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CORK Bibliography: Buprenorphine

112 citations. 2007 to present

Prepared: June 2009

Aalto M; Halme J; Visapaa JP; Salaspuro M. Buprenorphine misuse in Finland. (letter). Substance Use & Misuse 42(6): 1027-1028, 2007. (3 refs.)

Aitken CK; Higgs PG; Hellard ME. Buprenorphine injection in Melbourne, Australia - an update. Drug and Alcohol Review 27(2): 197-199, 2008. (18 refs.)

Objective. To investigate the prevalence and associations of buprenorphine injection among a field-recruited cohort of injecting drug users. Design. Cross-sectional data from a prospective longitudinal cohort. Setting. Metropolitan Melbourne, Australia. Subjects. Current injecting drug users (IDUs). Main Outcome Measures. Prevalence of buprenorphine injection, associations with location, buprenorphine as prescribed pharmacotherapy, markers of hepatitis C virus (HCV) exposure and risk behaviours for HCV. Results. More than 10% of our 316 participants reported buprenorphine as the drug they had most often injected, and 32% had injected buprenorphine at least once in the 3 months prior to interview. Primary buprenorphine injection was significantly more likely to be reported by IDUs recruited at one of our three research sites, and by those being prescribed buprenorphine for opioid dependence. Frequency of sharing a used needle was also associated with buprenorphine injection, but HCV exposure was not. Conclusions. Buprenorphine injection has become entrenched among some groups of Victorian IDUs. The practice carries serious risks to health, including some related to microbiological contamination of buprenorphine during diversion. While measures can be taken to reduce the occurrence of buprenorphine diversion and injection and the associated harm, an alternative harm reduction measure would be to provide IDUs with an injectable pharmacotherapy.

Alford DA; Salsitz EA; Martin J; Renner JA. Clinical case discussion: Treating opioid dependence with buprenorphine. Journal of Addiction Medicine 1(2): 73-78, 2007. (10 refs.)

Alho H; Sinclair D; Vuori E; Holopainen A. Abuse liability of buprenorphine-naloxone tablets in untreated IV drug users. Drug and Alcohol Dependence 88(1): 75-78, 2007. (15 refs.)

Buprenorphine (Subutex (R)) is widely abused in Finland. A combination of buprenorphine plus naloxone (Suboxone (R)) has been available since late 2004, permitting a comparison of the abuse of the two products among untreated intravenous (IV) users. A survey was distributed to attendees at a Helsinki needle exchange program over 2-weeks in April, 2005, At least 30% were returned anonymously. Survey variables included: years of prior IV opioid abuse, years of buprenorphine abuse, frequency, dosage, route of administration and reasons for use, concomitant IV abuse of other substances and amount paid on the street for both buprenorphine and buprenorphine + naloxone. Buprenorphine was the most frequently used IV drug for 73% of the respondents. More than 75% said they used IV buprenorphine to self-treat addiction or withdrawal. Most (68%) had tried the buprenorphine + naloxone combination IV, but 80% said they had a "bad" experience. Its street price was less than half that of buprenorphine alone. The buprenorphine + naloxone combination appears to be a feasible tool, along with easier access to addiction treatment, for decreasing IV abuse of buprenorphine.

Athanasos P; Farquharson AL; Compton P; Psaltis P; Hay J. Electrocardiogram characteristics of methadone and buprenorphine maintained subjects. Journal of Addictive Diseases 27(3): 31-35, 2008. (15 refs.)

There has been recent concern about the association between high dose methadone and prolongation of QTc in the electrocardiogram. QTc is the time from the beginning of the QRS complex to the end of the T have as measured on an electrocardiogram and corrected for heart rate. To date, no association has been made between methadone and buprenorphine in commonly used doses and prolonged QTc. Electrocardiograms were performed on groups of methadone (n = 35, mean daily dose standard deviation, 69 +/- 29 mg) and buprenorphine (n = 19, mean daily dose 11 5 mg) subjects and a group of non-opioid dependent controls (n = 17). Mean QTc did not differ (p = 0.45) between methadone, buprenorphine, or controls. Methadone subjects were significantly (odds ratio of 7.8) more likely to have U waves than buprenorphine and controls combined. Methadone subjects with U waves were maintained on higher (p = 0.004) doses (89 +/- 29 mg/day) than methadone subjects without U waves (60 +/- 24 mg/day). Methadone subjects taking 60 mg and above had higher (p = 0.02) QTc (405 +/- 29 milliseconds) than methadone subjects taking less than 60 mg per day (381 +/- 27 milliseconds). Although an association is thought to exist between high methadone doses and elongated QTc, methadone and buprenorphine, at commonly used daily doses, remain safe agents for opioid substitution therapy.

