Treating Homeless Opioid Dependent Patients with Buprenorphine in an Office-Based Setting

Context Although office-based opioid treatment with buprenorphine (OBOT-B) has been successfully implemented in primary care settings in the US, its use has not been reported in homeless patients. Objective To characterize the feasibility of OBOT-B in homeless relative to housed patients. Design A retrospective record review examining treatment failure, drug use, utilization of substance abuse treatment services, and intensity of clinical support by a nurse care manager (NCM) among homeless and housed patients in an OBOT-B program between August 2003 and October 2004. Treatment failure was defined as elopement before completing medication induction, discharge after medication induction due to ongoing drug use with concurrent nonadherence with intensified treatment, or discharge due to disruptive behavior. Results Of 44 homeless and 41 housed patients enrolled over 12 months, homeless patients were more likely to be older, nonwhite, unemployed, infected with HIV and hepatitis C, and report a psychiatric illness. Homeless patients had fewer social supports and more chronic substance abuse histories with a 3- to 6-fold greater number of years of drug use, number of detoxification attempts and percentage with a history of methadone maintenance treatment. The proportion of subjects with treatment failure for the homeless (21%) and housed (22%) did not differ (P = .94). At 12 months, both groups had similar proportions with illicit opioid use [Odds ratio (OR), 0.9 (95% CI, 0.5–1.7) P = .8], utilization of counseling (homeless, 46%; housed, 49%; P = .95), and participation in mutual-help groups (homeless, 25%; housed, 29%; P = .96). At 12 months, 36% of the homeless group was no longer homeless. During the first month of treatment, homeless patients required more clinical support from the NCM than housed patients. Conclusions Despite homeless opioid dependent patients’ social instability, greater comorbidities, and more chronic drug use, office-based opioid treatment with buprenorphine was effectively implemented in this population comparable to outcomes in housed patients with respect to treatment failure, illicit opioid use, and utilization of substance abuse treatment.     

A Comparison of Attitudes Toward Opioid Agonist Treatment among Short-Term Buprenorphine Patients

Background: Obtaining data on attitudes toward buprenorphine and methadone of opioid-dependent individuals in the United States may help fashion approaches to increase treatment entry and improve patient outcomes. Objectives: This secondary analysis study compared attitudes toward methadone and buprenorphine of opioid-dependent adults entering short-term buprenorphine treatment (BT) with opioid-dependent adults who are either entering methadone maintenance treatment or not entering treatment. Methods: The 417 participants included 132 individuals entering short-term BT, 191 individuals entering methadone maintenance, and 94 individuals not seeking treatment. Participants were administered an Attitudes toward Methadone scale and its companion Attitudes toward Buprenorphine scale. Demographic characteristics for the three groups were compared using χ² tests of independence and one-way analysis of variance. A repeated-measures multivariate analysis of variance with planned contrasts was used to compare mean attitude scores among the groups. Results: Participants entering BT had significantly more positive attitudes toward buprenorphine than toward methadone (p < .001) and more positive attitudes toward BT than methadone-treatment (MT) participants and out-of-treatment (OT) participants (p < .001). In addition, BT participants had less positive attitudes toward methadone than participants entering MT (p < .001). Conclusions: Participants had a clear preference for a particular medication. Offering a choice of medications to OT individuals might enhance their likelihood of entering treatment. Treatment programs should offer a choice of medications when possible to new patients, and future comparative effectiveness research should incorporate patient preferences into clinical trials. Scientific Significance: These data contribute to our understanding of why people seek or do not seek effective pharmacotherapy for opioid addiction.     

Buprenorphine tapering schedule and illicit opioid use

Aims   To compare the effects of a short or long taper schedule after buprenorphine stabilization on participant outcomes as measured by opioid-free urine tests at the end of each taper period.
Design   This multi-site study sponsored by Clinical Trials Network (CTN, a branch of the US National Institute on Drug Abuse) was conducted from 2003 to 2005 to compare two taper conditions (7 days and 28 days). Data were collected at weekly clinic visits to the end of the taper periods, and at 1-month and 3-month post-taper follow-up visits.
Setting   Eleven out-patient treatment programs in 10 US cities.
Intervention   Non-blinded dosing with Suboxone® during the 1-month stabilization phase included 3 weeks of flexible dosing as determined appropriate by the study physicians. A fixed dose was required for the final week before beginning the taper phase.
Measurements   The percentage of participants in each taper group providing urine samples free of illicit opioids at the end of the taper and at follow-up.
Findings   At the end of the taper, 44% of the 7-day taper group ( n  = 255) provided opioid-free urine specimens compared to 30% of the 28-day taper group ( n  = 261; P  = 0.0007). There were no differences at the 1-month and 3-month follow-ups (7-day = 18% and 12%; 28-day = 18% and 13%, 1 month and 3 months, respectively).
Conclusion   For individuals terminating buprenorphine pharmacotherapy for opioid dependence, there appears to be no advantage in prolonging the duration of taper.     

