Abuse Treatment Clinical Trials Network Research Articles

Empirically contrasting urine drug screening-based opioid use disorder treatment outcome definitions.

A lack of consensus on the optimal outcome measures to assess opioid use disorder (OUD) treatment efficacy and their precise definition and computation has hampered the pooling of research data for evidence synthesis and meta-analyses. This study aimed to empirically contrast multiple clinical trial definitions of treatment success by applying them to the same dataset. Data analysis used a suite of functions, developed as a software package for the R language, to operationalize 61 treatment outcome definitions based on urine drug screening (UDS) results. Outcome definitions were derived from clinical trials that are among the most influential in the OUD treatment field. Outcome functions were applied to a harmonized dataset from three large-scale National Drug Abuse Treatment Clinical Trials Network (CTN) studies, which tested various medication for OUD (MOUD) options (n = 2492). Hierarchical clustering was employed to empirically contrast outcome definitions. The optimal number of clusters identified was three. Cluster 1, comprising eight definitions focused on detecting opioid-positive UDS, did not include missing UDS in outcome calculations, potentially resulting in inflated rates of treatment success. Cluster 2, with the highest variability, included 10 definitions characterized by strict criteria for treatment success, relying heavily on UDS results from either a brief period or a single study visit. The 43 definitions in Cluster 3 represented a diverse range of outcomes, conceptualized as measuring abstinence, use reduction and relapse. These definitions potentially offer more balanced measures of treatment success or failure, as they avoid the extreme methodologies characteristic of Clusters 1 and 2. Clinical trials using urine drug screening (UDS) for objective substance use assessment in outcome definitions should consider (1) incorporating missing UDS data in outcome computation and (2) avoiding over-reliance on UDS data confined to a short time frame or the occurrence of a single positive urine test following a period of abstinence.

Research Priorities for Expansion of Opioid Use Disorder Treatment in the Community Pharmacy.

In the last decade, the U.S. opioid overdose crisis has magnified, particularly since the introduction of synthetic opioids, including fentanyl. Despite the benefits of medications for opioid use disorder (MOUD), only about a fifth of people with opioid use disorder (OUD) in the U.S. receive MOUD. The ubiquity of pharmacists, along with their extensive education and training, represents great potential for expansion of MOUD services, particularly in community pharmacies. The National Institute on Drug Abuse's National Drug Abuse Treatment Clinical Trials Network (NIDA CTN) convened a working group to develop a research agenda to expand OUD treatment in the community pharmacy sector to support improved access to MOUD and patient outcomes. Identified settings for research include independent and chain pharmacies and co-located pharmacies within primary care settings. Specific topics for research included adaptation of pharmacy infrastructure for clinical service provision, strategies for interprofessional collaboration including health service models, drug policy and regulation, pharmacist education about OUD and OUD treatment, including didactic, experiential, and interprofessional curricula, and educational interventions to reduce stigma towards this patient population. Together, expanding these research areas can bring effective MOUD to where it is most needed.

Lessons learned and future directions: A scoping review of American Indian and Alaska Native participants in the National Drug Abuse Treatment Clinical Trials Network

IntroductionAmerican Indian and Alaska Native (AI/AN) populations are disproportionately affected by substance use disorders (SUDs) and related health disparities in contrast to other ethnoracial groups in the United States. Over the past 20 years, substantial resources have been allocated to the National Institute on Drug Abuse Clinical Trials Network (CTN) to disseminate and implement effective SUD treatments in communities. However, we know little about how these resources have benefitted AI/AN peoples with SUD who arguably experience the greatest burden of SUDs. This review aims to determine lessons learned about AI/AN substance use and treatment outcomes in the CTN and the role of racism and Tribal identity. MethodWe conducted a scoping review informed by the Joanna Briggs framework and PRISMA Extension for Scoping Reviews checklist and explanation. The study team conducted the search strategy within the CTN Dissemination Library and nine additional databases for articles published between 2000 and 2021. The review included studies if they reported results for AI/AN participants. Two reviewers determined study eligibility. ResultsA systematic search yielded 13 empirical articles and six conceptual articles. Themes from the 13 empirical articles included: (1) Tribal Identity: Race, Culture, and Discrimination; (2) Treatment Engagement: Access and Retention; (3) Comorbid Conditions; (4) HIV/Risky Sexual Behaviors; and (5) Dissemination. The most salient theme was Tribal Identity: Race, Culture, and Discrimination, which was present in all articles that included a primary AI/AN sample (k = 8). Themes assessed but not identified for AI/AN peoples were Harm Reduction, Measurement Equivalence, Pharmacotherapy, and Substance Use Outcomes. The conceptual contributions used AI/AN CTN studies as exemplars of community-based and Tribal participatory research (CBPR/TPR). ConclusionCTN studies conducted with AI/AN communities demonstrate culturally congruent methods, including CBPR/TPR strategies; consideration/assessment of cultural identity, racism, and discrimination; and CBPR/TPR informed dissemination plans. Although important efforts are underway to increase AI/AN participation in the CTN, future research would benefit from strategies to increase participation of this population. Such strategies include reporting AI/AN subgroup data; addressing issues of cultural identity and experiences of racism; and adopting an overall effort for research aimed at understanding barriers to treatment access, engagement, utilization, retention, and outcomes for both treatment and research disparities for AI/AN populations.

