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Abstract: Background and Objectives: Tobacco smoking and alcohol use disorder (AUD) are highly prevalent among individuals receiving medication for opioid use disorder (MOUD) treatment, yet their combined impact on treatment outcomes remains underexplored. This study investigates the differences in clinical profiles and treatment outcomes based on smoking and AUD status among individuals initiating MOUD. Methods: This secondary analysis utilized data from a multi-site randomized clinical trial (CTN-0027) evaluating the hepatotoxicity during 24 weeks of buprenorphine or methadone treatment. Participants were categorized into four groups based on baseline smoking and AUD status: Non-AUD/Non-smoker, Smoker Only, AUD Only, and AUD+Smoker. Clinical profiles and treatment outcomes were compared across groups. Results: Among 973 participants (68.6% male, 70.5% White, mean age 37.5 years), 50% were Smoker Only, 16% AUD+Smoker, 8% AUD Only, and 27% Non-AUD/Non-smoker. Smoking prevalence was high (66%), while AUD prevalence was lower (24%). AUD+Smoker and AUD Only groups had significantly higher rates of additional substance use disorders (p < .01). However, treatment outcomes—measured by urinalysis results, retention, and completion—did not differ significantly across groups. Discussion and Conclusions: Smoking and AUD status were not associated with poorer MOUD outcomes, but the high prevalence of smoking, and the clustering of additional substance use disorders among individuals with AUD suggest the need for integrated care. These findings support inclusion of adjunctive behavioral and public health interventions within MOUD programs. Related protocols: CTN-0027

Abstract:

Illicit stimulant use among individuals initiating medication for opioid use disorder (MOUD) has significantly increased over the past decade. Co-use of these substances is associated with increased risk of mortality as well as worse treatment outcomes. This study examines the potential predictive role of stimulant urinalysis result at baseline on treatment retention and opioid and stimulant use outcomes amongst individuals initiating MOUD treatment.

This is a cross-sectional secondary analysis of data from a multi-site randomized clinical trial (CTN-0027). A total of 1269 individuals were randomized to receive 24 weeks of buprenorphine (n=740) or methadone (n=529) treatment across nine sites. Multiple linear and logistic regressions were conducted to determine the impact of baseline stimulant urinalysis results on treatment retention, and stimulant and opioid use outcomes.

Individuals initiating MOUD with a stimulant negative urinalysis result at baseline submitted more negative stimulant and opioid urinalyses during treatment, were more likely to complete treatment, and had better outcomes at six-month follow-up, measured as negative urinalysis for stimulant, and opioid.

Conclusions: Baseline stimulant use is associated with worse MOUD treatment outcomes, underscoring the need for novel integrated interventions designed to address opioid and stimulant co-use.

Related protocols: CTN-0027

Abstract:

Several large-scale, pragmatic clinical trials on opioid use disorder (OUD) have been completed in the National Drug Abuse Treatment Clinical Trials Network (CTN). However, the resulting data have not been harmonized between the studies to compare the patient characteristics. This paper provides lessons learned from a large-scale harmonization process that are critical for all biomedical researchers collecting new data and those tasked with combining datasets.

Researchers harmonized data from multiple domains from CTN-0027 (N = 1269), which compared methadone and buprenorphine at federally licensed methadone treatment programs; CTN-0030 (N = 653), which recruited patients who used predominantly prescription opioids and were treated with buprenorphine; and CTN-0051 (N = 570), which compared buprenorphine and extended-release naltrexone (XR-NTX) and recruited from inpatient treatment facilities. Patient-level data were harmonized and a total of 23 database tables, with meticulous documentation, covering more than 110 variables, along with three tables with “meta-data” about the study design and treatment arms, were created. Domains included: social and demographic characteristics, medical and psychiatric history, self-reported drug use details and urine drug screening results, withdrawal, and treatment drug details.

In this paper, the authors summarize the numerous issues with the organization and fidelity of the publicly available data which were noted and resolved, and present results on patient characteristics across the three trials and the harmonized domains, respectively. A systematic harmonization of OUD clinical trial data can be accomplished, despite heterogeneous data coding and classification procedures, by standardizing commonly assessed characteristics. Similar methods, embracing database normalization and/or “tidy” data, should be used for future datasets in other substance use disorder clinical trials.

