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Patients with opioid use disorder (OUD) tend to get assigned to one of 3 medications based on the treatment program to which the patient presents (e.g., opioid treatment programs tend to treat patients with methadone, while office-based practices tend to prescribe buprenorphine). It is possible that optimally matching patients with treatment type would reduce the risk of return to regular opioid use (RROU). We analyzed data from 3 comparative effectiveness trials from the US National Institute on Drug Abuse Clinical Trials Network (CTN0027, 2006–2010; CTN0030, 2006–2009; and CTN0051 2014–2017), in which patients with OUD (n = 1,459) were assigned to treatment with either injection extended-release naltrexone (XR-NTX), sublingual buprenorphine-naloxone (BUP-NX), or oral methadone. We learned an individualized rule by which to assign medication type such that risk of RROU during 12 weeks of treatment would be minimized, and then estimated the amount by which RROU risk could be reduced if the rule were applied. Applying our estimated treatment rule would reduce risk of RROU compared with treating everyone with methadone (relative risk (RR) = 0.79, 95% confidence interval (CI): 0.60, 0.97) or treating everyone with XR-NTX (RR = 0.71, 95% CI: 0.47, 0.96). Applying the estimated treatment rule would have resulted in a similar risk of RROU to that of with treating everyone with BUP-NX (RR = 0.92, 95% CI: 0.73, 1.11).

This study aims to describe which substance use service (SUS) organizations and who within these organizations support the maintenance of policies targeted at improving substance use treatment services. An online survey assessing respondent, organizational and program demographics, and knowledge and support regarding policy changes was distributed to all certified SUS and harm reduction programs in NYS. Bivariate and latent class analyses were used to identify patterns and associations to policy choices. Across the 227 respondents, there was a support for maintaining expansion of insurance coverage, virtual behavioral health/counseling and medication initiation/maintenance visits, reductions in prior authorizations, and access to prevention/harm reduction services. Three classes of support for policies were derived: (1) high-supporters (n = 49; 21%), (2) low-supporters (n = 66; 29%), and (3) selective-supporters. Having knowledge of policy changes was associated with membership in the high-supporters class. Implications regarding the role of knowledge in behavioral health policies dissemination structures, decision-making, and long-term expansion of SUS are discussed.

BACKGROUND: The comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT) trial showed that following induction, treatment with the sublingual agonist (buprenorphine-naloxone, BUP-NX) or injected antagonist (extended release naltrexone, XR-NTX) produced similar reductions in opioid relapse in injection users with opioid use disorder (OUD). Because XR-NTX reduces drinking in alcohol use disorder (AUD), we conducted a secondary analysis of the X:BOT sample of patients successfully inducted onto treatment to determine whether XR-NTX (n = 204) was superior to BUP-NX (n = 270) in reducing drinking or heavy drinking in patients with OUD. METHODS: Standard drink units consumed were measured using the Timeline Follow-back method. Mixed-models regression was used to examine the monthly frequency of any drinking and heavy drinking over 6 months of treatment. We used a proportional hazard survival analysis to examine the time to first drink. RESULTS: Both treatment groups reduced drinking from baseline to posttreatment (small to medium effect), but no differences between groups were detected. However, only 29% (n = 136) of the sample had AUD and 19% (n = 26/136) of those were abstinent before treatment. Analysis of a subsample enriched for possible drinking included 136 individuals with an AUD diagnosis plus 43 who did not have AUD, but reported at least one day of heavy drinking prior to the study. However, this subsample reported only 32% of days of any drinking with a median of only 13% of days designated as “heavy.” Within this subsample, at baseline, the BUP-NX group reported more mean drinks per drinking day than the XR-NTX group (p = 0.03); however, there were no other significant group differences on drinking observed before, during, or at the end of treatment. CONCLUSIONS: There was an overall reduction in drinking during treatment of OUD using both agonist and antagonist medications, so that the hypothesis that XR-NTX would be superior to BUP-NX was not supported. The study is limited by low levels of comorbid AUD or heavy drinking observed in X:BOT trial participants seeking treatment for OUD.

