Faculty Bibliography

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.

BACKGROUND:The number of opioid-involved overdose deaths in the United States remains a national crisis. The HEALing Communities Study (HCS) will test whether Communities That HEAL (CTH), a community-engaged intervention, can decrease opioid-involved deaths in intervention communities (n = 33), relative to wait-list communities (n = 34), from four states. The CTH intervention seeks to facilitate widespread implementation of three evidence-based practices (EBPs) with the potential to reduce opioid-involved overdose fatalities: overdose education and naloxone distribution (OEND), effective delivery of medication for opioid use disorder (MOUD), and safer opioid analgesic prescribing. A key challenge was delineating an EBP implementation approach useful for all HCS communities. METHODS:A workgroup composed of EBP experts from HCS research sites used literature reviews and expert consensus to: 1) compile strategies and associated resources for implementing EBPs primarily targeting individuals 18 and older; and 2) determine allowable community flexibility in EBP implementation. The workgroup developed the Opioid-overdose Reduction Continuum of Care Approach (ORCCA) to organize EBP strategies and resources to facilitate EBP implementation. CONCLUSIONS:The ORCCA includes required and recommended EBP strategies, priority populations, and community settings. Each EBP has a "menu" of strategies from which communities can select and implement with a minimum of five strategies required: one for OEND, three for MOUD, and one for prescription opioid safety. Identification and engagement of high-risk populations in OEND and MOUD is an ORCCArequirement. To ensure CTH has community-wide impact, implementation of at least one EBP strategy is required in healthcare, behavioral health, and criminal justice settings, with communities identifying particular organizations to engage in HCS-facilitated EBP implementation.

The health care field has integrated advances into digital technology at an accelerating pace to improve health behavior, health care delivery, and cost-effectiveness of care. The realm of behavioral science has embraced this evolution of digital health, allowing for an exciting roadmap for advancing care by addressing the many challenges to the field via technological innovations. Digital therapeutics offer the potential to extend the reach of effective interventions at reduced cost and patient burden and to increase the potency of existing interventions. Intervention models have included the use of digital tools as supplements to standard care models, as tools that can replace a portion of treatment as usual, or as stand-alone tools accessed outside of care settings or direct to the consumer. To advance the potential public health impact of this promising line of research, multiple areas warrant further development and investigation. The Center for Technology and Behavioral Health (CTBH), a P30 Center of Excellence supported by the National Institute on Drug Abuse at the National Institutes of Health, is an interdisciplinary research center at Dartmouth College focused on the goal of harnessing existing and emerging technologies to effectively develop and deliver evidence-based interventions for substance use and co-occurring disorders. The CTBH launched a series of workshops to encourage and expand multidisciplinary collaborations among Dartmouth scientists and international CTBH affiliates engaged in research related to digital technology and behavioral health (eg, addiction science, behavioral health intervention, technology development, computer science and engineering, digital security, health economics, and implementation science). This paper summarizes a workshop conducted on the Development and Evaluation of Digital Therapeutics for Behavior Change, which addressed (1) principles of behavior change, (2) methods of identifying and testing the underlying mechanisms of behavior change, (3) conceptual frameworks for optimizing applications for mental health and addictive behavior, and (4) the diversity of experimental methods and designs that are essential to the successful development and testing of digital therapeutics. Examples were presented of ongoing CTBH projects focused on identifying and improving the measurement of health behavior change mechanisms and the development and evaluation of digital therapeutics. In summary, the workshop showcased the myriad research targets that will be instrumental in promoting and accelerating progress in the field of digital health and health behavior change and illustrated how the CTBH provides a model of multidisciplinary leadership and collaboration that can facilitate innovative, science-based efforts to address the health behavior challenges afflicting our communities.

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.