Related protocols: CTN-0027, CTN-0030, CTN-0051

Abstract:

In the United States, one in 14 individuals experience a Substance Use Disorder (SUD). SAMHSA stated that in 2020, approximately 40 million individuals from ages 12 and above had a SUD (CDC, 2022 ; SAMHSA, 2021). There has been a 44% increase in overdose rates in Black communities between 1999 to 2023. One longitudinal study found that the opioid overdose fatality rate among “non-Hispanic Black men 55 years or older was 40.03 per 100,000 population, 4 times greater than the overall opioid overdose fatality rate of 10.70 per 100,000 for persons of the same age” (Mason, Soliman, Kim, & Post, 2022).

This poster describes CTN-0127, a pilot exploratory study that will pave the way for future initiatives focused on increasing SUD care in underserved Black communities through learning collaboratives (LC) between faith-based leaders (FBLs) and behavioral health providers (BHLs). An LC is a short-term (6- to 15-month) learning system that brings together teams (e.g., FBLs, community members, behavioral health/SUD, and social service providers) to seek improvement in a focused topic area.

Related protocols: CTN-0027

Abstract:

Racial and ethnic disparities in access to treatment and quality of treatment for opioid use disorder (OUD) have been identified in usual care settings. In contrast, disparities in treatment quality within clinical trials are relatively unexamined. This study aimed to estimate racial and ethnic differences in the dose of opioid agonist treatment for OUD in the first 4 weeks of treatment in clinical trials.

This cohort study performed analysis of the methadone and buprenorphine treatment arms of 3 trials conducted by the National Institute on Drug Abuse Clinical Trials Network between May 2006, and January 31, 2017, at multiple Clinical Trials Network sites across the US (CTN-0027, START, CTN-0030, POATS, and CTN-0051, X:BOT). Trial participants who were randomized to and initiated buprenorphine or methadone treatment and who identified as Hispanic, non-Hispanic Black, or non-Hispanic White were included in the present study. Data were analyzed from November 1, 2023, to August 5, 2024. THe main outcomes and measures were the maximum daily dose of buprenorphine or methadone received in each week for the first 4 weeks of treatment. The mean dose and percentage of patients receiving a higher dose (buprenorphine =16 mg and methadone =60 mg) were also compared across race and ethnicity groups.

A total of 1748 patients (1263 who initiated buprenorphine and 485 who initiated methadone treatment) were included in the analysis (1168 [66.8%] male; median age, 33 [IQR, 26-45] years). Of these, 138 patients (7.9%) identified as Black, 273 (15.6%) as Hispanic, and 1337 (76.5%) as White. In week 4, Black patients received buprenorphine doses 2.5 (95% CI -4.6 to -0.5) mg lower and methadone doses 16.7 (95% CI, -30.7 to -2.7) mg lower compared with White patients, after standardizing by age and sex. In week 4, the percentage of patients receiving a higher dose of medication (buprenorphine =16 mg; methadone =60 mg) was 16.9 (95% CI, -31.9 to -1.9) points lower for Black patients compared with White patients. Hispanic and White patients received similar buprenorphine doses; Hispanic patients received lower methadone doses than White patients.

Conclusions: In this cohort study of data from 3 clinical trials, White patients generally received higher doses of medication than Black patients. Future research is needed to understand the mechanisms of and interventions to reduce disparities in OUD treatment quality and how such disparities impact generalizability of trial results.

Note: An invited commentary piece on this article was also published by JAMA Network Open (Schiff DM, Nidey N, Tiako MJN. Dosing inequities in opioid use disorder treatment trials. JAMA Network Open 2024;7(10):e2436582.)

Related protocols: CTN-0027, CTN-0030, CTN-0051

Abstract:

No existing model allows clinicians to predict whether patients might return to opioid use in the early stages of treatment for opioid use disorder. The goal of this study was to develop an individual-level prediction tool for risk of return to use in opioid use disorder.