Opioid Detoxification and Naltrexone Induction Strategies: Recommendations for Clinical Practice

Background: Opioid dependence is a significant public health problem associated with high risk for relapse if treatment is not ongoing. While maintenance on opioid agonists (i.e., methadone, buprenorphine) often produces favorable outcomes, detoxification followed by treatment with the μ-opioid receptor antagonist naltrexone may offer a potentially useful alternative to agonist maintenance for some patients. Method: Treatment approaches for making this transition are described here based on a literature review and solicitation of opinions from several expert clinicians and scientists regarding patient selection, level of care, and detoxification strategies. Conclusion: Among the current detoxification regimens, the available clinical and scientific data suggest that the best approach may be using an initial 2–4 mg dose of buprenorphine combined with clonidine, other ancillary medications, and progressively increasing doses of oral naltrexone over 3–5 days up to the target dose of naltrexone. However, more research is needed to empirically validate the best approach for making this transition.     

Barriers to Obtaining Waivers to Prescribe Buprenorphine for Opioid Addiction Treatment Among HIV Physicians

Background Illicit drug use is common among HIV-infected individuals. Buprenorphine enables physicians to simultaneously treat HIV and opioid dependence, offering opportunities to improve health outcomes. Despite this, few physicians prescribe buprenorphine. Objective To examine barriers to obtaining waivers to prescribe buprenorphine. Design Cross-sectional survey study. Participants 375 physicians attending HIV educational conferences in six cities in 2006. Approach Anonymous questionnaires were distributed and analyzed to test whether confidence addressing drug problems and perceived barriers to prescribing buprenorphine were associated with having a buprenorphine waiver, using chi-square, t tests, and logistic regression. Results 25.1% of HIV physicians had waivers to prescribe buprenorphine. In bivariate analyses, physicians with waivers versus those without waivers were less likely to be male (51.1 vs 63.7%, p < .05), more likely to be in New York (51.1 vs 29.5%, p < .01), less likely to be infectious disease specialists (25.5 vs 41.6%, p < .05), and more likely to be general internists (43.6 vs 33.5%, p < .05). Adjusting for physician characteristics, confidence addressing drug problems (adjusted odds ratio [AOR] = 2.05, 95% confidence interval [95% CI] = 1.08–3.88) and concern about lack of access to addiction experts (AOR = 0.56, 95% CI = 0.32–0.97) were significantly associated with having a buprenorphine waiver. Conclusions Among HIV physicians attending educational conferences, confidence addressing drug problems was positively associated with having a buprenorphine waiver, and concern about lack of access to addiction experts was negatively associated with it. HIV physicians are uniquely positioned to provide opioid addiction treatment in the HIV primary care setting. Understanding and remediating barriers HIV physicians face may lead to new opportunities to improve outcomes for opioid-dependent HIV-infected patients.     

Tipranavir/Ritonavir Induction of Buprenorphine Glucuronide Metabolism in HIV-Negative Subjects Chronically Receiving Buprenorphine/Naloxone

Background: Previous reports on the pharmacokinetic of tipranavir (TPV) and buprenorphine (BUP)/ naloxone found that coadministration resulted in an 80% reduction in the area under the curve AUC of the primary BUP metabolite, norBUP, without any pharmacodynamic consequences. This study was conducted to characterize how tipranivir/ritonavir effects the glucuronide metabolites of BUP and may explain the reduction in the norBUP. Methods: HIV-seronegative subjects stabilized on at least 3 weeks of BUP/naloxone sequentially underwent baseline and steady-state pharmacokinetic evaluation of twice daily TPV 500 mg coadministered with ritonavir 200 mg (TPV/r). Results: Twelve subjects were enrolled and ten completed the study. The steady-state pharmacokinetics for BUP-3-glucuronide (BUP-3G) and norBUP-3-glucuronide (norBUP-3G) in the presence and absence of steady-state TPV/r were analyzed. The C_max of BUP-3G was 8.78 ± 5.23 ng/mL without TPV/r and increased to 12.7 ± 11.7 after steady state of TPV/r was achieved. The AUC of BUP-3G was 31.1 ± 19.4 (ng/mL) (h) without TPV/r and increased to 58. 6 ± 49.5 after steady state of TPV/r was achieved (p = .0966). In contrast, steady-state norBUP-3G AUC_{0–24 h} (p = .0216) and C_max (p = .0088) were significantly decreased in the presence of steady-state TPV/r. Conclusions and Scientific Significance: This study further elucidates the effects of TPV/r on glucuronidation. The current evaluation of glucuronide metabolites of BUP and norBUP are suggestive of combined inhibition of Uridine diphosphate (UDP)-glucuronosyltransferase of the 1A family and cytochrome P450 3A4 that spares UGT2B7 leading to a shunting of BUP away from production of norBUP and toward BUP-3G as seen by a statistically significant increase in the AUC of BUP-3G.     

