Unobserved versus observed office buprenorphine/naloxone induction: A pilot randomized clinical trial

Physician adoption of buprenorphine treatment of opioid dependence may be limited in part by concerns regarding the induction process. Although national guidelines recommend observed induction, some physicians utilize unobserved induction outside the office. The aim of this pilot randomized clinical trial was to assess preliminary safety and effectiveness of unobserved versus observed office buprenorphine/naloxone induction among patients entering a 12-week primary care maintenance study. Participants (N = 20) with DSM-IV opioid dependence were randomly assigned to unobserved or office induction, stratifying by past buprenorphine use. All patients received verbal and written instructions. A withdrawal scale was used during initiation and to monitor treatment response. Clinic visits occurred weekly for 4 weeks then decreased to monthly. The primary outcome, successful induction one week after the initial clinic visit, was defined as retention in buprenorphine/naloxone treatment and being withdrawal free. Secondary outcomes included prolonged withdrawal beyond 2 days after medication initiation and stabilization at week 4, defined as being in treatment without illicit opioid use for the preceding 2 weeks. Outcome results were similar in the two groups: 6/10 (60%) successfully inducted in each group, 3/10 (30%) experienced prolonged withdrawal, and 4/10 (40%) stabilized by week 4. These pilot study results suggest comparable safety and effectiveness of unobserved and office induction and point toward utilization of non-inferiority design during future definitive protocol development. By addressing an important barrier for physician adoption, further validation of the unobserved buprenorphine induction method will hopefully lead to increased availability of effective opioid dependence treatment.     

Buprenorphine and methadone maintenance in jail and post-release: a randomized clinical trial

Buprenorphine has rarely been administered as an opioid agonist maintenance therapy in a correctional setting. This study introduced buprenorphine maintenance in a large urban jail, Rikers Island in New York City. Heroin-dependent men not enrolled in community methadone treatment and sentenced to 10-90 days in jail (N=116) were voluntarily randomly assigned either to buprenorphine or methadone maintenance, the latter being the standard of care for eligible inmates at Rikers. Buprenorphine and methadone maintenance completion rates in jail were equally high, but the buprenorphine group reported for their designated post-release treatment in the community significantly more often than did the methadone group (48% vs. 14%, p<.001). Consistent with this result, prior to release from Rikers, buprenorphine patients stated an intention to continue treatment after release more often than did methadone patients (93% vs. 44%, p<.001). Buprenorphine patients were also less likely than methadone patients to withdraw voluntarily from medication while in jail (3% vs. 16%, p<.05). There were no post-release differences between the buprenorphine and methadone groups in self-reported relapse to illicit opioid use, self-reported re-arrests, self-reported severity of crime or re-incarceration in jail. After initiating opioid agonist treatment in jail, continuing buprenorphine maintenance in the community appears to be more acceptable to offenders than continuing methadone maintenance.     

Results of a pilot randomized controlled trial of buprenorphine for opioid dependent women in the criminal justice system

Aims

Recent studies have demonstrated the efficacy of both methadone and buprenorphine when used with opioid dependent men transitioning from prison to the community, but no studies have been conducted with women in the criminal justice (CJ) system. The aim of this study was to determine the efficacy of buprenorphine for relapse prevention among opioid dependent women in the CJ system transitioning back to the community.

Methods

36 women under CJ supervision were recruited from an inpatient drug treatment facility that treats CJ individuals returning back to the community. Nine were enrolled in an open label buprenorphine arm then 27 were randomized to buprenorphine (n = 15) or placebo (n = 12; double-blind). All women completed baseline measures and started study medication prior to release. Participants were followed weekly, provided urine drug screens (UDS), received study medication for 12 weeks, and returned for a 3-month follow-up. Intent-to-treat analyses were performed for all time points through 3 month follow-up.

Results

The majority of participants were Caucasian (88.9%), young (M ± SD = 31.8 ± 8.4 years), divorced/separated (59.2%) women with at least a high school/GED education (M ± SD = 12 ± 1.7 years). GEE analyses showed that buprenorphine was efficacious in maintaining abstinence across time compared to placebo. At end of treatment, 92% of placebo and 33% of active medication participants were positive for opiates on urine drug screen (Chi-Square = 10.9, df = 1; p < 0.001). However, by the three month follow-up point, no differences were found between the two groups, with 83% of participants at follow-up positive for opiates.