High suicidality predicts overdose events among people with substance use disorder: A latent class analysis.

Suicide is the tenth leading cause of death in the United States and continues to be a major public health concern. Suicide risk is highly prevalent among individuals with co-occurring substance use disorders (SUD) and mental health disorders, making them more prone to adverse substance use related outcomes including overdose. Identifying individuals with SUD who are suicidal, and therefore potentially most at risk of overdose, is an important step to address the synergistic epidemics of suicides and overdose fatalities in the United States. The current study assesses whether patterns of suicidality endorsement can indicate risk for substance use and overdose. Latent class analysis (LCA) was used to assess patterns of item level responses to the Concise Health Risk Tracking Self-Report (CHRT-SR), which measures thoughts and feelings associated with suicidal propensity. We used data from 2,541 participants with SUD who were enrolled across 8 randomized clinical trials in the National Drug Abuse Treatment Clinical Trials Network from 2012 to 2021. Characteristics of individuals in each class were assessed, and multivariable logistic regression was performed to examine class membership as a predictor of overdose. LCA was also used to analyze predictors of substance use days. Three classes were identified and discussed: Class (1) Minimal Suicidality, with low probabilities of endorsing each CHRT-SR construct; Class (2) Moderate Suicidality, with high probabilities of endorsing pessimism, helplessness, and lack of social support, but minimal endorsement of despair or suicidal thoughts; and Class (3) High Suicidality with high probabilities of endorsing all constructs. Individuals in the High Suicidality class comprise the highest proportions of males, Black/African American individuals, and those with a psychiatric history and baseline depression, as compared with the other two classes. Regression analysis revealed that those in the High Suicidality class are more likely to overdose as compared to those in the Minimal Suicidality class (p = 0.04). Suicidality is an essential factor to consider when building strategies to screen, identify, and address individuals at risk for overdose. The integration of detailed suicide assessment and suicide risk reduction is a potential solution to help prevent suicide and overdose among people with SUD.

Exploring the performance of during-treatment substance use outcome measures in predicting longer-term psychosocial functioning and post-treatment abstinence

BackgroundThe selection of appropriate efficacy endpoints in clinical trials has been a long-standing challenge for the substance use disorder field. Using data from a large, multi-site National Drug Abuse Treatment Clinical Trials Network trial (CTN-0044; n=474), this secondary data analysis aimed to explore whether specific proximal (during-treatment) substance use outcome measures predict longer-term improvements in psychosocial functioning and post-treatment abstinence, and whether predictions vary depending on the specific substance (cannabis, cocaine/stimulants, opioids, and alcohol). MethodsGeneralized linear mixed models examined associations between six during-treatment substance use outcome measures and social functioning impairment (Social Adjustment Scale Self-Report) and severity of psychiatric symptoms (Brief Symptom Inventory-18) at end-of-treatment, and 3- and 6-months after treatment as well as post-treatment abstinence. ResultsMaximum days of consecutive abstinence, proportion of days abstinent, ≥3 weeks of continuous abstinence, and the proportion of urine specimens negative for the primary substance were associated with post-treatment psychiatric and social functioning improvement and abstinence. However, only the effects of abstinence during the last 4 weeks of the treatment period on all three post-treatment outcomes was stable over time and did not differ between primary substance groups. In contrast, complete abstinence during the 12-week treatment period was not consistently associated with functioning improvements. ConclusionsSubstance use outcome measures capturing the duration of primary substance abstinence during treatment are suitable predictors of post-treatment abstinence and longer-term psychosocial functioning improvement. Binary outcomes, such as end-of-treatment abstinence, may be particularly stable predictors and attractive given their ease of computation and straightforward clinical interpretability.