Patient Satisfaction with Primary Care Office-Based Buprenorphine/Naloxone Treatment

Background Factors associated with satisfaction among patients receiving primary care–based buprenorphine/naloxone are unknown. Objective To identify factors related to patient satisfaction in patients receiving primary care–based buprenorphine/naloxone that varied in counseling intensity (20 vs 45 minutes) and office visit frequency (weekly vs thrice weekly). Design and Participants One hundred and forty-two opioid-dependent subjects. Measurements Demographics, drug treatment history, and substance use status at baseline and during treatment were collected. The primary outcome was patient satisfaction at 12 weeks. Results Patients’ mean overall satisfaction score was 4.4 (out of 5). Patients were most satisfied with the medication and ancillary services and indicated strong willingness to refer a substance-abusing friend for the same treatment. Patients were least satisfied with their interactions with other opioid-dependent patients, referrals to Narcotics Anonymous, and the inconvenience of the treatment location. Female gender (β = .17, P = .04) and non-White ethnicity/race (β = .17, P = .04) independently predicted patient satisfaction. Patients who received briefer counseling and buprenorphine/naloxone dispensed weekly had greater satisfaction than those whose medication was dispensed thrice weekly (mean difference 4.9, 95% confidence interval 0.08 to 9.80, P = .03). Conclusions Patients are satisfied with primary care office-based buprenorphine/naloxone. Providers should consider the identified barriers to patient satisfaction. The findings of this study were presented in part at the 67th annual scientific meeting of the College on Problems of Drug Dependence, Orlando, FL, 22 June 2005.     

Behavioral Counseling Content for Optimizing the Use of Buprenorphine for Treatment of Opioid Dependence in Community-Based Settings: A Review of the Empirical Evidence

There is growing empirical evidence of buprenorphine's effectiveness in treating opioid dependence in community-based settings in the U.S. Decades of research indicates that in order for buprenorphine to have a sizable effect, it must be appropriately supported by behavioral counseling. Studies to date have not established the optimal behavioral counseling content for supporting buprenorphine treatment. The objective of this article is: 1) to review evidence of the key treatment-relevant issues posed by opioid-dependent patients in community-based settings in the U.S.; and 2) to review behavioral counseling content that may optimize the use of buprenorphine for treating opioid dependence in such settings. Evidence points toward the use of behavioral counseling aimed at enhancing patients' motivation during treatment entry followed by an emphasis on improving coping/relapse prevention skills during the primary phase of treatment.     

Serious adverse events in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD)

Aims The study estimated serious adverse event (SAE) rates among entrants to pharmacotherapies for opioid dependence, during treatment and after leaving treatment. Design A longitudinal study based on data from 12 trials included in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD). Participants and settings A total of 1244 heroin users and methadone patients treated in hospital, community and GP settings. Intervention Six trials included detoxification; all included treatment with methadone, buprenorphine, levo‐alpha‐acetyl‐methadol (LAAM) or naltrexone. Findings During 394 person‐years of observation, 79 SAEs of 28 types were recorded. Naltrexone participants experienced 39 overdoses per 100 person‐years after leaving treatment (44% occurred within 2 weeks after stopping naltrexone). This was eight times the rate recorded among participants who left agonist treatment. Rates of all other SAEs were similar during treatment versus out of treatment, for both naltrexone‐treated and agonist‐treated participants. Five deaths occurred, all among participants who had left treatment, at a rate of six per 100 person‐years. Total SAE rates during naltrexone and agonist treatments were similar (20, 14 per 100 person‐years, respectively). Total SAE and death rates observed among participants who had left treatment were three and 19 times the corresponding rates during treatment. Conclusions Individuals who leave pharmacotherapies for opioid dependence experience higher overdose and death rates compared with those in treatment. This may be due partly to a participant self‐selection effect rather than entirely to pharmacotherapy being protective. Clinicians should alert naltrexone treatment patients in particular about heroin overdose risks. Duty of care may extend beyond cessation of dosing.     