Conclusions

Women in the CJ system who received buprenorphine prior to release from a treatment facility had fewer opiate positive UDS through the 12 weeks of treatment compared to women receiving placebo. Initiating buprenorphine in a controlled environment prior to release appears to be a viable strategy to reduce opiate use when transitioning back to the community.     

Brief versus extended counseling along with buprenorphine/naloxone for HIV-infected opioid dependent patients

Untreated opioid dependence adversely affects HIV outcomes. Integrating buprenorphine/naloxone into HIV treatment settings is feasible; however, the optimal level of counseling has not been established. We conducted a 12-week randomized clinical trial of physician management (PM) versus PM plus enhanced medical management (EMM) in 47 subjects. At 12 weeks, there were no differences between the two groups in percentage of opioid negative urines (63.6% PM vs. 69.0% PM + EMM, p = .5), maximum duration of continuous abstinence (4.9 weeks PM vs. 5.2 weeks PM + EMM, p = .8) or retention (80% PM vs. 59% PM + EMM, p = .1). The percentage of subjects with detectable HIV viral loads decreased from 58% at baseline to 40% at 12 weeks across both groups (p = .02 for time) with no between group differences (p = .84 and p = .27 for the interaction). Providing more extensive counseling beyond PM is feasible in an HIV clinic, but we are unable to detect an improvement in outcomes associated with these services.     

Leaving buprenorphine treatment: Patients' reasons for cessation of care

Many opioid-dependent patients leave treatment prematurely. This study is a planned secondary analysis from a randomized trial of counseling for African Americans (N = 297) entering buprenorphine treatment at one of two outpatient programs. This study examines: (1) whether patients’ initial treatment duration intentions prospectively predict retention; and (2) patients’ reasons for leaving treatment. Participants were queried about their treatment duration intentions at treatment entry, and their reasons for leaving treatment at 6-month follow-up. At baseline, 28.0% reported wanting to stay in buprenorphine treatment less than 6 months, while 42.1% actually left buprenorphine treatment within 6 months. However, participants intending short-term buprenorphine at the outset were not at elevated risk of early treatment discontinuation (OR = 1.15; p = .65). Participants attributed treatment cessation predominantly to conflicts with staff, involuntary discharge, and perceived inflexibility of the program. Future research should examine patient-centered models of buprenorphine treatment that could improve retention.     

Optimizing the impact of medications for opioid use disorder at release from prison and jail settings: A microsimulation modeling study

BackgroundWe examined the impact of expanded access to medications for opioid use disorder (MOUD) in a unified prison and jail system on post-release, opioid-related overdose mortality.MethodsWe developed a microsimulation model to simulate a population of 55,000 persons at risk of opioid-related overdose mortality in Rhode Island. The effect of an extended-release (XR) naltrexone only intervention and the effect of providing access to all three MOUD (i.e., methadone, buprenorphine, and XR-naltrexone) at release from incarceration on cumulative overdose death over eight years (2017–2024) were compared to the standard of care (i.e., limited access to MOUD).ResultsIn the standard of care scenario, the model predicted 2385 opioid-related overdose deaths between 2017 and 2024. An XR-naltrexone intervention averted 103 deaths (4.3% reduction), and access to all three MOUD averted 139 deaths (5.8% reduction). Among those with prior year incarceration, an XR-naltrexone only intervention and access to all three MOUD reduced overdose deaths by 22.8% and 31.6%, respectively.ConclusionsExpanded access to MOUD in prison and jail settings can reduce overdose mortality in a general, at-risk population. However, the real-world impact of this approach will vary by levels of incarceration, treatment enrollment, and post-release retention.     

Change in symptoms of erectile dysfunction in depressed men initiating buprenorphine therapy

Aims

The aim of this study is to describe the change in erectile dysfunction (ED) symptoms in the first 12 weeks of outpatient buprenorphine therapy.

