Secondary Analysis of Agreement Between Negative Timeline Follow Back Report and Negative Urine Toxicology in a Large Trial of Individuals with Opioid Use Disorder.

OBJECTIVES: Timeline follow-back (TLFB) is a self-report measure commonly used as a method of assessing historical drug use in both clinical and research settings. Our study considered rates of agreement between TLFB and an objective biological assay of opioid use. METHODS: We calculated the rates of agreement between negative report of opioid use for the most recent 8 days on TLFB and urine toxicology (UTOX) results in a large multisite opioid use disorder treatment trial. RESULTS: In total, 3986 assessments were provided by trial participants with both UTOX and TLFB during weeks 1 to 12, 2716 during weeks 13 to 24, and 325 at week 28. Rates of disagreement between negative TLFB and positive opioid UTOX were 2.33% of all assessments (21.68% of those with positive UTOX) over weeks 1 to 12, 2.06% of all assessment (25.00% of those with positive UTOX) over weeks 13 to 24, and 9.85% of all assessments (26.02% of those with positive UTOX) at week 28. CONCLUSIONS: Negative TLFB seems to be generally associated with negative results on urine toxicology.

Cardiovascular variability, sociodemographics, and biomarkers of disease: the MIDUS study.

Introduction: Like heart rate, blood pressure (BP) is not steady but varies over intervals as long as months to as short as consecutive cardiac cycles. This blood pressure variability (BPV) consists of regularly occurring oscillations as well as less well-organized changes and typically is computed as the standard deviation of multiple clinic visit-to-visit (VVV-BP) measures or from 24-h ambulatory BP recordings (ABPV). BP also varies on a beat-to-beat basis, quantified by methods that parse variation into discrete bins, e.g., low frequency (0.04-0.15 Hz, LF). However, beat-to-beat BPV requires continuous recordings that are not easily acquired. As a result, we know little about the relationship between LF-BPV and basic sociodemographic characteristics such as age, sex, and race and clinical conditions. Methods: We computed LF-BPV during an 11-min resting period in 2,118 participants in the Midlife in the US (MIDUS) study. Results: LF-BPV was negatively associated with age, greater in men than women, and unrelated to race or socioeconomic status. It was greater in participants with hypertension but unrelated to hyperlipidemia, hypertriglyceridemia, diabetes, elevated CRP, or obesity. LF-diastolic BPV (DBPV), but not-systolic BPV (SBPV), was negatively correlated with IL-6 and s-ICAM and positively correlated with urinary epinephrine and cortisol. Finally, LF-DBPV was negatively associated with mortality, an effect was rendered nonsignificant by adjustment by age but not other sociodemographic characteristics. Discussion: These findings, the first from a large, national sample, suggest that LF-BPV differs significantly from VVV-BP and ABPV. Confirming its relationship to sociodemographic risk factors and clinical outcomes requires further study with large and representative samples.

Homelessness and Treatment Outcomes Among Black Adults With Opioid Use Disorder: A Secondary Analysis of X:BOT.

OBJECTIVE: We sought to identify the sociodemographic and clinical characteristics associated with homelessnesss, and explore the relationship between homelessnesss and treatment outcomes among Black individuals. METHODS: This is a secondary analysis of the subgroup of Black participants (n = 73) enrolled in "X:BOT," a 24-week multisite randomized clinical trial comparing the effectiveness of extended-release naltrexone versus sublingual buprenorphine-naloxone (n = 570). Outcomes included medication initiation, return to extramedical use of opioids assessed by both self-report and urine toxicology, and engagement in medications for opioid use disorder (MOUD) treatment at 28 weeks postrandomization. Descriptive statistics were performed. RESULTS: Black participants were mostly unmarried and male, and about a third were aged 21-30 years. Among people experiencing homelessnesss, more were uninsured (45.5% [10/22] vs 19.6% [10/51]), unemployed (77.3% [17/22] vs 64.7% [33/51]), and reported alcohol (40.9% [9/22] vs 23.5% [12/51]) and sedative use (54.5% [12/22] vs 17.6% [9/51]) within the previous 30 days. Compared with housed Black individuals, a slightly higher proportion of Black individuals experiencing homelessnesss successfully initiated study medication (81.1% [18/22] vs 72.6% [37/51]); similar proportions returned to opioid use during the trial (68.2% [15/22] vs 68.6% [35/51]) and were engaged in MOUD at 28 weeks after trial entry (72.2% [13/18] vs 69.7% [23/33]) among participants located for follow-up. CONCLUSIONS: These descriptive results among Black patients participating in a trial of MOUD suggest that efficacious MOUD is possible despite homelessnesss with additional clinical supports such as those provided by a clinical trial.