Repurposing ketamine to treat cocaine use disorder: integration of artificial intelligence-based prediction, expert evaluation, clinical corroboration and mechanism of action analyses.

Cocaine use disorder (CUD) is a significant public health issue for which there is no Food and Drug Administration (FDA) approved medication. Drug repurposing looks for new cost-effective uses of approved drugs. This study presents an integrated strategy to identify repurposed FDA-approved drugs for CUD treatment. Our drug repurposing strategy combines artificial intelligence (AI)-based drug prediction, expert panel review, clinical corroboration and mechanisms of action analysis being implemented in the National Drug Abuse Treatment Clinical Trials Network (CTN). Based on AI-based prediction and expert knowledge, ketamine was ranked as the top candidate for clinical corroboration via electronic health record (EHR) evaluation of CUD patient cohorts prescribed ketamine for anesthesia or depression compared with matched controls who received non-ketamine anesthesia or antidepressants/midazolam. Genetic and pathway enrichment analyses were performed to understand ketamine's potential mechanisms of action in the context of CUD. The study utilized TriNetX to access EHRs from more than 90 million patients world-wide. Genetic- and functional-level analyses used DisGeNet, Search Tool for Interactions of Chemicals and Kyoto Encyclopedia of Genes and Genomes databases. A total of 7742 CUD patients who received anesthesia (3871 ketamine-exposed and 3871 anesthetic-controlled) and 7910 CUD patients with depression (3955 ketamine-exposed and 3955 antidepressant-controlled) were identified after propensity score-matching. EHR analysis outcome was a CUD remission diagnosis within 1 year of drug prescription. Patients with CUD prescribed ketamine for anesthesia displayed a significantly higher rate of CUD remission compared with matched individuals prescribed other anesthetics [hazard ratio (HR) = 1.98, 95% confidence interval (CI) = 1.42-2.78]. Similarly, CUD patients prescribed ketamine for depression evidenced a significantly higher CUD remission ratio compared with matched patients prescribed antidepressants or midazolam (HR = 4.39, 95% CI = 2.89-6.68). The mechanism of action analysis revealed that ketamine directly targets multiple CUD-associated genes (BDNF, CNR1, DRD2, GABRA2, GABRB3, GAD1, OPRK1, OPRM1, SLC6A3, SLC6A4) and pathways implicated in neuroactive ligand-receptor interaction, cAMP signaling and cocaine abuse/dependence. Ketamine appears to be a potential repurposed drug for treatment of cocaine use disorder.

Suicidality as a Predictor of Overdose among Patients with Substance Use Disorders

Increasing rates of overdose and overdose deaths are a significant public health problem. Research has examined co-occurring mental health conditions, including suicidality, as a risk factor for intentional and unintentional overdose among individuals with substance use disorder (SUD). However, this research has been limited to single site studies of self-reported outcomes. The current research evaluated suicidality as a predictor of overdose events in 2541 participants who use substances enrolled across eight multi-site clinical trials completed within the National Drug Abuse Treatment Clinical Trials Network between 2012 to 2021. The trials assessed baseline suicidality with the Concise Health Risk Tracking Self-Report (CHRT-SR). Overdose events were determined by reports of adverse events, cause of death, or hospitalization due to substance overdose, and verified through a rigorous adjudication process. Multivariate logistic regression was performed to assess continuous CHRT-SR score as a predictor of overdose, controlling for covariates. CHRT-SR score was associated with overdose events (p = 0.03) during the trial; the likelihood of overdose increased as continuous CHRT score increased (OR 1.02). Participants with lifetime heroin use were more likely to overdose (OR 3.08). Response to the marked rise in overdose deaths should integrate suicide risk reduction as part of prevention strategies.

