Quantitative testing of buprenorphine and norbuprenorphine to identify urine sample spiking during office-based opioid treatment

Background: Patients may spike urine samples with buprenorphine during office-based opioid treatment to simulate adherence to prescribed buprenorphine, potentially to conceal diversion of medications. However, routine immunoassay screens do not detect instances of spiking, as these would simply result in a positive result. The aim of this study was to report on the experience of using quantitative urine testing for buprenorphine and norbuprenorphine to facilitate the identification of urine spiking. Methods: This is a retrospective chart review of 168 consecutive patients enrolled in outpatient buprenorphine treatment at an urban academic medical setting between May 2013 and August 2014. All urine samples submitted were subjected to quantitative urine toxicology testing for buprenorphine and norbuprenorphine. Norbuprenorphine-to-buprenorphine ratio of less than 0.02 were further examined for possible spiking. Demographic and clinical variables were also extracted from medical records. Clinical and demographic variables of those who did and did not spike their urines were compared. Statistically significant variables from the univariate testing were entered as predictors of spiking in a regression analysis. Results: A total of 168 patients were included, submitting a total of 2275 urine samples. Patients provided on average 13.6 (SD = 9.9) samples, and were in treatment for an average 153.1 days (SD = 142.2). In total, 8 samples (0.35%) from 8 patients (4.8%) were deemed to be spiked. All of the samples suspected of spiking contained buprenorphine levels greater than 2000 ng/mL, with a mean norbuprenorphine level of 11.9 ng/mL. Spiked samples were submitted by 6 patients (75.0%) during the intensive outpatient (IOP) phase of treatment, 2 patients (25.0%) during the weekly phase, and none from the monthly phase. Regression analysis indicated that history of intravenous drug use and submission of cocaine-positive urine samples at baseline were significant predictors of urine spiking. Conclusions: Even though only a small number of patients were identified to have spiked their urine samples, quantitative testing may help identify urine spiking during office-based opioid treatment with buprenorphine.     

Randomized pilot trial of Web-based cognitive-behavioral therapy adapted for use in office-based buprenorphine maintenance

Background: Despite the clear success of office-based buprenorphine treatment in increasing availability of effective treatment for opioid use disorder, constraints on its effectiveness include high attrition and limited high-quality behavioral care in many areas. Web-based interventions may be a novel strategy for providing evidence-based behavioral care to individuals receiving office-based buprenorphine maintenance. This report describes modification and initial pilot testing of Web-based training in cognitive-behavioral therapy (CBT4CBT) specifically for use with individuals in office-based buprenorphine. Methods: Twelve-week randomized pilot trial evaluating effects of CBT4CBT-Buprenophine in retaining participants and reducing drug use with respect to standard office-based buprenorphine alone was carried out. Twenty individuals meeting DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) criteria for current opioid use disorder were randomized to standard buprenorphine treatment or buprenorphine plus access to CBT4CBT-Buprenorphine. Results: There were promising findings regarding rates of urine toxicology screens negative for opioids (91% versus 64%; P?=?.05, effect size d?=?0.88) and all drugs (82% versus 30%; P?=?.004, d?=?1.2). Individuals randomized to CBT4CBT-Buprenorphine completed a mean of 82.6 (SD?=?4.4) days of treatment (of a possible 84) compared with 68.6 (SD?=?32.6) for those assigned to standard buprenorphine treatment. Conclusions: Although preliminary and limited by the small sample size, this trial suggests the feasibility and promise of validated, Web-based interventions, tailored for this specific patient population, for improving outcomes in office-based buprenorphine.     