Prediction Tool for Individual Outcome Trajectories Across the Next Year in First-Episode Psychosis in Coordinated Specialty Care.

Importance: In coordinated specialty care (CSC) settings for people with a first episode of psychosis, the development of reliable, validated individual-level prediction tools for key outcomes may be informative for shared clinician and client decision-making. Objective: To develop an individual-level prediction tool using machine-learning methods that predicts a trajectory of education/work status or psychiatric hospitalization outcomes over a client's next year of quarterly follow-up assessments. Additionally, to visualize these predictions in a way that is informative to clinicians and clients. Design, Setting, and Participants: Individual-level data were collected for all patients enrolled in the OnTrackNY program at enrollment and at quarterly follow-ups using standardized forms. The OnTrackNY program, a network of CSC sites in New York State, provides person-centered, recovery-oriented, and evidence-based psychosocial and pharmaceutical interventions to individuals aged 16 to 30 years with recent-onset (<2 years) nonaffective psychosis. Although data collection is ongoing, data for this study were collected from October 2013 to December 2018, and the time frame for analysis was July 2020 to May 2021. Data were separated into a training/cross-validation set to perform internally validated model development and a separate holdout test set (~20% of the sample) for external validation. Random probability forest models were developed to predict individual-level trajectories of outcomes. Exposures: Forty-three individual-level demographic and clinical features collected at enrollment in OnTrackNY, 25 of which were time-varying and updated at quarterly follow-up assessments, and 13 site-level demographic and economic census variables. Main Outcomes and Measures: Individual-level education and/or employment status and psychiatric hospitalization trajectories at quarterly follow-up periods across the first 2 years of CSC. Results: The total study sample consists of 1298 individuals aged 16 to 30 years and included 341 women (26.3%), 949 men (73.1%), and 8 (<1%) with another gender. Prediction models performed well for 1-year trajectories of education/work across all validation sets, with areas under the receiver operating characteristic curve (AUCs) ranging from 0.68 (95% CI, 0.63-0.74) to 0.88 (95% CI, 0.81-0.96). Predictive accuracy for psychiatric hospitalization 3 months ahead reached AUC above 0.70; moreover, predictions of future psychiatric hospitalizations at 6 months and beyond were consistently poor, with AUCs below 0.60. Given the good externally validated performance for predicting education/work, a prototype interactive visualization tool displaying individual-level education/work trajectories and related features was developed. Conclusions and Relevance: This study suggests that accurate prediction tools can be developed for outcomes in people with first-episode psychosis, which may help inform shared clinician/client decision-making. Future work should study the effectiveness of its deployment, including proper communication to inform shared clinician/client decision-making in the context of a learning health care system. At present, more work is needed to develop better performing prediction models for future psychiatric hospitalizations before any tool is recommended for this outcome.

Prevalance and course of tobacco use among individuals receiving coordinated specialty care for first-episode psychosis.

AIM: Tobacco use is decreasing among the general population, but persistent use among individuals in treatment for first-episode psychosis (FEP) remains a problem. This study aimed to measure the prevalence and course of tobacco use and explore the associations between tobacco use and clinical outcomes in a FEP sample located in New York State (NYS). METHODS: Participants (N = 870) were from the OnTrackNY system of coordinated specialty care clinics in NYS. Participant data were collected at admission to the program and at every 3 months of follow-up using standardized forms based on reports from clients, client families and chart review. Course of tobacco use was categorized into four groups: no-use, cessation, persistent and initiation over 1 year of follow-up. RESULTS: The prevalence of tobacco use was 12.8% at baseline and 19.9% at 1-year follow-up. Only 3.8% of tobacco users stopped by 1 year follow-up, and 4.9% initiated use. Urbanicity of clinic location (p < .001); age at admission (p = .044); gender (p = .015); ethnoracial group (p = .007); baseline education/employment status (p = .004); and baseline use of any non-tobacco substances (p < .001), including alcohol (p < .001) and cannabis (p < .001), were associated with tobacco course. Findings suggest an association between tobacco use and reduced improvement in symptoms. CONCLUSION: Despite a lower prevalence of tobacco use among OnTrack participants than in other comparable samples, tobacco cessation was minimal and more individuals initiated tobacco use than ceased over the course of follow-up. Efforts to implement tobacco cessation interventions in coordinated specialty care are warranted, since tobacco use is associated with poor health outcomes.