Repeated measures analysis of opioid use disorder treatment on clinical opiate withdrawal scale in a randomized clinical trial: sex differences

Purpose Sex differences may exist in opioid use disorder (OUD) treatment. This study examined the treatment effects of buprenorphine/naloxone (BUP/NX) and methadone (MET) on the Clinical Opiate Withdrawal Scale (COWS) score in individuals with OUD and tested whether the associations differ by sex. Method We performed a secondary analysis of the data from the National Drug Abuse Treatment Clinical Trials Network (CTN) protocol-0027. A total of 1269 participants (861 males and 408 females) being aged 18 or older with OUD were randomly assigned to receive BUP/NX (n = 740) or MET (n = 529). The paired t test was initially used to compare the COWS scores between pre-dose and post-dose for BUP/NX and MET treatments, separately. The linear mixed model was used to examine the changes in COWS score adjusted for baseline demographic, substance use, and mental health disorders. The interaction of sex and treatment was detected and stratified analysis by sex was conducted. Results The paired t test showed that both BUP/NX and MET treatments significantly reduced the COWS scores (p values <0.0001). BUP/NX revealed higher COWS scores than MET (p = 0.0008) and females demonstrated significantly higher COWS scores than males (p = 0.0169). Stratified by sex, BUP/NX compared with MET revealed higher COWS scores only in males (p = 0.0043), whereas baseline amphetamines use disorder and major depressive disorder were significantly associated with COWS scores in females (p = 0.0158 and 0.0422, respectively). Conclusions Both BUP/NX and MET are effective in decreasing opioid withdrawal symptoms via COWS scores, however, treatment plans for OUD by clinical providers should consider sex differences.

Under-representation of key demographic groups in opioid use disorder trials

BackgroundThe extent to which clinical trials of medications for opioid use disorder (MOUD) are representative or not is unknown. Some patient characteristics modify MOUD effectiveness; if these same characteristics differ in distribution between the trial population and usual-care population, this could contribute to lack of generalizability—a discrepancy between trial and usual-care effectiveness. Our objective was to identify interpretable, multidimensional subgroups who were prescribed MOUD in substance use treatment programs in the US but who were not represented or under-represented by clinical trial participants. MethodsThis was a secondary descriptive analysis of trial and real-world data. The trial data included twenty-seven US opioid treatment programs in the National Drug Abuse Treatment Clinical Trials Network, N=2,199 patients. The real-world data included US substance use treatment programs that receive public funding, N=740,015 patients. We characterized real-world patient populations who were non-represented and under-represented in the trial data in terms of sociodemographic and clinical characteristics that could modify MOUD effectiveness. ResultsWe found that 10.7% of MOUD patients in TEDS-A were not represented in the three clinical trials. As expected, pregnant MOUD patients (n=19,490) were not represented. Excluding pregnancy, education and marital status from the characteristics, 2.6% of MOUD patients were not represented. Patients aged 65 years and older (n=11,204), and those 50-64 years who identified as other (non-White, non-Black, and non-Hispanic) race/ethnicity or multi-racial (n=7,281) were under-represented. ConclusionsQuantifying and characterizing non- or under-represented subgroups in trials can provide the data necessary to improve representation in future trials and address research-to-practice gaps.

Graded response item response theory in scaling suicidal thoughts and behaviors among trauma-exposed women with substance use disorders.

Objective: The co-occurrence of substance use disorders (SUD) and trauma-exposure is a risk factor for suicidal thoughts and behaviors (STB). However, traditional methods of measurement for suicidal thoughts and behaviors are limited by an overreliance on dichotomous (i.e., yes or no) and averaged/summed scale score measurements. Further, among trauma-exposed individuals with SUD, it remains unclear which specific demographic factors, types of SUDs, and trauma sequelae (e.g., posttraumatic stress disorder [PTSD] symptom clusters) may be associated with elevated STB. The present study utilized item response theory to (a) generate empirically derived STB severity scores and, (b) examine which demographic factors, SUD diagnoses, and DSM-IV PTSD symptom clusters are associated with suicidality in a trauma-exposed sample with SUDs. Method: Female trauma-exposed participants with SUDs (N = 544) were recruited from community substance use treatment facilities in the National Drug Abuse Treatment Clinical Trials Network (CTN). Clinician-administered interviews assessed STB, SUDs, and PTSD symptoms. Results: Results indicated that the unidimensional item response theory (IRT) model used to estimate latent STB severity scores fit well, with strong local reliability at higher levels of latent STB severity. Regression predictors of elevated STB severity included younger age, opioid dependence, and higher PTSD reexperiencing symptoms. Conclusions: Clinicians are advised to screen for and target opioid use disorders and reexperiencing symptoms when addressing suicidal thoughts and behavior in trauma-exposed individuals with SUDs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The Feasibility and Utility of Harnessing Digital Health to Understand Clinical Trajectories in Medication Treatment for Opioid Use Disorder: D-TECT Study Design and Methodological Considerations.