Brief report: Buprenorphine retention in primary care

BACKGROUND: This study assesses the rate and predictors of treatment retention for primary care patients with opioid dependence-prescribed buprenorphine, a long-acting partial opioid agonist. METHODS: Observational cohort study of patients prescribed buprenorphine/naloxone and followed for 6 months in the period after the adoption of buprenophine/naloxone by a primary care practice in Rhode Island. Practice policy precluded patient discharges due to continuing drug use. RESULTS: Patients (n=41) had a mean duration of opioid use of 15.7 years and most had a history of heroin use (63.4%). Thirty-nine percent of patients transferred from methadone maintenance. At 24 weeks, 59% remained in treatment. Nearly half of dropouts occurred in the first 30 days. Participants with opiate-positive toxicologies at week 1 were more likely to drop out of the program (P<.01) and had a significantly shorter retention time (P<.01) on average. Among other drug use and drug treatment variables, employment and addiction counseling during treatment were significantly associated with treatment retention (P=.03). CONCLUSION: Retention rates in a real world, primary care-based buprenorphine maintenance practice reflect those reported in clinical trials. Abstinence during the first week of treatment and receipt of counseling were critical to patient retention.     

Buprenorphine versus methadone maintenance therapy: a randomized double-blind trial with 405 opioid-dependent patients

Aims To assess the efficacy of buprenorphine compared with methadone maintenance therapy for opioid dependence in a large sample using a flexible dosing regime and the marketed buprenorphine tablet. Design Patients were randomized to receive buprenorphine or methadone over a 13‐week treatment period in a double‐blind, double‐dummy trial. Setting Three methadone clinics in Australia. Participants Four hundred and five opioid‐dependent patients seeking treatment. Intervention Patients received buprenorphine or methadone as indicated clinically using a flexible dosage regime. During weeks 1–6, patients were dosed daily. From weeks 7–13, buprenorphine patients received double their week 6 dose on alternate days. Measurements Retention in treatment, and illicit opioid use as determined by urinalysis. Self‐reported drug use, psychological functioning, HIV‐risk behaviour, general health and subjective ratings were secondary outcomes. Findings Intention‐to‐treat analyses revealed no significant difference in completion rates at 13 weeks. Methadone was superior to buprenorphine in time to termination over the 13‐week period (Wald χ² = 4.371, df = 1, P = 0.037), but not separately for the single‐day or alternate‐day dosing phases. There were no significant between‐group differences in morphine‐positive urines, or in self‐reported heroin or other illicit drug use. The majority (85%) of the buprenorphine patients transferred to alternate‐day dosing were maintained in alternate‐day dosing. Conclusions Buprenorphine did not differ from methadone in its ability to suppress heroin use, but retained approximately 10% fewer patients. This poorer retention was due possibly to too‐slow induction onto buprenorphine. For the majority of patients, buprenorphine can be administered on alternate days.     

Participant Characteristics and Buprenorphine Dose

Background: Clinical parameters for determining buprenorphine dose have not been adequately examined in treatment outcome research. Objectives: This study is a secondary analysis of data collected in a recently completed comparison of buprenorphine taper schedules conducted as part of the National Institute on Drug Abuse’s Clinical Trials Network to assess whether participant baseline characteristics are associated with buprenorphine dose. Methods: After 3 weeks of flexible dosing, 516 participants were categorized by dose provided in the final dosing week (9.3% received a final week dose of 8 mg buprenorphine, 27.3% received 16 mg, and 63.4% received 24 mg). Results: Findings show that final week dose groups differed in baseline demographic and drug use characteristics including education, heroin use, route of drug administration, withdrawal symptoms, and craving. These groups also differed in opioid use during the four dosing weeks, with the lowest use in the 8 mg group and highest use in the 24 mg group (p < .0001). Additional analyses address withdrawal symptoms and craving. Conclusions and Scientific Significance: Final week dose groups differed in demographic and drug use characteristics, and the group receiving the largest final week dose had the highest rate of continued opioid use. These findings may contribute to the development of clinical guidelines regarding buprenorphine dose in the treatment of opioid dependence; however, further investigations that include random assignment to dose by baseline characteristics are needed.