Patient Characteristics Associated with Opioid Abstinence after Participation in a Trial of Buprenorphine versus Injectable Naltrexone.

Background and Objectives: Better understanding of predictors of opioid abstinence among patients with opioid use disorder (OUD) may help to inform interventions and personalize treatment plans. This analysis examined patient characteristics associated with opioid abstinence in the X:BOT (Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment) trial. Methods: This post-hoc analysis examined factors associated with past-month opioid abstinence at the 36-week follow-up visit among participants in the X:BOT study. 428 participants (75% of original sample) attended the visit at 36 weeks. Logistic regression models were used to estimate the probability of opioid abstinence across various baseline sociodemographics, clinical characteristics, and treatment variables. Results: Of the 428 participants, 143 (33%) reported abstinence from non-prescribed opioids at the 36-week follow-up. Participants were more likely to be opioid abstinent if randomized to XR-NTX (compared to BUP-NX), were on XR-NTX at week 36 (compared to those off OUD pharmacotherapy), successfully inducted onto either study medication, had longer time on study medication, reported a greater number of abstinent weeks, or had longer time to relapse during the 24-week treatment trial. Participants were less likely to be abstinent if Hispanic, had a severe baseline Hamilton Depression Rating (HAM-D) score, or had baseline sedative use. Conclusions: A substantial proportion of participants was available at follow-up (75%), was on OUD pharmacotherapy (53%), and reported past-month opioid abstinence (33%) at 36 weeks. A minority of patients off medication for OUD reported abstinence and additional research is needed exploring patient characteristics that may be associated with successful treatment outcomes.

Diagnosing Prescription Opioid Use Disorder in Patients Using Prescribed Opioids for Chronic Pain.

OBJECTIVE: The diagnostic criteria for opioid use disorder, originally developed for heroin, did not anticipate the surge in prescription opioid use and the resulting complexities in diagnosing prescription opioid use disorder (POUD), including differentiation of pain relief (therapeutic intent) from more common drug use motives, such as to get high or to cope with negative affect. The authors examined the validity of the Psychiatric Research Interview for Substance and Mental Disorders, DSM-5 opioid version, an instrument designed to make this differentiation. METHODS: Patients (N=606) from pain clinics and inpatient substance treatment who ever received a ≥30-day opioid prescription for chronic pain were evaluated for DSM-5 POUD (i.e., withdrawal and tolerance were not considered positive if patients used opioids only as prescribed, per DSM-5 guidelines) and pain-adjusted POUD (behavioral/subjective criteria were not considered positive if pain relief [therapeutic intent] was the sole motive). Bivariate correlated-outcome regression models indicated associations of 10 validators with DSM-5 and pain-adjusted POUD measures, using mean ratios for dimensional measures and odds ratios for binary measures. RESULTS: The prevalences of DSM-5 and pain-adjusted POUD, respectively, were 44.4% and 30.4% at the ≥2-criteria threshold and 29.5% and 25.3% at the ≥4-criteria threshold. Pain adjustment had little effect on prevalence among substance treatment patients but resulted in substantially lower prevalence among pain treatment patients. All validators had significantly stronger associations with pain-adjusted than with DSM-5 dimensional POUD measures (ratios of mean ratios, 1.22-2.31). For most validators, pain-adjusted binary POUD had larger odds ratios than DSM-5 measures. CONCLUSIONS: Adapting POUD measures for pain relief (therapeutic intent) improved validity. Studies should investigate the clinical utility of differentiating between therapeutic and nontherapeutic intent in evaluating POUD diagnostic criteria.

An Intersectional Approach to Ethnoracial Disparities in Pathways to Care Among Individuals With Psychosis in Coordinated Specialty Care.