IntroductionAcross the U.S., the prevalence of opioid use disorder (OUD) and the rates of opioid overdoses have risen precipitously in recent years. Several effective medications for OUD (MOUD) exist and have been shown to be life-saving. A large volume of research has identified a confluence of factors that predict attrition and continued substance use during substance use disorder treatment. However, much of this literature has examined a small set of potential moderators or mediators of outcomes in MOUD treatment and may lead to over-simplified accounts of treatment non-adherence. Digital health methodologies offer great promise for capturing intensive, longitudinal ecologically-valid data from individuals in MOUD treatment to extend our understanding of factors that impact treatment engagement and outcomes.MethodsThis paper describes the protocol (including the study design and methodological considerations) from a novel study supported by the National Drug Abuse Treatment Clinical Trials Network at the National Institute on Drug Abuse (NIDA). This study (D-TECT) primarily seeks to evaluate the feasibility of collecting ecological momentary assessment (EMA), smartphone and smartwatch sensor data, and social media data among patients in outpatient MOUD treatment. It secondarily seeks to examine the utility of EMA, digital sensing, and social media data (separately and compared to one another) in predicting MOUD treatment retention, opioid use events, and medication adherence [as captured in electronic health records (EHR) and EMA data]. To our knowledge, this is the first project to include all three sources of digitally derived data (EMA, digital sensing, and social media) in understanding the clinical trajectories of patients in MOUD treatment. These multiple data streams will allow us to understand the relative and combined utility of collecting digital data from these diverse data sources. The inclusion of EHR data allows us to focus on the utility of digital health data in predicting objectively measured clinical outcomes.DiscussionResults may be useful in elucidating novel relations between digital data sources and OUD treatment outcomes. It may also inform approaches to enhancing outcomes measurement in clinical trials by allowing for the assessment of dynamic interactions between individuals' daily lives and their MOUD treatment response.Clinical Trial RegistrationIdentifier: NCT04535583.

The opioid use disorder core outcomes set (OUD-COS) for treatment research: findings from a Delphi consensus study.

Background and AimThere is no gold‐standard and considerable heterogeneity in outcome measures used to evaluate treatments for opioid use disorder (OUD) along the opioid treatment cascade. The aim of this study was to develop the US National Institute on Drug Abuse (NIDA) National Drug Abuse Treatment Clinical Trials Network (CTN) opioid use disorder core outcomes set (OUD–COS).DesignFour‐round, e‐Delphi expert panel consensus study and plenary research group discussion and targeted consultation.SettingUnited States.ParticipantsA panel of 25 members including clinical practitioners, clinical researchers and administrative staff from the CTN, the network's affiliated clinical and community sites and the NIDA Centre for the CTN.MeasurementsFrom a pool of 24 candidate items in four domains (biomedical/disease status; behaviors, symptoms and functioning; opioid treatment cascade; and morbidity and mortality), the panel completed an on‐line questionnaire to rank items with defined specification on a 9‐point scale for importance, with a standard 70% consensus criterion.FindingsAfter the fourth round of the questionnaire and subsequent discussion, consensus was reached for five outcomes: two patient‐reported (global impression of improvement and incident non‐fatal overdose); one clinician‐reported (illicit/non‐medical drug toxicology); and two from administrative records (duration of treatment and fatal opioid poisoning).ConclusionsAn e‐Delphi consensus study has produced the US National Institute on Drug Abuse (NIDA) National Drug Abuse Treatment Clinical Trials Network opioid use disorder core outcomes set (version 1) for opioid use disorder treatment efficacy and effectiveness research.

