Recent incarceration and buprenorphine maintenance treatment outcomes among human immunodeficiency virus–positive patients

Background: Opioid use disorder is a common cause of morbidity and mortality among people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Buprenorphine maintenance treatment (BMT) is an effective means of therapy, but patients with recent criminal justice involvement may need more support during BMT than other patients. The authors hypothesized that recently incarcerated BMT patients who initiated treatment in primary care would have poorer treatment outcomes than those who were not recently incarcerated. Methods: Investigators analyzed data from a multisite cohort study of BMT integrated into HIV care. Patients were stratified by self-reported incarceration in the 30 days before initiation of BMT. The outcomes of interest were 6- and 12-month treatment retention and self-reported opioid use. Investigators used multivariable logistic regression and hierarchical linear model, respectively, to evaluate the association between recent incarceration and these outcomes while adjusting for potential confounding variables. Results: Among 305 BMT patients living with HIV/AIDS, 39 (13%) reported recent incarceration. Patients with recent incarceration (vs. without) were more likely to be homeless, unemployed, and previously diagnosed with mental illness. Recent incarceration was not significantly associated with differences in 6-month (odds ratio [OR] = 0.95; 95% confidence interval [CI] = 0.46–1.98) and 12-month (OR = 0.57; 95% CI = 0.27–1.18) treatment retention or in self-reported opioid use (OR = 0.99; 95% CI = 0.51–1.92) after adjustment for potential confounding variables. Conclusions: Those with incarceration in the 30 days prior to BMT initiation were more likely to be homeless, unemployed, and previously diagnosed with mental illness than those without recent incarceration. However, no significant difference in self-reported opioid use or 6-month or 12-month retention in treatment was detected between those with and without recent incarceration. Future studies should confirm these findings with larger sample sizes. Encouraging formerly incarcerated individuals with opioid use disorder to initiate evidence-based treatments, including BMT, should be part of efforts to confront the opioid addiction epidemic in the United States.     

A Case Series of Buprenorphine/Naloxone Treatment in a Primary Care Practice

ABSTRACT

Physicians’ adoption of buprenorphine/naloxone treatment is hindered by concerns over feasibility, cost, and lack of comfort treating patients with addiction. We examined the use of buprenorphine/naloxone in a community practice by two generalist physicians without addiction training, employing a retrospective chart review. From 2006–2010, 228 patients with opiate abuse/dependence were treated with buprenorphine/naloxone using a home-induction protocol. Multiple co-morbidities including diabetes (23% of patients), hypertension (36%), Hepatitis C (43%), and depression (74%) were concurrently managed. In this diverse sample, 1/228 experienced precipitated withdrawal during induction. Of the convenience subsample analyzed (n = 28), 82% (+/?10%) had negative urine drug tests for opioids; 92% (+/?11%) were negative for cocaine; 88% (+/?12%) were positive for buprenorphine. This case series demonstrated feasibility and safety of a low-cost buprenorphine/naloxone home induction protocol employed by generalists. Concurrent treatment of multiple comorbidities conforms with the patient-centered medical home ideal. Randomized trials of this promising approach are needed.     

Effects of a High-Dose,Fast Tapering Buprenorphine Detoxification Program on Symptom Relief and Treatment Retention

Abstract

A large number of patients with heroin dependency fail to enter a treatment program because of dropping out during or immediately after detoxification. This article presents an open study of symptom relief of 10 patients withdrawing from heroin with a high-dose rapid tapering buprenorphine detoxification protocol. It also presents a pseudo-experimental comparison between 208 patients treated with a clonidine/dextropropoxiphene detoxification protocol and 246 patients treated with the high-dose rapid tapering buprenorphine detoxification protocol to evaluate differences in patients' ability to continue in treatment of addiction immediately after detoxification. The results indicate that 24 mg of sublingually administered buprenorphine beginning when the patient judges himself to be in a withdrawal state followed by another three days of daily administered and rapidly decreased doses resulted in a significant reduction of withdrawal symptoms. Also, when the clonidine/dextropropoxiphene protocol was replaced with this buprenorphine protocol the number of patients continuing in treatment immediately after discharge from the detoxification ward increased from 41.3% to 58.1%. Buprenorphine given in high doses with rapid tapering when withdrawal symptoms occur seems to offer an effective symptom-alleviating treatment, probably also decreasing the number of drop-outs after detoxification.     