This decision analytical model (CTN-0094) used predictive modeling with individual-level data harmonized in June 1, 2019, to October 1, 2022, from 3 multicenter, pragmatic, randomized clinical trials of at least 12 weeks’ duration within the National Institute on Drug Abuse Clinical Trials Network (CTN) performed between 2006 and 2016 (CTN-0027 [START], CTN-0030 [POATS], and CTN-0051 [X:BOT]). The clinical trials covered a variety of treatment settings, including federally licensed treatment sites, physician practices, and inpatient treatment facilities. All 3 trials enrolled adult participants older than 18 years, with broad pragmatic inclusion and few exclusion criteria except for major medical and unstable psychiatric comorbidities.

All participants received 1 of 3 medications for opioid use disorder: methadone, buprenorphine, or extended-release naltrexone. Predictive models were developed for return to use, which was defined as 4 consecutive weeks of urine drug screen (UDS) results either missing or positive for nonprescribed opioids by week 12 of treatment.

The overall sample included 2199 trial participants (mean [SD] age, 35.3 [10.7] years; 728 women [33.1%] and 1471 men [66.9%]). The final model based on 4 predictors at treatment entry (heroin use days, morphine- and cocaine-positive UDS results, and heroin injection in the past 30 days) yielded an area under the receiver operating characteristic curve (AUROC) of 0.67 (95% CI, 0.62-0.71). Adding UDS in the first 3 treatment weeks improved model performance (AUROC, 0.82; 95% CI, 0.78-0.85). A simplified score (CTN-0094 OUD Return-to-Use Risk Score) provided good clinical risk stratification wherein patients with weekly opioid-negative UDS results in the 3 weeks after treatment initiation had a 13% risk of return to use compared with 85% for those with 3 weeks of opioid-positive or missing UDS results (AUROC, 0.80; 95% CI, 0.76-0.84).

Conclusions: The prediction model described in this study may be a universal risk measure for return to opioid use by treatment week 3. Interventions to prevent return to regular use should focus on this critical early treatment period.

Related protocols: CTN-0027, CTN-0030, CTN-0051, CTN-0094

Abstract:

Patients in treatment with medications for opioid use disorder (MOUD) often report use of other substances in addition to opioids. Few studies exist that examine the relationship between use at treatment entry and early non-opioid use in opioid treatment outcome.

In this study, researchers combined and harmonized three randomized, controlled MOUD clinical trials from the National Institutes of Drug Abuse (NIDA) Clinical Trials Network (CTN) (N=2,197) and investigated the association of non-opioid substance use at treatment entry and during early treatment with a return to opioid use. The trials (CTN-0027 [START], CTN-0030 [POATS], and CTN-0051 [X:BOT]) compared MOUD treatment (buprenorphine, methadone, extended-release naltrexone) in populations with opioid use disorder (OUD). Non-opioid substances were identified through harmonizing self-reported use. The primary outcomes were markers of return to opioid use by 12 weeks.

When treatment cohorts were adjusted, no association between self-reported treatment entry use of non-opioid substances and week-12 opioid use was detected. During the first month of treatment, higher use of cocaine and amphetamine was found to be associated with higher likelihood of illicit opioid use by week 12. Exploratory analyses of potential treatment cohort-by-predictor interactions showed that those with heavier cocaine use had a lower rate of returning to opioid use in the extended-release naltrexone group than in the methadone group.

Conclusions: Substance use other than opioids at treatment entry is not associated with relapse. Use of cocaine or amphetamines during the first few weeks of MOUD treatment may signal a worse outcome, suggesting a need for additional interventions.

Related protocols: CTN-0027, CTN-0030, CTN-0051

Abstract:

Overdose risk during a course of treatment with medication for opioid use disorder (MOUD) has not been clearly delineated. In this study, the authors sought to address this gap by leveraging a new data set from three large pragmatic clinical trials of MOUD: CTN-0027 (START), CTN-0030 (POATS), and CTN-0051 (X:BOT).

Adverse event logs, including overdose events, from the three trials (N=2,199) were harmonized, and the overall risk of having an overdose event in the 24 weeks after randomization was compared for each study arm (one methadone, one naltrexone, and three buprenorphine groups), using survival analysis with time-dependent Cox proportional hazard models.