Predictors of therapeutic alliance, treatment feedback, and clinical outcomes among African American women in treatment for co-occurring PTSD and SUD

IntroductionBlack women are at heightened risk for trauma exposure, post-traumatic stress disorder (PTSD), and substance use disorders (SUDs), compared to White women and the general population. However, disparities in treatment engagement and retention persist, particularly for Black women with co-occurring PTSD+SUD. Although therapeutic alliance is an important predictor and mediator of treatment retention and outcomes, we know little about predictors of alliance and the mediating role of alliance for PTSD+SUD outcomes among Black women. MethodsThis study utilized data previously collected for the National Drug Abuse Treatment Clinical Trials Network (CTN) Women and Trauma Study. Participants were 88 Black/African American women (Mage = 41.90, SD = 7.72) participating in a clinical trial comparing Seeking Safety (a cognitive-behavioral intervention for PTSD+SUD) to Women's Health Education (control). This study includes participants from both arms. Measures included the Helping Alliance Questionnaire, Addiction Severity Index-Lite, and Clinician Administered PTSD Scale. Women in the intervention arm also completed the Seeking Safety Feedback Questionnaire. ResultsStepwise, hierarchical linear regressions indicated that years of education and previous alcohol/drug treatment attempts significantly predicted early alliance in the second week of therapy (β = 0.411, p = .021 and β = 0.383, p = .011, respectively), but not late alliance in the last week of therapy (ps > .794). Greater education and more treatment attempts were associated with higher early alliance. Alliance did not mediate relationships between these significant predictors and treatment outcomes (e.g., attendance, post-treatment PTSD and SUD symptoms) or treatment feedback in the Seeking Safety group. ConclusionsEducation and prior treatment attempts predicted early alliance among Black/African American women in PTSD+SUD group treatment, and higher education level was associated with poorer Seeking Safety feedback topic ratings. Educational level and treatment history should be considered during alliance building in therapeutic interventions with Black women. Clinicians may consider the integration of pre-treatment alliance-building strategies with Black female patients who have lower levels of education. This study provides insight into the relative impact of several important factors that influence early alliance among Black women with co-occurring PTSD+SUD.

Concomitant Cannabis Misuse and Associations with Depression, Pain and Substance Misuse among Patients Prescribed Opioids.

Background: Cannabis use is common among individuals with pain who are prescribed opioids, occurring in approximately 10% of this population. This study aims to explore the relationship between non-medical cannabis use and other health risks among individuals filling opioids at community pharmacies. Methods: This study was an exploratory secondary data analysis of a National Drug Abuse Treatment Clinical Trials Network (CTN)-sponsored study, Validation of a Community Pharmacy-Based Prescription Drug Monitoring Program Risk Screening, examining the relationship between risky cannabis use and depressive symptoms, pain, overdose, and other substance misuse among individuals filling opioid prescriptions in community pharmacies (N = 1440). Results: Participants reporting moderate- to high-risk compared to low-risk cannabis use were more likely to report depressive symptoms (adjusted OR = 1.67, 95% CI = 1.11–2.56), history of overdose (adjusted OR = 2.15, 95% CI = 1.34–3.44), and moderate- to high-risk use of alcohol (adjusted OR = 2.10, 95% CI = 1.28–3.45), opioids (adjusted OR = 2.50, 95% CI = 1.67–3.76), sedatives (adjusted OR = 2.58, 95% CI = 1.72–3.86), stimulants (adjusted OR = 4.79, 95% CI = 2.83–8.01), and tobacco (adjusted OR = 3.60, 95% CI = 2.47–5.24). Conclusions: Community pharmacies may be valuable sites for identifying, studying, and intervening with substance use problems.

Reductions in tobacco use in naltrexone, relative to buprenorphine-maintained individuals with opioid use disorder: Secondary analysis from the National Drug Abuse Treatment Clinical Trials Network