Badger GJ; Bickel WK; Giordano LA; Jacobs EA; Loewenstein G; Marsch L. Altered states: The impact of immediate craving on the valuation of current and future opioids. Journal of Health Economics 26(5): 865-876, 2007. (33 refs.)

Based on prior research showing that people underestimate the influence of motivational states they are not currently experiencing, we predicted and found that heroin addicts would value an extra dose of the heroin substitute Buprenorphine more highly when they were currently craving (right before receiving BUP) than when they were currently satiated (right after receiving BUP)-even when the extra BUP was to be received 5 days later. If addicts cannot appreciate the intensity of craving when they are not currently experiencing it, as these results suggest, it seems unlikely that those who have never experienced craving could predict its motivational force. Under-appreciation of craving by non-addicts may contribute to initial decisions to experiment with drugs.

Bammer G; Ritter A; Kutin JJ; Lintzeris N. Fast-tracking implementation through trial design: the case of buprenorphine treatment in Victoria. Australian and New Zealand Journal of Public Health 33(1): 34-39, 2009. (35 refs.)

Objectives: We investigated how a randomised controlled trial (RCT) could be designed to incorporate features known or thought likely to enhance the uptake of the new treatment into clinical practice post-trial. Method and Results: Between 1999 and 2001, we trialled buprenorphine treatment for heroin dependence in community settings throughout Victoria, using 28 experienced methadone prescribers and 34 pharmacists across 19 sites. In this case study, we describe how we incorporated seven features considered important in treatment uptake: skilled and experienced practitioners, government and policy support, incentives to prescribe the new treatment, specialist support services, clinical guidelines, training programs and patient involvement and information. We also present information showing that uptake of buprenorphine treatment was substantially boosted in Victoria compared with other Australian jurisdictions immediately after the trial in 2001 and that this increase was sustained until at least 2006. Conclusion: While we cannot prove that our trial design was responsible for the increased uptake of buprenorphine treatment in Victoria, we do show that design has been a neglected aspect of clinical trials in terms of enhancing post-trial uptake of the treatment being tested. Implications: Those interested in closing the 'know-do' gap between research and practice may wish to further explore this very promising lead. Imaginative linking of features known to enhance treatment uptake to pressing research questions may lead to new information on efficacy, as well as getting valuable drugs into the treatment system more rapidly.

Barry DT; Irwin KS; Jones ES; Becker WC; Tetrault JM; Sullivan LE et al. Integrating buprenorphine treatment into office-based practice: A qualitative study. Journal of General Internal Medicine 24(2): 218-225, 2009. (32 refs.)

Despite the availability and demonstrated effectiveness of office-based buprenorphine maintenance treatment (BMT), the systematic examination of physicians' attitudes towards this new medical practice has been largely neglected. To identify facilitators and barriers to the potential or actual implementation of BMT by office-based medical providers. Qualitative study using individual and group semi-structured interviews. Twenty-three practicing office-based physicians in New England. Interviews were audiotaped, transcribed, and entered into a qualitative software program. The transcripts were thematically coded using the constant comparative method by a multidisciplinary team. Eighty percent of the physicians were white; 55% were women. The mean number of years since graduating medical school was 14 (SD = 10). The primary areas of clinical specialization were internal medicine (50%), infectious disease (20%), and addiction medicine (15%). Physicians identified physician, patient, and logistical factors that would either facilitate or serve as a barrier to their integration of BMT into clinical practice. Physician facilitators included promoting continuity of patient care, positive perceptions of BMT, and viewing BMT as a positive alternative to methadone maintenance. Physician barriers included competing activities, lack of interest, and lack of expertise in addiction treatment. Physicians' perceptions of patient-related barriers included concerns about confidentiality and cost, and low motivation for treatment. Perceived logistical barriers included lack of remuneration for BMT, limited ancillary support for physicians, not enough time, and a perceived low prevalence of opioid dependence in physicians' practices. Addressing physicians' perceptions of facilitators and barriers to BMT is crucial to supporting the further expansion of BMT into primary care and office-based practices.

Bell J; Butler B. Health care utilization and morbidity associated with methadone and buprenorphine treatment. (review). Heroin Addiction and Related Clinical Problems 10(2): 21-26, 2008. (20 refs.)