Importance: Intersecting factors of social position including ethnoracial background may provide meaningful ways to understand disparities in pathways to care for people with a first episode of psychosis. Objective: To examine differences in pathways to care by ethnoracial groups and by empirically derived clusters combining multiple factors of social and clinical context in an ethnoracially diverse multisite early-intervention service program for first-episode psychosis. Design, Setting, and Participants: This cohort study used data collected on individuals with recent-onset psychosis (<2 years) by clinicians with standardized forms from October 2013 to January 2020 from a network of 21 coordinated specialty care (CSC) programs in New York State providing recovery-oriented, evidence-based psychosocial interventions and medications to young people experiencing early psychosis. Exposures: Ethnoracial group and other factors of social position (eg, insurance status, living situation, English fluency, geographic region) intersecting with first-contact experiences (ie, type of first service, referral source, and symptoms at referral). Main Outcomes and Measures: Outcome measures were time from onset to first contact, first contact to CSC, and onset to CSC. Results: The total study sample consists of 1726 individuals aged 16 to 30 years and included 452 women (26%), 1263 men (73%), and 11 (<1%) with another gender enrolled in the network of CSC programs. The total sample consisted of 153 Asian (9%), 599 Black (35%), 454 Latinx (26%), and 417 White individuals (24%). White individuals had a significantly shorter time from onset to first contact (median [IQR], 17 [0-80] days) than Asian (median [IQR], 34 [7-94] days) and Black (median [IQR], 30 [1-108] days) individuals but had the longest period from first contact to CSC (median [IQR], 102.5 [45-258] days). Five distinct clusters of individuals emerged that cut across ethnoracial groups. The more disadvantaged clusters in terms of both social position and first-contact experiences had the longest time from onset to first contact, which were longer than for any single ethnoracial group. Conclusions and Relevance: In this cohort study of individuals with recent-onset psychosis, time-to-treatment outcomes differed by ethnoracial group and by empirically derived clusters combining multiple factors of social and clinical context. The examination of disparities in durations to treatment through an intersectional, ethnoracial lens may improve understanding of the inequities resulting from the various intersecting factors that may compound delays in treatment initiation.

Co-occurring Depression and Suicidal Ideation in Opioid Use Disorder: Prevalence and Response During Treatment With Buprenorphine-Naloxone and Injection Naltrexone.

Objective: The concept of "deaths of despair" (suicide, overdose, and alcohol-related liver disease) highlights the importance of detecting and understanding the course of co-occurring depression in patients with opioid use disorder (OUD).Methods: In a 24-week trial of 570 patients with DSM-5-defined OUD randomized to buprenorphine-naloxone (BUP-NX) or extended-release naltrexone (XR-NTX) from January 2014 to January 2017, the prevalence of depression (assessed with Hamilton Depression Rating Scale [HDRS]) was examined at baseline and after 4 weeks of treatment, and the association between depression and relapse to opioid use was explored using logistic regression.Results: Among 473 patients who initiated medication, 14.2% (67/473) had moderate/severe depression (HDRS ≥ 17) and 34.9% (165/473) had mild depression (8 ≤ HDRS ≤ 16) at baseline. Patients with moderate/severe depression had more frequent histories of anxiety disorders and suicidal ideation. After 4 weeks of treatment, approximately two-thirds of participants with depression either responded (HDRS reduced ≥ 50% from baseline) or remitted (HDRS ≤ 7), with no significant differences between medication treatment groups. Those with moderate/severe depression were less likely to remit (52.8%; 28/53) compared to those with mild depression (76%; 98/129) at week 4 (OR = 0.43, 95% CI = 0.21-0.89, P = .02). Further, those who remitted at week 4 had lower, but not significantly different, risk of relapse to opioids compared to those who did not remit (OR = 0.55, 95% CI = 0.28-1.08, P = .08).Conclusions: Depression is common among patients with OUD and often remits after initiation of BUP-NX or XR-NTX, although when it does not remit it may be associated with worse opioid use outcome. Depression should be screened and followed during initiation of treatment and, when it does not remit, specific depression treatment should be considered.Trial Registration: ClinicalTrials.gov identifier: NCT02032433.

Feasibility and Utility of Different Approaches to Violence Risk Assessment for Young Adults Receiving Treatment for Early Psychosis.