BACKGROUND AND AIMS: Dynamic, adaptive pharmacologic treatment for opioid use disorder (OUD) has been previously recommended over static dosing to prevent relapse, and is aligned with personalized medicine. However, there has been no quantitative evidence demonstrating its advantage. Our objective was to estimate the extent to which a hypothetical intervention that increased buprenorphine dose in response to opioid use would affect risk of relapse over 24 weeks of follow-up. DESIGN: A secondary analysis of the buprenorphine arm of an open-label randomized controlled 24-week comparative effectiveness trial, 2014–17. SETTING: Eight community addiction treatment programs in the United States. PARTICIPANTS: English-speaking adults with DSM-5 OUD, recruited during inpatient admission (n = 270). Participants were mainly white (65%) and male (72%). INTERVENTION(S): Participants were treated with daily sublingual buprenorphine–naloxone (BUP–NX), with dose based on clinical indication, determined by the provider. We examined a hypothetical intervention of increasing dose in response to opioid use. MEASUREMENTS: Outcome was relapse to regular opioid use during the 24 weeks of outpatient treatment, assessed in a survival framework. We estimated the relapse-free survival curves of participants under a hypothetical (i.e. counterfactual) intervention in which their BUP–NX dosage would be increased following their own subject-specific opioid use during the first 12 weeks of treatment versus a hypothetical intervention in which dose would remain constant. FINDINGS: We estimated that increasing BUP–NX dose in response to recent opioid use would lower risk of relapse by 19.17 percentage points [95% confidence interval (CI) = −32.17, −6.18) (additive risk)] and 32% (0.68, 95% CI = 0.49, 0.86) (relative risk). The number-needed-to-treat with this intervention to prevent a single relapse is 6. CONCLUSIONS: In people with opioid use disorder, a hypothetical intervention that increases sublingual buprenorphine–naloxone dose in response to opioid use during the first 12 weeks of treatment appears to reduce risk of relapse over 24 weeks, compared with holding the dose constant after week 2.

Repetitive transcranial magnetic stimulation (rTMS) is a non‐invasive brain stimulation method increasingly used to treat psychiatric disorders, primarily depression. Initial studies suggest that rTMS may help to treat addictions, but evaluation in multicenter randomized controlled trials (RCTs) is needed. We conducted a multicenter double‐blind RCT in 262 chronic smokers meeting DSM‐5 criteria for tobacco use disorder, who had made at least one prior failed attempt to quit, with 68% having made at least three failed attempts. They received three weeks of daily bilat­eral active or sham rTMS to the lateral prefrontal and insular cortices, followed by once weekly rTMS for three weeks. Each rTMS session was administered following a cue‐induced craving procedure, and participants were monitored for a total of six weeks. Those in abstinence were monitored for additional 12 weeks. The primary outcome measure was the four‐week continuous quit rate (CQR) until Week 18 in the intent‐to‐treat efficacy set, as determined by daily smoking diaries and verified by urine cotinine measures. The trial was registered at ClinicalTrials.gov (NCT02126124). In the intent‐to‐treat analysis set (N=234), the CQR until Week 18 was 19.4% following active and 8.7% following sham rTMS (X(2)=5.655, p=0.017). Among completers (N=169), the CQR until Week 18 was 28.0% and 11.7%, respectively (X(2)=7.219, p=0.007). The reduction in cigarette consumption and craving was significantly greater in the active than the sham group as early as two weeks into treatment. This study establishes a safe treatment protocol that promotes smoking cessation by stimulating relevant brain circuits. It represents the first large multicenter RCT of brain stimulation in addiction medicine, and has led to the first clearance by the US Food and Drug Administration for rTMS as an aid in smok­ing cessation for adults.

BACKGROUND Despite advances in the development of pharmacotherapy for alcohol use disorder (AUD), there remains a need for medications that can be administered to actively drinking outpatients to promote a reduction in harmful alcohol consumption. The primary aim of this pilot study was to determine whether high-dose gabapentin (3600 mg/daily) is more effective than placebo in reducing harmful alcohol consumption in outpatients with AUD. METHODS Forty patients (27 men) who met DSM-IV-TR criteria for alcohol dependence and reporting at least 4 heavy drinking days (HDD) per week were recruited at a single site. Participants were actively drinking at study entry and received double-blind gabapentin (3600 mg/day; n = 19) or placebo (n = 20) for 8 weeks. Study medication was titrated over 5 days and administered in three divided doses (1200 mg three times per day). The proportion of HDD (primary outcome) and percent days abstinent (PDA; secondary outcome) were analyzed using generalized longitudinal mixed models with the predictors being study arm, week, study arm by week interaction, and corresponding baseline drinking measure. RESULTS There was a significant interaction between study arm and week for the proportion of HDD per week, F (7, 215) = 3.33, p = 0.002 . There was also a significant interaction between study arm and week for PDA per week, F (7, 215) = 3.11, p = 0.004. The overall retention rate was 67.5% with no significant difference in time-to-dropout between treatment groups. There were no serious adverse events. No participants were removed from the trial due to the development of moderate-to-severe alcohol withdrawal (CIWA-Ar ≥ 13). CONCLUSIONS Gabapentin treatment rapidly titrated to a dosage of 3600 mg/day is associated with a reduction in the proportion of HDD per week and an increase in PDA per week in actively drinking outpatients with AUD. High-dose gabapentin is potentially a feasible approach to treating AUD and deserving of further study.