Background: Methadone and buprenorphine treatment reduce the high mortality associated with heroin addiction, but even in-treatment, Standardised Mortality Rates are high. Aim: This study investigates the nature of morbidity associated with methadone and buprenorphine treatment, and investigates predictors of health care utilization among people in a variety of treatment settings. Methods: Collation of data from earlier studies, and from publicished reports. Findings: In a recent study of an entry cohort, the SMR was 5.52 [4.62, 5.65]; suicide and overdose accounted for 2/3 of the mortality, but allowing for this, mortality rates remain elevated. Cancer, heart disease and respiratory disease were the three major contributors to mortality. Taken in conjunction with a recent study of medical co-morbidity, this suggests that alcohol, tobacco and other drug use represent the major factors contributing to serious illness in treated opioid addicts. In addition, side-effects of treatment may themselves contribute to some morbidity. Lack of access to health care does not appear to be a contributing factor, as opioid users consult doctors (other than their methadone doctors) at rates far higher than the general population. Predictors of doctor attendance "outside" doctors were psychological distress, and benzodiazepine use. Adjusting for these factors, we found evidence that quality of methadone treatment was a significant predictor of doctor attendance, with better clinical care being associated with less Outside doctor attendance. Conclusion: There is a paradox; heroin users have significant physical illness, but their attendance for health care tends to be driven by psychological distress, and can be improved by good care within treatment programs. The priority in addressing health problems of stabilised heroin users is dealing with alcohol and tobacco problems.

Berg ML; Idrees U; Ding R; Nesbit SA; Liang HK; McCarthy ML. Evaluation of the use of buprenorphine for opioid withdrawal in an emergency department. Drug and Alcohol Dependence 86(2/3): 239-244, 2007. (13 refs.)

Objectives: To examine the use of buprenorphine for the treatment of opioid withdrawal in an emergency department (ED) setting. Methods: The medical records of all adult patients who presented to the study ED during a 10 week period for opioid withdrawal were abstracted. Subjects were categorized as receiving buprenorphine, symptomatic treatment or no pharmacologic treatment for their opioid withdrawal. The three groups were compared by patient and service characteristics, withdrawal symptoms and outcomes. Results: Of the 11,019 patients who presented to the ED during the 10 week study period, 158 (1.4%) were eligible. Subjects were more likely to receive buprenorphine (56%) compared to symptomatic treatment only (26%) or no pharmacologic treatment (18%). Subjects who received buprenorphine were more likely to have a history of suicide ideation (34% versus 12% p < 0.05) compared to subjects who received symptomatic treatment(s) and were less likely to present with a gastrointestinal complaint (9% versus 25% p < 0.05). Subjects who received buprenorphine were less likely to return to the same ED within 30 days for a drug-related visit (8%) compared to those who received symptomatic treatment (17%) (p < 0.05). Conclusions: Buprenorphine was a common treatment for opioid withdrawal in this ED without any documented adverse outcomes. Given that it did not result in an increase in drug-related return ED visits and its proven efficacy in other settings, a prospective evaluation of its potential value to ED patients who present with opioid withdrawal is warranted.

Blondell RD; Frydrych LM; Arber BC; Bashaw HL; Vexler A; Purdy CH; Sawyer RM; Okazaki S. Randomized trial of extended buprenorphine detoxification for opioid dependency. Journal of Addiction Medicine 2(3): 139-146, 2008. (20 refs.)

Objective: The objective of this study was to determine whether additional "take-home" medication after impatient opioid detoxification would lead to improved rates of subsequent treatment initiation and abstinence. Methods: We randomly assigned 60 inpatients to a 7-day or 37-day extension of sublingual buprenorphine/naloxone after hospitalization. Follow-up telephone interviews were conducted approximately 5 weeks after discharge. The primary outcomes were abstinence, initiation of aftercare outpatient counseling, and initiation of self-help meeting attendance. Results: Of the 30 participants in each group, outcome data were obtained for 25 (83%) in the 7-day extension group and 27 (90%) in the 37-day extension group. There was not a significant difference in the rates of abstinence (53% versus 41%) or initiation of self-help (57% versus 54%) between the 7-day and 37-day groups, respectively. Of those in the 7-day group, 15 (65%) initiated outpatient treatment compared with 21 (88%) of those assigned to the 37-day group. Although not significant in unadjusted analysis (P = 0.093), this difference was significant in regression analysis when controlling for a history of intravenous drug use (P = 0.034). Among all participants, individual characteristics at the time of hospital adimission (eg, age of first drug use, previous history of intravenous drug, type of health insurance) were predictive of outcomes. Conclusions: In this preliminary study, additional medication beyond a week after inpatient detoxification was not associated with clinically important improvements in rates of abstinence or treatment initiation. Baseline patient characteristics seem to affect these clinical outcomes after hospitalization.