Preference for brand-name buprenorphine is related to severity of addiction among outpatients in opioid maintenance treatment

As a form of opioid maintenance treatment, high-dose buprenorphine is increasingly being used in the United States. On the French market since 1996, it is the most commonly prescribed and frequently employed opioid maintenance treatment. For unknown reasons, the brand-name form is used far more often than the generic form (76–24%). The objective was to show that the patients' levels of addiction were differentiated according to the form of buprenorphine currently being used and to their previous experience of a different form. An observational study in 9 sites throughout France used self-assessment questionnaires filled out in retail pharmacies by all patients to whom their prescribed buprenorphine treatment was being delivered. The 151 canvassed pharmacies solicited 879 patients, of whom 724 completed the questionnaires. Participants were statistically similar to non-participants. The patients using the brand-name form subsequent to experience with the generic form exhibited a more elevated addiction severity index and a higher dosage than brand-name form users with no experience of a different form. Compared to generic users, their doses were higher, their was addiction more severe, and their alcohol consumption was more excessive; they were also more likely to make daily use of psychotropic substances. However, the level of misuse or illicit consumption was similar between these groups. Preferring the brand-name buprenorphine form to the generic form is associated with a higher level of severe addiction, a more frequent need for daily psychotropics, and excessive drinking; but the study was unable to show a causal link.     

Relapse prevention medications in community treatment for young adults with opioid addiction

ABSTRACT

Background: Despite the well-known effectiveness and widespread use of relapse prevention medications such as extended release naltrexone (XR-NTX) and buprenorphine for opioid addiction in adults, less is known about their use in younger populations. Methods: This was a naturalistic study using retrospective chart review of N = 56 serial admissions into a specialty community treatment program that featured the use of relapse prevention medications for young adults (19–26 years old) with opioid use disorders. Treatment outcomes over 24 weeks included retention and weekly opioid-negative urine tests. Results: Patients were of mean age 23.1, 70% male, 86% Caucasian, 82% with history of injection heroin use, and treated with either buprenorphine (77%) or XR-NTX (23%). The mean number of XR-NTX doses received was 4.1. Retention was approximately 65% at 12 weeks and 40% at 24 weeks, and rates of opioid-negative urine were 50% at 12 weeks and 39% at 24 weeks, with missing samples imputed as positive. There were no statistically significant differences in retention (t = 1.87, P = .06) or in rates of weekly opioid-negative urine tests (t = 1.96, P = .06) between medication groups, over the course of 24 weeks. The XR-NTX group had higher rates of weekly negative urine drug tests for other nonopioid substances (t = 2.83, P < .05) compared with the buprenorphine group. Males were retained in treatment longer and had higher rates of opioid-negative weeks compared with females. Conclusions: These results suggest that relapse prevention medications including both buprenorphine and XR-NTX can be effectively incorporated into standard community treatment for opioid addiction in young adults with good results. Specialty programming focused on opioid addiction in young adults may provide a promising model for further treatment development.     

Behavioral drug and HIV risk reduction counseling (BDRC) with abstinence-contingent take-home buprenorphine: a pilot randomized clinical trial

This pilot randomized clinical trial evaluated whether the efficacy of office-based buprenorphine maintenance treatment (BMT), provided with limited counseling or oversight of medication adherence is improved by the addition of individual drug counseling and abstinence-contingent take-home doses of buprenorphine. After a 2-week buprenorphine and stabilization period, heroin dependent individuals (n=24) in Muar, Malaysia were randomly assigned to Standard Services BMT (physician administered advice and support, and weekly, non-contingent medication pick-up) or Enhanced Services (nurse-delivered manual-guided behavioral drug and HIV risk reduction counseling (BDRC) and abstinence-contingent take-home buprenorphine (ACB), 7 day supply maximum). Outcomes included retention, proportion of opioid-negative urine tests, self-reported drug use, and self-reported HIV risk behaviors. 12/12 (100%) of Enhanced Services and 11/12 (92%) of Standard Services participants completed the entire protocol. The proportion of opioid-negative urine tests increased significantly over time for both groups (p<0.001), and the reductions were significantly greater in the Enhanced Services group (p<0.05); Enhanced Services group achieved higher overall proportions of opiate negative urine toxicology tests (87% vs. 69%, p=0.04) and longer periods of consecutive abstinence from opiates (10.3 weeks vs. 7.8 weeks, p=0.154). Both groups significantly reduced HIV risk behaviors during treatment (p<0.05), but the difference between Enhanced and Standard Services (26% vs. 17% reductions from the baseline levels, respectively) was not statistically significant (p=0.9). Manual-guided behavioral drug and HIV risk reduction counseling and abstinence-contingent take-home buprenorphine appear promising for adding to the efficacy of office-based BMT provided with limited drug counseling and medication oversight.     