In the US, methadone treatment can only be provided to patients with opioid use disorder (OUD) through federal and state-regulated opioid treatment programs (OTPs). There is a shortage of OTPs, and racial and geographic inequities exist in access to methadone treatment. The National Institute on Drug Abuse Clinical Trials Network convened the Methadone Access Research Task Force to develop a research agenda to expand and create more equitable access to methadone treatment for OUD. This research agenda included mechanisms that are available within and outside the current regulations. The task force identified 6 areas where research is needed: (1) access to methadone in general medical and other outpatient settings; (2) the impact of methadone treatment setting on patient outcomes; (3) impact of treatment structure on outcomes in patients receiving methadone; (4) comparative effectiveness of different medications to treat OUD; (5) optimal educational and support structure for provision of methadone by medical providers; and (6) benefits and harms of expanded methadone access. In addition to outlining these research priorities, the task force identified important cross-cutting issues, including the impact of patient characteristics, treatment, and treatment system characteristics such as methadone formulation and dose, concurrent behavioral treatment, frequency of dispensing, urine or oral fluid testing, and methods of measuring clinical outcomes. Together, the research priorities and cross-cutting issues represent a compelling research agenda to expand access to methadone in the US.

BACKGROUND AND AIMS: In a United States randomized-effectiveness trial comparing extended-release naltrexone (XR-NTX) with buprenorphine-naloxone (BUP-NX) for the prevention of opioid relapse among participants recruited during inpatient detoxification (CTN-0051), the requirement to complete opioid detoxification prior to initiating XR-NTX resulted in lower rates of initiation of XR-NTX (72%-XR-NTX vs. 94%-BUP-NX). This led to higher relapse rates and average healthcare costs among XR-NTX participants. This study estimated the extent to which a more efficient model of XR-NTX induction would improve the economic value of XR-NTX relative to BUP-NX. DESIGN: This was a retrospective secondary analysis of CTN-0051 trial data, including follow up data over 24–36 weeks. SETTING: Eight community-based, inpatient-detoxification and follow-up outpatient treatment facilities in the USA. PARTICIPANTS: 283 participants randomized to receive XR-NTX. MEASUREMENTS: Efficiency was estimated using a multivariable generalized-structural-equation model to explore simultaneous determinants of XR-NTX induction and induction duration (detoxification + residential days). Cost-effectiveness was estimated from the healthcare sector perspective and included expected costs and quality-adjusted life-years (QALYs). FINDINGS: Treatment site was the only modifiable factor that simultaneously increased the likelihood of XR-NTX induction and decreased induction duration. Incorporating the higher predicted probability of XR-NTX induction, and fewer predicted days of detoxification and subsequent residential treatment into the cost-effectiveness framework, reduced the incremental average 24-week total cost of XR-NTX treatment from $5,317 more than that of BUP-NX (p=0.01) to a non-statistically-significant difference of $1,016 (p=0.63). QALYs gained remained similar across arms. CONCLUSION: Adopting an efficient model of extended-release naltrexone initiation could result in extended-release naltrexone and buprenorphine-naloxone being of comparable economic value from the healthcare sector perspective over 24–36 weeks for patients seeking treatment for opioid use disorder at an inpatient detoxification facility.

Substance use disorders (SUD) are chronic relapsing medical conditions characterised by compulsive substance seeking and use. They constitute a substantial disease burden globally. Labelling of persons with SUD has created barriers to treatment but there are effective management strategies. The dental profession has embraced reforms designed to address the SUD epidemic by promoting continuing education for practitioners and initiating curriculum changes in dental schools. Screening, Brief Intervention and Referral to Treatment (SBIRT) is an evidence-based model for managing patients with SUD. The use of a formative 1-station Objective Structured Clinical Examination (OSCE) for learning and assessment in SBIRT, operationalised with the MD3 rating scale is presented in this study. In 3 years of implementation, the SBIRT OSCE successfully integrated into the curriculum of the College of Dental Medicine, Columbia University. Mean score of total adherent behaviours was 11.80 (SD =4.23) (range: 2 – 24) and Cronbach’s coefficient alpha for across-items reliability in adherent behaviours was 0.66. Adherent behaviours correlated with the global ratings (r = 0.66). Mean of global rating scores were 2.90 (SD =1.01) for collaboration and 2.97 (SD =1.00) for empathy and the global rating scores correlated with each other (r = 0.85). Histograms of global rating scores resembled normal distribution. The 1-station OSCE is a good model for learning about SBIRT. Psychometric analysis was useful in understanding the underlying construct of the MD3 rating scale and supported its reliability, validity and utility in dental education.