Brigham GS; Amass L; Winhusen T; Harrer JM; Pelt A. Using buprenorphine short-term taper to facilitate early treatment engagement. Journal of Substance Abuse Treatment 32(4): 349-356, 2007. (43 refs.)

The U.S. Federal Food and Drug Administration approved buprenorphine for drug abuse treatment in 2002, and it became available for clinical use in early 2003. Maryhaven, a community treatment program, participated in a National Institute on Drug Abuse Clinical Trials Network trial evaluating buprenorphine-naloxone (BNX; Suboxone) short-term taper for medically managed opioid withdrawal and later adopted this treatment. In a retrospective review, the first 64 patients treated with a BNX taper were compared with two groups of patients treated with clonidine before and after the implementation of the BNX program. Significantly more patients (about 80%) receiving BNX continued in further treatment compared to about 30% of those receiving clonidine. Patient outcomes are discussed in the context of the critical need for treatment continuation following detoxification. Common questions of potential adopters of the BNX taper are presented and addressed. Overall, BNX was readily integrated into the existing treatment service.

Brown RT; Zueldorff M. Opioid substitution with methadone and buprenorphine: Sexual dysfunction as a side effect of therapy. Heroin Addiction and Related Clinical Problems 9(1): 35-44, 2007

Opioid substitution is the most widespread and well-researched treatment modality for opioid dependence. Methadone and buprenorphine are currently the most commonly used pharmacotherapeutic agents. Sexual dysfunction has been reported as an adverse effect of opioids including methadone and buprenorphine. The current article describes proposed mechanisms for sexual dysfunction as an adverse effect of methadone and buprenorphine, summarizes research conducted on subjects on these agents, and explores appropriate evaluation and intervention in the management of the types of sexual dysfunction most commonly encountered during opioid substitution treatment (libido, erectile, and orgasm dysfunction).

Bruce RD; Altice FL. Case series on the safe use of buprenorphine/naloxone in individuals with acute hepatitis C infection and abnormal hepatic liver transaminases. American Journal of Drug and Alcohol Abuse 33(6): 869-874, 2007. (13 refs.)

Background: Hepatitis C virus (HCV) is the most prevalent chronic viral illness in the United States. Many individuals with virus HCV are opioid dependent requiring treatment with opiate substitution treatment such as buprenorphine. Previous reports in the literature have suggested hepatotoxicity with buprenorphine tempering initial enthusiasm of the safety of buprenorphine in HCV-infected patients. Methods: As part of an ongoing SAMHSA-funded grant to expand opiate substitution therapy with buprenorphine, all opioid-dependent patients seeking treatment with buprenorphine undergo a laboratory evaluation including transaminases (AST/ALT) as well as laboratory evaluation for acute and chronic hepatitis. Results: Of the 121 patients screened for entry into buprenorphine treatment, 4 patients had evidence of acute HCV infection. Conclusions: Despite markedly elevated transaminases in the setting of acute hepatitis C nfection, these patients tolerated buprenorphine treatment with improvement in their transaminases during the course of buprenorphine treatment.

Bruce RD; Govindasamy S; Sylla L; Haddad MS; Kamarulzaman A; Altice FL. Case series of buprenorphine injectors in Kuala Lumpur, Malaysia. American Journal of Drug and Alcohol Abuse 34(4): 511-517, 2008. (25 refs.)

Diversion of buprenorphine has been described in settings where it is legally prescribed and has become an increasing concern in Malaysia; it resulted in banning of buprenorphine in Singapore where unsubstantiated case reports suggested that buprenorphine injection was associated with particularly poor outcomes. We therefore conducted a case series of qualitative interviews with buprenorphine injectors in Kuala Lumpur, Malaysia to examine further the issues surrounding buprenorphine injection as well as the abuse of midazolam in combination with buprenorphine. Interviews with 19 men do not suggest significant adverse health consequences from buprenorphine injection alone and injectors have adapted diverted buprenorphine as a treatment modality. A subset of these injectors, however, combined buprenorphine and midazolam for euphoric effects with resultant symptoms of a possible pharmacological interaction. Prospective cohort studies, rather than hospital-derived samples, are needed to better understand the safety of buprenorphine injection.

Bruce RD; Govindasamy S; Sylla L; Kamarulzaman A; Altice FL. Lack of reduction in buprenorphine injection after introduction of co-formulated buprenorphine/naloxone to the Malaysian market. American Journal of Drug and Alcohol Abuse 35(2): 68-72, 2009. (26 refs.)