Integrating buprenorphine treatment into a public healthcare system: the San Francisco Department of Public Health's office-based Buprenorphine Pilot Program

Despite well-documented efficacy, US physicians have been relatively slow to embrace the use of buprenorphine for the treatment of opioid dependence. In order to introduce and support the use of buprenorphine across the San Francisco Department of Public Health system of care, the Buprenorphine Pilot Program was initiated in 2003. Program treatment sites included a centralized buprenorphine induction clinic and program pharmacy, and three community-based treatment sites; two primary care clinics and a private dual diagnosis group practice. The target patient population consisted of opioid-dependent patients typically seen in an urban, public health setting, including individuals experiencing extreme poverty, homelessness/unstable housing, unemployment, polysubstance abuse/dependence, coexisting mental health disorders, and/or little psychosocial support. This program evaluation reviews patient characteristics, treatment retention, substance use over time, patient impressions, and provider practices for the 57 patients admitted between 9/1/03 and 8/31/05. At baseline, over 80% of patients were injecting heroin, over 40% were homeless, and over one-third were using cocaine. Outcomes included an overall one-year retention rate of 61%, a rapid and dramatic decline in opioid use, very positive patient impressions of the program and of buprenorphine, and significant shifts in provider practices over time.     

A Preliminary Investigation of Outcome Following Gradual or Rapid Buprenorphine Detoxification

Eight opioid-dependent individuals were maintained on daily sublingual buprenorphine (8 mg) for 28 days and assigned randomly to one of two outpatient detoxification schedules under double-blind, double-dummy conditions. The two detoxification schedules were buprenorphine gradual (36 days; N = 3) or buprenorphine rapid (12 days; N = 5). Outcome variables were subject- and observer-ratings of opioid withdrawal, treatment retention and illicitopioid use. Outcome measures were similar for the two groups during buprenorphine maintenance. Increases in subject-rated opioid withdrawal and illicit-opioid use, and a drop in treatment retention occurred during rapid detoxification. Stable subject-rated opioid withdrawal and treatment retention, and less illicit-opioid use occurred during gradual detoxification. These data suggest that gradual reduction in buprenorphine dose is likely to produce superior treatment outcomes than more rapid buprenorphine detoxification.     

Problem drinking in relation to treatment outcome among opiate addicts in methadone maintenance treatment

This study analyzed indicators of alcohol-related problems in opiate addicts before, during, and after leaving methadone maintenance treatment (MMT), in relation to illicit drug use and retention in treatment. The study was based on 204 patients, admitted to MMT for the first time between 1 January 1995 and 31 July 2000, and followed until 31 December 2000. Three measures were used to indicate alcohol use and alcohol-related problems; records of hospital care with an alcohol-related diagnosis, any treatment with alcohol-sensitizing drugs (disulfiram or calcium carbimide) during MMT, and results of the 5-hydroxytryptophol to 5-hydroxyindoleacetic acid ratio (5HTOL/5HIAA) in urine, a sensitive biomarker for recent drinking. Use of illicit drugs was determined by routine urine drug testing. About one third of the patients (n = 69) had a lifetime prevalence of hospital treatment for an alcohol-related diagnosis, 45 of whom had been hospitalized (mean 4.2 stays) prior to the start of MMT. There was a significant association (p<0.05) between the number of alcohol-related diagnoses prior to treatment and a positive 5HTOL/5HIAA test during MMT. The alcohol indicators first became positive on average 1.6 years after admission to treatment, compared with after about 4 months for illicit drugs. Use of cannabis or benzodiazepines was significantly associated with alcohol use. Female methadone patients with indications of alcohol-related problems relapsed more often into illicit drug use than did women without such indications (3.9 vs. 2.5 relapse periods/year; p<0.005), whereas no significant association was found for men. The results of the present study indicate that drinking problems among patients undergoing MMT is associated with an increased risk of relapse into illicit drug use and with discharge from treatment. Concurrent treatment of alcohol-related problems, including systematic monitoring of alcohol use, therefore should be recommended to reduce the risk for relapse into illicit drug use and improve overall treatment outcome in MMT.     