BACKGROUND: The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied. METHODS: We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone–bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone–bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses. RESULTS: A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone–bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone–bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone–bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P

Purpose Young adults are disproportionately affected by the current opioid crisis. Although medications for opioid use disorder are broadly effective, with reductions in morbidity and mortality, the particular effectiveness of medications for opioid use disorder among young adults is less well understood. Methods This secondary analysis compared young adults (aged 18–25 years) with older adults (aged ≥26 years) in a large comparative effectiveness trial (“XBOT”) that randomized subjects to extended-release naltrexone or sublingual buprenorphine–naloxone for 6 months. Opioid relapse was defined by opioid use over four consecutive weeks or seven consecutive days, using urine testing and self-report. Results Among subjects in the intention-to-treat sample (n = 570, all randomized participants), a main effect of age group was found, with higher relapse rates among young adults (70.3%) compared with older adults (58.2%), with an odds ratio of 1.72 (95% confidence interval = 1.08–2.70), p = .02. In the per-protocol sample (n = 474, only participants who started medication), relapse rates were higher among young adults (66.3%) compared with older adults (50.8%), with an odds ratio of 1.91 (95% confidence interval = 1.19–3.06). Among the intention-to-treat sample, survival analysis revealed a significant time-by-age group interaction (p = .01) with more relapse over time in young adults. No significant interactions between age and medication group were detected. Conclusions Young adults have increased rates of relapse compared with older adults, perhaps because of vulnerabilities that increase their risk for treatment dropout and medication nonadherence, regardless of medication assignment. These results suggest that specialized, developmentally informed interventions may be needed to improve retention and successful treatment of opioid use disorder among young adults.

Addiction Psychiatry and Addiction Medicine are two physician subspecialities recognized by the American Board of Medical Specialties (ABMS) that focus on providing care for patients with substance use disorders. Their shared and distinct historical roots are reviewed, and their respective ABMS board examination content areas and Accreditation Council on Graduate Medical Education (ACGME) fellowship training program requirements are compared. Addiction Psychiatry, a subspecialty under the American Board of Psychiatry and Neurology, began certifying diplomates in 1993, currently has 1202 active diplomates, and certifies around 150 diplomates every 2 years through 50 ACGME-accredited fellowships. Addiction Medicine, a subspecialty under the American Board of Preventive Medicine, began certifying diplomates in 2018, has 2604 diplomates with more expected before the practice pathway closes (anticipated in 2021), after which a fellowship training becomes required. Currently there are 78 accredited Addiction Medicine fellowships and more under development. The fields display substantial overlap between their respective examination content areas and fellowship training requirements, covering similar knowledge and skills for evaluation and treatment of substance use disorders and psychiatric and medical comorbidities across the full range of clinical settings, from general medical to addiction specialty settings. Key differences include that Addiction Psychiatry is open only to Board-certified psychiatrists and places extra emphasis on psychotherapeutic and psychopharmacological management strategies. Addiction Medicine is open to any ABMS primary specialty, including psychiatry. Opportunities for collaboration are discussed as both fields pursue the common goal of providing a well-trained workforce of physicians to meet the public health challenge presented by addiction. (Am J Addict 2020;00:00-00).

Background and objectives We examined age differences across genders in clinical characteristics in emerging adult (≤25 years) vs older adult patients (26+ years) with opioid use disorder (OUD). Methods Participants (N = 570; 30% female) entering a comparative effectiveness medication trial of buprenorphine vs extended-release naltrexone. Results Differences in clinical characteristics in emerging adult vs older participants were similar across genders. However, women 26+ years reported more mental health problems compared with women ≤25, while men ≤25 years reported more mental health problems compared with men 26+ years. Discussion and conclusion Different strategies for emerging adult and older patients seeking OUD treatment may be necessary to address psychiatric comorbidities that differ across genders in this population. Scientific significance Comprehensive psychiatric assessment should be systematically included in OUD treatment for all genders. Treatment should focus on the emerging adult developmental phase when appropriate, with psychiatric treatment tailored for women and men, separately, across the lifespan. (Am J Addict 2020;29:536-542).

Identifying clinical differences between opioid users (OU) and alcohol and other drug users (AOD) may help to tailor treatment to OU, particularly among the majority of OU who are not on opioid agonist treatments. Given the dearth of research on these differences, this study explored gender differences in demographic and clinical characteristics between OU and AOD. Participants (N = 506) were from a multisite, randomized controlled clinical trial of an Internet-delivered psychosocial intervention conducted in 2010-2011. Logistic regression models explored differences in demographic and clinical characteristics by substance use category within and between women and men. Women OU were more likely to be younger, White, employed, benzodiazepine users, and less likely to have children or use cocaine and cannabis than women AOD. Men OU, compared to men AOD, were more likely to be younger, White, younger at first abuse/dependence, benzodiazepine users, and reported greater psychological distress, but were less likely to be involved in criminal justice or use stimulants. Interactions by gender and substance use were also detected for age of first abuse/dependence, employment, and criminal justice involvement. These findings provide a nuanced understanding of gender differences within substance use groups to inform providers for OU seeking treatment.

