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This paper reports on a cost-effectiveness study of protocol CTN-0007, designed to determine if prize-based contingency management (CM), which has been shown to improve treatment outcomes over usual care (UC) alone, is worth the additional cost to treatment agencies. Six methadone maintenance community-based treatment programs (CTPs) in the CTN participated, with a study sample of 388 participants, 190 in the UC condition and 198 in the CM condition (which combined usual care with contingency management).

The authors found that prize-based contingency management provided better patient outcomes than usual care, but required additional costs. Compared to usual care, the incremental cost of using prize-based contingency management to lengthen the longest duration of abstinence (LDA) by one week was $141. The incremental cost to obtain an additional stimulant-negative urine sample was $70. Whether this extra expenditure is worthwhile depends upon the value placed on these outcomes. Using only the benefit of averted crime, an acceptability curve developed by the authors demonstrates a cost-effectiveness benefit of 90%. However, this estimate is quite conservative because averted crime is only one of the many potential benefits of a reduction in substance abuse. By comparing this study to a companion study, the authors also found that adding prize-based contingency management to usual care may be more cost-effective in methadone maintenance clinics than in counseling-based drug-free clinics. Further empirical analyses are needed to help policy makers decide whether CM is worth the extra expense; this paper helps to build an empirical basis for these important decisions.

Related protocols: CTN-0007-A-2

A trial comparing extended-release naltrexone and sublingual buprenorphine-naloxone demonstrated higher relapse rates in individuals randomized to extended-release naltrexone. The effectiveness of treatment might vary based on patient characteristics. We hypothesized that causal machine learning would identify individualized treatment effects for each medication.

This is a secondary analysis of a multicenter randomized trial (CTN-0051, X:BOT) that compared the effectiveness of extended-release naltrexone versus buprenorphine-naloxone for preventing relapse of opioid misuse. Three machine learning models were derived using all trial participants with 50% randomly selected for training (n = 285) and the remaining 50% for validation. Individualized treatment effect was measured by the Qini value and c-for-benefit, with the absence of relapse denoting treatment success. Patients were grouped into quartiles by predicted individualized treatment effect to examine differences in characteristics and the observed treatment effects.

The best-performing model had a Qini value of 4.45 (95% confidence interval, 1.02–7.83) and a c-for-benefit of 0.63 (95% confidence interval, 0.53–0.68). The quartile most likely to benefit from buprenorphine-naloxone had a 35% absolute benefit from this treatment, and at study entry, they had a high median opioid withdrawal score (P < 0.001), used cocaine on more days over the prior 30 days than other quartiles (P < 0.001), and had highest proportions with alcohol and cocaine use disorder (P = 0.02). Quartile 4 individuals were predicted to be most likely to benefit from extended-release naltrexone, with the greatest proportion having heroin drug preference (P = 0.02) and all experiencing homelessness (P < 0.001).

Conclusions: Causal machine learning identified differing individualized treatment effects between medications based on characteristics associated with preventing relapse.

Related protocols: CTN-0051

This is the primary outcomes paper for CTN-0124.

This paper aims to address the challenges in providing adequate access to Medications for Opioid Use Disorder (MOUDs) within underserved areas by examining the potential role of pharmacies and proposing actionable strategies for improvement. The health system faces increasing criticism for failure to provide adequate access to MOUDs. Pharmacies are being promoted as an asset to increase MOUD access in rural and underserved areas.

Method: An engineering systems analysis approach was employed to investigate ways to enhance pharmacy roles in delivering MOUDs in underserved regions. Interviews were conducted with community pharmacists, pharmacy associations, and addiction treatment experts. Innovation development techniques with experts from inside and outside the field were used to create recommendations.

Results: The findings underscore the importance of embracing technological advancements to overcome resource limitations and expand MOUD access in underserved areas. When our project began, we believed pharmacy roles related to MOUD distribution could expand through traditional means. We now feel that expansion is practical only through adoption of recent developments in information and communication technology. Our recommendations offer actionable strategies to expand MOUD availability in underserved areas. Technological changes can address stigma and mindsets, workflow simplification, family engagement, integration with other parts of the health system, reimbursement practice, and regulation.