Background: Diversion of buprenorphine (BPN) has been described in settings where it is legally prescribed and has resulted in increasing concern. To address this concern, co-formulation of buprenorphine/naloxone (BPN/NLX) replaced buprenorphine alone in Malaysia in December 2006. Methods: To assess the significance of BPN/NLX introduction, 41 BPN/NLX injectors in Kuala Lumpur, Malaysia were recruited using a modified snowball recruitment technique. Results: In January 2007, all subjects had previously injected BPN alone. During the transition from injecting BPN alone to co-formulated BPN/NLX, the mean daily BPN injection dose increased from 1.88 mg (range 1.0-4.0 mg) to 2.49 mg/day (p .001). Overall, 18 (44%) subjects increased their daily amount of injection while 22 (54%) had no change in dose; only one subject reduced the amount of injection. Development of opioid withdrawal symptoms was the primary outcome, however the only symptom that was significantly associated with BPN/NLX dosage was the report of stomach pains (p = .01). In logistic regression analysis, the development of opioid withdrawal symptoms was associated with increased benzodiazepine injection and increased syringe sharing. Conclusion and Scientific Significance: These data suggests that the introduction of BPN/NLX did not reduce injection related risk behaviors such as syringe sharing and was associated with increased benzodiazepine use. Evidence-based approaches to treat BPN injection are urgently needed.

Ciccocioppo R; Economidou D; Rimondini R; Sommer W; Massi M; Heilig M. Buprenorphine reduces alcohol drinking through activation of the nociceptin/orphanin FQ-NOP receptor system. Biological Psychiatry 61(1): 4-12, 2007. (93 refs.)

Background: Activation of the NOP receptor by its endogenous ligand nociceptin/orphanin FQ reduces ethanol intake in genetically selected alcohol preferring Marchigian Sardinian alcohol preferring (msP) rats. Here we evaluated whether buprenorphine, a partial agonist at [mu]-opioid and NOP receptors, would reduce ethanol consumption in msP rats via activation of NOP receptors.MethodsMarchigian Sardinian alcohol preferring rats trained to drink 10% alcohol 2 hours/day were injected with buprenorphine (.03, .3, 3.0, or 6.0 mg/kg intraperitoneally [IP]) 90 min before access to ethanol. Results: Similar to prototypical [mu]-agonists, the two lowest doses of buprenorphine significantly increased ethanol consumption. Conclusions: Buprenorphine has dualistic effects on ethanol drinking; low doses increase alcohol intake via stimulation of classic opioid receptors, whereas higher doses reduce it via activation of NOP receptors. We suggest that NOP agonistic properties of buprenorphine might be useful in the treatment of alcoholism.

Cicero TJ; Surratt H; Inciardi JA; Munoz A. Relationship between therapeutic use and abuse of opioid analgesics in rural, suburban, and urban locations in the United States. Pharmacoepidemiology and Drug Safety 16(8): 827-840, 2007. (38 refs.)

Purpose: The goal of these studies was to determine the relationship between prescribed use of opioid analgesics and their non-medically related use (abuse) at a regional level across the country. Methods To gather information about prescription drug abuse, we asked 233 drug abuse treatment specialists to provide us Quarterly reports on the number of cases of prescription opioid analgesic abusers who used opioid analgesics to get high in the past 30 days. Results and Conclusions We found that there was a very strong correlation between therapeutic exposure to opioid analgesics, as measured by prescriptions filled, and their abuse. There were, however, geographical loci that represented outliers in which abuse was disproportionately high relative to therapeutic use (> 95th percentile), most of which were in very small urban, suburban, and rural areas. The rank order of abuse shows that buprenorphine products, extended release (ER) oxycodone and methadone are the most intensely abused prescription opioid analgesics, with hydrocodone the least abused, when the data are corrected for degree of exposure, i.e., cases/1000 persons filling a prescription. If, on the other hand, one uses the number of cases/100000 population, hydrocodone ranked as high as ER oxycodone and all other drugs grouped together at very low levels of abuse. Since the latter conclusion ignores therapeutic exposure, we conclude that the rate of abuse of highly efficacious opioid analgesics is best expressed as cases of abuse/1000 persons filling a prescription, which yields the best possible estimate of the risk-benefit ratio of these drugs.

Colameco S; Coren JS; Zimmerman DJ. Buprenorphine-induced symptomatic hypogonadism in men: Case reports and discussion. Journal of Addiction Medicine 2(3): 147-150, 2008. (19 refs.)

Collins ED; Horton T; Reinke K; Amass L; Nunes EV. Using buprenorphine to facilitate entry into residential therapeutic community rehabilitation. Journal of Substance Abuse Treatment 32(2): 167-175, 2007. (33 refs.)