Introduction The “Women and Trauma” Study (WTS) conducted in the National Drug Abuse Treatment Clinical Trials Network (CTN-0015) resulted in research publications, presentations, and a train-the-trainer workshop to support dissemination efforts for skills-based trauma treatment in substance use community treatment. Twelve years after its completion, this paper aims to examine whether and how the WTS contributed to knowledge in the field of trauma and addictions and inspired community treatment programs (CTPs) to train staff to identify and provide trauma-related services. Method: We present findings from two different analyses that explored longer term study impacts on treatment and dissemination: (1) a post-study site survey covering 4 domains from 4/7 programs that participated in delivering the WTS to evaluate their perceptions of study impact on their treatment community; and (2) an analysis of citations of its publications to determine impact on the scientific community. Results: Surveys from responding sites indicated that participation in the study significantly increased their agencies’' awareness of the need to take a focused approach to treating trauma issues in this population. Specifically, these sites increased their commitment to using skills-based trauma treatment with the study's target population of female patients with SUD and trauma histories, as well as expanding it to other groups affected by trauma. Citation analysis revealed that according to the Web of Science, as of August 2019, the number of citations of 24 CTN-0015 articles, ranged from 1 to 135 (Mean = 20, SD = 33; Median = 6). Four of the most influential are discussed. Conclusions: This manuscript provides original information about the contributions of the WTS study, demonstrating how the study contributed to serving women with trauma in community substance use treatment.

Objective Opioid use disorder (OUD) is associated with chronic pain. We investigated the association between medication treatments for OUD and pain in a post-hoc secondary analysis of a randomized trial of methadone versus buprenorphine/naloxone. Methods 1241 individuals with OUD participated in an open label, pragmatic randomized trial of methadone versus buprenorphine/naloxone in nine treatment programs licensed to dispense agonist medication for OUD between 2006 to 2009. In this post-hoc analysis, pain was dichotomized (present or not present) using responses from the Short Form-36. Logistic regression models were fit to test the effect of (1) having baseline pain on week 24 retention, (2) treatment assignment on improvement in pain among those reporting pain at baseline, and (3) pain improvement at week 4 on week 24 retention among those reporting pain at baseline. Results Almost half (48.2%) of the sample reported pain at baseline. Participants with baseline pain did not significantly differ in week 24 retention compared to those without baseline pain. Among those reporting pain at baseline, there was no significant difference between treatment arms in improvement of pain at week 4, but improvement in pain at week 4 was associated with significantly greater odds of being retained at week 24 (OR [95% CI] = 1.76 [1.10, 2.82], P = 0.020). Conclusion and relevance In this large multisite randomized trial of medication treatments for OUD, nearly half of the participants reported pain at baseline, and improvement in pain early in treatment was associated with increased likelihood of retention in treatment.

Objectives The effectiveness of treatment incorporating relapse prevention medications for opioid use disorder (OUD) is typically examined in research using rigidly predefined endpoints of success versus failure, usually over a single episode of care. But this perspective may not adequately portray the nonlinear trajectories typical of real-world treatment courses in this chronic, remitting, and relapsing disorder. Methods This descriptive study examined 12-month treatment trajectories of n = 60 patients enrolled at a single site of a larger multisite randomized controlled trial examining the comparative effectiveness of buprenorphine versus extended-release naltrexone. While the parent study provided medication treatment through the research protocol for 6 months, this study documents treatment up to 12 months, including medications, provided through standard community resources (treatment as usual) outside of the protocol. Results Some patients continued medications past the end of the study intervention, whereas others did not. Some patients initiated medications other than the one assigned by the study. Some patients switched from 1 medication to the other. Many patients returned to treatment after 1 or more periods of dropout and/or relapse. Patients utilized multiple episodes of bed-based care, including short-term acute residential and long-term residential treatment, and also recovery housing supports. Described trajectories are also depicted graphically. At 12 months, while rates of continuous treatment retention were low (8%), rates of cross-sectional treatment engagement including return to treatment after drop out were higher (35%). Conclusions This description of nonlinear treatment trajectories highlights the potential benefits of flexibility and optimism in the promotion of re-engagement, despite interim outcomes that might traditionally be considered "failure" endpoints.

HIV prevention for women with substance use disorders is a public health priority. To identify characteristics associated with sexual risk among women in outpatient substance abuse treatmen...

