Toward AI-driven neuroepigenetic imaging biomarker for alcohol use disorder: A proof-of-concept study.

Alcohol use disorder (AUD) is a disorder of clinical and public health significance requiring novel and improved therapeutic solutions. Both environmental and genetic factors play a significant role in its pathophysiology. However, the underlying epigenetic molecular mechanisms that link the gene-environment interaction in AUD remain largely unknown. In this proof-of-concept study, we showed, for the first time, the neuroepigenetic biomarker capability of non-invasive imaging of class I histone deacetylase (HDAC) epigenetic enzymes in the in vivo brain for classifying AUD patients from healthy controls using a machine learning approach in the context of precision diagnosis. Eleven AUD patients and 16 age- and sex-matched healthy controls completed a simultaneous positron emission tomography-magnetic resonance (PET/MR) scan with the HDAC-binding radiotracer [11C]Martinostat. Our results showed lower HDAC expression in the anterior cingulate region in AUD. Furthermore, by applying a genetic algorithm feature selection, we identified five particular brain regions whose combined [11C]Martinostat relative standard uptake value (SUVR) features could reliably classify AUD vs. controls. We validate their promising classification reliability using a support vector machine classifier. These findings inform the potential of in vivo HDAC imaging biomarkers coupled with machine learning tools in the objective diagnosis and molecular translation of AUD that could complement the current diagnostic and statistical manual of mental disorders (DSM)-based intervention to propel precision medicine forward.

Discontinuation of medication treatment for opioid use disorder after a successful course: The discontinuation phase of the CTN-0100 (RDD) trial.

INTRODUCTION AND BACKGROUND: Buprenorphine, and extended-release naltrexone, are effective in decreasing opioid use, morbidity and mortality. The available evidence suggests that these medications should be used for long term treatment; however, patients often ask how long they need to be on medication, and whether it would be safe to discontinue. There are sparse data to guide us. The CTN-0100 trial will address this gap in our knowledge by studying participants who have decided to discontinue buprenorphine and extended-release naltrexone for OUD. RESEARCH DESIGN AND METHODS: The trial is a multicenter, randomized, non-blinded study. Participants are stable adult volunteers, on sublingual buprenorphine, extended-release buprenorphine, or extended-release naltrexone, expressing an interest in discontinuing medication. Participants on buprenorphine must be stable for at least 1 year and participants on extended-release naltrexone must be stable for at least 6 months. Participants are engaged in the study for up to 96 weeks, including a flexible taper period, and are then transitioned to follow-up within the trial. All participants are randomly assigned to the study Medical Management (MM) or to MM plus Connections (CHESS health) digital smartphone application aimed at recovery and abstinence (MMD). Sublingual Buprenorphine participants are also randomized (2 × 2 design) to a taper using either sublingual or extended-release buprenorphine. DISCUSSION/CONCLUSION: It is hoped that this trial will provide a rich source of data on management of patients discontinuing medication for opioid use disorder (MOUD) to inform future research and practice. The trial will shed light on which strategies are most likely to lead to long-term success (absence of relapse), and what participant characteristics distinguish those who can safely discontinue MOUD from those who remain at risk of relapse should they discontinue. CLINICALTRIALS: gov Identifier: NCT04464980.

Correlates of optimism among patients in substance use disorder inpatient treatment.

BACKGROUND AND OBJECTIVES: Early recovery from substance use disorder (SUD) is often characterized by hopelessness and despair about the future. Optimism, or the expectation that good things will happen, may provide a buffer against despair, and motivate adaptive goal engagement and coping. Study objectives were to (1) compare levels of optimism among individuals in substance use disorder inpatient treatment to other populations and (2) examine correlates of optimism. METHODS: This exploratory study utilized a cross-sectional survey design. Participants (n = 355) completed self-report measures assessing sociodemographic and clinical characteristics. The main variable of interest, optimism, was assessed by Life Orientation Test-Revised scores. Multivariate regression was used to examine the association among sociodemographic and clinical variables and optimism. RESULTS: Our sample (n = 342) scored lower on optimism (mean = 11.7) than general population and SUD patients reported in the literature (range = 13.0-18.5). Optimism was higher for SUD inpatients who were college-educated and those with higher scores on the recovery protection factor, while greater anxiety severity was associated with lower optimism scores. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This study contributes to emerging research on the association between optimism and SUDs. Optimism has not been previously studied among patients in acute, short-term inpatient SUD treatment and doing so may be clinically useful in addressing low optimism as an obstacle to motivation for treatment. Bolstering optimism may be a promising target for intervention and future research.