Conclusions: Implementing pertinent technological innovations could augment MOUD availability within the pharmacy sector, thus addressing the pressing need for improved access to treatment in underserved communities. These technological changes would expand MOUD access within a field constrained by limited and diminishing resources.

Related protocols: CTN-0124

Opioid use disorder (OUD) is associated with chronic pain. This study investigated the association between medication treatments for OUD and pain in a post-hoc secondary analysis of a randomized trial of methadone versus buprenorphine.

1241 individuals with OUD participated in an open label, pragmatic randomized trial of methadone vs. buprenorphine/naloxone in nine treatment programs licensed to dispense agonist medication for OUD between 2006 and 2009. In this post-hoc analysis, pain was dichotomized (present or not present) using responses from the Short Form-36. Logistic regression models were fit to test the effect of (1) having baseline pain on week 24 retention, (2) treatment assignment on improvement in pain among those reporting pain at baseline, and (3) pain improvement at week 4 on 233k 24 retention among those reporting pain at baseline.

Analysis revealed that almost half (48.2%) of the sample reported pain at baseline. Participants with baseline pain did not significantly differ in week 24 retention compared to those without baseline pain. Among those reporting pain at baseline, there was no significant difference between treatment arms in improvement of pain at week 4, but improvement in pain at week 4 was associated with significantly greater odds of being retained at week 24.

Conclusions: Despite limitations, this study highlights the high prevalence of baseline pain in individuals with OUD and the significant portion of those individuals who continue to report pain despite treatment with agonist medication. Further research is needed to confirm the findings of this study, including the association between pain and retention and pain outcomes in individuals on medications for OUD.

Related protocols: CTN-0027

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

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

The natural course of prescription opioid use disorder has not been examined in longitudinal studies. This study examined correlates of opioid abstinence over time after completing a treatment trial for prescription opioid dependence.

The multi-site Prescription Opioid Addiction Treatment Study (POATS) examined different durations of buprenorphine-naloxone and different intensities of counseling to treat prescription opioid dependence. Following the clinical trial, a longitudinal study was conducted from March 2009-January 2013. At 18, 30, and 42 months after treatment entry, telephone interviews were conducted (N=375). In this exploratory, naturalistic study, logistic regression analyses examined the association between treatment modality (including formal treatment and mutual help (i.e., 12-step programs)) and opioid abstinence rates at the follow-up assessments.

At the three follow-up assessments, approximately half of the participants reported engaging in current substance use disorder treatment (47-50%). The most common treatments were buprenorphine maintenance (27-35%) and mutual-help group attendance (27-30%), followed by outpatient counseling (18-23%) and methadone maintenance (4%).

In adjusted analyses, current opioid agonist treatment showed the strongest association with current opioid abstinence (ORs=5.4, 4.6, and 2.8 at the three assessments), followed by current mutual-help attendance (ORs=2.2, 2.7, and 1.9); current outpatient counseling was not significantly associated with abstinence in the adjusted models.

Conclusions: This study, using long-term follow-up data from the largest randomized trial of treatment for prescription opioid dependence to date, found that ongoing treatment was strongly associated with odds of opioid abstinence up to 42 months following the trial. Although current opioid agonist treatment had the strongest association with abstinence, mutual-help attendance was also significantly associated with abstinence. Critically, mutual-help attendance was associated with an additive benefit among those receiving opioid agonist treatment and was also associated with abstinence in those not receiving agonist treatment. Adults with prescription opioid dependence appear to benefit from continued medication and mutual-help participation as part of long-term, ongoing care.

Related protocols: CTN-0030, CTN-0030-A-3

Addressing opioid use disorder (OUD), heroin and fentanyl use, and escalating rates of overdose deaths in the United States is a top priority. FDA-approved medications to treat OUD include methadone, buprenorphine, and naltrexone. Both naltrexone and buprenorphine have short- and long-acting formulations, and, unlike methadone, which can be dispensed only from approved facilities, naltrexone and buprenorphine can be prescribed in office-based settings by physicians or other prescribing providers. As new evidence regarding the effectiveness and cost-effectiveness of these treatment is established, providers, payers, and other stakeholders need to understand the resources and associated costs of implementation and ongoing provision of different treatment models.