Results found that by week 24, 39 participants had =1 overdose event. The observed frequency of having an overdose event was 15 (5.30%) among 283 patients assigned to naltrexone, eight (1.51%) among 529 patients assigned to methadone, and 16 (1.15%) among 1,387 patients assigned to buprenorphine. Notably, 27.9% of patients assigned to extended-release naltrexone never initiated the medication, and their overdose rate was 8.9% (7/79), compared with 3.9% (8/204) among those who initiated naltrexone.

Controlling for sociodemographic and time-varying medication adherence variables and baseline substance use, a proportional hazard model did not show a significant effect of naltrexone assignment. Significantly higher probabilities of experiencing an overdose event were observed among patients with baseline benzodiazepine use (hazard ratio=3.36, 95% CI=1.76, 6.42) and those who either were never inducted on their assigned study medication (hazard ratio=6.64, 95% CI=2.12, 19.54) or stopped their medication after initial induction (hazard ratio=4.04, 95% CI=1.54, 10.65).

Conclusions: Patients undergoing MOUD treatment remain at risk of overdose events in the first 24 weeks after seeking treatment. The strongest message from these data is that patients who fail to initiate medication, or stop their medication, are at greater risk of experiencing an overdose event. The pharmacology of methadone, buprenorphine, and naltrexone is such that they all substantially lower overdose risk if taken as prescribed. Patients should be educated about overdose risk, the protective effect of MOUD, and the danger of discontinuing medication. Benzodiazepine use is also a signal of risk, and patients taking benzodiazepines should be evaluated and treated for mental health problems as part of an effort to wean them off benzodiazepines. The risk of overdose after discontinuing naltrexone may be greater than for other medications, although the present data are not definitive on this point, and the overall effect of naltrexone assignment on overdose was not statistically significant. Future large trials should implement more systematic assessments of overdose events based on a clear operationalization of overdose, querying actively rather than relying on spontaneous report, with detailed characterization of the event, including the substances involved and whether there was suicidal intent.

Related editorial: An editorial about this paper was published in the American Journal of Psychiatry in May 2023: Connery HS & Weiss RD. Drug overdose prevention: An exercise in optimism. American Journal of Psychiatry 2023;180:5. [doi: 10.1176/appi.ajp.20230170]

Related protocols: CTN-0027, CTN-0030, CTN-0051

Abstract:

While polysubstance use has consistently been associated with higher rates of relapse, few studies have examined subgroups with specific combinations and time course of polysubstance use (i.e., polysubstance use patterns). This study aimed to classify and compare polysubstance use patterns and their associations with relapse to opioid use in 2637 participants in three large opioid use disorder (OUD) treatment trials in the NIDA Clinical Trials Network (CTN-0027, CTN-0030, and CTN-0051).

Researchers explored the daily patterns of self-reported substance use in the 28 days prior to treatment entry. Market basket analysis (MBA) and repeated measure latent class analysis (RMLCA) were used to examine the subgroups of polysubstance use patterns, and multiple logistic regression was used to examine associations between identified classes and relapse.

MBA and RMLCA identified 34 “associations rules” and 6 classes, respectively. Specific combinations of polysubstance use and time course (high baseline use and rapid decrease of use prior to initiation) predicts a worse relapse outcome. MBA showed individuals who co-used cocaine, heroin, prescription opioids, and cannabis had a higher risk for relapse (OR=2.82, 95%CI=1.13, 7.03). In RMLCA, higher risk of relapse was observed in individuals who presented with high baseline prescription opioid (OR = 1.9, 95% CI = 1.3, 2.76) or heroin use (OR = 3.54, 95%CI = 1.86, 6.72), although use decreased in both cases prior to treatment initiation.

Conclusions: Our analyses identified subgroups with distinct patterns of polysubstance use. Different patterns of polysubstance use differentially predict relapse outcomes. Interventions tailored to these individuals with specific polysubstance use patterns prior to treatment initiation may increase the effectiveness of relapse prevention.

Related protocols: CTN-0027, CTN-0030, CTN-0051

Abstract:

Although there is consensus that having a “high-enough” dose of buprenorphine (BUP-NX) or methadone is important for reducing relapse to opioid use, there is debate about what this dose is and how it should be attained. We estimated the extent to which different dosing strategies would affect risk of relapse over 12 weeks of treatment, separately for BUP-NX and methadone.