To examine whether the March 2020 New York State (NYS) SARS-CoV-2 Emergency Orders were associated with an initial surge in opioid dispensing and a longer-term reduction in access to medications for opioid use disorder (MOUD).Time-series analyses of the dispensing of non-MOUD opioid and MOUD prescriptions using IQVIA's Longitudinal Prescription Claims Database (n=16,087,429) in NYS by week, from 1/1/2018, to 7/31/2020. IQVIA is a multinational company that provides biopharmaceutical development and commercial outsourcing services.NYS Zone Improvement Plan (ZIP) Codes (n=1,218) in which prescriptions were dispensed.For each ZIP Code, for each week, the following dispensing measures were calculated: total weekly morphine milligram equivalents/day (MME/day); total weekly MME/day dispensed via prescriptions for ≤7 days; and the count of MOUD prescriptions dispensed. Differences in dispensing metrics, comparing each week in 2020 with corresponding weeks in 2019, were calculated for each ZIP Code.During the study period, weekly MME/day per ZIP Code of dispensed non-MOUD opioids steadily declined. Compared with the difference in dispensing between 2019 and 2020 during the first week in 2020, there was a significantly larger drop in dispensed weekly total MME/day beginning March 21 2020 and lasting until the week of April 17 (p0.05 for each week). Mean weekly total MME/day dispensed from March 21 to April 17, 2020 was 17.07% lower (95% confidence interval [CI] 13.97%, 20.17%) than in the 4 weeks before March 21, almost entirely due to a drop in MME/day dispensed for prescriptions of ≤7 days. There was not a discernable drop in MOUD dispensing associated with the period of the Emergency Orders.New York State Emergency Orders in March 2020 to reduce SARS-CoV-2 transmission and preserve hospital capacity appeared to be associated with a decline in dispensing of opioids not used as MOUD. Access to MOUD appeared to be unaffected by the Orders, likely because of policy initiatives by the Substance Abuse and Mental Health Services Administration.

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.

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.

BACKGROUND: Extended-release injectable naltrexone (XR-naltrexone) is effective for treatment of patients with opioid use disorder (OUD), but initiation remains a barrier due to the challenge of tolerating opioid withdrawal prior to administration. Understanding factors associated with successful initiation of XR-naltrexone could facilitate its implementation through patient-treatment matching. METHODS: We combined data from five consecutive studies that sought to initiate patients with active opioid use onto XR-naltrexone using a rapid procedure consisting of minimal buprenorphine, non-opioid medications for treating opioid withdrawal, and ascending low doses of oral naltrexone. Associations between patient characteristics and initiating naltrexone were estimated with logistic regression models. To evaluate whether associations differed between inpatient and outpatient settings, patient characteristic-by-setting interactions were also estimated. RESULTS: 409 patients were included in the analyses and 228 (56%) received the first injection. A significantly greater percent of inpatients (62%) vs outpatients (48%) initiated XR-naltrexone. Initiation success was significantly more likely on an inpatient basis for heroin (60.9% inpatient vs 36.2% outpatient), intravenous (56.3% inpatient vs 22.5% outpatient), and speedball users (68.1% inpatient vs 32.3% outpatient). Prescription opioid users showed similar, higher initiation rates across settings (68.9% inpatient; 73.7% outpatient). CONCLUSIONS: An inpatient setting may be the preferred strategy for rapid initiation of XR-naltrexone for opioid users with greater severity, including heroin or speedball injection users or those who use opioids intravenously. Initiation on an outpatient basis may be more likely to succeed for prescription opioid users.

This report examined naturalistic opioid use outcomes and utilization of medications for opioid use disorder (MOUD) 36 weeks post-randomization in the National Drug Abuse Treatment Clinical Trials Network (CTN) Extended-Release Naltrexone (XR-NTX) versus Buprenorphine-Naloxone (BUP-NX) for Opioid Treatment trial (CTN-0051, X:BOT).X:BOT was a multisite, randomized, 24-week comparative effectiveness trial of BUP-NX (N = 287) and XR-NTX (N = 283). Study medications were discontinued following treatment completion, relapse, or dropout. Participants were encouraged to continue MOUD. This report examined opioid use outcomes in 428 (75%) of the 570 participants who attended the 36-week follow-up visit.Adults with opioid use disorder recruited from 8 community treatment programs across the United States.Outcomes included medication status (on/off MOUD), type of MOUD (BUP-NX, XR-NTX, or methadone), abstinence from non-prescribed opioids, opioid use days, relapse, and other substance use 30 days prior to the 36-week visit. Relapse was defined as opioid use for 4 consecutive weeks or 7 consecutive days in the past month. Baseline and clinical variables included opioid use severity, intravenous drug use, study medication assignment, and induction status.Of the 428 participants who completed the 36-week visit, 225 (53%) of participants were receiving MOUD and 203 (47%) were not. Compared to those off medication, participants on medication had fewer opioid use days (4.4 days (SD 9.0) versus 9.8 days (SD 12.1)), fewer met relapse criteria (37 (16.4%) versus 79 (38.9%)), and reported less stimulant use (34 (15.2%) versus 56 (27.7%)) and sedative use (14 (6.3%) versus 31 (15.3%)). There was no difference in abstinence rates between those on or off MOUD. A greater proportion of participants on XR-NTX (47 (53.4%) of 88 participants) were abstinent from non-prescribed opioids compared to those on buprenorphine (28 (23.3%) of 120 participants).Naturalistic outcomes data showed that despite potential barriers to continuing treatment in the community, about half of individuals were on opioid use disorder pharmacotherapy at follow-up and those on medication generally had better outcomes. Future research should explore barriers and facilitators to treatment retention in community settings; and developing interventions tailored to improve treatment engagement and adherence.