For opioid-dependent patients, the need for detoxification has been a barrier to entry into long-term residential treatment. This report describes a retrospective observational cohort study with the first 38 opioid-dependent patients entering First Step, a 14-day buprenorphine-naloxone (Suboxone) detoxification regimen integrated into a long-term residential therapeutic community (TC) program. Eighty-nine percent (34 of 38) of First Step patients completed a 14-day buprenorphine taper protocol, 50% (19 of 38) completed an initial 3- to 4-weck stay, and 39% (15 of 38) completed at least 3 months of residential treatment at the TC. Retention did not differ significantly in a demographically matched concurrently admitted control group without impending opioid withdrawal, in which 65% (24 of 37) completed an initial 3- to 4-week stay (p =.20) and 57% (21 of 37) completed at least 3 months of treatment (p --.14). Withdrawal symptoms were mild, and there were no instances of precipitated withdrawal. The findings suggest the potential for buprenorphine to serve as a bridge, improving the viability of long-term residential treatment for managing opioid dependence.

Compton P; Ling W; Chiang NC; Moody DE; Huber A; Ling D et al. Pharmacokinetics of buprenorphine: A comparison of sublingual tablet versus liquid after chronic dosing. Journal of Addiction Medicine 1(2): 88-95, 2007. (29 refs.)

Although buprenorphine is approved for use in the outpatient treatment of opioid addiction in 2 tablet formulations, a monoproduct containing buprenorphine only (Subutex) and a buprenorphine/naloxone combination product (Suboxone), much of the clinical data that support the approval by the U.S. Food and Drug Administration were generated by using a sublingual liquid. To interpret the literature in prescribing parameters for tablet buprenorphine, this study was designed to determine steady state buprenorphine plasma levels for the 2 formulations and to assess the relative bioavailability of each. A randomized, double-blind, crossover study with dose increases was conducted during a 12-week period at an outpatient treatment clinic. Of the 184 subjects initially randomized to treatment, 133 (72.3%) were evaluated for the steady-state trough plasma concentration, 16 (8.7%) for relative bioavailability, and 31 (16.8%) for dose proportionality. At steady state, differences in the trough plasma concentrations of buprenorphine between the 2 formulations were found across all the dose levels. Average plasma concentration (Cavg) of the tablet at twice the milligram dose of the liquid was twice that of the liquid; intersubject variability was greater for the tablet. At double the dose of tablet, there is no difference in steady state plasma concentrations. The bioavailability seems equivalent for the 2 formulations across all the dose levels.

Connock M; Juarez-Garcia A; Jowett S; Frew E; Liu Z; Taylor R et al. Methadone and buprenorphine for the management of opioid dependence: A systematic review and economic evaluation. (review). Health Technology Assessment 11(9): 1-190, 2007. (249 refs.)

