Association between treatment setting and outcomes among oregon medicaid patients with opioid use disorder: a retrospective cohort study.

BACKGROUND: Residential treatment is a common approach for treating opioid use disorder (OUD), however, few studies have directly compared it to outpatient treatment. The objective of this study was to compare OUD outcomes among individuals receiving residential and outpatient treatment. METHODS: A retrospective cohort study used linked data from a state Medicaid program, vital statistics, and the Substance Abuse and Mental Health Services Administration (SAMHSA) Treatment Episodes Dataset (TEDS) to compare OUD-related health outcomes among individuals treated in a residential or outpatient setting between 2014 and 2017. Multivariable Cox proportional hazards and logistic regression models examined the association between treatment setting and outcomes (i.e., opioid overdose, non-overdose opioid-related and all-cause emergency department (ED) visits, hospital admissions, and treatment retention) controlling for patient characteristics, co-morbidities, and use of medications for opioid use disorders (MOUD). Interaction models evaluated how MOUD use modified associations between treatment setting and outcomes. RESULTS: Of 3293 individuals treated for OUD, 957 (29%) received treatment in a residential facility. MOUD use was higher among those treated as an outpatient (43%) compared to residential (19%). The risk of opioid overdose (aHR 1.39; 95% CI 0.73-2.64) or an opioid-related emergency department encounter or admission (aHR 1.02; 95% CI 0.80-1.29) did not differ between treatment settings. Independent of setting, MOUD use was associated with a significant reduction in overdose risk (aHR 0.45; 95% CI 0.23-0.89). Residential care was associated with greater odds of retention at 6-months (aOR 1.71; 95% CI 1.32-2.21) but not 1-year. Residential treatment was only associated with improved retention for individuals not receiving MOUD (6-month aOR 2.05; 95% CI 1.56-2.71) with no benefit observed in those who received MOUD (aOR 0.75; 95% CI 0.46-1.29; interaction p = 0.001). CONCLUSIONS: Relative to outpatient treatment, residential treatment was not associated with reductions in opioid overdose or opioid-related ED encounters/hospitalizations. Regardless of setting, MOUD use was associated with a significant reduction in opioid overdose risk.

The application of digital health to the assessment and treatment of substance use disorders: The past, current, and future role of the National Drug Abuse Treatment Clinical Trials Network.

The application of digital technologies to better assess, understand, and treat substance use disorders (SUDs) is a particularly promising and vibrant area of scientific research. The National Drug Abuse Treatment Clinical Trials Network (CTN), launched in 1999 by the U.S. National Institute on Drug Abuse, has supported a growing line of research that leverages digital technologies to glean new insights into SUDs and provide science-based therapeutic tools to a diverse array of persons with SUDs. This manuscript provides an overview of the breadth and impact of research conducted in the realm of digital health within the CTN. This work has included the CTN's efforts to systematically embed digital screeners for SUDs into general medical settings to impact care models across the nation. This work has also included a pivotal multi-site clinical trial conducted on the CTN platform, whose data led to the very first "prescription digital therapeutic" authorized by the U.S. Food and Drug Administration (FDA) for the treatment of SUDs. Further CTN research includes the study of telehealth to increase capacity for science-based SUD treatment in rural and under-resourced communities. In addition, the CTN has supported an assessment of the feasibility of detecting cocaine-taking behavior via smartwatch sensing. And, the CTN has supported the conduct of clinical trials entirely online (including the recruitment of national and hard-to-reach/under-served participant samples online, with remote intervention delivery and data collection). Further, the CTN is supporting innovative work focused on the use of digital health technologies and data analytics to identify digital biomarkers and understand the clinical trajectories of individuals receiving medications for opioid use disorder (OUD). This manuscript concludes by outlining the many potential future opportunities to leverage the unique national CTN research network to scale-up the science on digital health to examine optimal strategies to increase the reach of science-based SUD service delivery models both within and outside of healthcare.

Using ecological momentary assessment to examine the relationship between craving and affect with opioid use in a clinical trial of clonidine as an adjunct medication to buprenorphine treatment.