This study describes the approach and results of a comprehensive multisite cost analysis of the first head-to-head randomized clinical trial in the U.S. of extended-release injectable naltrexone (XR-NTX) and buprenorphine-naloxone (BUP-NX) for preventing opioid relapse (NIDA Clinical Trials Network study CTN-0051). Cost data were collected for 3 intervention phases: program start-up, inpatient detoxification, and up to 24 weeks of medication induction and management visits (post detoxification). Cost analyses were from the healthcare sector perspective (2015 US$); patient costs are also reported. Site visits were conducted, with a cost survey administered to each of the 8 participating treatment programs, and study data on medication and services utilization were analyzed. Nationally representative sources were used to estimate unit costs. Uncertainty was evaluated in sensitivity analyses.

Analysis revealed that mean start-up costs were $1071 per program for XR-NTX and $828 per program for BUP-NX. Mean costs per participant were $5416 for XR-NTX (57% detoxification, 37% medication, 3% provider, 3% patient) and $4148 for BUP-NX (64% detoxification, 12% medication, 10% provider, 14% patient). Total cost per participant ranged by site from $2979 to $8963 for XR-NTX and from $2521 to $6486 for BUP-NX.

Conclusions: For treatment providers, offering XR-NTX and/or BUP-NX as part of existing detoxification treatment modalities generates modest costs in addition to the costs of detoxification, which vary substantially among the 8 sites. From the patient’s perspective, the costs associated with medication management visits may be a barrier for some individuals considering these treatments.

Related protocols: CTN-0051

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

Currently, no pharmacogenetic tests for selecting an opioid-dependence pharmacotherapy have been approved by the U.S. Food and Drug Administration. This study aimed to determine the effects of variants in 11 genes on dropout rate and dose in patients receiving methadone or buprenorphine/naloxone. Variants in 6 pharmacokinetic genes (CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4) and 5 pharmacodynamic genes (HTR2A, OPRM1, ADRA2A, COMT, SLC6A4) were genotyped in samples from a 24-week, randomized, open-label trial of methadone and buprenorphine/naloxone for the treatment of opioid dependence (n=764; 68.7% male). Genotypes were then used to determine the metabolism phenotype for each pharmacokinetic gene. Phenotypes or genotypes for each gene were analyzed for association with dropout rate and mean dose.

Results found that the genotype for 5-HTTLPR in the SLC6A4 gene was nominally associated with dropout rate when the methadone and buprenorphine/naloxone groups were combined. When the most significant variants associated with dropout rate were analyzed using pairwise analyses, SLC6A54 (5-HTTLPR) and COMT (Val158Met; rs4860) had nominally significant associations with dropout rate in methadone patients. None of the genes analyzed in the study were associated with mean dose of methadone or buprenorphine/naloxone.

Conclusions: This study suggests that functional polymorphisms related to synaptic dopamine or serotonin levels may predict dropout rates during methadone treatment. Patients with the S/S genotype at 5-HTTLPR in SLC6A4 or the Val/Val genotype at Val158Met in COMT may require additional treatment to improve their chances of completing addiction treatment. Replication in other methadone patient populations will be necessary to ensure the validity of these findings.

Related protocols: CTN-0027, CTN-0027-A-1

The mu-opioid receptor (MOR) is the primary target of methadone and buprenorphine. The primary neuronal transcript of the OPRM1 gene, MOR-1, contains a ~13kb 3′ untranslated region with five common haplotypes in European-Americans. We analyzed the effects of these haplotypes on the percentage of opioid positive urine tests in European-Americans (n=582) during a 24-week, randomized, open-label trial of methadone or buprenorphine/naloxone (Suboxone) for the treatment of opioid dependence. A single haplotype, tagged by rs10485058, was significantly associated with patient urinalysis data in the methadone treatment group. Methadone patients with the A/A genotype at rs10485058 were less likely to have opioid-positive urine drug screens than those in the combined A/G and G/G genotypes group (relative risk = 0.76, 95% confidence intervals = 0.73-0.80, P=0.0064). Genotype at rs10485058 also predicted self-reported relapse rates in an independent population of Australian patients of European descent (n=1215) who were receiving opioid substitution therapy (P=0.003). In silico analysis predicted that miR-95-3p would interact with the G, but not the A allele of rs10485058, suggesting a potential mechanism for the observed pharmacogenetic effect.

