Faculty Bibliography

Few studies examine the effectiveness of treatments for opioid use disorder (OUD) among Black individuals despite recent evidence suggesting opioid overdose death rates are, in some cases, highest and increasing at a faster rate among Black people compared to other racial/ethnic groups. This secondary analysis study investigated treatment preference, retention, and relapse rates amongst a subgroup of 73 Black participants with OUD (81% male, mean age 39.05, SD = 11.80) participating in a 24-week multisite randomized clinical trial ("X:BOT") comparing the effectiveness of extended-release naltrexone (XR-NTX) and sublingual buprenorphine-naloxone (BUP-NX) between 2014 and 2017. Chi-square analyses were used to investigate treatment preference assessed at baseline, and logistic regression analyses were used to investigate differences in the odds of retention and relapse assessed over the 24-week course of treatment between treatment groups. Our findings suggest no differences in preference for XR-NTX versus BUP-NX. However, similar to the parent trial, there was an induction hurdle such that only 59.5% of those randomized to XR-NTX successfully initiated medication compared to 91.6% of those randomized to BUP-NX (OR = 0.13, 95% CI = 0.04, 0.52). No significant differences were found in treatment retention (intention-to-treat: OR = 1.19, 95% CI = 0.43, 3.28; per-protocol [i.e., those who initiated medication]: OR = 0.60, 95% CI = 0.20, 1.82) or relapse rates between treatment groups (intention-to-treat: OR = 1.53, 95% CI = 0.57, 4.13; per-protocol: OR = 0.69, 95% CI = 0.23, 2.06). Although there is a significant initiation hurdle with XR-NTX, once inducted, both medications appear similar in effectiveness, but as in the main study, dropout rates were high. Future research is needed on how to improve adherence.

Background and Objectives: To rapidly develop, implement, and evaluate emergency department (ED) clinical protocols for initiation of buprenorphine (E

Purpose: Almost uniformly, patients with frequent Emergency Department (ED) use and severe alcohol use disorders (AUDs) do not receive alcohol pharmacotherapy and are excluded from research as they are difficult to engage and retain and suffer from myriad bio-psychosocial comorbidities. We assessed the feasibility and acceptability of initiating and continuing treatment with extended-release naltrexone (XR-NTX) as well as studying its effects in this challenging population and clinical setting.
Method(s): In this randomized, open-label study, ED patient-participants with > 4 ED visits and moderate- severe AUD were randomized (1:1) to XR-NTX and research assistant-delivered care management or treatment as usual enhanced by a one-time warm referral and motivation enhancement. XR-NTX was first administered during the index ED visit. Thereafter, participants could receive up to 11 additional doses at clinic visits with arrangements to allow unscheduled visits. Non-clinical research visits (both arms) were scheduled at 3, 6, and 12 months with a considerable date variation permitted and expected. Drinking was assessed via 30-day timeline followback with heavy drinking day (HDD) thresholds of 5 for males and 4 for females. Resuts: The 48 participants were aged 55.0 +/- 8.2, 88% male, 51% white, 79% homeless, and reported an average of 23.4 HDDs in the priormonth and 24.4 standard drinks/drinking day. Approximately 70%lacked reliable contact information. Research visit attendance was 70.8%, 77.1%, and 70.8%with a median time to first visit of 126 days [Interquartile Range: 89-242]. In the XR-NTX arm (N = 24), a total of 173 injections were administered with amean of 7.2 per participant; 20 (83%) participants received 2 or more injections, 14 (56%) received 6 or more injections, and 6 (24%) received 12 injections. There was a significantly greater decrease in HDDs per month among those receiving XR-NTX compared to those who did not: 15.3 (95%CI 9.7-21.0) and 9.6 (95%CI 1.5-17.6), respectively. Baseline rates were imputed for two missing participants in each arm.
Conclusion(s): Among this population whose complicated AUDs pose considerable challenges from clinical and research perspectives, initiating and continuing treatment with XR-NTX was feasible, acceptable, and demonstrated promising preliminary drinking outcomes. Additional sensitivity analyses and evaluation of other outcomes of interest are underway. Further study on a larger scale is warranted

BACKGROUND AND OBJECTIVES/OBJECTIVE: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/CONCLUSIONS: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/CONCLUSIONS: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;00:00-00).

