Stigma towards opioid use disorder in primary care remain a barrier to integrating software-based measurement based care.

BACKGROUND: Opioid use disorder (OUD) is a deadly illness that remains undertreated, despite effective pharmacological treatments. Barriers, such as stigma, treatment affordability, and a lack of training and prescribing within medical practices result in low access to treatment. Software-delivered measurement-based care (MBC) is one way to increase treatment access. MBC uses systematic patient symptom assessments to inform an algorithm to support clinicians at critical decision points. METHOD: Focus groups of faculty clinicians (N = 33) from 3 clinics were conducted to understand perceptions of OUD diagnosis and treatment and whether a computerized MBC model might assist with diagnosis and treatment. Themes from the transcribed focus groups were identified in two phases: (1) content analysis focused on uncovering general themes; and (2) systematic coding and interpretation of the data. RESULTS: Analysis revealed six major themes utilized to develop the coding terms: "distinguishing between chronic pain and OUD," "current practices with patients using prescribed or illicit opioids or other drugs," "attitudes and mindsets about providing screening or treatment for OUD in your practice," "perceived resources needed for treating OUD," "primary care physician role in patient care not specific to OUD," and "reactions to implementation of proposed clinical decision support tool." CONCLUSION: Results revealed that systemic and attitudinal barriers to screening, diagnosing, and treating OUD continue to persist. Providers tended to view the software-based MBC program favorably, indicating that it may be a solution to increasing accessibility to OUD treatment; however, further interventions to combat stigma would likely be needed prior to implementation of these programs. TRIAL REGISTRATION: ClinicalTrials.gov; NCT04059016; 16 August 2019; retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT04059016 .

A randomized control trial of a combined community health worker and re-entry intervention for people with HIV recently released from jail who use substances.

INTRODUCTION: People with human immunodeficiency virus (HIV; PWH) who use substances are disproportionately involved in the criminal justice system. While HIV viral suppression typically improves during incarceration, these gains are frequently lost after release. We evaluated the impact of a combined intervention (formerly incarcerated community health workers [CHW] plus a re-entry organization; CHW+) on postrelease HIV- and substance use-related outcomes. METHODS: We conducted a pilot randomized controlled trial of a CHW+ for PWH who use substances, within 30 days of release from a large southern, urban jail. Between February 2019 and August 2021, participants were recruited, enrolled, and randomized to treatment as usual (TAU; passive referral to care) or CHW+. Follow up study visits occurred at 3, 6, and 12 months. The primary outcome was HIV VL at 6 months; secondary outcomes included 6-month urinary toxicology and high-risk substance use at 12 months. RESULTS: A total of 31 participants were enrolled who were primarily male (n = 24; 77 %), Black (n = 22; 71 %), unemployed (n = 23; 74.2 %), had unstable housing (n = 18; 58 %), had food insecurity (n = 14; 45 %), and reported their drug of choice was stimulants (n = 24; 77 %). The study identified no significant difference in HIV VL suppression at 6 months (20 % v. 37 %; [CHW+ v. TAU], p = 0.61). We observed improved substance use outcomes in CHW+ v. TAU, including fewer positive urinary toxicology screens for stimulants (40 % v. 100 %; p = 0.01) and a trend toward less high-risk substance use (30 % v. 43 %). The CHW+ group met more basic needs, such as food security [+32 % v. +11 %], housing security [+52 % v. -7 %] and full-time employment [+20 % v. +5 %] compared to TAU. CONCLUSIONS: PWH who use substances assigned to a combined intervention of CHW+ after jail release did not achieve higher rates of HIV VL suppression than TAU; however, they had improved substance use outcomes and met more basic subsistence needs. Results highlight the potential of culturally informed interventions to address the competing needs of PWH who use substances after release from jail and call for further development of innovative solutions to successfully bridge to HIV care in the community.

Moderation of buprenorphine therapy for cocaine dependence efficacy by variation of the Prodynorphin gene.