Conclusions: These findings suggest that selection of a medication for opioid dependence based on rs10485058 genotype might improve outcomes in this ethnic group.

Related protocols: CTN-0027, CTN-0027-A-1

This is the Results Article for CTN-0066-Ot.

Elevated mortality has been observed among individuals with opioid use disorder (OUD) treated in addiction specialty clinics or programs. Information about OUD patients in general healthcare settings is needed in light of the current effort to integrate addiction services into primary healthcare systems. This study examined mortality rates, causes of death, and associated risk factors among patients with OUD in a large general healthcare system. Mortality data were linked with the electronic health records of 1,683 OUD patients cared for in a large university health system from 2006-2014 (UCLA of the former CTN Pacific Region Node).

There were 465 deaths confirmed (27.6% of the study participants), corresponding to a crude mortality rate of 68.7 per 1000 person-years and SMR of 15.9 (95% CI, 14.5-17.4). Drug overdose and disorder (19.4%), cardiovascular diseases (16.9%), cancer (16.3%), and infectious diseases (14.5%, including 12% hepatitis C virus [HCV]) were the leading causes of death. HCV (HR: 2.08, 95% CI, 1.68-2.59) and cannabis use disorder (HR: 1.63, 95% CI, 1.28-2.07) were two clinically important indicators of overall mortality risk. Chronic pain (AHR: 1.92, 95% CI, 1.16-3.19) and tobacco use disorder (AHR: 2.88; 95% CI, 1.80-4.63) were associated with increased risk of cardiovascular death, HCV infection with cancer mortality risk (AHR: 2.51, 95% CI, 1.47-4.28), and alcohol use disorder with liver-related mortality risk (AHR: 5.06, 95% CI, 2.72-9.42).

Conclusions: Patients with OUD in a general healthcare system demonstrated alarmingly high morbidity and mortality, which challenges health care systems to find innovative ways to identify and treat patients with substance use disorder. Given the chronic, relapsing nature of OUD, and high medical and psychiatric comorbidity, continued care encompassing screening, early intervention, support, and monitoring is essential.

Related protocols: CTN-0066-Ot

Although individuals in substance use disorders (SUD) treatment continue to smoke at high rates, regulatory policy and programming changes promoting tobacco cessation are being implemented, and some patients quit successfully. This study examined associations of smoking patterns, tobacco advertising receptivity, anti-tobacco message awareness, health risk perception, attitudes toward addressing smoking and availability of smoking cessation services with quitting smoking during SUD treatment. Surveys were completed by 1127 patients in 24 programs chosen randomly, stratified by program type (residential, methadone maintenance, outpatient), from among publicly funded, adult treatment programs within the NIDA Clinical Trials Network. Among respondents who had been in SUD treatment for at least one month, there were 631 current smokers and 52 former smokers who reported quitting smoking during treatment for at least one month prior to survey completion; these respondents comprised our sample (N=683). Results showed that participants who reported health concerns as a reason for quitting were 1.27 times more likely to have quit during treatment than those reporting health concerns affected quitting a little or not at all. Additionally, participants who reported that smoking cessation was part of their personal treatment plan during SUD treatment were 1.08 times more likely to have quit during treatment. Participants in methadone treatment were 49% less likely to report successfully quitting during treatment than those in outpatient treatment.

Conclusions: Results indicated that some smokers in SUD treatment successfully quit smoking during treatment, although their numbers were low. Participants’ reports of health concerns as a reason for quitting and including smoking cessation in personal, SUD treatment plans may hold promise for inclusion in smoking cessation interventions. The challenge of developing cost-effective, easy to implement, and individualized smoking cessation interventions to increase quit rates among smokers in SUD treatment continues.

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

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