Objectives: To study the health-related quality of life (HRQoL) of persons with opioid use disorder (OUD) initiating medication treatment.
Method(s): We conducted a secondary analysis of data collected from a clinical trial funded by the National Drug Abuse Treatment Clinical Trials Network, where participants (N=570) in residential treatment were randomized to initiating extended-release naltrexone (XR-NTX) or buprenorphine-naloxone (BUP-NX) for the prevention of opioid relapse. A generalized structural equation latent-class model was used to identify associations and describe HRQoL trajectories over the 24-week trial and subsequent 28- and 36-week follow-ups for all participants regardless of success initiating treatment.
Result(s): Two latent classes were identified and defined: HRQoL "pharmacotherapy responsive" (82.3%), and HRQoL "baseline sensitive" (17.7%). The pharmacotherapy responsive class was characterized by HRQoL that tended to increase over time and a significant positive association between HRQoL and whether BUP-NX or XR-NTX was received in the past 30 days. The baseline sensitive class was characterized by lower average receipt of pharmacotherapy, initial increase in HRQoL with gradual decrease over time, and no significant HRQoL response to pharmacotherapy. HRQoL changes over time among patients in this class were sensitive to age, race, marital status, and motivation at baseline. Compared to the pharmacotherapy responsive class, the baseline sensitive class included higher proportions of participants who were female, white, married, less educated, and less motivated at baseline. The pharmacotherapy responsive class participants had, on average, less severe medical, drug, legal, and psychiatric problems at baseline.
Conclusion(s): The majority of persons with OUD enrolled in this trial experienced improvements in HRQoL that were associated with pharmacotherapy, while a smaller sub-group with lower average receipt of pharmacotherapy had HRQoL changes that were associated with baseline characteristics but not pharmacotherapy. Our analysis provides insights for improved person-centered care for OUD patients receiving pharmacotherapy who are not adherent to treatment.
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OBJECTIVES/OBJECTIVE: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.

This chapter describes recent clinical trials for opioid use disorder (OUD), an area that has rapidly accelerated in response to the opioid overdose crisis in the USA and newly appropriated funding. Trials involve a wide range of compounds including cannabinoids and psychedelics, new and existing compounds targeting domains emerging from addiction neuroscience, agents repurposed from other indications, and novel strategies including vaccines, enzymes, and other biologicals. In parallel, new formulations of existing compounds offer immediate promise, as do a variety of web-based interventions and smartphone-delivered apps. Trials focused on implementing existing effective interventions in mainstream healthcare settings, and others focused on special populations, e.g., adolescents, criminal justice, pregnant women, native Americans, etc., have the potential to vastly expand treatment in the near term. Given the range of ongoing and recent trials, this chapter is not intended to be an exhaustive review but rather to present an overview of approaches within the framework of the opioid treatment cascade and the context of current OUD pharmacotherapies.