Text message content preferences to improve buprenorphine maintenance treatment in primary care

Few studies have evaluated text message content preferences to support evidence-based treatment approaches for opioid use disorders, and none in primary care office-based buprenorphine treatment settings. This study assessed the acceptability and preferences for a tailored text message intervention in support of core office-based buprenorphine treatment medical management components (e.g., treatment adherence, encouraging abstinence, 12-step group participation, motivational interviewing, and patient-provider communication as needed). There were 97 patients enrolled in a safety net office-based buprenorphine treatment program who completed a 24-item survey instrument that consisted of multiple-choice responses, 7-point Likert-type scales, binomial “Yes/No” questions, and open-ended responses. The sample was predominately male (81%), had an average age of 46 years, and was diverse (64% ethnic/racial minorities); 56% lacked stable employment. Respondents were interested in receiving text message appointment reminders (90%), information pertaining to their buprenorphine treatment (76%), supportive content (70%), and messages to reduce the risk of relapse (88%). Participants preferred to receive relapse prevention text messages during all phases of treatment: immediately after induction into buprenorphine treatment (81%), a “few months” into treatment (57%), and after discontinuing buprenorphine treatment (72%). Respondents also expressed interest in text message content enhancing self-efficacy, social support, and frequent provider communication to facilitate unobserved “home” induction with buprenorphine. Older participants were significantly less receptive to receiving text message appointment reminders; however, they were as interested in receiving supportive, informational, and relapse prevention components compared to younger respondents. Implications for integrating a text message support system in office-based buprenorphine treatment are discussed.     

Home- versus office-based buprenorphine inductions for opioid-dependent patients

Recent legislation permits the treatment of opioid-dependent patients with buprenorphine in the primary care setting, opening doors for the development of new treatment models for opioid dependence. We modified national buprenorphine treatment guidelines to emphasize patient self-management by giving patients the opportunity to choose to have buprenorphine inductions at home or the physician's office. We examined whether patients who had home-based inductions achieved greater 30-day retention than patients who had traditional office-based inductions in a study of 115 opioid-dependent patients treated in an inner-city health center. Retention was similar in both groups: 50 (78.1%) in office-based group versus 40 (78.4%) in home-based group, p = .97. Several patient characteristics were associated with choosing office- versus home-based inductions, which likely influenced these results. We conclude that opioid dependence can be successfully managed in the primary care setting. Approaches that encourage patient involvement in treatment for opioid dependence can be beneficial.     

Criminal Charges Prior to and After Enrollment in Opioid Agonist Treatment: A Comparison of Methadone Maintenance and Office-based Buprenorphine

Background: Entry into methadone maintenance is associated with a reduction in criminal activity; less is known about the effects of office-based buprenorphine. Objective: To compare criminal charges before and after enrollment in methadone maintenance or office-based buprenorphine. Methods: Subjects were opioid-dependent adults who initiated either methadone maintenance (n = 252) or office-based buprenorphine (n = 252) between 2003 and 2007. Medical records were reviewed to gather demographic data and a state-maintained web-based database to collect data on criminal charges. Overall charges and drug charges in the 2 years prior to and after treatment enrollment were compared. Multivariable analysis was used to examine risk factors for charges after treatment enrollment. Results: In the 2 years after enrolling in treatment, subjects receiving methadone had a significant decline in the proportion of subjects with any charges (49.6% vs. 32.5%, p < .001) or drug charges (25.0% vs. 17.5%, p = .015), as well as the mean number of cases (0.97 vs. 0.63, p = .002) and drug cases (0.38 vs. 0.23, p = .008), while those who initiated buprenorphine did not have significant changes in any of these measures. On multivariable analysis, the strongest predictor of criminal charges in the 2 years after treatment enrollment was prior charges (adjusted odds ratio 3.35, 95% confidence interval, 2.24–5.01). Conclusions: Enrollment in office-based buprenorphine treatment did not appear to have the same beneficial effect on subsequent criminal charges as methadone maintenance. If this observation is replicated in other settings, it may have implications for matching individuals to these treatment options.     

Provider Satisfaction with Office-Based Treatment of Opioid Dependence

Abstract

Purpose: New federal regulations allow for office-based treatment of opioid dependent patients with opioid agonist medication (e.g., buprenorphine). We sought to evaluate the literature on office-based physicians' acceptance of this practice.

Methods: We searched the MEDLINE database for original research examining office-based providers' acceptance or satisfaction with office-based treatment. Articles included in the analysis met the following criteria: (1) discussed the treatment of patients with substance abuse disorders, (2) focused on the treatment of opioid dependent patients, (3) discussed treatment with opioid agonist therapy, (4) discussed treatment by office-based physicians, (5) presented original research, and (6) provided data examining physician acceptance or satisfaction.