Objectives: To assess the clinical effectiveness and cost-effectiveness of buprenorphine maintenance therapy (BMT) and methadone maintenance therapy (MMT) for the management of opioid-dependent individuals. Data sources: Major electronic databases were searched from inception to August 2005. Industry submissions to the National Institute for Health and Clinical Excellence were accessed. Review methods: The assessment of clinical effectiveness was based on a review of existing reviews plus an updated search for randomised controlled trials (RCTs). A decision tree with Monte Carlo simulation model was developed to assess the cost-effectiveness of BMT and MMT. Retention in treatment and opiate abuse parameters were sourced from the meta-analysis of RCTs directly comparing flexible MMT with flexible dose BMT. Utilities were derived from a panel representing a societal perspective. Results: Most of the included systematic reviews and RCTs were of moderate to good quality, and focused on short-term (up to 1-year follow-up) outcomes of retention in treatment and the level of opiate use (self-report or urinalysis). Most studies employed a trial design that compared a fixed-dose strategy (i.e. all individuals received a standard dose) of MMT or BMT and were conducted in predominantly young men who fulfilled criteria as opiate-dependent or heroin-dependent users, without significant co-morbidities. RCT meta-analyses have shown that a fixed dose of MMT or BMT has superior levels of retention in treatment and opiate use than placebo or no treatment, with higher fixed doses being more effective than lower fixed doses. There was evidence, primarily from non-randomised observational studies, that fixed-dose MMT reduces mortality, HIV risk behaviour and levels of crime compared with no therapy and one small RCT has shown the level of mortality with fixed-dose BMT to be significantly less than with placebo. Flexible dosing (i.e. individualised doses) of MMT and BMT is more reflective of real-world practice. Retention in treatment was superior for flexible MMT than flexible BMT dosing but there was no significant difference in opiate use. Indirect comparison of data from population cross-sectional studies suggests that mortality with BMT may be lower than that with MMT. A pooled RCT analysis showed no significant difference in serious adverse events with MMT compared with BMT. Although treatment modifier evidence was limited, adjunct psychosocial and contingency interventions (e. g. financial incentives for opiate-free urine samples) appeared to enhance the effects of both MMT and BMT. Also, MMT and BMT appear to be similarly effective whether delivered in a primary care or outpatient clinic setting. Although most of the included economic evaluations were considered to be of high quality, none used all of the appropriate parameters, effectiveness data, perspective and comparators required to make their results generalisable to the NHS context. One company (Schering-Plough) submitted cost-effectiveness evidence based on an economic model that had a 1-year time horizon and sourced data from a single RCT of flexible-dose MMT compared with flexible-dose BMT and utility values obtained from the literature; the results showed that for MMT vs no drug therapy, the incremental cost-effectiveness ratio (ICER) was pound 12,584/quality-adjustedlife-year (QALY), for BMT versus no drug therapy, the ICER was pound 30,048/QALY and in a direct comparison, MMT was found to be slightly more effective and less costly than BMT. The assessment group model found for MMT versus no drug therapy that the ICER was pound 13,697/ QALY, for BMT versus no drug therapy that the ICER was pound 26,429/QALY and, as with the industry model, in direct comparison, MMT was slightly more effective and less costly than BMT. When considering social costs, both MMT and BMT gave more health gain and were less costly than no drug treatment. These findings were robust to deterministic and probabilistic sensitivity analyses. Conclusions: Both flexible-dose MMT and BMT are more clinically effective and more cost-effective than no drug therapy in dependent opiate users. In direct comparison, a flexible dosing strategy with MMT was found be somewhat more effective in maintaining individuals in treatment than flexible-dose BMT and therefore associated with a slightly higher health gain and lower costs. However, this needs to be balanced by the more recent experience of clinicians in the use of buprenorphine, the possible risk of higher mortality of MMT and individual opiate-dependent users' preferences. Future research should be directed towards the safety and effectiveness of MMT and BMT; potential safety concerns regarding methadone and buprenorphine, specifically mortality and key drug interactions; efficacy of substitution medications (in particular patient subgroups, such as within the criminal justice system, or within young people); and uncertainties in cost-effectiveness identified by current economic models.

Copenhaver MM; Bruce RD; Altice FL. Behavioral counseling content for optimizing the use of buprenorphine for treatment of opioid dependence in community-based settings: A review of the empirical evidence. American Journal of Drug and Alcohol Abuse 33(5): 643-654, 2007. (35 refs.)

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.

Cowan J. Buprenorphine: The basic pharmacology revisited. Journal of Addiction Medicine 1(2): 68-72, 2007

The historical background leading to the current use of buprenorphine as an analgesic and its role in the management of opioid dependence is summarized. The popular description of buprenorphine as a "partial agonist" is discussed in relation to efficacy in animal models of antinociception and clinical analgesia. The latest information on the respiratory depressant effects of buprenorphine and its N-dealkylated metabolite (norbuprenorphine) is presented. New data on the buprenorphine withdrawal syndrome in rats are described.

Cunningham CO; Kunins HV; Roose RJ; Elam RT; Sohler NL. Barriers to obtaining waivers to prescribe buprenorphine for opioid addiction treatment among HIV physicians. Journal of General Internal Medicine 22(9): 1325-1329, 2007. (34 refs.)

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.

DeMaria PA; Patkar AA. The implementation of buprenorphine/naloxone in college health practice. Journal of American College Health 56(4): 391-393, 2008. (19 refs.)

Opiate abuse and dependence have become important concerns for college healthcare providers. The passage of the Drug Addiction Treatment Act of 2000 and the approval of the combination buprenorphine/naloxone for office-based treatment of opiate dependence have increased the options available for college students and their helath care providers. The authors review the pharmacology of buprenorphine/naloxone and discuss how it can be implemented in college health practice. They also present a case report.

Ducharme LJ; Abraham AJ. State policy influence on the early diffusion of buprenorphine in community treatment programs. Substance Abuse Treatment, Prevention and Policy 3(e-article 17), 2008. (42 refs.)

Background: Buprenorphine was approved for use in the treatment of opioid dependence in 2002, but its diffusion into everyday clinical practice in community-based treatment programs has been slow. This study examines the net impact of efforts by state agencies, including provision of Medicaid coverage, on program-level adoption of buprenorphine as of 2006. Methods: Interviews were conducted with key informants in 49 of the 50 state agencies with oversight responsibility for addiction treatment services. Information from these interviews was integrated with organizational data from the 2006 National Survey of Substance Abuse Treatment Services. A multivariate logistic regression model was estimated to identify the effects of state efforts to promote the use of this medication, net of a host of organizational characteristics. Results: The availability of Medicaid coverage for buprenorphine was a significant predictor of its adoption by treatment organizations. Conclusion: Inclusion of buprenorphine on state Medicaid formularies appears to be a key element in ensuring that patients have access to this state-of-the-art treatment option. Other potential barriers to the diffusion of buprenorphine require identification, and the value of additional state-level policies to promote its use should be evaluated.