Background

Erectile dysfunction is highly prevalent in men who use illicit opioids when compared with the general population. To date, no study has examined ED symptoms over time in men initiating buprenorphine therapy for opioid dependence.

Methods

A randomized, double blind, placebo-controlled trial was conducted to determine whether escitalopram treatment of depressive symptoms begun 1 week prior to buprenorphine induction would improve treatment retention. Male patients completed the International Index of Erectile Function scale at baseline prior to induction and monthly thereafter. A score of 25 or less on the erectile function domain (range 1–30) is considered indicative of erectile dysfunction.

Findings

A total of 111 male subjects enrolled: mean age 38.5 (± 9.7) years, 80.1% non-Hispanic Caucasian; 67.3% reported heroin as their opioid of choice. Mean IIEF at baseline was 20.4 (± 10.5). At baseline, 44.1% of the entire cohort had erectile dysfunction; among those who identified as sexually active at baseline, 26.1% had ED. Baseline erectile function was inversely and significantly correlated with age (r = − .27, p = .006), but was not associated significantly with race, heroin use, years of opioid use, smoking, or hazardous use of alcohol. Compared to baseline, mean erectile function was significantly improved (p = .001) at 3 months, and sexual desire (p = .002) improved significantly at both 2- and 3-month assessments.

Conclusion

Erectile dysfunction is highly prevalent in depressed males using illicit opioids. Men who remain in buprenorphine treatment for 3 months show improvement in erectile function and sexual desire.     

Time to initiation of treatment for neonatal abstinence syndrome in neonates exposed in utero to buprenorphine or methadone

Background

The recommended standard of care calls for treating opioid-dependent pregnant women with methadone and observing neonates exposed in utero for five to seven postnatal days to see if treatment for neonatal abstinence syndrome (NAS) is needed. Data from a large multi-site randomized clinical trial comparing buprenorphine vs. methadone for the treatment of opioid dependence during pregnancy suggest buprenorphine-exposed neonates had less severe NAS, but may require pharmacologic treatment for NAS later than methadone-exposed neonates. The present study examined whether time to pharmacologic treatment initiation differed in a relatively large non-blinded clinical sample of buprenorphine- vs. methadone-exposed neonates treated for NAS.

Methods

Medical records for 75 neonates exposed to buprenorphine (n = 47) or methadone (n = 28) in utero who required treatment for NAS were examined. Time elapsed between birth and initiation of pharmacologic treatment was calculated for each neonate and time to treatment initiation compared between groups.

Results

Median time to treatment initiation (hours:minutes, IQR) was significantly later in buprenorphine- vs. methadone-exposed neonates (71:02, 44:21–96:27 vs. 34:12, 21:00–55:41, respectively, p < .001). Estimates of mean time to treatment initiation from parametric analyses that adjusted for maternal and neonatal characteristics were very similar (73:10 (95% CI: 61:00–87:18) vs. 42:36 (95% CI: 33:06–53:30), respectively, p = .0005). This difference was not dependent on maternal age or neonatal sex, gestational age, or birth weight.

Conclusions

These findings confirm results from randomized clinical trials, adding generality to the observation that buprenorphine-exposed neonates require treatment significantly later than methadone-exposed neonates.     

Retention in methadone and buprenorphine treatment among African Americans

Methadone has been the most commonly used pharmacotherapy for the treatment of opioid dependence in U.S. public sector treatment, but availability of buprenorphine as an alternative medication continues to increase. Drawing data from two community-based clinical trials that were conducted nearly contemporaneously, this study examined retention in methadone versus buprenorphine treatment over 6 months among urban African Americans receiving treatment in one of four publicly-funded programs (N = 478; 178 methadone; 300 buprenorphine). Adjusting for confounds related to medication selection, survival analysis revealed that buprenorphine patients are at substantially higher risk of dropout compared to methadone patients (HR = 2.43; p < .001). Buprenorphine's retention disadvantage appears to be concentrated in the earlier phases of treatment (approximately the first 50 days), after which risk of subsequent dropout becomes similar for the two medications. These findings confirm a retention disparity between methadone and buprenorphine in this population, and suggest potential avenues for future research to enhance retention in buprenorphine treatment.     