Results: Eight studies met the criteria. Their heterogeneity precluded aggregate analysis. Four of 8 studies revealed that providers had a positive perception concerning the efficacy of opioid agonist treatment, 4/8 indicated that providers believed that opioid dependent patients were more complex than others in their practices, and 3/8 studies indicated the need for additional support services.

Conclusions: There are few studies of provider satisfaction with office-based treatment of opioid dependence. This literature reveals overall provider acceptance of this practice but highlights the need for support services. Further research, designed to identify the barriers to provider satisfaction with office-based opioid agonist therapy, is needed to ensure that these barriers do not limit expansion of this practice.     

Perceived need and availability of psychosocial interventions across buprenorphine prescriber specialties

IntroductionPsychosocial interventions are often recommended as part of buprenorphine treatment for patients with opioid use disorder, but little is known about prescriber perspectives on their use and how this varies across buprenorphine prescriber specialties.MethodsA large US sample of physicians actively prescribing buprenorphine (n = 1174) was surveyed from July 2014 to January 2017. Analyses examined prescriber characteristics and their perceptions and use of psychosocial interventions across three groups of physicians: primary care providers (PCPs), addiction physicians/psychiatrists, and other physicians.ResultsAcross all prescribers, 93.3% (n = 1061) report most patients would benefit from formal counseling during buprenorphine treatment while only 36.4% (n = 414) believe there are adequate number of counselors in their communities. Among addiction physicians/psychiatrists, 75.9% (n = 416) report their treatment settings have the resources to provide psychiatric services to patients with complex psychiatric problems compared to 29.1% (n = 130) of PCPs and 29.6% (n = 39, p < .001) of other physicians. Addiction physicians/psychiatrists report a higher percentage of patients receive counseling from clinicians in their practice while PCPs report a higher percentage of patients receive counseling from external providers.ConclusionsThe majority of prescribers believe patients receiving buprenorphine would benefit from psychosocial interventions and there is variation in how these services are delivered. However, many prescribers, especially those without addiction or psychiatry backgrounds, report their settings do not have adequate psychosocial treatment resources for patients with complex psychosocial needs. Future work developing novel models of psychosocial interventions may be helpful to support prescribers to effectively treat complex patients with opioid use disorders.     

The Pregnancy Recovery Center: A women-centered treatment program for pregnant and postpartum women with opioid use disorder

ObjectiveTo evaluate the impact of women-centered substance abuse treatment programming on outcomes among pregnant women with opioid use disorder (OUD).MethodsWe compared two retrospective cohorts of pregnant women with OUD on buprenorphine maintenance therapy who delivered an infant at the University of Pittsburgh from 2014 to 2016. Cohort 1 was composed of pregnant women who received women-centered OUD treatment services through the Pregnancy Recovery Program (PRC) and Cohort 2 was composed of pregnant women who received buprenorphine at OUD programs without women-centered services (non-PRC). Women-centered outcomes were defined as a) pregnancy-specific buprenorphine dosing, b) prenatal and postpartum care attendance, c) breastfeeding and d) highly effective contraception utilization. Chi-square and t-tests were used to compare outcomes between PRC and non-PRC patients.ResultsAmong 248 pregnant women with OUD, 71 (28.6%) were PRC and 177 (71.4%) were non-PRC patients. PRC patients were significantly more likely to initiate buprenorphine during vs. prior to their pregnancy (81.4% vs. 44.2%; p < .01) and have a higher buprenorphine dose at the time of delivery (16.0 mg vs. 14.1 mg; p = .02) compared to non-PRC patients. Likewise, PRC patients were significantly more likely to attend their postpartum visit (67.9% vs. 52.6%; p = .05) and receive a long-acting reversible contraceptive (LARC) method (23.9% vs. 13.0%, p = .03) after delivery compared to non-PRC patients. Finally, PRC patients had a smaller percent decrease in the rate of breastfeeding during their delivery hospitalization (−14.7% vs. −37.1%).ConclusionsIncorporating women-centered services into OUD treatment programming may improve gender-specific outcomes among women with OUD.     

