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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

Abstract:

Efforts to address the opioid epidemic include increasing access to medications for opioid use disorder (OUD), particularly with buprenorphine. A poorly understood challenge is that among individuals with OUD who do receive buprenorphine, many do not adhere to the pharmacotherapy long enough to achieve sustained benefits. This study aimed to identify factors associated with buprenorphine treatment utilization over time.

Using random-intercept modeling, the authors identified factors associated with buprenorphine treatment utilization over 2 years after first follow-up of 789 individuals with OUD who had participated in a multi-site randomized clinical trial of buprenorphine compared to methadone. (CTN-0050). Key predictors were participants’ reports of buprenorphine treatment accessibility and acceptability (assessed at first follow-up) and their interaction effects, controlling for baseline randomization status, sociodemographics, and other covariates.

Results: Approximately 9.3–11.2% of participants utilized buprenorphine treatment over the 2 years of follow-up. Interaction effects indicated that individuals who perceived buprenorphine to be both accessible and acceptable were most likely to use buprenorphine during follow-up, controlling for other factors. In contrast, individuals who perceived buprenorphine to be unacceptable were least likely to use buprenorphine, regardless the level of perceived access to the medication. Buprenorphine treatment utilization was also negatively associated with Hispanic ethnicity, West coast context, and cumulative months receiving methadone treatment and incarceration during follow-up.

Conclusions: To engage more individuals with OUD in long-term treatment with buprenorphine, interventions should target buprenorphine treatment acceptability, in addition to increasing buprenorphine access, and tailor efforts to meet the needs of vulnerable populations.

Related protocols: CTN-0050

Abstract:

A critical strategy to address the opioid epidemic is increasing access to pharmacotherapy, particularly buprenorphine/naloxone (BUP). BUP is a partial agonist that has a superior safety profile than methadone (MET), a full agonist, in terms of overdose risk. Few studies have compared the long-term outcomes of participants randomized to BUP or MET treatment for opioid use disorder (OUD), however, and differences in treatment retention by medication type may translate into variation in criminal justice outcomes.

This study aimed to compare long-term criminal justice outcomes among opioid dependent individuals randomized to receive buprenorphine or methadone. Five-year follow-up was conducted in 2011-2014 of 303 opioid-dependent participants entering three opioid treatment programs in California in 2006-2009 (as part of CTN-0050, “Starting Treatment with Agonist Replacement Therapy (START)”) and randomized to receive either buprenorphine/naloxone or methadone.

Participants received BUP (n=179) or MET (n=124) for 24 weeks and then were tapered off their treatment over 8 weeks or less or referred for ongoing clinical treatment. Midway through the study, the randomization scheme was switched from 1:1 BUP:MET to 2:1 because of higher drop out in the BUP arm.

Study outcomes included arrests and self-reported incarceration. Predictors included randomization condition (BUP vs. MET), age, gender, race/ethnicity, use of cocaine, drug injection in the 30 days prior to baseline, and study site. Treatment status (BUP, MET, none) during follow-up was included as a time-varying covariate.

There was no significant difference by randomization condition in the proportion arrested (BUP: 55.3%, MET: 54%) or incarcerated (40.9%, 47.3%) during follow-up. Among methadone-randomized individuals, arrest was less likely with methadone treatment (0.50, 0.35-0.72) during follow-up (relative to no treatment) and switching to buprenorphine had a lower likely likelihood of arrest than those receiving no treatment (0.39, 0.18-0.87). Among buprenorphine-randomized individuals, arrest was less likely with receipt of buprenorphine (0.49, 0.33-0.75) during follow-up and switching to methadone had a similar likelihood of arrest as methadone-randomized individuals receiving no treatment. Likelihood of arrest was also negatively associated with older age (0.98, 0.96-1.00); it was positively associated with Hispanic ethnicity (1.63, 1.04-2.56), cocaine use (2.00, 1.33-3.03), injection drug use (2.19, 1.26-3.83), and study site.