This pilot study examined violence risk assessment among a sample of young adults receiving treatment for early psychosis. In this study, thirty participants were assessed for violence risk at baseline. Participants completed follow-up assessments at 3, 6, 9 and 12 months to ascertain prevalence of violent behavior. Individuals were on average 24.1 years old (SD = 3.3 years) and predominantly male (n = 24, 80%). In this sample, six people (20%) reported engaging in violence during the study period. Individuals who engaged in violence had higher levels of negative urgency (t(28) = 2.21, p = 0.035) This study sought to establish the feasibility, acceptability, and clinical utility of violence risk assessment for clients in treatment for early psychosis. Overall, this study found that most individuals with early psychosis in this study (who are in treatment) were not at risk of violence. Findings suggest that violent behavior among young adults with early psychosis is associated with increased negative urgency.

Predictors of Persistent Symptoms in People in Coordinated Specialty Care Services for Early Psychosis in New York State.

OBJECTIVE: This study aimed to determine the prevalence and predictors of persistent transdiagnostic symptoms in the first year of enrollment in OnTrackNY, a coordinated specialty care (CSC) program for individuals with recent-onset nonaffective psychosis. METHODS: Three groups were defined by using the Mental Illness Research, Education, and Clinical Centers Global Assessment of Functioning symptom subscale: persistently symptomatic, intermittent, and improving to moderate. The authors compared groups on baseline demographic characteristics, family and living situation, clinical measures, and pathways to care. RESULTS: Of 1,129 eligible participants, 12% were persistently symptomatic through follow-up. Being medication nonadherent, being homeless, having a diagnosis of schizophrenia, and having a longer duration between symptom onset and program enrollment were predictive of persistent symptoms during the first year of CSC. CONCLUSIONS: Findings suggest that despite intensive treatment, severe symptoms in young people with psychosis may persist because of economic barriers, treatment delays, and lack of stability.

Time-lagged association between counseling and/or 12-Step attendance with subsequent opioid use in a secondary analysis from a randomized, clinical trial of medications for opioid use disorder.

Introduction: Psychosocial support is recommended in conjunction with medication for opioid use disorder (MOUD), although optimal "dose," modality, and timing of participation is not established. This study comprised a secondary analysis of counseling and 12-Step attendance and subsequent opioid use in a MOUD randomized clinical trial. Methods: The parent study randomly assigned 570 participants to receive buprenorphine-naloxone (BUP-NX, n=287) or extended-release injectable naltrexone (XR-NTX, n=283). Mixed-effects logistic regression models were fit with opioid use as the response variable, and a counseling/12-Step attendance predictor. Differences by treatment assignment were examined. Results: Any counseling or 12-Step attendance was associated with reduced odds of opioid use at the subsequent visit, whether considered individually or aggregated across type. A continuous relationship was observed for 12-Step attendance (F(1,5083)=5.01, p=.025); with each additional hour associated with 13% (95% CI: 0.83, 0.90) reduction in odds of opioid use. The strength of this association grew over time. In the BUP-NX arm, group counseling was associated with a greater reduction in odds of opioid use than for XR-NTX, (OR=0.32 (95% CI: .22, 0.48) vs. OR=0.69 (95% CI: 0.43, 1.08)). For XR-NTX, 12-Step was associated with a greater reduction in odds of opioid use (OR=0.35 (95% CI: 0.22, 0.54) vs. OR=0.65 (95% CI: 0.47, 0.89) for BUP-NX)). Conclusions: Psychosocial engagement has a proximal association with opioid use, the strength of that association may grow with dose and time. Alternatively, more motivated individuals may both attend more counseling/12-Step and have better treatment outcomes, or the relationship may be reciprocal.

The relationship of frequency of cocaine use to substance and psychiatric disorders in the U.S. general population.