BACKGROUND: In a recent clinical trial (NCT00295308), we demonstrated that clonidine decreased the association between opioid craving and moderate levels of stress and affect in patients receiving buprenorphine-based opioid agonist therapy. OBJECTIVES: To examine the relationship between illicit opioid use and craving and affect during the evaluation of clonidine as an adjunct medication in buprenorphine treatment for opioid use disorder. Secondarily, to examine whether those relationships are driven by within- or between-participant factors. METHODS: This was a secondary data analysis from our original trial. Participants (N = 108, female: n = 23, male n = 85) receiving buprenorphine were randomized to receive adjunct clonidine or placebo. Participants used portable electronic devices to rate stress, mood, and craving via ecological momentary assessment (EMA) four times randomly each day. To associate the EMA data with illicit opioid use, each EMA report was linked to participants' next urine drug screen (thrice weekly). We used generalized linear mixed models to examine the interaction between treatment group and illicit opioid use, as well as to decompose the analysis into within- and between-participant effects. RESULTS: Craving for opioids and cocaine was increased when participants were using illicit opioids; this effect was greater in the clonidine group. For affect, mood was poorer during periods preceding opioid-positive urines than opioid-negative urines for clonidine-treated participants, whereas there was no difference for placebo participants. CONCLUSION: This secondary analysis provides evidence that for participants maintained on opioid agonist therapy, clonidine minimized the behavioral impact of moderate levels of negative affect and craving.

Aripiprazole for cocaine abstinence: a randomized-controlled trial with ecological momentary assessment.

Aripiprazole blocks psychostimulant seeking in a rat model of relapse. However, in humans, it may increase ongoing use. We tested aripiprazole specifically for relapse prevention. Methadone-maintained outpatients who were abstinent from cocaine in weeks 11-12 were randomized to double-blind aripiprazole (15 mg daily) or placebo in weeks 13-27 after 12 weeks of contingency management. Participants reported craving through ecological momentary assessment. We stopped the trial because very few (18/41) participants fulfilled the abstinence criterion. The results suggested that aripiprazole delayed lapse [hazard ratio (HR)=0.45, 95% confidence interval (CI)=0.14-1.42, P=0.17] and relapse (HR=0.31, 95% CI=0.07-1.27, P=0.10), but the effects did not reach statistical significance. Unexpectedly, the proportion of participants reporting cocaine craving was higher in the aripiprazole group (Fisher's exact P=0.026), although the frequency of craving was similar in the aripiprazole and placebo groups (1.89 vs. 1.16%, reffect=0.43, 95% CI=-0.08-0.76). The results suggest that in recently abstinent cocaine users, aripiprazole might delay relapse, but might also slightly increase craving. Difficulty in trial implementation underscores the fact that initial abstinence from cocaine is not a trivial hurdle.

Cost-effectiveness of an internet-delivered treatment for substance abuse: Data from a multisite randomized controlled trial.

BACKGROUND: Substance misuse and excessive alcohol consumption are major public health issues. Internet-based interventions for substance use disorders (SUDs) are a relatively new method for addressing barriers to access and supplementing existing care. This study examines cost-effectiveness in a multisite, randomized trial of an internet-based version of the community reinforcement approach (CRA) with contingency management (CM) known as the Therapeutic Education System (TES). METHODS: Economic evaluation of the 12-week trial with follow-up at 24 and 36 weeks. 507 individuals who were seeking therapy for alcohol or other substance use disorders at 10 outpatient community-based treatment programs were recruited and randomized to either treatment as usual (TAU) or TES+TAU. Sub-analyses were completed on participants with a poorer prognosis (i.e., those not abstinent at study entry). RESULTS: From the provider's perspective, TES+TAU as it was implemented in this study costs $278 (SE=87) more than TAU alone after 12 weeks. The quality-adjusted life years gained by TES+TAU and TAU were similar; however, TES+TAU has at least a 95% chance of being considered cost-effective for providers and payers with willingness-to-pay thresholds as low as $20,000 per abstinent year. Findings for the subgroup not abstinent at study entry are slightly more favorable. CONCLUSIONS: With regard to the clinical outcome of abstinence, our cost-effectiveness findings of TES+TAU compare favorably to those found elsewhere in the CM literature. The analyses performed here serve as an initial economic framework for future studies integrating technology into SUD therapy.