Italy's electronic health record system for opioid agonist treatment

Electronic health record systems (EHRs) play an increasingly important role in opioid agonist treatment. In Italy, an EHR called the Multi Functional Platform (MFP) is in use in 150 opioid-agonist treatment facilities in 8 of Italy's 23 regions. This report describes MFP and presents 2010 data from 65 sites that treated 8145 patients, of whom 72.3% were treated with methadone and 27.7% with buprenorphine. Patients treated with buprenorphine compared to methadone were more likely to be male (p < .01) and younger (p < .001). Methadone compared to buprenorphine patients had a higher percentage of opioid-positive urine tests (p < .001) and longer mean length of stay (p = .004). MFP has been implemented widely in Italy and has been able to track patient outcomes across treatment facilities. In the future, this EHR system can be used for performance improvement initiatives.     

From methadone to buprenorphine: Changes during a 10 year period within a national opioid maintenance treatment programme

Opioid maintenance treatment (OMT) is the most widely used treatment for opioid dependence. Maintenance programmes differ in various aspects and may also change over time. This paper investigates the changes in treatment practices within a national OMT programme during a 10 year period (2002–2011), especially with regard to the prescribing of methadone and buprenorphine. Data (n = 34,001) were collected by annual assessments questionnaires. In 2002, only 16% of the OMT patients received buprenorphine as their maintenance medication. By 2011 this percentage had increased significantly (p < .001) to 50.3%. In the same period the number of patients more than tripled (from 1,984 to 6,640, p < .001), and programme attrition rates decreased (p = .020). This relatively rapid shift is a part of the increasing reliance of addiction medicine upon a range of medications administered by different routes which has not been previously charted within a national treatment programme.     

Transitioning opioid-dependent patients from detoxification to long-term treatment: efficacy of intensive role induction

Despite findings that opioid detoxification serves little more than a palliative function, few patients who enter detoxification subsequently transition to long-term treatment. The current study evaluated intensive role induction (IRI), a strategy adapted from a single-session intervention previously shown to facilitate engagement of substance-dependent patients in drug-free treatment. IRI was delivered either alone or combined with case management (IRI + CM) to determine the capacity of each condition to enhance transition and engagement in long-term treatment of detoxification patients. Study participants were 240 individuals admitted to a 30-day buprenorphine detoxification delivered at a publicly funded outpatient drug treatment clinic. Following clinic intake, participants were randomly assigned to IRI, IRI + CM, or standard clinic treatment (ST). Outcomes were assessed in terms of adherence and satisfaction with the detoxification program, detoxification completion, and transition and retention in treatment following detoxification. Participants who received IRI and IRI + CM attended more counseling sessions during detoxification than those who received ST (both ps < .001). IRI, but not IRI + CM participants, were more likely to complete detoxification (p = .017), rated their counselors more favorably (p = .01), and were retained in long-term treatment for more days following detoxification (p = .005), than ST participants. The current study demonstrated that an easily administered psychosocial intervention can be effective for enhancing patient involvement in detoxification and for enabling their engagement in long-term treatment following detoxification.     

A randomized trial of intensive outpatient (IOP) vs. standard outpatient (OP) buprenorphine treatment for African Americans

Background

Buprenorphine is increasingly being used in community-based treatment programs, but little is known about the optimal level of psychosocial counseling in these settings. The aim of this study was to compare the effectiveness of OP and IOP level counseling when provided as part of buprenorphine treatment for opioid-dependent African Americans.

Methods

Participants were African American men and women starting buprenorphine treatment at one of two community-based clinics (N = 300). Participants were randomly assigned to OP or IOP. Measures at baseline, 3- and 6-month included the primary outcome of DSM-IV opioid and cocaine dependence criteria, as well as additional outcomes of illicit opioid and cocaine use (urine test and self-report), criminal activity, retention in treatment, Quality of Life, Addiction Severity Index composite scores, and HIV risk behaviors.