The United States is facing both the coronavirus disease 2019 (COVID-19) pandemic and an ongoing epidemic of opioid overdose. Opioid use disorder is associated with other mental health problems, trauma, and social and health disparities. While the United States has acted to improve access to treatment for mental health and opioid use, research will be needed to understand the effectiveness of new policies in the context of COVID-19. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Preclinical data indicate that selective kappa opioid receptor antagonists reduce nicotine self-administration and withdrawal symptoms. The aim of the current study was to determine whether treatment with CERC-501, an orally available, potent, and selective kappa opioid receptor antagonist, could alleviate nicotine withdrawal and craving and mitigate mood alterations associated with nicotine withdrawal in humans. Healthy, adult cigarette smokers were enrolled into this randomized, multisite, double-blind, placebo-controlled, crossover study. Participants completed two 8-day treatment phases during which they received either CERC-501 (15 mg, p.o., once daily) or placebo. On the seventh day of each dosing phase, participants were admitted as inpatients for an 18-hour cigarette abstinence period followed by experimental testing. The primary outcome measures were (a) performance on the McKee Smoking Lapse test (ie, latency to smoke in exchange for money) and (b) number of cigarettes self-administered during a 60-minute ad lib smoking period. Other outcomes included measures of craving, mood, anxiety, nicotine withdrawal, and subjective effects of cigarette smoking. A total of 71 participants who smoked an average of approximately 23 cigarettes per day were enrolled, and 56 subjects completed the study. CERC-501 was well tolerated, but it did not significantly alter the latency to start smoking (CERC-501: 16.5 min vs placebo: 17.7 min) or the number of cigarettes smoked (CERC-501: 3.3 cigarettes vs placebo: 3.1 cigarettes). Compared with placebo, CERC-501 also did not affect cigarette craving, mood, anxiety, nicotine withdrawal, or subjective effects of smoking. These findings do not support a role for CERC-501 in the treatment of nicotine use disorder.

BACKGROUND:Extended-release (XR) naltrexone can prevent relapse to opioid use disorder following detoxification. However, one of the barriers to initiating XR-naltrexone is the recommendation for a 7-10-day period of abstinence from opioids prior to the first dose. OBJECTIVES:The current study evaluated the feasibility of an XR-naltrexone induction protocol that can be implemented over 1 week in the outpatient clinic. METHODS:Participants (N = 44) were seen in the clinic daily. On Day 1, after abstaining from opioids for at least 12 h, they received buprenorphine 6-8 mg. Adjunctive medications (clonidine, clonazepam, zolpidem, trazodone, and prochlorperazine) were dispensed on Days 2-5, while ascending oral doses of naltrexone were given on Days 3-5 starting with 1 mg dose. An injection of XR-naltrexone was given on Day 5, 1 h after receiving and tolerating naltrexone 24 mg. RESULTS:Of the 44 participants (38 males), 35 (80%) were heroin users and 9 (20%) used prescription opioids. A total of 26 participants (59%) completed the induction and received their first injection of XR-naltrexone. XR-naltrexone was initiated in 54% (19/35) of heroin users and 78% (7/9) of prescription opioid users. CONCLUSION:The results support the feasibility of a week-long outpatient induction onto XR-naltrexone with ascending doses of naltrexone and standing doses of adjunctive medications. By circumventing the need for a protracted period of abstinence and mitigating the severity of withdrawal symptoms experienced during naltrexone titration, this strategy has the potential to increase patient acceptability and access to relapse prevention treatment with XR-naltrexone.

BACKGROUND:The distinct pharmacological properties and clinical uses of extended-release naltrexone (XR-NTX) and sublingual buprenorphine-naloxone (BUP-NX) present challenges in analyzing patient outcomes. METHODS:We conducted a secondary analysis of a multi-site randomized trial comparing XR-NTX with sublingual BUP-NX treatment for opioid use disorder initiated during inpatient detoxification and continued in outpatient treatment. Urine testing data for non-study opioids from the last 22 weeks of the 24-week trial were analyzed in both a per-protocol sample (n = 474 participants who received at least one dose of medication) and a completers sample (n = 211 participants who received all XR-NTX doses or all BUP-NX prescriptions). The present analyses sought to identify differences in the weekly percentages of opioid-positive urine tests between participants treated with the two medications. RESULTS:The proportion of opioid-positive tests in both conditions was less than 20 % for 21 of the 22 weeks in the per-protocol sample and all 22 weeks in the completers sample. Generalized linear mixed model analyses revealed a significant treatment (XR-NTX vs. BUP-NX) X week (weeks 3-24) interaction in the per-protocol sample but not the completers sample. In the per-protocol analysis, the BUP-NX, compared to XR-NTX, had significantly greater proportions of opioid-positive tests in 14 out of the 22 weeks. CONCLUSIONS:Longitudinal modeling approaches that utilize flexible procedures for handling missing data can offer a different perspective on study findings. Results from the present analyses suggest that XR-NTX appeared to be somewhat more effective than BUP-NX in reducing illicit opioid use in the per-protocol sample.