PURPOSE: The aim of this secondary analysis was to identify prodynorphin (PDYN) genetic markers moderating the therapeutic response to treatment of cocaine dependence with buprenorphine/naloxone (Suboxone®; BUP). METHODS: Cocaine-dependent participants (N = 302) were randomly assigned to a platform of injectable, extended-release naltrexone (XR-NTX) and one of three daily medication arms: 4 mg BUP (BUP4), 16 mg BUP (BUP16), or placebo (PLB) for 8 weeks (Parent Trial Registration: Protocol ID: NIDA-CTN-0048, Clinical Trials.gov ID: NCT01402492). DNA was obtained from 277 participants. Treatment response was determined from weeks 3 to 7 over each 1-week period by the number of cocaine-positive urines per total possible urines. RESULTS: In the cross-ancestry group, the PLB group had more cocaine-positive urines than the BUP16 group (P = 0.0021). The interactions of genetic variant × treatment were observed in the rs1022563 A-allele carrier group where the BUP16 group (N = 35) had fewer cocaine-positive urines (P = 0.0006) than did the PLB group (N = 26) and in the rs1997794 A-allele carrier group where the BUP16 group (N = 49) had fewer cocaine-positive urines (P = 0.0003) than did the PLB group (N = 58). No difference was observed in the rs1022563 GG or rs1997794 GG genotype groups between the BUP16 and PLB groups. In the African American-ancestry subgroup, only the rs1022563 A-allele carrier group was associated with treatment response. CONCLUSION: These results suggest that PDYN variants may identify patients who are best suited to treatment with XR-NTX plus buprenorphine for cocaine use disorder pharmacotherapy.

Reaching nontreatment-seeking cannabis users: Testing an extended marijuana check-up intervention.

Some adult cannabis users report negative consequences of use but do not seek treatment. Nonjudgmental, brief interventions incorporating motivational interviewing techniques may be able to reach users who otherwise would not seek treatment and increase their motivation to change use. Previous studies have shown brief interventions with this population are efficacious in reducing use, but the absolute amount of change has not clearly translated into meaningful reductions in associated negative consequences. The current study used a marijuana check-up (MCU) model to attract nontreatment-seeking adults who used cannabis at levels that may have caused negative consequences. The study randomly assigned participants to 2-session (n = 93) and 6-session (n = 93) versions of the intervention and followed them for 12 months. The study designed the extended 6-session condition to build on the efficacy of the previously tested 2-session intervention. The study hypothesized that the opportunity to continue to consider the consequences of cannabis use would have the greatest impact on those who were in earlier stages of readiness for change. We used cognitive behavioral techniques to assist with change efforts when indicated. Results showed significant reductions in the frequency and daily duration of cannabis use at all follow-ups in both intervention conditions. The extended 6-session condition produced greater change only on a measure of the number of periods of the day in which cannabis was used. Reductions in dependence symptoms and problems related to cannabis use occurred in both conditions, but there was no effect of intervention condition. Participants who were less ready to make changes at the outset decreased use and negative consequences the least. Results suggested that some benefit of the extended session format of the check-up in reducing daily use, but the lack of a corresponding reduction in consequences suggested that the original 2-session MCU may be more cost effective.

Creation of an algorithm for clinical decision support for treatment of opioid use disorder with buprenorphine in primary care.

BACKGROUND: The treatment capacity for opioid use disorder (OUD) lags far behind the number of patients in need of treatment. Capacity is limited, in part, by the limited number of physicians who offer office based OUD treatment with buprenorphine. Measurement based care (MBC) has been proposed as a means to support primary care physicians in treating OUD. Here, we propose a set of measures and a clinical decision support algorithm to provide MBC for the treatment of OUD. METHODS: We utilized literature search and expert consensus to identify measures for universal screening and symptom tracking. We used expert consensus to create the clinical decision support algorithm. RESULTS: The Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) tool was selected as the best published measure for universal screening in primary care. No published measure was identified as appropriate for symptom tracking or medication adherence; therefore, we created the OUD Symptom Checklist from the DSM-5 criteria for OUD and the Patient Adherence Questionnaire for Opioid Use Disorder Treatment (PAQ-OUD) to assess medication adherence. We developed and present a clinical decision support algorithm to provide direct guidance regarding treatment interventions during the first 12 weeks of buprenorphine treatment. CONCLUSION: Creation of these tools is the necessary first step for implementation of MBC for the treatment of OUD with buprenorphine in primary care. Further work is needed to test the feasibility and acceptability of these tools. Trial Registration ClinicalTrials.gov; NCT04059016; 16 August 2019; retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT04059016.

Bupropion and Naltrexone in Methamphetamine Use Disorder.

BACKGROUND: The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied. METHODS: We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone-bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone-bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses. RESULTS: A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone-bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone-bupropion during the trial. CONCLUSIONS: Among adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo. (Funded by the National Institute on Drug Abuse and others; ADAPT-2 ClinicalTrials.gov number, NCT03078075.).