Importance/UNASSIGNED:Opioid addiction is a major public health problem. Despite availability of evidence-based treatments, relapse and dropout are common outcomes. Efforts aimed at identifying reuse risk and gaining more precise understanding of the mechanisms conferring reuse vulnerability are needed. Objective/UNASSIGNED:To use tools from computational psychiatry and decision neuroscience to identify changes in decision-making processes preceding opioid reuse. Design, Setting, and Participants/UNASSIGNED:A cohort of individuals with opioid use disorder were studied longitudinally at a community-based treatment setting for up to 7 months (1-15 sessions per person). At each session, patients completed a risky decision-making task amenable to computational modeling and standard clinical assessments. Time-lagged mixed-effects logistic regression analyses were used to assess the likelihood of opioid use between sessions (t to t + 1; within the subsequent 1-4 weeks) from data acquired at the current session (t). A cohort of control participants completed similar procedures (1-5 sessions per person), serving both as a baseline comparison group and an independent sample in which to assess measurement test-retest reliability. Data were analyzed between January 1, 2018, and September 5, 2019. Main Outcomes and Measures/UNASSIGNED:Two individual model-based behavioral markers were derived from the task completed at each session, capturing a participant's current tolerance of known risks and ambiguity (partially unknown risks). Current anxiety, craving, withdrawal, and nonadherence were assessed via interview and clinic records. Opioid use was ascertained from random urine toxicology tests and self-reports. Results/UNASSIGNED:Seventy patients (mean [SE] age, 44.7 [1.3] years; 12 women and 58 men [82.9% male]) and 55 control participants (mean [SE] age, 42.4 [1.5] years; 13 women and 42 men [76.4% male]) were included. Of the 552 sessions completed with patients (mean [SE], 7.89 [0.59] sessions per person), 252 (45.7%) directly preceded opioid use events (mean [SE], 3.60 [0.44] sessions per person). From the task parameters, only ambiguity tolerance was significantly associated with increased odds of prospective opioid use (adjusted odds ratio, 1.37 [95% CI, 1.07-1.76]), indicating patients were more tolerant specifically of ambiguous risks prior to these use events. The association of ambiguity tolerance with prospective use was independent of established clinical factors (adjusted odds ratio, 1.29 [95% CI, 1.01-1.65]; P = .04), such that a model combining these factors explained more variance in reuse risk. No significant differences in ambiguity tolerance were observed between patients and control participants, who completed 197 sessions (mean [SE], 3.58 [0.21] sessions per person); however, patients were more tolerant of known risks (B = 0.56 [95% CI, 0.05-1.07]). Conclusions and Relevance/UNASSIGNED:Computational approaches can provide mechanistic insights about the cognitive factors underlying opioid reuse vulnerability and may hold promise for clinical use.

Objectives: In a US randomized clinical trial testing the effectiveness of preventing opioid relapse among individuals initiating extended-release naltrexone (XR-NTX) compared to buprenorphine-naloxone (BUP-NX) in an inpatient detoxification setting, the additional time required to detoxify from opioids prior to initiating XR-NTX resulted in fewer persons initiating XR-NTX, leading to a higher opioid relapse rate, and higher detoxification costs compared to BUP-NX. The objective of this study was to use trial data to estimate whether an efficient model of inpatient opioid detoxification would improve the economic value of XR-NTX compared to BUP-NX.
Method(s): We identified efficient models of inpatient detoxification for trial participants assigned to XR-NTX using 1) latent class analysis to identify detoxification pharmacotherapy use patterns, 2) a multivariable generalized structural equation model to explore determinants of XR-NTX initiation and detoxification duration, while controlling for endogeneity, and 3) data from the trial on detoxification daily cost by site. We then estimated trial cost-effectiveness outcomes from the healthcare sector perspective assuming alternative detoxification models for trial participants.
Result(s): Five latent pharmacotherapy classes were identified and included in the multivariable model. Site effects were the largest determinants of both XRT-NTX initiation and detoxification duration. The predicted probabilities of successful initiation per detoxification-day ranged from 0.13-0.15 at the four sites with significant effects, and the predicted durations ranged from 5.5 to 6.9 days. The predicted cost/detoxification-day varied from $115-$348, largely due to different staffing models. We estimated that the most efficient site model would result in non-significant cost and effectiveness differences between initiating XR-NTX or BUP-NX.
Conclusion(s): Adopting an efficient model of XR-NTX initiation could result in XR-NTX and BUP-NX having similar economic value from the healthcare sector perspective for the average patient requiring residential detoxification before initiating XR-NTX. The feasibility of implementing more efficient detoxification models needs to be explored.
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