Long-term naturalistic follow-up of chronic pain in adults with prescription opioid use disorder.

BACKGROUND: Chronic pain is common in patients with prescription opioid use disorder (OUD), and pain severity has been shown to predict opioid use for those with chronic pain. However, recent research suggests that focusing on pain status (i.e., the presence or absence of chronic pain) at treatment initiation may not reflect the clinical significance of pain over the long-term course of OUD. Reports of variability in chronic pain and its clinical significance over time have yet to be investigated in patients with prescription OUD. The present study examined variability in chronic pain status from entry into prescription OUD treatment through 3.5-year follow-up. Additionally, we examined the association between concurrent chronic pain and opioid use at three follow-up time points. METHODS: This secondary analysis (N = 309) of a national, randomized, controlled trial of prescription OUD treatment used generalized estimating equations to assess variability in the prevalence of chronic pain from study entry to 3.5-year follow-up, and the association between chronic pain status and concurrent opioid use. RESULTS: Fifty-three percent of participants reported variability in chronic pain status over time. The prevalence of chronic pain decreased from study entry through follow-up (aOR = 0.47, p < 0.001). Chronic pain was associated with increased opioid use at each follow-up assessment (aOR = 3.56, p < 0.001). CONCLUSIONS: Chronic pain status may vary over time in those with prescription OUD, and chronic pain appears to be associated with concurrent opioid use. The present findings highlight the importance of assessing chronic pain throughout the course of prescription OUD.

Focus Group Study to Examine Content of Family Meetings in Short-term Substance Use Disorder Treatment.

This study explores the content family members find helpful in family meetings that occur while patients are in short-term treatment for substance use disorders. Three focus groups were conducted; two with 23 family members and one with 10 patients who were asked to identify those topics that are helpful or unhelpful for families with and without prior treatment experiences. Families identified education about substance use disorders and an overview of treatment options as useful for family members new to treatment, and an emphasis on response to relapse and family supports as important for those with prior treatment experiences.

Health-related quality of life among prescription opioid-dependent patients: Results from a multi-site study.

BACKGROUND: Although prescription opioid use disorder has recently increased sharply in the United States, relatively little is known about the general well-being of this population. Assessment of quality of life in patients with substance use disorders has been recommended to improve clinical care. OBJECTIVES: Health-related quality of life was examined in prescription opioid-dependent patients at entry to a national multi-site clinical trial, to compare quality of life scores in the study sample to other populations; further, background variables associated with quality of life in the literature were examined. METHODS: Prescription opioid-dependent patients (N = 653) were compared to general populations on the Medical Outcome Study Short Form-36 (SF-36) quality of life measure; and the association between patient background variables and quality of life was examined. RESULTS: Compared to a general population, the current sample of prescription opioid-dependent patients had worse physical (-1.7 points, p < .001) and mental quality of life (-12.3 points, p < .001) as measured by the SF-36, similar to other opioid-use disorder populations. Within our sample, women showed more impairment than men in mental quality of life (-4.3 points, p < .001); older patients scored worse on physical (-5.2 points, p < .001), but not mental, quality of life. Chronic pain was associated with poorer physical quality of life (-9.0 points, p < .001). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The growing focus on wellness underscores the importance of measuring quality of life in addition to substance use outcomes. Routine assessment of health-related quality of life can add an important dimension to overall evaluation of patients' treatment response.

Long-term outcomes from the National Drug Abuse Treatment Clinical Trials Network Prescription Opioid Addiction Treatment Study.

BACKGROUND: Despite the growing prevalence of prescription opioid dependence, longitudinal studies have not examined long-term treatment response. The current study examined outcomes over 42 months in the Prescription Opioid Addiction Treatment Study (POATS). METHODS: POATS was a multi-site clinical trial lasting up to 9 months, examining different durations of buprenorphine-naloxone plus standard medical management for prescription opioid dependence, with participants randomized to receive or not receive additional opioid drug counseling. A subset of participants (N=375 of 653) enrolled in a follow-up study. Telephone interviews were administered approximately 18, 30, and 42 months after main-trial enrollment. Comparison of baseline characteristics by follow-up participation suggested few differences. RESULTS: At Month 42, much improvement was seen: 31.7% were abstinent from opioids and not on agonist therapy; 29.4% were receiving opioid agonist therapy, but met no symptom criteria for current opioid dependence; 7.5% were using illicit opioids while on agonist therapy; and the remaining 31.4% were using opioids without agonist therapy. Participants reporting a lifetime history of heroin use at baseline were more likely to meet DSM-IV criteria for opioid dependence at Month 42 (OR=4.56, 95% CI=1.29-16.04, p<.05). Engagement in agonist therapy was associated with a greater likelihood of illicit-opioid abstinence. Eight percent (n=27/338) used heroin for the first time during follow-up; 10.1% reported first-time injection heroin use. CONCLUSIONS: Long-term outcomes for those dependent on prescription opioids demonstrated clear improvement from baseline. However, a subset exhibited a worsening course, by initiating heroin use and/or injection opioid use.