This was a secondary analysis of three comparative effectiveness trials (CTN-0027, CTN-0030, and CTN-0051). We examined four dosing strategies: 1) increasing dose in response to participant-specific opioid use, 2) increasing dose weekly until some minimum dose (16 mg BUP, 100 mg methadone) was reached, 3) increasing dose weekly until some minimum and increasing dose in response to opioid use thereafter (referred to as the “hybrid strategy”), and 4) keeping dose constant after the first 2 weeks of treatment. We used a longitudinal sequentially doubly robust estimator to estimate contrasts between dosing strategies on risk of relapse.

For BUP-NX, increasing dose following the hybrid strategy resulted in the lowest risk of relapse. For methadone, holding dose constant resulted in greatest risk of relapse; the other three strategies performed similarly. For example, the hybrid strategy reduced week 12 relapse risk by 13 % (RR: 0.87, 95 %CI: 0.83–0.95) and by 20 % (RR: 0.80, 95 %CI: 0.71–0.90) for BUP-NX and methadone respectively, as compared to holding dose constant.

Conclusions: Doses should be targeted toward minimum thresholds and, in the case of BUP-NX, raised when patients continue to use opioids.

Related protocols: CTN-0027, CTN-0030, CTN-0051

Abstract:

The extend 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. The objective of this study 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.

This study was a secondary descriptive analysis of trial and real-world data. The trial data included 27 US opioid treatment programs in the NIDA National Drug Abuse Treatment Clinical Trials Network (CTN-0027, CTN-0051, and CTN-0030), N=2,199 patients. The real-world data included US substance use treatment programs that receive public funding, N=740,015 patients (TEDS-A data). The authors 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.

The authors found that 10.7% of MOUD patients in TEDS-A (real-world sample) 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.

Conclusions: Quantifying 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.

Related protocols: CTN-0027, CTN-0030, CTN-0051

Abstract:

This study examined the associations of multiple psychiatric and chronic conditions with the self-reported history of major depressive disorder (MDD) among patients with opioid use disorder (OUD) and tested whether the associations differed by gender. Using data from CTN-0027 (START), a clinical trial including 1,646 participants with OUD, of which 465 had MDD, a variable cluster analysis was used to classify chronic medical and psychiatric conditions. Multivariate logistic regression analyses were used to estimate their associations with MDD in subjects with OUD.

Nine variables were divided into three clusters: cluster 1 included heart condition, hypertension, and liver problems; cluster 2 included gastrointestinal (GI) problems and head injury; and cluster 3 included anxiety disorder, bipolar disorder, and schizophrenia. The overall prevalence of MDD in participants with OUD was 28.3% (22.8% for males and 39.5% for females). Gender, anxiety disorder, schizophrenia, liver problems, heart condition, GI problems, and head injury were significantly associated with MDD. Gender-stratified analyses showed that bipolar disorder, liver problems and individuals with one chronic condition were associated with MDD only in males, whereas heart condition, hypertension, and GI problems were associated with MDD only in females. In addition, anxiety disorder, head injury, individuals with one or more than two psychiatric conditions, and individuals with more than two chronic conditions were associated with MDD regardless of gender.

Conclusions: This study showed a high prevalence of MDD in individuals with OUD as compared to the general population. In those with OUD, there is a significant association between MDD and gender, anxiety disorder, liver problems, heart condition, GI problems, and head injury. Furthermore, multiple psychiatric and chronic conditions were significantly associated with MDD. Additionally, gender-stratified analyses showed that bipolar disorder, liver problems and one chronic condition was associated with MDD in males, while heart condition, hypertension, and GI problems were associated with MDD only in females. Treatment plans in patients with OUD should not only address MDD but also co-morbid psychiatric and chronic medical conditions that occur with MDD.