Consideration of opioid agonist treatment in a pregnant adolescent: A case report and literature review

Abstract

Background: Opioid use greatly increases the risk of overdose death, as well as contracting human immunodeficiency virus (HIV) and hepatitis. Opioid agonist treatment is recommended for pregnant women who are dependent on opioids. However, there is a dearth of studies on the use of opioid agonist treatment in pregnant teenagers. Case: Ms. A, a 15?year-old G1PO in foster care, presented to our tertiary women’s hospital requesting opioid agonist treatment for use of pill opioids. She reported nasal inhalation of 5–6 opioid tablets daily, with recent attempts to self-taper using nonprescribed buprenorphine since learning of her pregnancy. Last reported opioid use was >24?hours prior to admission. Urine drug testing was positive only for opioids (negative for buprenorphine and methadone). She did not exhibit significant withdrawal symptoms while hospitalized. The psychiatric treatment team recommended deferring opioid agonist treatment and pursuing outpatient substance use treatment. Unfortunately, Ms. A did not attend outpatient treatment and was lost to follow up. Discussion: Based upon our experience and review of the studies regarding opioid use disorder (OUD) and perinatal and adolescent opioid use, we recommend that pregnant adolescents with OUD be referred to opioid agonist treatment with buprenorphine or methadone. Studies specifically addressing opioid agonist treatment in pregnant teenagers are needed.     

Pain Is Not Associated with Worse Office-Based Buprenorphine Treatment Outcomes

ABSTRACT

Physical pain is common among individuals seeking treatment for opioid dependence. Pain may negatively impact addiction treatment. The authors prospectively studied opioid-dependent individuals initiating office-based buprenorphine treatment, comparing buprenorphine treatment outcomes (treatment retention and opioid use) among participants with and without pain (baseline pain or persistent pain). Among 82 participants, 60% reported baseline pain and 38% reported persistent pain. Overall, treatment retention was 56% and opioid use decreased from 89% to 26% over 6 months. In multivariable analyses, the authors found no association between pain and buprenorphine treatment outcomes. Opioid-dependent individuals with and without pain can achieve similar success with buprenorphine treatment.     

Prevalence of mood and substance use disorders among patients seeking primary care office-based buprenorphine/naloxone treatment

BackgroundPsychiatric comorbidity can adversely affect opioid dependence treatment outcomes. While the prevalence of psychiatric comorbidity among patients seeking methadone maintenance treatment has been documented, the extent to which these findings extend to patients seeking primary care office-based buprenorphine/naloxone treatment is unclear.AimsTo determine the prevalence of mood and substance use disorders among patients seeking primary care office-based buprenorphine/naloxone treatment, via cross sectional survey.Methods237 consecutive patients seeking primary care office-based buprenorphine/naloxone treatment were evaluated using modules from the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Current (past 30 days) and past diagnoses were cataloged separately.ResultsPatients ranged in age from 18 to 62 years old (M = 33.9, SD = 9.9); 173 (73%) were men; 197 (83%) were white. Major depression was the most prevalent mood disorder (19% current, 24% past). A minority of patients met criteria for current dysthymia (6%), past mania (1%), or past hypomania (2%). While 37 patients (16%) met criteria for current abuse of or dependence on at least one non-opioid substance (7% cocaine, 4% alcohol, 4% cannabis, 2% sedatives, 0.4% stimulants, 0.4% polydrug), 168 patients (70%) percent met criteria for past abuse of or dependence on at least one non-opioid substance (43% alcohol, 38% cannabis, 30% cocaine, 9% sedatives, 8% hallucinogens, 4% stimulants, 1% polydrug, and 0.4% other substances).ConclusionMood and substance use comorbidity is prevalent among patients seeking primary care office-based buprenorphine/naloxone treatment. The findings support the need for clinicians to assess and address these conditions.     

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.     

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.     