BackgroundSmoking prevalence in individuals with opioid use disorder (OUD) is over 80%. Research suggests that opioid use significantly increases smoking, which could account for the strikingly low smoking-cessation rates observed in both methadone- and buprenorphine-maintained patients, even with the use of first-line smoking-cessation interventions. If opioids present a barrier to smoking-cessation, then better smoking outcomes should be observed in OUD patients treated with extended-release naltrexone (XR-NTX, an opioid antagonist) compared to those receiving buprenorphine (BUP-NX, a partial opioid agonist). MethodsThe current study is a secondary analysis of a 24-week, multi-site, open-label, randomized clinical trial conducted within the National Drug Abuse Treatment Clinical Trials Network comparing the effectiveness of XR-NTX vs. BUP-NX for adults with OUD. Longitudinal mixed effects models were used to determine if there was a significant reduction in cigarette use among daily smokers successfully inducted to treatment (n = 373) and a subset of those who completed treatment (n = 169). ResultsAmong daily smokers inducted onto OUD medication, those in the XR-NTX group smoked fewer cigarettes per day (M = 11.36, SE = 0.62) relative to smokers in the BUP-NX group (M = 13.33, SE = 0.58) across all study visits, (b (SE) = −1.97 (0.55), p < .01). Results were similar for the treatment completers. ConclusionsOUD patients treated with XR-NTX reduced cigarette use more than those treated with BUP-NX, suggesting that XR-NTX in combination with other smoking cessation interventions might be a better choice for OUD smokers interested in reducing their tobacco use.

Naturalistic follow-up after a trial of medications for opioid use disorder: Medication status, opioid use, and relapse

AimThis 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). DesignX: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. Setting and participantsAdults with opioid use disorder recruited from 8 community treatment programs across the United States. MeasurementsOutcomes 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. FindingsOf 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). ConclusionsNaturalistic 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.

Core outcomes set for research on the treatment of opioid use disorder (COS-OUD): the National Institute on Drug Abuse Clinical Trials Network protocol for an e-Delphi consensus study

BackgroundA lack of consensus on the optimal outcome measures to assess the efficacy and effectiveness of interventions for the treatment of opioid use disorder (OUD) has hampered the pooling of research data for evidence synthesis and clinical guidelines. A core outcome set (COS) is a minimum set of outcome measures that are recommended for all studies of a particular condition. The National Drug Abuse Treatment Clinical Trials Network (CTN) Core Outcome Set for OUD (COS-OUD) is a development study to identify core constructs, meaningful outcomes, and their optimal measurement for all efficacy and effectiveness studies of OUD treatment and service delivery.Methods/designOverseen by an expert workgroup, a modified, stepwise, e-Delphi methodology will be used to gain consensus among a panel of clinical practitioners and researchers involved in the treatment of OUD, who are members of the CTN. Sequential rounds of anonymous, online questionnaires will be used to identify, rate the importance of, and refine a core outcome set. A consensus threshold will be achieved if at least 70% of the panel rate the measure as critical for inclusion in the COS-OUD. Where consensus is not reached or there are suggestions for new measures, these will be brought forward to a further round of review prior to a consensus meeting. Products from this study will be communicated via peer-reviewed scientific journals and conferences.DiscussionThis initiative will develop a COS for OUD intervention trials, treatment studies, and service delivery and will support the pooling of research and clinical practice data and efforts to develop measurement-based care within the OUD treatment cascade.Trial registrationhttp://www.comet-initiative.org/Studies/Details/1579

Measurement nonequivalence of the Clinician-Administered PTSD Scale by race/ethnicity: Implications for quantifying posttraumatic stress disorder severity.

Research studies suggest racial/ethnic differences in posttraumatic stress disorder (PTSD) diagnosis and symptom severity. Few studies to date, however, have examined the extent to which these findings are due to differences in measurement properties of existing PTSD scales. This study examined measurement equivalence across race/ethnicity in the Clinician-Administered PTSD Scale (CAPS) by testing for differential item functioning (DIF) in the item response theory (IRT) framework. Participants were 506 trauma-exposed women (M = 39.41 years, SD = 8.94) who participated in the National Drug Abuse Treatment Clinical Trials Network Women and Trauma Study. PTSD severity score estimates were improved upon as part of IRT estimation incorporating symptom "weights" (i.e., factor loadings) and group-specific DIF. Six symptoms from the CAPS showed DIF, with the majority of differences in measurement driven by White/African American and White/Latina differences, particularly for (a) avoidance of thoughts and (b) a sense of foreshortened future. Despite both racial/ethnic minority groups being slightly (not significantly) more likely to receive a PTSD diagnosis, African Americans (p = .014; Cohen's d = -.22) and Latinas (p < .001; d = -.73) had significantly lower PTSD severity scores than Whites as estimated under IRT with group-specific DIF. Examination of PTSD severity scores based on symptom counts revealed these differences were either dampened (White/Latina difference d = -.39) or entirely negated (White/African American difference d = -.08). The findings suggest the importance of considering differences in symptom relevance across race/ethnicity and their impact on capturing symptom severity parallel to diagnostic criteria. Implications for clinical practice are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Patients' perspectives on initiating treatment with extended-release naltrexone (XR-NTX)