Treating cannabis use disorder: Exploring a treatment as needed model with 34-month follow-up.

Research has demonstrated that motivational enhancement (MET) and cognitive behavioral therapy (CBT) are some of the most effective interventions for adults with cannabis use disorder (CUD). As few as two sessions of combined MET and CBT has produced abstinence and reductions in cannabis use greater than delayed treatment controls. Despite their efficacy, outcomes in previous studies yielded abstinence rates from cannabis in the range of 20-30% at follow-ups of 6 to 12 months, and CUD remained a chronic condition for many. Additional models of providing treatment "as needed" (PRN), rather than as a single fixed-dose, are necessary to meet the different needs of adults with CUD and reengage those who do not respond to treatment initially or who relapse later. In the current study, 87 adults who met DSM-IV criteria for cannabis dependence were randomly assigned to receive either a fixed-dose of nine sessions of MET/CBT or to a PRN condition that provided a smaller initial dose of treatment, but allowed repeated access to treatment for 28 months. Cannabis use and associated problems were assessed every six months throughout a 34-month period. More than one-third of participants in the PRN condition accessed additional treatment episodes, but the total number of treatment sessions that participants utilized was comparable across conditions. Both treatments yielded significant reductions in cannabis use and associated problems at each follow-up. Contrary to hypotheses, the PRN condition did not yield better outcomes at the longer-term follow-ups. The fixed-dose condition produced greater rates of abstinence at the first follow-up, but otherwise there were no between group differences in outcomes. Future studies should test active approaches to reengaging participants with treatment when initial outcomes are less than optimal.

Identifying and responding to trial implementation challenges during multisite clinical trials.

INTRODUCTION: The National Drug Abuse Treatment Clinical Trials Network (CTN) was initiated by the National Institute on Drug Abuse (NIDA) in 2000 with the aim of improving substance use treatment and reducing the time between the discovery of effective treatments and their implementation into clinical practice. While initial trials were conducted almost exclusively in specialty addiction treatment settings, the CTN began evolving strategically in 2010 to conduct research in general medical settings, including healthcare systems, primary care settings, emergency departments, and pharmacies, to broaden impact. The advantages of a research network like the CTN is not only the collective content expertise that investigators contribute to the network, but the collective experience gained by conducting studies in the network and then applying those lessons to future studies. OBJECTIVE: To summarize trial implementation challenges encountered, and the process by which solutions were identified and implemented, within one of the last early-phase CTN Stage II behavioral intervention studies conducted in a specialty addiction treatment setting. METHOD AND RESULTS: We describe the implementation of the CTN-0037 STimulant Reduction Intervention using Dosed Exercise (STRIDE) trial. Issues encountered during study implementation are categorized into four major areas, described in terms useful to future study teams: 1) study team infrastructure challenges, 2) participant- and site- level challenges, 3) intervention-related challenges, and 4) longitudinal study design challenges. Potential consequences of identified problems and the solutions developed to manage these problems are discussed within the context of these four areas. We propose how to extend these implementation lessons and apply them in other healthcare settings to expand the CTN. CONCLUSIONS: Effective study management allows for flexible, collaborative solutions to expected and unexpected obstacles to study success. Implementation strategies derived from the first 15 to 20 years of CTN studies are a result of working with providers and participants, and the ongoing collaboration among CTN investigators and network staff. Timely identification and response to problems during study implementation are critical to the success of a trial, regardless of its design. We believe a collaborative approach to identifying and responding to study implementation challenges will increase the likelihood of successful adoption of relevant, efficacious interventions. As the CTN continues to expand, the wealth of successful trial implementation strategies developed during the first 20 years of the CTN need to be applied and adapted to studies in broader network settings, and considered in conjunction with more formalized implementation science processes that are currently available.

Acute and long-term cannabis use among stimulant users: Results from CTN-0037 Stimulant Reduction Intervention using Dosed Exercise (STRIDE) Randomized Control Trial.