A Buprenorphine Education and Training Program for Primary Care Residents: Implementation and Evaluation

ABSTRACT. Background: Although substance use disorders are highly prevalent, resident preparation to care for patients with these disorders is frequently insufficient. With increasing rates of opioid abuse and dependence, and the availability of medication-assisted treatment, one strategy to improve resident skills is to incorporate buprenorphine treatment into training settings. Methods: In this study, esidency faculty delivered the BupEd education and training program to 71 primary care residents. BupEd included (1) a didactic session on buprenorphine, (2) an interactive motivational interviewing session, (3) monthly case conferences, and (4) supervised clinical experience providing buprenorphine treatment. To evaluate BupEd, the authors assessed (1) residents’ provision of buprenorphine treatment during residency, (2) residents’ provision of buprenorphine treatment after residency, and (3) treatment retention among patients treated by resident versus attending physicians. Results: Of 71 residents, most served as a covering or primary provider to at least 1 buprenorphine-treated patient (84.5 and 66.2%, respectively). Of 40 graduates, 27.5% obtained a buprenorphine waiver and 17.5% prescribed buprenorphine. Treatment retention was similar between patients cared for by resident PCPs versus attending PCPs (90-day retention: 63.6% [n = 35] vs. 67.9% [n = 152]; P = .55). Conclusion: These results show that BupEd is feasible, provides residents with supervised clinical experience in treating opioid-dependent patients, and can serve as a model to prepare primary care physicians to care for patients with opioid dependence.     

Buprenorphine Maintenance Treatment of Opiate Dependence: Correlations Between Prescriber Beliefs and Practices

Background: Despite the existence of evidence-based guidelines, different prescriber practices around buprenorphine maintenance treatment (BMT) of opiate dependence exist. Moreover, certain prescriber beliefs may influence their practice patterns. Objective: To understand community BMT practice patterns and discern their relationship to practitioner beliefs. Method: Survey of 30 local BMT prescribers about aspects of BMT, and analysis of correlations between practices and practitioner beliefs. Results: Practitioners generally followed standard treatment guidelines, though the most-common maintenances dosages of BMT (4–12 mg) were lower than recommended by some studies. Endorsement of belief in a “spiritual basis” of addiction correlated with lower average BMT doses and less frequent endorsement of the belief that BMT-treated patients are “in recovery.” Conclusions/Importance: These data suggest that relatively standardized, longer-term BMT of opiate dependence is accepted among the majority of surveyed prescribers, and certain provider beliefs about addiction may influence prescribing habits and attitudes. Future studies should: (1) assess these findings in larger samples; (2) examine how prescriber beliefs about addiction and BMT compare with those of other addiction treatment providers; and (3) ascertain whether individual prescriber beliefs influence patient outcomes.     

The practice of office-based buprenorphine treatment of opioid dependence: is it associated with new patients entering into treatment?

Office-based buprenorphine holds the promise of bringing patients who have never received pharmacotherapy into treatment. In a cross-sectional and longitudinal analysis, we compared patients entering a clinical trial of buprenorphine in a Primary Care Clinic (PCC) and those entering a local Opioid Treatment Program (OTP) and we compared the clinical characteristics and treatment outcomes of PCC patients with no history of methadone treatment (new-to-treatment) to those with prior methadone treatment. PCC subjects (N=96) were enrolled in a 26-week randomized clinical trial of office-based buprenorphine/naloxone provided in a PCC. OTP subjects (N=94) were enrolled in methadone maintenance during the same time period. PCC subjects compared with OTP subjects were more likely to be male (77% versus 55%, p<0.01), full-time employed (46% versus 15%, p<0.001), have no history of methadone treatment (46% versus 61%, p<0.05), have fewer years of opioid dependence (10 versus 15, p<0.001), and lower rates of injection drug use (IDU) (44% versus 60%, p=0.03). The new-to-treatment PCC subjects were younger (36 years versus 41 years, p=0.001), more likely to be white (77% versus 57%, p=0.04), had fewer years of opioid dependence (7 versus 14, p<0.001), were less likely to have a history of IDU (35% versus 54%, p=0.07), and had lower rates of hepatitis C (25% versus 61%, p=0.002) than subjects with prior methadone treatment. Abstinence and treatment retention were comparable in both groups. The results suggest that office-based treatment of opioid dependence is associated with new types of patients entering into treatment. Treatment outcomes with buprenorphine in a PCC do not vary based on history of prior methadone treatment.