Feasibility of collaborative care treatment of opioid use disorders with buprenorphine during pregnancy

Background: Medication-assisted treatment with buprenorphine or methadone is recommended for pregnant patients with opioid use disorders (OUDs) to minimize adverse maternal and neonatal outcomes. Collaborative care approaches have been successfully utilized with office-based opioid treatment with buprenorphine in primary care settings, but research is significantly limited in the obstetric setting. Our aim with this study is to demonstrate the feasibility of a collaborative care model for pregnant patients with opioid use disorder. Methods: This is a case series of 16 pregnancies in 14 women initiated on office-based opioid treatment with buprenorphine in a perinatal mental health service embedded in 2 obstetric clinics. Patients are treated by a psychiatrist alongside their prenatal care provider and followed for up to 6 months postpartum and referred to ongoing substance abuse treatment to a community prescriber. Results: The average age of the patients was 30.3 years, and an average gestational age of 23.6 weeks at the time of referral. Treatment continued until delivery in 15 (93.8%) pregnancies, with an average duration of treatment of 14.5 weeks. The majority (60%) had a cesarean delivery. Twelve (80%) infants were admitted to the Neonatal Intensive Care Unit (NICU) for monitoring or treatment of neonatal abstinence syndrome, 14 (87.5%) patients continued or resumed treatment with buprenorphine postpartum at the time of discharge from our program, and 13 (81.3%) were referred to a community prescriber. Conclusions: A collaborative care approach to buprenorphine treatment is feasible during pregnancy. Further research is needed to improve the treatment of OUD during pregnancy.     

Abstinence-orientated buprenorphine replacement therapy for young adults in out-patient counselling

This study assessed treatment retention, compliance and completion of a 9-month buprenorphine replacement programme. In addition, changes in drug use and other relevant variables, as well as predictors of completion, were examined. Seventy-five opioid-dependent out-patients (mean age 26 years; 33% females) who aimed for opioid abstinence were enrolled into the study. Assessments were undertaken prior to buprenorphine induction and again at 3, 6 and 9 months. Forty patients (53%) completed the buprenorphine programme. At 9 months, 67 patients (87%) were still in counselling. Mean attendance rates for buprenorphine dosing and counselling sessions were 0.91 and 0.74, respectively. There were significant and persistent reductions in drug use during treatment with, however, a reversed tendency in the 9th month. Psychiatric problems escalated at 9 months, and three patients died during the detoxification phase. Completion was predicted by fewer previous treatment episodes. Detoxification from buprenorphine is associated with substantial psychological distress and an increased death risk. Buprenorphine replacement therapy should be continued until the patient chooses to leave, and close monitoring during the detoxification phase is essential.     

Integrating Buprenorphine Treatment into a Public Healthcare System: The San Francisco Department of Public Health's Office-Based Buprenorphine Pilot Program

Abstract

Despite well-documented efficacy, US physicians have been relatively slow to embrace the use of buprenorphine for the treatment of opioid dependence. In order to introduce and support the use of buprenorphine across the San Francisco Department of Public Health system of care, the Buprenorphine Pilot Program was initiated in 2003. Program treatment sites included a centralized buprenorphine induction clinic and program pharmacy, and three community-based treatment sites; two primary care clinics and a private dual diagnosis group practice. The target patient population consisted of opioid-dependent patients typically seen in an urban, public health setting, including individuals experiencing extreme poverty, homelessness/unstable housing, unemployment, polysubstance abuse/dependence, coexisting mental health disorders, and/or little psychosocial support. This program evaluation reviews patient characteristics, treatment retention, substance use over time, patient impressions, and provider practices for the 57 patients admitted between 9/1/03 and 8/31/05. At baseline, over 80% of patients were injecting heroin, over 40% were homeless, and over one-third were using cocaine. Outcomes included an overall one-year retention rate of 61%, a rapid and dramatic decline in opioid use, very positive patient impressions of the program and of buprenorphine, and significant shifts in provider practices over time.     