AIMS: The aim of this study was to examine the impact of vigorous intensity, high dose exercise (DEI) on cannabis use among stimulant users compared to a health education intervention (HEI) using data from the Stimulant Reduction Intervention using Dosed Exercise, National Institute of Drug Abuse National Drug Treatment Clinical Trials Network Protocol Number 0037 (STRIDE). METHODS: Adults (N = 302) enrolled in the STRIDE randomized clinical trial were randomized to either the DEI or the HEI. Interventions included supervised sessions three times a week during the Acute phase (12 weeks) and once a week during the Follow-up phase (6 months). Cannabis use was measured at each assessment via Timeline Follow Back and urine drug screens. Cannabis use was compared between the groups during the Acute and Follow-up phases using both the intent-to-treat sample and a complier average causal effects (CACE) analysis. FINDINGS: Approximately 43% of the sample reported cannabis use at baseline. The difference in cannabis use between the DEI and HEI groups during the Acute phase was not significant. During the Follow-up phase, the days of cannabis use was significantly lower among those in the DEI group (1.20 days) compared to the HEI group (2.15 days; p = 0.04). CONCLUSIONS: For those who adhered to the exercise intervention, vigorous intensity, high dose exercise resulted in less cannabis use. Results suggest that there were no significant short-term differences in cannabis use between the groups. Further study on the long-term impact of exercise as a treatment to reduce cannabis use should be considered.

Clinical and Sociobehavioral Prediction Model of 30-Day Hospital Readmissions Among People With HIV and Substance Use Disorder: Beyond Electronic Health Record Data.

BACKGROUND: Under the Affordable Care Act, hospitals receive reduced reimbursements for excessive 30-day readmissions. However, the Centers for Medicare and Medicaid Services does not consider social and behavioral variables in expected readmission rate calculations, which may unfairly penalize systems caring for socially disadvantaged patients, including patients with HIV. SETTING: Randomized controlled trial of patient navigation with or without financial incentives in HIV-positive substance users recruited from the inpatient setting at 11 US hospitals. METHODS: External validation of an existing 30-day readmission prediction model, using variables available in the electronic health record (EHR-only model), in a new multicenter cohort of HIV-positive substance users was assessed by C-statistic and Hosmer-Lemeshow testing. A second model evaluated sociobehavioral factors in improving the prediction model (EHR-plus model) using multivariable regression and C-statistic with cross-validation. RESULTS: The mean age of the cohort was 44.1 years, and participants were predominantly males (67.4%), non-white (88.0%), and poor (62.8%, <$20,000/year). Overall, 17.5% individuals had a hospital readmission within 30 days of initial hospital discharge. The EHR-only model resulted in a C-statistic of 0.65 (95% confidence interval: 0.60 to 0.70). Inclusion of additional sociobehavioral variables, food insecurity and readiness for substance use treatment, in the EHR-plus model resulted in a C-statistic of 0.74 (0.71 after cross-validation, 95% confidence interval: 0.64 to 0.77). CONCLUSIONS: Incorporation of detailed social and behavioral variables substantially improved the performance of a 30-day readmission prediction model for hospitalized HIV-positive substance users. Our findings highlight the importance of social determinants in readmission risk and the need to ask about, adjust for, and address them.

Anxiety and anhedonia in depression: Associations with neuroticism and cognitive control.

BACKGROUND: Despite the fact that higher levels of anxiety and anhedonia in Major Depressive Disorder (MDD) are linked to poorer treatment outcomes, mechanisms contributing to these clinical presentations remain unclear. Neuroticism, impaired cognitive control, and blunted reward learning may be critical processes involved in MDD and may help to explain symptoms of anxiety and anhedonia. METHODS: Using baseline data from patients with early-onset MDD (N = 296) in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) trial, we conducted a path analysis to model relationships between neuroticism, cognitive control, and reward learning to levels of anxiety and anhedonia. RESULTS: Neuroticism was positively associated with both anhedonia (standardized coefficient = 0.26, p < .001) and anxiety (standardized coefficient = 0.40, p < .001). Cognitive control was negatively associated with anxiety (standardized coefficient = -0.18, p < .05). Reward learning was not significantly associated with either anxiety or anhedonia. LIMITATIONS: Extraneous variables not included in the model may have even more influence in explaining symptoms of anxiety and anhedonia. Restricted range in these variables may have attenuated some of the hypothesized relationships. Most important, because this was a cross-sectional analysis in a currently depressed sample, we cannot draw any causal conclusions without experimental and longitudinal data. CONCLUSIONS: These cross-sectional findings suggest that neuroticism may contribute to anxiety and anhedonia in patients with early onset and either chronic or recurrent MDD, while enhanced cognitive control may protect against anxiety.