Related protocols: CTN-0027

Abstract:

This study examined the associations of polysubstance use, mood disorders, and chronic conditions with the history of anxiety disorder among patients with opioid use disorder (OUD). Researchers performed a secondary analysis of the baseline data from NIDA-CTN-0027 (“Starting Treatment with Agonist Replacement Therapies (START)”), a clinical trial that included 1,645 individuals with OUD, of which 513 had anxiety disorder. Substance use disorder (SUDs) included alcohol, amphetamines, cannabis, cocaine, and sedative use disorders. Mood disorders included major depressive disorder (MDD) and bipolar disorder (BD). Chronic conditions were allergies, gastrointestinal problem(s), skin problem(s), and hypertension. Sedative use disorder, MDD, BD, skin problems, and hypertension were significantly associated with anxiety disorder. Additionally, more than two SUDs, two mood disorders, and more than two chronic conditions were significantly associated with anxiety disorder.

Conclusions: These findings highlight the comorbid mental health and physical health problems in individuals with OUD, as well as the need for integrated multidisciplinary treatment plans. Future areas of research should focus on not only OUD, but also patients presenting with other comorbidities to identify more vulnerable groups, discover effective solutions, and reduce the prevalence of OUD.

Related protocols: CTN-0027

Abstract:

Individuals treated for opioid use disorder (OUD) have high rates of psychiatric disorders potentially diminishing treatment outcomes. This study examined long-term treatment experiences and outcomes by type of psychiatric disorder among participants in the NIDA Clinical Trials Network Starting Treatment with Agonist Replacement Therapies (START) study (CTN-0027) and its follow-up study (CTN-0050).

Researchers categorized the 593 participants who completed the Mini-International Neuropsychiatric Interview (MINI) during the START follow-up study into four mutually exclusive groups to indicate current psychiatric diagnosis: 1) bipolar disorder (BPD; n=51), 2) major depressive disorder (MDD; n=85), 3) anxiety disorder (AXD; n=121), and 4) no comorbid mental disorder (NMD; n=336). Participants’ baseline characteristics and treatment outcomes were then compared.

Groups with mental disorders had worse substance use outcomes and poorer psychosocial functioning than the NMD group. Participants with BPD had significantly more self-reported days using opioids (mean: 8.6 for BPD vs. 3.4 days for NMD) and heroin (mean: 6.4 for BPS vs. 2 for MDD, 3.1 days for NMD) in the 30 days prior to the final interview. Compared to patients without mental disorders, patients with MDD spent more time engaged with OUD pharmacotherapy during the ~16 month period between MINI and final interview (mean: 71.6% vs. 50.6%).

Conclusions: Results show that treatment outcomes in individuals with OUD vary by psychiatric comorbidity groups, which supports the need for mental health assessment and treatment for psychiatric conditions in the context of pharmacotherapy for patients with OUD.

Related protocols: CTN-0027, CTN-0050

Abstract:

Mental disorders among individuals with opioid use disorder (OUD) are common. The purpose of this study was to investigate whether there were differential effects on opioid use among OUD patients with specific life-time psychiatric diagnoses (mood disorder, mental disorder other than mood disorder, none) who received medication treatment for OUD (MOUD) with either methadone (MET) or buprenorphine (BUP).

In a randomized controlled trial (CTN-0027, the START study), adults with OUD were randomized to 24 weeks of either BUP or MET treatment and were followed up in 3-yearly assessments. The present secondary analyses of data from CTN-0050 (Long-Term Follow-Up of START Patients) were based on 597 participants who completed all assessments.

The outcome measure was the number of days of using opioids per month during the follow-up period. The Mini-International Neuropsychiatric Interview (MINI) was used to classify participants into three groups: lifetime mood disorder (n=302), lifetime mental disorder other than mood disorder (n=114), and no mental disorder (n=181). Medication treatment (BUP, MET, no treatment) during the follow-up period was a time-varying predictor.

Based on zero-inflated Poisson (ZIP) mixed regression analysis, it was found that relative to no treatment, opioid use during the follow-up was significantly reduced by BUP and by MET. Relative to MET, BUP was associated with a lower likelihood of any opioid use among participants with mood disorders and for participants without mental disorder, and fewer number of days using opioids among participants with other mental disorders.

Conclusions: Among adults with comorbid opioid use disorder and mental disorders, treatment with buprenorphine-naloxone produced greater reductions in opioid use than treatment with methadone.

Related protocols: CTN-0027, CTN-0050