Using electronic health record data for substance use Screening, Brief Intervention, and Referral to Treatment among adults with type 2 diabetes: Design of a National Drug Abuse Treatment Clinical Trials Network study.

BACKGROUND: The Affordable Care Act encourages healthcare systems to integrate behavioral and medical healthcare, as well as to employ electronic health records (EHRs) for health information exchange and quality improvement. Pragmatic research paradigms that employ EHRs in research are needed to produce clinical evidence in real-world medical settings for informing learning healthcare systems. Adults with comorbid diabetes and substance use disorders (SUDs) tend to use costly inpatient treatments; however, there is a lack of empirical data on implementing behavioral healthcare to reduce health risk in adults with high-risk diabetes. Given the complexity of high-risk patients' medical problems and the cost of conducting randomized trials, a feasibility project is warranted to guide practical study designs. METHODS: We describe the study design, which explores the feasibility of implementing substance use Screening, Brief Intervention, and Referral to Treatment (SBIRT) among adults with high-risk type 2 diabetes mellitus (T2DM) within a home-based primary care setting. Our study includes the development of an integrated EHR datamart to identify eligible patients and collect diabetes healthcare data, and the use of a geographic health information system to understand the social context in patients' communities. Analysis will examine recruitment, proportion of patients receiving brief intervention and/or referrals, substance use, SUD treatment use, diabetes outcomes, and retention. DISCUSSION: By capitalizing on an existing T2DM project that uses home-based primary care, our study results will provide timely clinical information to inform the designs and implementation of future SBIRT studies among adults with multiple medical conditions.

Clonidine Maintenance Prolongs Opioid Abstinence and Decouples Stress From Craving in Daily Life: A Randomized Controlled Trial With Ecological Momentary Assessment.

OBJECTIVE: The authors tested whether clonidine blocks stress-induced seeking of heroin and cocaine. The study was also intended to confirm translational findings from a rat model of drug relapse by using ecological momentary assessment of patients' stress to test hypotheses about clonidine's behavioral mechanism of action. METHOD: The authors conducted a randomized double-blind placebo-controlled clinical trial with 208 opioid-dependent patients at an outpatient buprenorphine clinic. The 118 participants (57%) who maintained abstinence during weeks 5-6 were continued on buprenorphine and randomly assigned to receive clonidine (N=61) or placebo (N=57) for 14 weeks. Urine was tested thrice weekly. Lapse was defined as any opioid-positive or missed urine test, and relapse as two or more consecutive lapses. Time to lapse and relapse were examined with Cox regressions; longest period of abstinence was examined with a t test, and ecological momentary assessment data were examined with generalized linear mixed models. RESULTS: In an intent-to-treat analysis, clonidine produced the longest duration (in consecutive days) of abstinence from opioids during the intervention phase (34.8 days [SD=3.7] compared with 25.5 days [SD=2.7]; Cohen's d=0.38). There was no group difference in time to relapse, but the clonidine group took longer to lapse (hazard ratio=0.67, 95% CI=0.45-1.00). Ecological momentary assessment showed that daily-life stress was partly decoupled from opioid craving in the clonidine group, supporting the authors' hypothesized mechanism for clonidine's benefits. CONCLUSIONS: Clonidine, a readily available medication, is useful in opioid dependence not just for reduction of withdrawal signs, but also as an adjunctive maintenance treatment that increases duration of abstinence. Even in the absence of physical withdrawal, it decouples stress from craving in everyday life.

Patient registries for substance use disorders.