Medication Adherence Monitoring Using Smartphone Video Dosing in an Open-label Pilot Study of Monthly Naltrexone Plus Once-daily Bupropion for Methamphetamine Use Disorder: Feasibility and Acceptability.

OBJECTIVES: This article describes how smartphones were used to monitor and encourage medication adherence in a pilot study evaluating the potential efficacy of a combination pharmacotherapy for methamphetamine use disorder. We examine the feasibility, utility, and acceptability of using smartphones to capture dosing videos from the perspectives of participants and staff. METHODS: The study was an 8-week, open-label evaluation of extended-release injectable naltrexone combined with once-daily oral extended-release bupropion (BRP, Welbutrin XL, 450 mg/day). Participants attended visits twice-weekly for observed BRP dosing, assessments, and medical management. BRP was dispensed once weekly for dosing on nonclinic days. Medication adherence was assessed objectively (by observation in the clinic and smartphone videos for dosing at home) and subjectively (self-reports of dosing). Surveys assessing the smartphone component were completed by participants and study staff. RESULTS: Participants (N = 49) reported taking 93.6% of the dispensed BRP doses while 86.6% of dispensed doses were confirmed via dosing video and in-person observations. Most participants who completed the survey agreed that the smartphone was easy to use (92.6%) and that taking the dosing videos helped to remember to take the study medication (80.5%). Staff agreed that the smartphone helped collect accurate dosing data for most (77.5%) participants. CONCLUSIONS: The use of smartphones for video-based oral medication dosing in this study provided a feasible and acceptable mechanism to encourage, monitor, and confirm medication adherence. Video-confirmed dosing adherence provides an objective numerical indicator of the lowest medication adherence rate participants achieve, allowing investigators to more confidently interpret results.

The Stimulant Selective Severity Assessment: A replication and exploratory extension of the Cocaine Selective Severity Assessment.

BACKGROUND: Cocaine and methamphetamine have similar withdrawal symptoms and many individuals concurrently use both substances; however, no measures concurrently assess withdrawal from multiple stimulants. OBJECTIVES: This study's aim was to explore the Stimulant Selective Severity Assessment (SSSA), a modified version of the Cocaine Selective Severity Assessment (CSSA), in a sample of stimulant users to determine if it can assess withdrawal symptoms in users of one or more stimulants. METHODS: Baseline data were analyzed from the STimulant Reduction Intervention using Dosed Exercise trial, a multisite randomized clinical trial that evaluated exercise versus health education on drug use outcomes in individuals with stimulant use disorders. Data were analyzed for internal consistency, construct validity, and scale dimensionality. RESULTS: Internal consistency for the full sample was good (α = 0.81; N = 302), with similar alphas in Cocaine (0.81; n = 177) and Cocaine/Other Stimulant (0.82; n = 92) groups, but with much lower alpha for the group without cocaine use (Other Stimulant, i.e., primarily methamphetamine, α = 0.66; n = 32). Support for construct validity was evidenced by significant positive correlations (r = 0.17 to 0.67) with measures of stimulant craving, depressive symptoms, and pain. Four factors were revealed. Conclusions/Importance: The Stimulant Selective Severity Assessment is a new measure that can be used to assess withdrawal symptoms in users of cocaine or cocaine plus methamphetamine, but it should not be administered to users of methamphetamine only.

Differences in pituitary-adrenal reactivity in Black and White men with and without alcohol use disorder.

BACKGROUND: Treatment-seeking men with alcohol use disorder (AUD) classically exhibit a blunted hypothalamic-pituitary-adrenal (HPA) axis response to pharmacologic and behavioral provocations during the early phases of abstinence from alcohol. Independent of alcohol, a significant muting of HPA axis reactivity is also observed among racial minority (e.g. Black) individuals. The effect of AUD upon the altered HPA axis response of racial minority individuals has not been explored. The current work represents a secondary analysis of race and AUD status among a sample of men. METHODS: Healthy male controls (17 White, 7 Black) and four-to six-week abstinent men with AUD (49 White, 13 Black) were administered a psychosocial stressor and two pharmacologic probes [ovine corticotropin releasing hormone (oCRH) and cosyntropin] to assess HPA axis reactivity. Plasma cortisol and adrenocorticotropin hormone (ACTH) were assessed at 10-20 min intervals prior to and following behavioral and pharmacological stimulation. Basal and net-integrated responses following provocations were analyzed to identify potential group differences. A measure of childhood adversity was also obtained to consider the implications of prior stressors upon HPA axis function. RESULTS: A three-fold increase in oCRH-induced ACTH was seen in Black men relative to White men regardless of AUD status. Adversity exerted a dampening effect on this pituitary sensitivity within Black controls only. Adjusted for adversity, a significant blunting effect of AUD status on ACTH reactivity was identified within White participants following oCRH. No group differences were present following cosyntropin administration. In response to the psychosocial stressor, White, but not Black, men with AUD experienced the expected blunting of cortisol reactivity relative to White controls. Rather, Black men with AUD exhibited greater cortisol reactivity relative to White men with AUD. CONCLUSIONS: Differences in HPA axis reactivity associated with race were present in men with and without AUD. Explanatory biological mechanisms of the relationship between alcohol use and/or stress, in both healthy and unhealthy populations, may require a reassessment in different racial populations.