BACKGROUND: In clinical trials of pharmacotherapy for substance use, abstinence is the primary endpoint accepted by regulatory agencies. However, this endpoint could be overly restrictive, impeding efforts to identify effective medications for cocaine use disorder. To examine non-abstinent gradations in cocaine use as potential indicators of improvement, we investigated the relationship of frequency of cocaine use to clinical correlates in national survey data. METHODS: Lifetime cocaine users (n = 2501) were interviewed in the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) in 2001-2002 and re-interviewed in 2004-2005. Adjusted odds ratios (aORs) indicated associations between heaviest frequency of cocaine use and use of other substances, DSM-IV substance use disorders, psychiatric disorders, and change between 2001-2002 and 2004-2005. The reference category for all aORs was non-users. RESULTS: Greater lifetime cocaine use frequency was associated with lifetime cocaine, alcohol, and cannabis dependence (aOR for a linear trend = 2.80, 1.22, 1.22, respectively) and past-year cocaine, alcohol, and cannabis dependence (aOR = 1.78, 1.13, 1.16, respectively). Greater lifetime cocaine use frequency was associated with past-year depressive, panic, and generalized anxiety disorders (aOR = 1.07, 1.09, 1.12, respectively). Among cocaine users in 2001-2002, compared to the reference group using less than monthly, use ≥1x/week and use 1-3 times a month was associated with cocaine use disorder in 2004-2005 (aOR = 2.13 and aOR = 1.67, respectively). CONCLUSION: Gradations in risk for dependence on cocaine, other substances and psychiatric disorders by frequency of cocaine use indicates a promising direction for more sensitive outcome measures of treatment effects on cocaine outcomes than binary indicators (e.g., any use vs. none). Study results add to findings suggesting that non-abstinent measures might be useful indicators of treatment efficacy in clinical trials.

Comparison of counseling methods to promote employment for HIV+ ADULTS.

BACKGROUND: Despite improved health and during a strong job market (pre-COVID-19), a substantial proportion of HIV+ adults remained unemployed. This study sought to provide time-limited counseling to promote employment goals. OBJECTIVE: To determine whether behavioral activation (BA) or supportive counseling (SC), would be more effective in promoting vocational goals (full or part-time, paid or volunteer). METHODS: The study included two groups: those with clinically significant fatigue, who were first treated with armodafinil. Once their fatigue diminished, they were enrolled in the counseling program. Those without fatigue were enrolled directly. Both BA and SC interventions were manualized, consisting of eight individual sessions plus a follow-up. RESULTS: 116 participants entered counseling, including 87 assigned to BA and 29 to SC. Of these, 79 completed counseling or found a job by session eight. By follow-up, 51%of BA versus 41%of SC participants had found jobs, a non-significant difference either clinically or statistically. CONCLUSIONS: Multiple issues contributed to difficulty in employment, including gaps in resumes, loss of contact with former colleagues, and uncertainty about career direction. Ongoing barriers included substance use, housing instability, ambivalence about forfeiting government benefits, as well as inadequately treated depression. Success in employment for about half of participants is, in this context, a reasonable outcome.

Examination of Correlates of OUD Outcomes in Young Adults: Secondary Analysis From the XBOT Trial.

BACKGROUND AND OBJECTIVES: Opioid use disorder (OUD) treatment outcomes are poorer for young adults than older adults. Developmental differences are broadly implicated, but particular vulnerability factor interactions are poorly understood. This study sought to identify moderators of OUD relapse between age groups. METHODS: This secondary analysis compared young adults (18-25) to older adults (26+) from a comparative effectiveness trial ("XBOT") that randomized (N = 570) participants to extended-release naltrexone or sublingual buprenorphine-naloxone. We explored the relationship between 25 prespecified patient baseline characteristics and relapse to regular opioid use by age group and treatment condition, using logistic regression. RESULTS: Young adults (n = 111) had higher rates of 24-week relapse than older adults (n = 459) (70.3% vs 58.8%) and differed on a number of specific characteristics, including more smokers, more intravenous opioid use, and more cannabis use. No significant moderators predicted relapse, in either three-way or two-way interactions. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: No baseline factors were identified as moderating the relationship between age group and opioid relapse, nor any interactions between baseline characteristics, age group, and treatment condition to predict opioid relapse. Poorer treatment outcomes for young adults are likely associated with multiple developmental vulnerabilities rather than any single predominant factor. Although not reaching significance, several characteristics (using heroin, smoking tobacco, high levels of depression/anxiety, or treatment because of family/friends) showed higher odds ratio point estimates for relapse in young adults than older adults. This is the first study to explore moderators of worse OUD treatment outcomes in young adults, highlighting the need to identify predictor variables that could inform treatment enhancements. (Am J Addict 2021;00:1-12).