Sublingual buprenorphine-naloxone and extended-release injection naltrexone are effective treatments, with distinct mechanisms, for opioid use disorder. The authors examined whether patients' demographic and clinical characteristics were associated with better response to one medication or the other.In a multisite 24-week randomized comparative-effectiveness trial of assignment to buprenorphine-naloxone (N=287) compared with extended-release naltrexone (N=283) comprising inpatients planning to initiate medication treatment for opioid use disorder, 50 demographic and clinical characteristics were examined as moderators of the effect of medication assignment on relapse to regular opioid use and failure to initiate medication. Moderator-by-medication interactions were estimated using logistic regression with correction for multiple testing.In the intent-to-treat sample, patients who reported being homeless had a lower relapse rate if they were assigned to receive extended-release naltrexone (51.6%) compared with buprenorphine-naloxone (70.4%) (odds ratio=0.45, 95% CI=0.22, 0.90); patients who were not homeless had a higher relapse rate if they were assigned to extended-release naltrexone (70.9%) compared with buprenorphine-naloxone (53.1%) (odds ratio=2.15, 95% CI=1.44, 3.21). In the subsample of patients who initiated medication, the interaction was not significant, with a similar pattern of lower relapse with extended-release naltrexone (41.4%) compared with buprenorphine (68.6%) among homeless patients (odds ratio=0.32, 95% CI=0.15, 0.68) but less difference among those not homeless (extended-release naltrexone, 57.2%; buprenorphine, 52.0%; odds ratio=1.24, 95% CI=0.80, 1.90). For failure to initiate medication, moderators were stated preference for medication (failure was less likely if the patient was assigned to the medication preferred), parole and probation status (fewer failures with extended-release naltrexone for those on parole or probation), and presence of pain and timing of randomization (more failure with extended-release naltrexone for patients endorsing moderate to severe pain and randomized early while still undergoing medically managed withdrawal).Among patients with opioid use disorder admitted to inpatient treatment, homelessness, parole and probation status, medication preference, and factors likely to influence tolerability of medication initiation may be important in matching patients to buprenorphine or extended-release naltrexone.

BACKGROUND AND OBJECTIVES: Opioid use disorder treatment outcomes are poorer for young adults than older adults. Developmental differences are broadly implicated, but particular vulnerability factor interactions are poorly understood. This study sought to identify moderators of OUD relapse between age-groups METHODS: This secondary analysis compared young adults (18-25) to older adults (26+) from a comparative effectiveness trial (“XBOT”) that randomized participants to extended-release naltrexone or sublingual buprenorphine-naloxone. We explored the relationship between twenty-five pre-specified patient baseline characteristics and relapse to regular opioid use by age-group and treatment condition, using logistic regression. RESULTS: Young adults (n=111) had higher rates of 24-week relapse than older adults (n=459) (70.3% vs 58.8%) and differed on a number of specific characteristics, including more smokers, more intravenous opioid use, more cannabis use. No significant moderators predicted relapse, in either 3-way or 2-way interactions. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: No baseline factors were identified as moderating the relationship between age group and opioid relapse, nor any interactions between baseline characteristics, age group, and treatment condition to predict opioid relapse. Poorer treatment outcomes for young adults are likely associated with multiple developmental vulnerabilities rather than any single predominant factor. Although not reaching significance, several characteristics (using heroin, smoking tobacco, high levels of depression/anxiety, or treatment because of family/friends) showed higher odds ratio point-estimates for relapse in young adults than older adults. This is the first study to explore moderators of worse OUD treatment outcomes in young adults, highlighting the need to identify predictor variables that could inform treatment enhancements. CLINICAL TRIAL REGISTRY FOR THE PARENT STUDY: ClinicalTrials.gov NCT02032433