Conclusions: In a US sample of people treated for opioid use disorder, continued treatment with either buprenorphine or methadone was associated with a reduction in arrests relative to no treatment. Cocaine use, injection drug use, Hispanic ethnicity, and younger age were associated with higher likelihood of arrest.

Related protocols: CTN-0050

Abstract:

Opioid use disorder (OUD) is a chronic, relapsing condition with severe negative health consequences. Previous studies have reported that 5-year abstinence is a good predictor of reduced likelihoods of relapse, but factors that shape long-term opioid abstinence are poorly understood.

The present study is based on data from a prospective study of 699 adults with OUD who had been randomized to either methadone or buprenorphine/naloxone and who were followed for at least 5 years (CTN-0050, Long Term Follow-Up of START Patients). During the 5 years prior to the participants’ last follow-up interview, 232 (33.2%) had achieved 5-year abstinence from heroin. Of those 232, 145 (20.7% of the total) had remained abstinent from both heroin and other opioids (e.g., hydrocodone, oxycodone, other opioid analgesics, excluding methadone or buprenorphine). Compared to non-abstinent individuals, those in both categories of opioid abstinence had lower problem severity in health and social functioning at the final follow-up. Logistic regression results indicated that cocaine users and injection drug users were less likely to achieve 5-year heroin abstinence, whereas Hispanics (vs. whites) and those treated in clinics on the West Coast (vs. East) were less likely to achieve 5-year abstinence from heroin and other opioids. For both abstinence category groups, abstinence was positively associated with older age at first opioid use, lower impulsivity, longer duration of treatment for OUD, and greater social support.

Conclusions: Given the current opioid crisis, this study contributes valuable information by identifying correlates of long-term opioid abstinence that are important for efforts to facilitate stable recovery. Reducing cocaine use and injection drug use and increasing social support and retention in treatment may help maintain long-term abstinence from opioids among individuals treated with agonist pharmacotherapy.

Related protocols: CTN-0050

Abstract:

Uncovering heterogeneities in longitudinal patterns (trajectories) of opioid use among individuals with opioid use disorder can increase our understanding of disease progression and treatment responses to improve care. The present study aims to identify distinctive opioid use trajectories and factors associated with those patterns among participants randomized to treatment with methadone (MET) or buprenorphine + naloxone (BUP). Growth mixture modeling was applied to identify distinctive opioid use trajectories among 795 opioid users after their enrollment in CTN-0027 (CTN START trial), a multisite trial during 2006 to 2009, with follow-up interviews conducted during 2011 to 2014 (CTN-0050 START Follow-up trial).

Four distinctive trajectories were identified based on opioid use over the follow-up period: low use (42%), high use (22.3%), increasing use (17.1%), and decreasing use (18.6%). Greater odds of being in the high use group (relative to low use) was associated with Hispanics (relative to African American, odds ratio [OR] 3.21), injection drug use (OR 2.12), higher mental health functioning at baseline (OR 1.23), location on the West Coast (vs. East Coast, OR 2.15), and randomization to BUP (relative to MET, OR 1.53). High use and increasing use groups had greater severity in problems related to drug, employment, legal, and social/family relationships, and worsened mental health functioning at follow-up. Participation in treatment significantly accounted for both within and between-group differences in opioid use.

A very promising finding is that the largest group (more than 40% of the sample) demonstrated a consistently low level of use after entering the medication trial. In contrast, approximately 17% of the participants gradually increased their opioid use after they initially reduced use, and another 19% did not respond well initially, but gradually decreased use over time.

Conclusions: The study findings underscore the importance of keeping opioid-dependent individuals in treatment and making treatment more widely available and accessible. Identifying factors that may account for distinctive opioid use trajectory patterns can further information policy decisions and clinic practice in targeting those at greatest need for opioid treatment.

Related protocols: CTN-0027, CTN-0050

Abstract:

This is the primary outcomes article for CTN-0050.