The multi-site prescription opioid addiction treatment study: 18-month outcomes.

Despite the high prevalence of prescription opioid dependence in the U.S., little is known about the course of this disorder and long-term response to treatment. We therefore examined 18-month post-randomization outcomes of participants in the Prescription Opioid Addiction Treatment Study, a multi-site, randomized controlled trial examining varying durations of buprenorphine-naloxone treatment and different intensities of counseling for prescription opioid dependence. Thus the current follow-up study provides a unique contribution to the field by reporting longer-term outcomes of a well-characterized population of treatment-seeking prescription opioid dependent patients. Participants from the treatment trial (N=252/653) completed an 18-month follow-up telephone assessment. Multivariable analyses examined associations between participant characteristics and key indicators of month-18 status: opioid abstinence, DSM-IV opioid dependence, and opioid agonist treatment. Overall, participants showed improvement from baseline to month 18: 49.6% were abstinent in the previous 30 days, with only 16.3% opioid-dependent. Some participants, however, had initiated past-year heroin use (n=9) or opioid injection (n=17). Most participants (65.9%) engaged in substance use disorder treatment during the past year, most commonly opioid agonist therapy (48.8%). Of particular interest in this population, multivariable analysis showed that greater pain severity at baseline was associated with opioid dependence at 18 months. In conclusion, although opioid use outcomes during the treatment trial were poor immediately following a buprenorphine-naloxone taper compared to those during 12 weeks of buprenorphine-naloxone stabilization, opioid use outcomes at 18-month follow-up showed substantial improvement over baseline and were comparable to the rate of successful outcomes during buprenorphine-naloxone stabilization in the treatment trial.

Randomized multi-site trial of the Job Seekers' Workshop in patients with substance use disorders.

BACKGROUND: Unemployment is associated with negative outcomes both during and after drug abuse treatment. Interventions designed to increase rates of employment may also improve drug abuse treatment outcomes. The purpose of this multi-site clinical trial was to evaluate the Job Seekers' Workshop (JSW), a three session, manualized program designed to train patients in the skills needed to find and secure a job. METHOD: Study participants were recruited through the NIDA Clinical Trials Network (CTN) from six psychosocial counseling (n=327) and five methadone maintenance (n=301) drug treatment programs. Participants were randomly assigned to either standard care (program-specific services plus brochure with local employment resources) (SC) or standard care plus JSW. Three 4-h small group JSW sessions were offered weekly by trained JSW facilitators with ongoing fidelity monitoring. RESULTS: JSW and SC participants had similar 12- and 24-week results for the primary outcome measure (i.e., obtaining a new taxed job or enrollment in a training program). Specifically, one-fifth of participants at 12weeks (20.1-24.3%) and nearly one-third at 24 weeks (31.4-31.9%) had positive outcomes, with "obtaining a new taxed job" accounting for the majority of cases. CONCLUSION: JSW group participants did not have higher rates of employment/training than SC controls. Rates of job acquisition were modest for both groups, suggesting more intensive interventions may be needed. Alternate targets (e.g., enhancing patient motivation, training in job-specific skills) warrant further study as well.

Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: a 2-phase randomized controlled trial.