Extended-release formulations of naltrexone have emerged as effective treatment options for opioid use disorder. This post-hoc analysis examined the temporal relationship between episodes of opioid use and subsequent dropout in a placebo-controlled trial of extended-release injection naltrexone (XR-NTX) to draw inferences about the mechanism by which extended blockade of opioid receptors translates into clinical effectiveness.This was a 24-week multiple-site, double-blind, randomized trial of monthly XR-NTX versus placebo injections. We analyzed time to dropout from treatment using survival analysis with an extended Cox model as a function of treatment (XR-NTX versus placebo) and with weekly urine drug test (UDT) results for opioids at each week as a time-dependent covariate.Thirteen addiction treatment programs in Russia, 2008-09.A total of 250 adults with opioid use disorder who had completed in-patient detoxification.XR-NTX injection or placebo injection every 4 weeks with weekly clinic visits and biweekly counseling.Urine toxicology for opioids measured weekly and week of dropout from treatment.The Cox model yielded a significant interaction of time-dependent urine toxicology by treatment (P = 0.024). Among patients receiving placebo, a positive UDT in a given week increased the risk for dropout from treatment in the subsequent week [hazard ratio (HR) = 6.25; 95% confidence interval (CI) = 3.6-10.0], whereas among patients receiving XR-NTX, a positive UDT result showed no significant effect on risk for dropout (HR = 1.67; 95% CI = 0.6-4.5). The proportion of patients who completed all 24 weeks without any positive UDT result was 31% on XR-NTX compared with 20% on placebo (P = 0.051).Extended-release injection naltrexone was effective at reducing the risk of dropout from opioid use disorder treatment after an episode of opioid use. Just under a third of patients (31%) on XR-NTX had no opioid-positive urine tests across the trial, but the hypothesis that this would differ from placebo (20%) was not confirmed.

Background and objectives In a multisite, randomized study (CTN-0029), a 3-month course of Osmotic-Release Oral System Methylphenidate (OROS-MPH) improved smoking cessation in a group of patients with higher baseline severity in Attention-Deficit/Hyperactivity Disorder (ADHD). This treatment, however, worsened smoking cessation outcome in the group with lower baseline ADHD severity. We want to examine whether this differential treatment effect persisted after OROS-MPH was discontinued. Methods We conducted a secondary analysis of the 1-month follow-up data from CTN-0029 after the discontinuation of OROS-MPH (N = 134). Nicotine patch was tapered during this month. We tested whether OROS-MPH had an effect on self-reported 7-day abstinence by week, as well as possible treatment by baseline ADHD severity interactions. Results Abstinence diminished overall in time after the end of the treatment. In the high baseline severity group, patients who received OROS-MPH had an advantage in 7-day abstinence at week 15 (40% for OROS-MPH vs 20% for placebo, odds ratio = 2.63, P = .028). In the lower severity group (n = 121), no difference was detected (29% for OROS-MPH vs 32% for placebo, P = 1.00) between the two treatment groups. There was also a significant treatment by baseline ADHD severity interaction (P = .03). Conclusions and scientific significance OROS-MPH promotes abstinence beyond the course of treatment for patients with more severe ADHD, while the paradoxical effects in the lower baseline severity group is not persistent after medication discontinuation. Targeting ADHD in smoking cessation as a comorbidity therefore can have broader impact with more precise patient selection. (Am J Addict).

Background Treatment with opioid agonists is effective for opioid use disorder, but early discontinuation of treatment is a major obstacle to success. Intensive longitudinal methods — which take many repeated measurements over time, usually in the field— have provided unique insight into the effects of stress, mood and craving on drug use while people are being treated; these methods might also be useful for studying the processes that lead people to drop out of treatment. Methods Ecological momentary assessment (EMA) was conducted for up to 17 weeks by obtaining multiple electronic diary entries per day from 238 participants being treated with methadone or buprenorphine-naloxone. Survival analysis was used to study two outcomes: dropping out of treatment and noncompliance with EMA self-report requirements. Self-reports of stress, craving, and mood were used as time-varying predictors. Demographic and psychosocial variables measured with the Addiction Severity Index at the start of treatment were used as time-invariant predictors. Results Dropping out of treatment was more likely in participants with more reported hassles (a measure of stress), higher levels of cocaine craving, lower levels of positive mood, a recent history of emotional abuse, a recent history of being bothered frequently by psychological problems, and with buprenorphine rather than methadone as their medication. In contrast, study noncompliance was not significantly associated with any of the variables analyzed. Conclusions Assessment of stress, craving and mood during treatment might identify people who are at greater risk of dropping out, and therapeutic interventions targeting these processes might increase retention.