This commentary discusses the need for developing patient registries of substance use disorders (SUD) in general medical settings. A patient registry is a tool that documents the natural history of target diseases. Clinicians and researchers use registries to monitor patient comorbidities, care procedures and processes, and treatment effectiveness for the purpose of improving care quality. Enactments of the Affordable Care Act 2010 and the Mental Health Parity and Addiction Equity Act 2008 open opportunities for many substance users to receive treatment services in general medical settings. An increased number of patients with a wide spectrum of SUD will initially receive services with a chronic disease management approach in primary care. The establishment of computer-based SUD patient registries can be assisted by wide adoption of electronic health record systems. The linkage of SUD patient registries with electronic health record systems can facilitate the advancement of SUD treatment research efforts and improve patient care.

Challenges and opportunities for integrating preventive substance-use-care services in primary care through the Affordable Care Act.

Undertreated or untreated substance use disorders (SUD) remain a pervasive, medically-harmful public health problem in the United States, particularly in medically underserved and low-income populations lacking access to appropriate treatment. The need for greater access to SUD treatment was expressed as policy in the Final Rule on standards related to essential health benefits, required to be covered through the 2010 Affordable Care Act (ACA) health insurance exchanges. SUD treatment services have been included as an essential health benefit, in a manner that complies with the Mental Health Parity and Addiction Equity Act (MHPAEA) of 2008. Consequently, with the ACA, a vast expansion of SUD-care services in primary care is looming. This commentary discusses challenges and opportunities under the ACA for equipping health care professionals with appropriate workforce training, infrastructure, and resources to support and guide science-based Screening, Brief Intervention, and Referral to Treatment (SBIRT) for SUD in primary care.

Selection and utilization of assessment instruments in substance abuse treatment trials: the National Drug Abuse Treatment Clinical Trials Network experience.

Based on recommendations from a US Institute of Medicine report, the National Institute on Drug Abuse established the National Drug Abuse Treatment Clinical Trials Network (CTN) in 1999, to accelerate the translation of science-based addiction treatment research into community-based practice, and to improve the quality of addiction treatment, using science as the vehicle. One of the CTN's primary tasks is to serve as a platform to forge bi-directional communications and collaborations between providers and scientists, to enhance the relevance of research, which generates empirical results that impact practice. Among many obstacles in moving research into real-world settings, this commentary mainly describes challenges and iterative experiences in regard to how the CTN develops its research protocols, with focus on how the CTN study teams select and utilize assessment instruments, which can reasonably balance the interests of both research scientists and practicing providers when applied in CTN trials. This commentary also discusses the process by which the CTN further selects a core set of common assessment instruments that may be applied across all trials, to allow easier cross-study analyses of comparable data.

Design and methodological considerations of an effectiveness trial of a computer-assisted intervention: an example from the NIDA Clinical Trials Network.

Computer-assisted interventions hold the promise of minimizing two problems that are ubiquitous in substance abuse treatment: the lack of ready access to treatment and the challenges to providing empirically-supported treatments. Reviews of research on computer-assisted treatments for mental health and substance abuse report promising findings, but study quality and methodological limitations remain an issue. In addition, relatively few computer-assisted treatments have been tested among illicit substance users. This manuscript describes the methodological considerations of a multi-site effectiveness trial conducted within the National Institute on Drug Abuse's (NIDA's) National Drug Abuse Treatment Clinical Trials Network (CTN). The study is evaluating a web-based version of the Community Reinforcement Approach, in addition to prize-based contingency management, among 500 participants enrolled in 10 outpatient substance abuse treatment programs. Several potential effectiveness trial designs were considered and the rationale for the choice of design in this study is described. The study uses a randomized controlled design (with independent treatment arm allocation), intention-to-treat primary outcome analysis, biological markers for the primary outcome of abstinence, long-term follow-up assessments, precise measurement of intervention dose, and a cost-effectiveness analysis. Input from community providers during protocol development highlighted potential concerns and helped to address issues of practicality and feasibility. Collaboration between providers and investigators supports the utility of infrastructures that enhance research partnerships to facilitate effectiveness trials and dissemination of promising, technologically innovative treatments. Outcomes from this study will further the empirical knowledge base on the effectiveness and cost-effectiveness of computer-assisted treatment in clinical treatment settings.