CONTEXT: No randomized trials have examined treatments for prescription opioid dependence, despite its increasing prevalence. OBJECTIVE: To evaluate the efficacy of brief and extended buprenorphine hydrochloride-naloxone hydrochloride treatment, with different counseling intensities, for patients dependent on prescription opioids. DESIGN: Multisite, randomized clinical trial using a 2-phase adaptive treatment research design. Brief treatment (phase 1) included 2-week buprenorphine-naloxone stabilization, 2-week taper, and 8-week postmedication follow-up. Patients with successful opioid use outcomes exited the study; unsuccessful patients entered phase 2: extended (12-week) buprenorphine-naloxone treatment, 4-week taper, and 8-week postmedication follow-up. SETTING: Ten US sites. Patients A total of 653 treatment-seeking outpatients dependent on prescription opioids. INTERVENTIONS: In both phases, patients were randomized to standard medical management (SMM) or SMM plus opioid dependence counseling; all received buprenorphine-naloxone. MAIN OUTCOME MEASURES: Predefined "successful outcome" in each phase: composite measures indicating minimal or no opioid use based on urine test-confirmed self-reports. RESULTS: During phase 1, only 6.6% (43 of 653) of patients had successful outcomes, with no difference between SMM and SMM plus opioid dependence counseling. In contrast, 49.2% (177 of 360) attained successful outcomes in phase 2 during extended buprenorphine-naloxone treatment (week 12), with no difference between counseling conditions. Success rates 8 weeks after completing the buprenorphine-naloxone taper (phase 2, week 24) dropped to 8.6% (31 of 360), again with no counseling difference. In secondary analyses, successful phase 2 outcomes were more common while taking buprenorphine-naloxone than 8 weeks after taper (49.2% [177 of 360] vs 8.6% [31 of 360], P < .001). Chronic pain did not affect opioid use outcomes; a history of ever using heroin was associated with lower phase 2 success rates while taking buprenorphine-naloxone. CONCLUSIONS: Prescription opioid-dependent patients are most likely to reduce opioid use during buprenorphine-naloxone treatment; if tapered off buprenorphine-naloxone, even after 12 weeks of treatment, the likelihood of an unsuccessful outcome is high, even in patients receiving counseling in addition to SMM.

Predicting outpatient treatment entry following detoxification for injection drug use: the impact of patient and program factors.

This article examines variables that predicted outpatient treatment entry within 6 months of residential detoxification. Patient data were collected from 632 injection drug users enrolled in a randomized trial conducted at eight detoxification programs within the National Drug Abuse Treatment Clinical Trials Network (CTN) with follow-up assessments conducted at 2, 8, 16, and 24 weeks. Detoxification program characteristics were collected during this study and from a survey of CTN treatment organizations. Survival analysis found that estimated proportions of reported outpatient treatment entry varied across sites from .06 to .72. A model-building approach determined variables significantly associated with outpatient treatment entry. The best predictive model contained five program-level variables: accreditation, fewer beds, longer stays, shorter distance between detoxification and outpatient unit, and larger city population. Results suggest the importance of detoxification program characteristics in facilitating further treatment and the need for systems modifications to improve continuity of care.

A multi-site, two-phase, Prescription Opioid Addiction Treatment Study (POATS): rationale, design, and methodology.

The National Institute on Drug Abuse Clinical Trials Network launched the Prescription Opioid Addiction Treatment Study (POATS) in response to rising rates of prescription opioid dependence and gaps in understanding the optimal course of treatment for this population. POATS employed a multi-site, two-phase adaptive, sequential treatment design to approximate clinical practice. The study took place at 10 community treatment programs around the United States. Participants included men and women age > or =18 who met Diagnostic and Statistical Manual, 4th Edition criteria for dependence upon prescription opioids, with physiologic features; those with a prominent history of heroin use (according to pre-specified criteria) were excluded. All participants received buprenorphine/naloxone (bup/nx). Phase 1 consisted of 4 weeks of bup/nx treatment, including a 14-day dose taper, with 8 weeks of follow-up. Phase 1 participants were monitored for treatment response during these 12 weeks. Those who relapsed to opioid use, as defined by pre-specified criteria, were invited to enter Phase 2; Phase 2 consisted of 12 weeks of bup/nx stabilization treatment, followed by a 4-week taper and 8 weeks of post-treatment follow-up. Participants were randomized at the beginning of Phase 1 to receive bup/nx, paired with either Standard Medical Management (SMM) or Enhanced Medical Management (EMM; defined as SMM plus individual drug counseling). Eligible participants entering Phase 2 were re-randomized to either EMM or SMM. POATS was developed to determine what benefit, if any, EMM offers over SMM in short-term and longer-term treatment paradigm. This paper describes the rationale and design of the study.

Conducting clinical research with prescription opioid dependence: defining the population.