Results

Participants assigned to OP received, on average, 3.67 (SD = 1.30) h of counseling per active week in treatment. IOP participants received an average of 5.23 (SD = 1.68) h of counseling per active week (less than the anticipated 9 h per week of counseling). Both groups showed substantial improvement over a 6-month period on nearly all measures considered. There were no significant differences between groups in meeting diagnostic criteria for opioid (p = .67) or cocaine dependence (p = .63). There were no significant between group differences on any of the other outcomes. A secondary analysis restricting the sample to participants meeting DSM-IV criteria for baseline cocaine dependence also revealed no significant between-group differences (all ps > .05).

Conclusions

Buprenorphine patients receiving OP and IOP levels of care both show short-term improvements.     

Referral for substance abuse treatment and depression improvement among patients with co-occurring disorders seeking behavioral health services in primary care

This study examined the relationship between substance treatment referrals and depression improvement among 2,373 participants with concurrent substance use and depressive disorders enrolled in an integrated behavioral health program. Three groups of substance treatment referral status were identified: accessed treatment (n = 780), declined treatment (n = 315), and no referral for treatment (n = 1278). The primary outcome is improvement in depressive symptoms (PHQ-9 < 10 or ≥ 50% reduction). Using propensity score adjustments, patients accessing substance treatment were significantly more likely to achieve depression improvement than those who declined receiving treatment services (hazard ratio (HR) = 1.82, 95% confidence interval (CI): 1.50–2.20, p < 0.001) and those without a referral for treatment (HR = 1.13, 95% CI: 1.03–1.25, p = 0.014). Each 1 week delay in initiating a referral was associated with a decreased likelihood of depression improvement (HR = 0.97, 95% CI: 0.96–0.98, p < 0.001). Study findings highlight the need of enhancing early treatment contact for co-occurring substance use disorders in primary care.     

Criminal justice referral and incentives in outpatient substance abuse treatment

A substantial number of substance abusers entering outpatient psychosocial counseling treatment are referred from the criminal justice (CJ) system. This secondary analysis of previously published findings from a large (N = 415) multi-site trial of a prize-based abstinence incentive intervention ( Petry et al., 2005) examined the influence of CJ referral on usual care outcomes and response to the incentive procedure. CJ referrals (n = 138) were more likely than those not CJ referred (n = 277) to provide stimulant negative urine samples whether missing samples were counted as positive (50 versus 41%, p = .016) or as missing (96 versus 91%, p < .001). A significant interaction term was found only for percentage of treatment completers (p = .027). However, on that retention variable, and three additional drug use measures, significant incentive effects were confined to participants who entered treatment without referral from the criminal justice system. The study suggests that abstinence incentives should be offered as a first priority to stimulant users entering treatment without criminal justice referral. However, incentives can be considered for use with CJ-referred stimulant users based on the observation that best outcomes were obtained in CJ referrals who also received the abstinence incentive program.     

Methadone maintenance treatment may improve completion rates and delay opioid relapse for opioid dependent individuals under community corrections supervision

Aims

Several studies have demonstrated the importance of agonist therapies such as methadone and buprenorphine for preventing relapse for individuals being released from jail or prison to the community. No studies have examined the impact of methadone for increasing the completion of community supervision requirements and preventing opioid relapse for individuals under community corrections supervision. This observational study compared the community corrections completion rate and opioid relapse rate of individuals receiving methadone maintenance therapy (MMT) to individuals who did not.

Methods

Of the 2931 individuals enrolled under criminal justice supervision in the community, Treatment Accountability for Safer Communities (TASC), and who met criteria for opioid dependence, 329 (11%) individuals reported receiving MMT in the community.

Results

The majority of participants were White (79.8%) and male (63.5%), with a mean age of 31.33 years (SD = 9.18), and were under supervision for 10.4 months (SD = 9.1). MMT participants were less likely to fail out of supervision compared to individuals not in MMT (39.0% vs. 52.9%, p < 0.001), and had a lower rate of relapse (32.9%) and longer time to relapse (average days = 89.7, SD = 158.9) compared to the relapse rate (55.9%) and time to relapse (average days = 60.5, SD = 117.9) of those not on MMT.

Conclusions

While the observational nature of this study prevents causal inferences, these results suggest that utilization of MMT in community corrections may increase the likelihood of completing supervision requirements and delay time to opioid relapse. Providing agonist therapies to opioid dependent individuals under supervision appears to be a critical strategy in this important population.