Sublingual Buprenorphine-Naloxone Compared With Injection Naltrexone for Opioid Use Disorder: Potential Utility of Patient Characteristics in Guiding Choice of Treatment.

OBJECTIVE: Sublingual buprenorphine-naloxone and extended-release injection naltrexone are effective treatments, with distinct mechanisms, for opioid use disorder. The authors examined whether patients' demographic and clinical characteristics were associated with better response to one medication or the other. METHODS: In a multisite 24-week randomized comparative-effectiveness trial of assignment to buprenorphine-naloxone (N=287) compared with extended-release naltrexone (N=283) comprising inpatients planning to initiate medication treatment for opioid use disorder, 50 demographic and clinical characteristics were examined as moderators of the effect of medication assignment on relapse to regular opioid use and failure to initiate medication. Moderator-by-medication interactions were estimated using logistic regression with correction for multiple testing. RESULTS: In the intent-to-treat sample, patients who reported being homeless had a lower relapse rate if they were assigned to receive extended-release naltrexone (51.6%) compared with buprenorphine-naloxone (70.4%) (odds ratio=0.45, 95% CI=0.22, 0.90); patients who were not homeless had a higher relapse rate if they were assigned to extended-release naltrexone (70.9%) compared with buprenorphine-naloxone (53.1%) (odds ratio=2.15, 95% CI=1.44, 3.21). In the subsample of patients who initiated medication, the interaction was not significant, with a similar pattern of lower relapse with extended-release naltrexone (41.4%) compared with buprenorphine (68.6%) among homeless patients (odds ratio=0.32, 95% CI=0.15, 0.68) but less difference among those not homeless (extended-release naltrexone, 57.2%; buprenorphine, 52.0%; odds ratio=1.24, 95% CI=0.80, 1.90). For failure to initiate medication, moderators were stated preference for medication (failure was less likely if the patient was assigned to the medication preferred), parole and probation status (fewer failures with extended-release naltrexone for those on parole or probation), and presence of pain and timing of randomization (more failure with extended-release naltrexone for patients endorsing moderate to severe pain and randomized early while still undergoing medically managed withdrawal). CONCLUSIONS: Among patients with opioid use disorder admitted to inpatient treatment, homelessness, parole and probation status, medication preference, and factors likely to influence tolerability of medication initiation may be important in matching patients to buprenorphine or extended-release naltrexone.

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

AIM: This 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). DESIGN: X: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 PARTICIPANTS: Adults with opioid use disorder recruited from 8 community treatment programs across the United States. MEASUREMENTS: Outcomes 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. FINDINGS: Of 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). CONCLUSIONS: Naturalistic 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.

Maximizing remission from cognitive-behavioral therapy in medicated adults with obsessive-compulsive disorder.

Practice guidelines for adults with obsessive-compulsive disorder (OCD) recommend augmenting serotonin reuptake inhibitors (SRIs) with exposure and ritual prevention (EX/RP). However, fewer than half of patients remit after a standard 17-session EX/RP course. We studied whether extending the course increased overall remission rates and which patient factors predicted remission. Participants were 137 adults with clinically significant OCD (Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score ≥18) despite an adequate SRI trial (≥12 weeks). Continuing their SRI, patients received 17 sessions of twice-weekly EX/RP (standard course). Patients who did not remit (Y-BOCS ≤12) received up to 8 additional sessions (extended course). Of 137 entrants, 123 completed treatment: 49 (35.8%) remitted with the standard course and another 46 (33.6%) with the extended course. Poorer patient homework adherence, more Obsessive-Compulsive Personality Disorder (OCPD) traits, and the Brain-Derived Neurotrophic Factor (BDNF) Val66MET genotype were associated with lower odds of standard course remission. Only homework adherence differentiated non-remitters from extended course remitters. Extending the EX/RP course from 17 to 25 sessions enabled many (69.3%) OCD patients on SRIs to achieve remission. Although behavioral (patient homework adherence), psychological (OCPD traits), and biological (BDNF genotype) factors influenced odds of EX/RP remission, homework adherence was the most potent patient factor overall.

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.

BACKGROUND: Smoking 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). METHODS: The 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). RESULTS: Among 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. CONCLUSIONS: OUD 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.