This study, a long-term follow-up of patients from the NIDA Clinical Trials Network’s Starting Treatment with Agonist Replacement Therapy (START, CTN-0027), aimed to compare long-term outcomes among participants randomized to buprenorphine (BUP) or methadone (MET), including mortality, opioid use status during/after 60-month follow-up, treatment participation status and retention over the 60-month period, and the effects of each type of opioid replacement treatment (BUP or MET) on level of opioid use over the 60-month period. Follow-up was conducted in 2011-2014 on 1,080 opioid-dependent participants entering 7 opioid treatment programs in the US between 2006-2009 and randomized (within each program) to receive open-label buprenorphine/naloxone or methadone for up to 24 weeks; 795 participants completed in-person interviews (~74% follow-up interview rate) covering, on average, 4.5 years.

Analysis revealed no difference in mortality between the two randomized conditions, with 23 (3.6%) of 630 participants randomized to buprenorphine having died, versus 26 (5.8%) of 450 randomized to methadone. Opioid use at follow-up was higher among participants randomized to buprenorphine relative to methadone (42.8% vs. 31.7% positive opioid urine specimens; 5.8 days vs. 4.4 days of past 30-day heroin use). Opioid use over the follow-up period by randomization condition was also significant, mostly due to less treatment participant among participants randomized to buprenorphine than methadone. Less opioid use was associated with both buprenorphine and methadone treatment (relative to no treatment); no difference was found between the two treatments. Individuals who are white or used cocaine at baseline responded better to methadone than to buprenorphine.

Conclusions: There are few differences in long-term outcomes between buprenorphine and methadone treatment for opioid dependence, and treatment with each medication is associated with a strong reduction in opioid use. This study, the first to follow opioid dependent individuals randomized to two opioid maintenance treatments prospectively over 5 or more years, is instructive about longer term outcomes and poses a challenge to the field to enhance retention in the opioid maintenance treatment. Many individuals with opioid use disorder cycle in and out of maintenance treatment, and this study confirms they show better outcomes when retained in that treatment instead. Efforts are needed, especially in the context of the current opioid epidemic, to improve both BUP and MET treatment retention.

Related protocols: CTN-0027, CTN-0050

Abstract:

This study examines the barriers and facilitators of retention among patients receiving buprenorphine/naloxone at eight community-based opioid treatment programs across the United States, as part of the National Drug Abuse Treatment Clinical Trials Network Long-Term Follow-Up of START (Starting Treatment with Agonist Replacement Therapies) Patients protocol, CTN-0050. Participants (n=105) were recruited up to three and a half years after having participated in a randomized clinical trial comparing the effect of buprenorphine/naloxone and methadone on liver function. Semi-structured interviews were conducted with 67 patients provided with buprenorphine/naloxone who had terminated early and 38 patients who had completed at least 24 weeks of the trial. Qualitative data were analyzed using the constant comparison method.

Barriers to buprenorphine/naloxone retention that emerged included factors associated with: (1) the design of the clinical trial; (2) negative medication or treatment experience; and (3) personal circumstances. The facilitators comprised: (1) positive experience with the medication; (2) personal determination and commitment to complete; and (3) staff encouragement and support. The themes drawn from interviews highlight the importance of considering patients’ prior experience with buprenorphine/naloxone and methadone, medication preference, personal circumstances, and motivation to abstain from illicit use or misuse of opioids, as these may influence retention.

Conclusions: These findings contribute to the sparse literature on patient perspectives of barriers to retention among individuals receiving treatment with buprenorphine/naloxone for opioid dependence. Findings suggests a patient-centered approach to identify the treatment option that best meets the patients’ needs at the time may be the most effective method. Ongoing education of patients and staff regarding buprenorphine/naloxone, especially in comparison to methadone, and support from staff and peers are essential. Finally, local, state, and federal regulations and policies may need to be revisited to increase patient options to be treated with all FDA-approved medications for opioid dependence in as many practices as possible.

Related protocols: CTN-0050