Efficacy and safety of a sublingual buprenorphine/naloxone rapidly dissolving tablet for the treatment of adults with opioid dependence: A randomized trial

This prospective, randomized, active-controlled, non-inferiority study evaluated the efficacy and safety of a sublingual buprenorphine/naloxone rapidly dissolving tablet (Zubsolv^®; buprenorphine/naloxone rapidly dissolving tablet) versus generic buprenorphine for induction of opioid maintenance among dependent adults. The study, conducted at 13 sites from June 2013 to January 2014, included a 2-day blinded induction phase and a 27-day open-label stabilization/maintenance phase. During the blinded induction, patients received fixed doses of buprenorphine/naloxone rapidly dissolving tablets or generic buprenorphine. During open-label stabilization/early maintenance, all patients received buprenorphine/naloxone rapidly dissolving tablets. The primary efficacy assessment was treatment retention at day 3; buprenorphine/naloxone rapidly dissolving tablets were considered non-inferior to generic buprenorphine if the lower limit of the 95% confidence interval for the difference between the treatments was ≥–10% in patients retained on day 3. Secondary assessments included opioid withdrawal symptoms and cravings as measured using the Clinical Opiate Withdrawal Scale, the Subjective Opiate Withdrawal Scale, and the opioid cravings visual analogue scale. Safety was also assessed. A total of 313 patients were randomly assigned to induction with generic buprenorphine or buprenorphine/naloxone rapidly dissolving tablets. The mean age was 38.4 years, and the mean duration of opioid dependence was 12.4 years. For the primary efficacy assessment, 235 of 256 patients (91.8%) were retained at day 3 and continued to the maintenance phase. The lower limit of the 95% confidence interval was ?13.7; thus, buprenorphine/naloxone rapidly dissolving tablets did not demonstrate non-inferiority to generic buprenorphine, and significantly more patients who received induction with generic buprenorphine (122/128 [95.3%]) were retained at day 3 compared with those who received induction with buprenorphine/naloxone rapidly dissolving tablets (113/128 [88.3%]; 95% confidence interval: ?13.7, ?0.4; p = 0.040). The rates of clinical response, as measured by the Clinical Opiate Withdrawal Scale, the Subjective Opiate Withdrawal Scale, and the visual analogue scale, were comparable among patients regardless of the induction medication. Treatment with buprenorphine/naloxone rapidly dissolving tablets was generally safe and reduced the severity of withdrawal symptoms and cravings.     

Colocating buprenorphine with methadone maintenance and outpatient chemical dependency services

Buprenorphine may be used to treat opioid dependence in office-based settings, but treatment models are needed to ensure access to psychosocial services needed by many patients. We describe a novel buprenorphine treatment program colocated with methadone maintenance and outpatient chemical dependency services. We conducted a retrospective chart review of the first 40 consecutive patients initiating buprenorphine treatment in this program to determine characteristics associated with treatment retention. Exclusion criteria were current alcohol or benzodiazepine dependence. Secondary drug users and patients who were psychiatrically or medically ill were included. At 6 months, 60% (n = 24) were retained, 13% (n = 5) tested positive for opiates, and 25% (n = 10) tested positive for secondary substances. Patients who were older (odds ratio [OR] per year of age = 1.1, confidence interval [CI] = 1.0-1.2) and those who were employed (OR = 9.8, CI = 1.8-53.1) were more likely to remain in treatment, but other variables were not associated with retention. Our experience demonstrates that buprenorphine can be successfully integrated into outpatient substance abuse treatment.     