A Complier Average Causal Effect Analysis of the Stimulant Reduction Intervention using Dosed Exercise Study.

OBJECTIVE: Exercise is a promising treatment for substance use disorders, yet an intention-to-treat analysis of a large, multi-site study found no reduction in stimulant use for exercise versus health education. Exercise adherence was sub-optimal; therefore, secondary post-hoc complier average causal effects (CACE) analysis was conducted to determine the potential effectiveness of adequately dosed exercise. METHOD: The STimulant use Reduction Intervention using Dosed Exercise study was a randomized controlled trial comparing a 12 kcal/kg/week (KKW) exercise dose versus a health education control conducted at nine residential substance use treatment settings across the U.S. that are affiliated with the National Drug Abuse Treatment Clinical Trials Network. Participants were sedentary but medically approved for exercise, used stimulants within 30 days prior to study entry, and received a DSM-IV stimulant abuse or dependence diagnosis within the past year. A CACE analysis adjusted to include only participants with a minimum threshold of adherence (at least 8.3 KKW) and using a negative-binomial hurdle model focused on 218 participants who were 36.2% female, mean age 39.4 years (SD =11.1), and averaged 13.0 (SD=9.2) stimulant use days in the 30 days before residential treatment. The outcome was days of stimulant use as assessed by the self-reported TimeLine Follow Back and urine drug screen results. RESULTS: The CACE-adjusted analysis found a significantly lower probability of relapse to stimulant use in the exercise group versus the health education group (41.0% vs. 55.7%, p<.01) and significantly lower days of stimulant use among those who relapsed (5.0 days vs. 9.9 days, p<.01). CONCLUSIONS: The CACE adjustment revealed significant, positive effects for exercise. Further research is warranted to develop strategies for exercise adherence that can ensure achievement of an exercise dose sufficient to produce a significant treatment effect.

A psychometric evaluation of the Concise Health Risk Tracking Self-Report (CHRT-SR)- a measure of suicidality-in patients with stimulant use disorder.

Stimulant use disorders are both common and associated with suicidal ideation and attempts. The psychometric properties of the 12-item Concise Health Risk Tracking Scale Self-Report (CHRT-SR), a measure that was created to assess suicidal thinking and several factors associated with a propensity to act, has been established in persons with mood disorders. This is a secondary analysis to assess the CHRT-SR in 302 stimulant abusing patients that had participated in a clinical trial. A confirmatory factor analysis (CFA) was conducted to assess the factor validity of the 12-item CHRT-SR model with a second-order Propensity factor. The CHRT-SR total score and 2 factor scores (Propensity and Suicidal Thoughts) demonstrated acceptable internal consistency and test-retest reliabilities. These two subscales and the total score were modestly but significantly associated with measures of depression and life satisfaction, demonstrating construct validity. Two additional items assessing Impulsivity were also analyzed, and demonstrated acceptable internal consistency, test-retest reliability, and construct validity. The CHRT-SR appears to be a reliable and valid tool to assess suicidality in persons with stimulant use disorder.

Psychometrics of the Self-Report Concise Associated Symptoms Tracking Scale (CAST-SR): Results From the STRIDE (CTN-0037) Study.