Most treatment studies of opioid-dependent populations have focused predominantly on heroin users, despite a recent increase in those dependent upon prescription opioids. A key methodological challenge involved in studying the latter group involves defining the population. Specifically, researchers must decide whether to include (1) concurrent heroin users and (2) individuals with pain. The multi-site Prescription Opioid Addiction Treatment Study is examining treatments for this population. This paper describes various inclusion criteria considered by the study team related to heroin use and pain. The goal was to recruit a distinct but generalizable population of individuals dependent upon prescription opioids. (Am J Addict 2010;00:1-6).

Statistical benchmarks for process measures of quality of care for mental and substance use disorders.

OBJECTIVE: Benchmarks, representing the level of performance achieved by the best-performing providers, can be used to set achievable goals for improving care, but they have not heretofore been available for mental health care. This article describes the application of a method for developing statistical benchmarks for 12 process measures of quality of care for mental and substance use disorders. METHODS: Twelve quality measures--taken from a core measure set selected by a multistakeholder panel through a formal consensus process--were constructed from 1994-1995 administrative data on care received by Medicaid beneficiaries in six states. Conformance rates were calculated at the provider level and presented as means, 90th-percentile results, and statistical benchmarks. Sample sizes for each measure ranged from 356 to 4,494 providers and from 1,205 to 78,627 cases. Three measures involved antidepressant treatment, two involved antipsychotic treatment, and one involved mood stabilizers for bipolar disorder. Six other measures involved follow-up treatment visits. RESULTS: Benchmarks for provider-level performance ranged from 59.7 percent to 97.7 percent, markedly higher than the mean results, which ranged from 9.4 percent to 65.4 percent. Benchmark results varied widely-in contrast to results for these measures at the 90th percentile of providers and in contrast to performance standards that apply the same numerical goal across varied clinical processes. CONCLUSIONS: Statistical benchmarks can be applied to results from quality assessment of mental health care. Further research should examine whether incorporating benchmarks into quality improvement activities leads to better mental health care and substance-related care and improved outcomes.

Achieving consensus across diverse stakeholders on quality measures for mental healthcare.

OBJECTIVE: Quality-improvement efforts are hindered by a lack of consensus on meaningful and feasible measures of care. The objective of this study was to develop a core set of quality measures for mental health and substance-related care that are meaningful to stakeholders, feasible to implement, and broadly representative of diverse dimensions of the mental health system. METHOD: A 12-member panel of stakeholders from national organizations evaluated 116 process measures in a 2-stage modified Delphi consensus development process. Drawing on a conceptual framework and literature review, panelists rated each measure on 7 domains using a 9-point scale (1 = best). Measures were then mapped to a framework of system dimensions to identify a core set with the highest ratings for system characteristics within each dimension. RESULTS: Twenty-eight measures were identified assessing treatment (12), access (2), assessment (2), continuity (4), coordination (2), prevention (1), and safety (5). Overall, mean ratings for meaningfulness were: clinical importance 2.29; perceived gap between actual and optimal care 2.59; association between improved performance and outcome 2.61. For feasibility, mean ratings were clarity of specifications 3.39; acceptability of data collection burden 4.77; and adequacy of case mix adjustment 4.20. The measures address a range of treatment modalities, clinical settings, diagnostic categories, vulnerable populations, and other dimensions of mental healthcare. CONCLUSIONS: A structured consensus process identified a core set of quality measures that are meaningful and feasible to multiple stakeholders, as well as broadly representative of the mental healthcare system. By yielding quantitative assessments of meaningfulness, feasibility and degree of consensus among stakeholders, these results can inform ongoing national efforts to adopt common quality measures for mental healthcare.

Process measures for the assessment and improvement of quality of care for schizophrenia.

The development of process measures for the assessment and improvement of care for schizophrenia is at an early stage. As part of a national inventory of mental health quality measures, we identified 42 process measures developed to assess the quality of schizophrenia care. A greater proportion of measures assessed pharmacotherapy than assessed psychosocial interventions or other clinical processes, such as assessment, continuity, or coordination. Twenty-five measures (60%) were based on research evidence linking measure conformance with improved patient outcomes, while 17 (40%) were based on clinical consensus or opinion. Only 12 measures (29%) were fully operationalized. Few were tested for validity or reliability. A number of demonstration projects currently under way should expand the pool of well-developed and tested measures. Further research and consensus development will be needed to identify common measurement priorities, reduce the data collection burden, enhance the interpretability of results, and allow for comparisons of clinical practice across facilities and health care systems.