Psychiatric Comorbidity and Substance Use Outcomes in an Office-Based Buprenorphine Program Six Months Following Hurricane Sandy

Background: On October 2012, Hurricane Sandy struck New York City, resulting in unprecedented damages, including the temporary closure of Bellevue Hospital Center and its primary care office-based buprenorphine program. Objectives: At 6 months, we assessed factors associated with higher rates of substance use in buprenorphine program participants that completed a baseline survey one month post-Sandy (i.e. shorter length of time in treatment, exposure to storm losses, a pre-storm history of positive opiate urine drug screens, and post-disaster psychiatric symptoms). Methodology: Risk factors of interest extracted from the electronic medical records included pre-disaster diagnosis of Axis I and/or II disorders and length of treatment up to the disaster. Factors collected from the baseline survey conducted approximately one month post-Sandy included self-reported buprenorphine supply disruption, health insurance status, disaster exposure, and post-Sandy screenings for PTSD and depression. Outcome variables reviewed 6 months post-Sandy included missed appointments, urine drug results for opioids, cocaine, and benzodiazepines. Results: 129 (98%) patients remained in treatment at 6 months, and had no sustained increases in opioid-, cocaine-, and benzodiazepine-positive urine drug tests in any sub-groups with elevated substance use in the baseline survey. Contrary to our initial hypothesis, diagnosis of Axis I and/or II disorders pre-Sandy were associated with significantly less opioid-positive urine drug findings in the 6 months following Sandy compared to the rest of the clinic population. Conclusion: These findings demonstrate the adaptability of a safety net buprenorphine program to ensure positive treatment outcomes despite disaster-related factors.     

Effect of buprenorphine dose on treatment outcome

The goal of this meta-analysis is to provide evidence based information about proper dosing for buprenorphine maintenance treatment to improve treatment outcome. To be selected for the review and inclusion in the meta-analysis, articles had to be randomized, controlled, or double-blind clinical trials, with buprenorphine as the study drug; the length of buprenorphine maintenance treatment had to be 3 weeks or longer; doses of buprenorphine had to be clearly stated; outcome measures had to include retention rates in buprenorphine treatment; outcome measures had to include illicit opioid use based on analytical determination of drugs of abuse in urine samples as outcome variables; and outcome measures had to include illicit cocaine use based on analytical determination of drugs of abuse in urine samples as outcome variables. Twenty-nine articles were excluded because they did not meet the inclusion criteria. The authors present the results of 21 articles that met inclusion criteria. The higher buprenorphine dose (16-32 mg per day) predicted better retention in treatment compared with the lower dose (less than 16 mg per day) (P = .009, R(2) adjusted = 0.40), and the positive urine drug screens for opiates predicted dropping out of treatment (P = .019, R(2) Adjusted = 0.40). Retention in treatment predicted less illicit opioid use (P = .033, R(2) Adjusted = 0.36), and the positive urine drug screens for cocaine predicted more illicit opioid use (P = .021, R(2) Adjusted = 0.36). Strong evidence exists based on 21 randomized clinical trials that the higher buprenorphine dose may improve retention in buprenorphine maintenance treatment.     

Antidepressant treatment does not improve buprenorphine retention among opioid-dependent persons

Our goal was to determine whether treatment of depressive symptoms with escitalopram during buprenorphine treatment for opioid dependence would improve treatment retention compared to placebo in a 12-week, randomized, double-blind trial. Treatment dropout was defined as missing seven consecutive buprenorphine dosing days. Participants were 76% male, 80% non-Hispanic Caucasian, and 64% heroin users. At baseline, the mean Beck Depression Inventory II (BDI-II) score was 28.4 (±9.7). Sixty-one percent of participants completed the 12-week buprenorphine protocol. Dropout rates were 33.3% and 44.0% among those randomized to escitalopram or placebo, respectively (p = .19). Relative to baseline, mean BDI-II scores were significantly lower at all follow-up assessments, but the Treatment × Time interaction effect was not statistically significant (p = .18). Participants randomized to escitalopram also did not have a significantly lower likelihood of testing positive for either opiates or other drugs during follow-up. Depressive symptoms often resolved with buprenorphine treatment, and the immediate initiation of escitalopram does not improve treatment retention, depression outcomes, or illicit drug use. Clinicians should determine the need for antidepressant treatment later in buprenorphine care.