OBJECTIVE: The self-report Concise Associated Symptoms Tracking Scale (CAST-SR) was developed to track mania, irritability, anxiety, panic, and insomnia symptoms among depressed outpatients receiving antidepressant medication. Given the overlap between these domains, depression, and stimulant use disorders, we reexamined CAST-SR psychometrics in a novel sample: individuals with stimulant use disorder receiving aerobic exercise or health education interventions. METHODS: Using the subsample of stimulant-dependent (following DSM-IV criteria) individuals prescribed antidepressants (N = 124) from the multisite Stimulant Reduction Intervention Using Dosed Exercise (CTN-0037) trial (total sample N = 302), conducted July 2010 to February 2013, we analyzed CAST-SR data collected at the first assessment after participant's discharge from residential treatment. We also evaluated the convergent/discriminant validity of the CAST-SR with several self-report questionnaires. RESULTS: Confirmatory factor analysis revealed a 12-item measure composed of 4 factors: irritability, anxiety, panic, and insomnia. This factor structure loaded only in participants prescribed antidepressant medication, not in those who were not prescribed antidepressants. These results replicate the original CAST-SR factor structure, except for the mania factor, which failed to load. Internal consistency was high (α = 0.92 for total scale and α = 0.78-0.89 for the 4 factors), and convergent validity was established, especially for the insomnia and irritability factors, alongside the total score with depressive symptoms, insomnia, quality of life, suicide risk, and physical health measures. CONCLUSIONS: These results demonstrate the factor structure, reliability, and validity of the CAST-SR in a novel population of only individuals with stimulant use disorders receiving both exercise/health education interventions and antidepressant medication. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01141608.

Psychosocial relationship status and quality as predictors of exercise intervention adherence and substance use outcomes: Results from the STRIDE (CTN-0037) study.

Social/intimate relationship status and quality are associated with health-promoting behaviors, while living alone or being isolated are adversely associated with physical and mental health outcomes. Limited work has investigated how particular components of one's social environment - usual living arrangements, satisfaction with those arrangements, and global social and family discord - are related to substance use reduction and intervention adherence. We investigated these questions in 270 individuals receiving study intervention for stimulant abuse/dependence through the multi-site Stimulant Reduction Intervention using Dosed Exercise (CTN-0037) trial. Using mixed effects modeling, results indicated that individuals with baseline social discord used stimulants on more days throughout the intervention period than those without social discord (d=0.39). An interaction between gender, usual living arrangements, and satisfaction with those arrangements indicated that women who lived alone and were dissatisfied with that arrangement reported greater days of stimulant use compared to several other groups (d≥1.46). Finally, individuals who reported usually living with a non-partner over the past three years attended a greater percentage of intervention sessions compared to those usually living with a partner (d=0.34). These results identify sample subgroups with adverse stimulant use and intervention adherence outcomes and suggest areas for future inquiry/intervention.

Randomized Controlled Trial Comparing Exercise to Health Education for Stimulant Use Disorder: Results From the CTN-0037 STimulant Reduction Intervention Using Dosed Exercise (STRIDE) Study.

OBJECTIVE: To evaluate exercise as a treatment for stimulant use disorders. METHODS: The STimulant Reduction Intervention using Dosed Exercise (STRIDE) study was a randomized clinical trial conducted in 9 residential addiction treatment programs across the United States from July 2010 to February 2013. Of 497 adults referred to the study, 302 met all eligibility criteria, including DSM-IV criteria for stimulant abuse and/or dependence, and were randomized to either a dosed exercise intervention (Exercise) or a health education intervention (Health Education) control, both augmenting treatment as usual and conducted thrice weekly for 12 weeks. The primary outcome of percent stimulant abstinent days during study weeks 4 to 12 was estimated using a novel algorithm adjustment incorporating self-reported Timeline Followback (TLFB) stimulant use and urine drug screen (UDS) data. RESULTS: Mean percent of abstinent days based on TLFB was 90.8% (SD = 16.4%) for Exercise and 91.6% (SD = 14.7%) for Health Education participants. Percent of abstinent days using the eliminate contradiction (ELCON) algorithm was 75.6% (SD = 27.4%) for Exercise and 77.3% (SD = 25.1%) for Health Education. The primary intent-to-treat analysis, using a mixed model controlling for site and the ELCON algorithm, produced no treatment effect (P = .60). In post hoc analyses controlling for treatment adherence and baseline stimulant use, Exercise participants had a 4.8% higher abstinence rate (78.7%) compared to Health Education participants (73.9%) (P = .03, number needed to treat = 7.2). CONCLUSIONS: The primary analysis indicated no significant difference between exercise and health education. Adjustment for intervention adherence showed modestly but significantly higher percent of abstinent days in the exercise group, suggesting that exercise may improve outcomes for stimulant users who have better adherence to an exercise dose. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01141608.