BackgroundThe National Drug Abuse Treatment Clinical Trials Network (CTN) multisite comparative-effectiveness study (“X:BOT”) by Lee et al. (2018) found that, once initiated, extended-release naltrexone (XR-NTX) is as similarly safe and effective as sublingual buprenorphine-naloxone (BUP-NX) for the treatment of opioid use disorder (OUD). However, the detoxification hurdle makes XR-NTX much more difficult to initiate than BUP-NX. This hurdle highlights the need to better understand how patients transition from active opioid use to XR-NTX treatment. ObjectiveTo explore patient-identified barriers and facilitators to initiating antagonist treatment (XR-NTX) within the context of an inpatient hospital setting and to reflect postdischarge experiences of those who did and did not initiate XR-NTX treatment. MethodWe used a convenience sampling strategy to identify study candidates, with the intention of recruiting approximately an equal number of medication-initiated and noninitiated patients. Study participants (N = 14) included 13 males and 1 female with OUD randomized to the XR-NTX arm of the X:BOT study at 1 of the 8 study sites. Seven participants in this sample initiated XR-NTX treatment, and seven did not. Each participant completed one semistructured qualitative interview. We analyzed transcripts using deductive and inductive approaches to conventional content analysis. ResultsAlthough the majority of participants viewed opioid blockade, once-monthly dosing, and no dependence or withdrawal as favorable attributes of XR-NTX, participant ambivalence and lack of familiarity with antagonist treatment were barriers to treatment initiation. The long duration of action and the perceived “commitment” to the medication (e.g., “At the time, a month sounded like a year”) compounded the patients' concerns and ambivalence. The majority of those who initiated XR-NTX described it as an effective treatment for OUD, with treatment satisfaction and sustained abstinence emerging as central themes among this population. Some participants who did not successfully initiate XR-NTX expressed regret and a willingness to try XR-NTX in the future. ConclusionAchieving full opioid detoxification is one, but not the only, barrier to initiating treatment with XR-NTX. Additional participant-identified barriers to XR-NTX initiation include fears and ambivalence regarding antagonist treatment. Once initiated, participants perceive XR-NTX to be an effective treatment for maintaining abstinence from opioids. XR-NTX appealed to participants due to the autonomy it affords with once-monthly dosing and no physical dependence.

Gender and racial/ethnic differences in physiologic responses in the Stimulant Reduction Intervention using Dosed Exercise Study

Exercise may be beneficial for individuals in substance use disorder (SUD) treatment given the higher rates of both medical and psychiatric comorbidity, namely mood and anxiety disorders, compared to the general population. Gender and/or racial/ethnic differences in health benefits and response to prescribed exercise have been reported and may have implications for designing exercise interventions in SUD programs. MethodData are from the National Drug Abuse Treatment Clinical Trials Network (NIDA/CTN) Stimulant Reduction Intervention using Dosed Exercise (STRIDE) trial. Gender differences across racial/ethnic groups in physiological responses and stimulant withdrawal severity across time were analyzed using linear mixed effects models. ResultsMales completed significantly more exercise sessions than females and were more adherent to the prescribed exercise dose of 12 Kcal/Kg/Week. Controlling for age, race/ethnicity, treatment group and stimulant withdrawal severity, there was a significant gender by time interaction for body mass index (BMI) (p < 0.001), waist circumference (p < 0.001) and heart rate measured prior to exercise sessions (p < 0.01). For females, body mass index (BMI) and waist circumference increased over time while for males BMI and waist circumference stayed unchanged or slightly decreased with time. Heart rate over time significantly increased for females at a higher rate than in males. Stimulant withdrawal severity was similar in males and females at baseline but males exhibited a significant decrease over time while females did not.Although baseline differences were observed, there were no time by race/ethnicity differences in physiologic responses. DiscussionGender differences in response to exercise may have implications for developing gender specific exercise interventions in SUD programs.