high-enough" dose of buprenorphine (BUP-NX) or methadone is important for reducing relapse to opioid use, there is debate about what this dose is and how it should be attained. We estimated the extent to which different dosing strategies would affect risk of relapse over 12 weeks of treatment, separately for BUP-NX and methadone. METHODS: This was a secondary analysis of three comparative effectiveness trials. We examined four dosing strategies: 1) increasing dose in response to participant-specific opioid use, 2) increasing dose weekly until some minimum dose (16 mg BUP, 100 mg methadone) was reached, 3) increasing dose weekly until some minimum and increasing dose in response to opioid use thereafter (referred to as the "hybrid strategy"), and 4) keeping dose constant after the first 2 weeks of treatment. We used a longitudinal sequentially doubly robust estimator to estimate contrasts between dosing strategies on risk of relapse. RESULTS: For BUP-NX, increasing dose following the hybrid strategy resulted in the lowest risk of relapse. For methadone, holding dose constant resulted in greatest risk of relapse; the other three strategies performed similarly. For example, the hybrid strategy reduced week 12 relapse risk by 13 % (RR: 0.87, 95 %CI: 0.83-0.95) and by 20 % (RR: 0.80, 95 %CI: 0.71-0.90) for BUP-NX and methadone respectively, as compared to holding dose constant. CONCLUSIONS: Doses should be targeted toward minimum thresholds and, in the case of BUP-NX, raised when patients continue to use opioids.

Patient Characteristics Associated with Opioid Abstinence after Participation in a Trial of Buprenorphine versus Injectable Naltrexone.

Background and Objectives: Better understanding of predictors of opioid abstinence among patients with opioid use disorder (OUD) may help to inform interventions and personalize treatment plans. This analysis examined patient characteristics associated with opioid abstinence in the X:BOT (Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment) trial. Methods: This post-hoc analysis examined factors associated with past-month opioid abstinence at the 36-week follow-up visit among participants in the X:BOT study. 428 participants (75% of original sample) attended the visit at 36 weeks. Logistic regression models were used to estimate the probability of opioid abstinence across various baseline sociodemographics, clinical characteristics, and treatment variables. Results: Of the 428 participants, 143 (33%) reported abstinence from non-prescribed opioids at the 36-week follow-up. Participants were more likely to be opioid abstinent if randomized to XR-NTX (compared to BUP-NX), were on XR-NTX at week 36 (compared to those off OUD pharmacotherapy), successfully inducted onto either study medication, had longer time on study medication, reported a greater number of abstinent weeks, or had longer time to relapse during the 24-week treatment trial. Participants were less likely to be abstinent if Hispanic, had a severe baseline Hamilton Depression Rating (HAM-D) score, or had baseline sedative use. Conclusions: A substantial proportion of participants was available at follow-up (75%), was on OUD pharmacotherapy (53%), and reported past-month opioid abstinence (33%) at 36 weeks. A minority of patients off medication for OUD reported abstinence and additional research is needed exploring patient characteristics that may be associated with successful treatment outcomes.

Opioid use disorder Cascade of care framework design: A roadmap.

Unintentional overdose deaths, most involving opioids, have eclipsed all other causes of US deaths for individuals less than 50 years of age. An estimated 2.4 to 5 million individuals have opioid use disorder (OUD) yet a minority receive treatment in a given year. Medications for OUD (MOUD) are the gold standard treatment for OUD however early dropout remains a major challenge for improving clinical outcomes. A Cascade of Care (CoC) framework, first popularized as a public health accountability strategy to stem the spread of HIV, has been adapted specifically for OUD. The CoC framework has been promoted by the NIH and several states and jurisdictions for organizing quality improvement efforts through clinical, policy, and administrative levers to improve OUD treatment initiation and retention. This roadmap details CoC design domains based on available data and potential linkages as individual state agencies and health systems typically rely on limited datasets subject to diverse legal and regulatory requirements constraining options for evaluations. Both graphical decision trees and catalogued studies are provided to help guide efforts by state agencies and health systems to improve data collection and monitoring efforts under the OUD CoC framework.

Towards an International Consensus on the Prevention, Treatment, and Management of High-Risk Substance Use and Overdose among Youth.

Background and Objectives: Now more than ever, there is an obvious need to reduce the overall burden of disease and risk of premature mortality that are associated with mental health and substance use disorders among young people. However, the current state of research and evidence-based clinical care for high-risk substance use among youth is fragmented and scarce. The objective of the study is to establish consensus for the prevention, treatment, and management of high-risk substance use and overdose among youth (10 to 24 years old). Materials and Methods: A modified Delphi technique was used based on the combination of scientific evidence and clinical experience of a group of 31 experts representing 10 countries. A semi-structured questionnaire with five domains (clinical risks, target populations, intervention goals, intervention strategies, and settings/expertise) was shared with the panelists. Based on their responses, statements were developed, which were subsequently revised and finalized through three iterations of feedback. Results: Among the five major domains, 60 statements reached consensus. Importantly, experts agreed that screening in primary care and other clinical settings is recommended for all youth, and that the objectives of treating youth with high-risk substance use are to reduce harm and mortality while promoting resilience and healthy development. For all substance use disorders, evidence-based interventions should be available and should be used according to the needs and preferences of the patient. Involuntary admission was the only topic that did not reach consensus, mainly due to its ethical implications and resulting lack of comparable evidence. Conclusions: High-risk substance use and overdoses among youth have become a major challenge. The system's response has been insufficient and needs substantial change. Internationally devised consensus statements provide a first step in system improvement and reform.