Dvoryak S; Grishayeva I. First experience of opioid therapy with buprenorphine in Ukraine. Heroin Addiction and Related Clinical Problems 10(1): 13-17, 2008. (5 refs.)

Ukraine is the country that has the highest rate of HIV/AIDS among IDUs in Europe. The development of opioid maintenance treatment for opioid users is an important public health issue. The earliest utilization of buprenorphine for OMT was made in 2004-5, within the framework of the UNDP Applied Human Rights Project. It was accompanied by research which was a part of the WHO Collaborative Study on Opioid Treatment of Opioid Dependence and HIV/AIDS. There were 67 opioid drug users under observation. This was a prospective observational study with assessments at baseline, and at 3- and 6-month follow-ups. All assessments refer to the period of one month prior to interview. The main aims of outcome evaluation were to explore changes in the following domains: health status and well-being of individuals in opioid treatment; community/social benefits and also programme performance. Improvements in the main indicators were documented after 6 months of treatment. The retention level was 66% and the mean buprenorphine dose was about 8 mg/day. The main conclusion is that buprenorphine treatment is effective in the context of Ukrainian social conditions.

Elsner H. Outpatient short-term detoxification treatment of heroin-consumption: 5 days buprenorphine in descending dosage. Suchttherapie 8(3): 119-122, 2007. (1 refs.)

The heroin-consumption only for a short time is a treatment-strategic problem, when the users could not stop the consumption with a 'cold turkey': Mostly a withdrawal-treatment in hospital is not indicated as well as a fairly long-term substitution-treatment. An outpatient withdrawal treatment with methadone often takes several weeks and can impair seriously the general condition and the everyday life function. The following pattern describes an outpatient withdrawal-treatment ("Bochumer Schema") which was found empirically to have an answer for this problem. It uses buprenorphine in descending dosage for 5 days: 8 mg, 6 mg, 4 mg, 2 mg, 1,2 mg. The somatic withdrawal symptoms are suppressed well, but the lack of the psychotropic effects limits the method.

Escher M; Daali Y; Chabert J; Hopfgartner G; Dayer P; Desmeules J. Pharmacokinetic and pharmacodynamic properties of buprenorphine after a single intravenous administration in healthy volunteers: A randomized, double-blind, placebo-controlled, crossover study. Clinical Therapeutics 29(8): 1620-1631, 2007. (51 refs.)

Background: Buprenorphine is used as an analgesic for postoperative and chronic pain. The usual sublingual dose is 0.2 to 0.8 mg, and the usual parenteral dose is 0.3 mg for acute postoperative pain. The pharmacokinetic and related pharmacodynamic properties of buprenorphine at these doses have not been characterized. Objective: The aim of this study was to assess the pharmacokinetic properties of buprenorphine 0.002 mg/kg IV (0.15 mg/70 kg) and its antinociceptive and psychomotor effects. Methods: Healthy male volunteers received 0.002 mg/kg buprenorphine IV in a randomized, double blind, placebo-controlled, crossover design. Blood samples were collected at 0.5, 1, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, and 8 hours for the determination of plasma concentrations. Pharmacokinetic parameters were estimated by a compartmental model using specialized software. Antinociceptive and psychomotor effects were determined for 8 hours. Quantitative sensory testing with thermal and electrical (nociceptive flexion RIII reflex) stimulations was performed. The cold pressor test was used to assess pain tolerance to a tonic, intense pain stimulation. Psychomotor performance was assessed by the digit symbol substitution test (DSST). Participants also rated sedation on an 11-point numeric scale (0 = none to 10 = severe). A selective liquid chromatography-tandem mass spectrometry assay was developed for the determination of buprenorphine; the limit of quantification was 0.05 ng/mL using a 0.25-mL plasma aliquot. Participants were instructed to report adverse effects, which were recorded for type, time of onset, seriousness, and duration. Results: The study enrolled 12 participants, all of whom were white. Mean (SD) age was 26 (3.5) years, and mean weight was 67 (9) kg. None of the participants had a history of opiate abuse. Buprenorphine significantly increased the objective (nociceptive flexion RIII reflex) and Subjective pain thresholds for > 4 hours and pain tolerance (cold pressor test) for 2 hours. The mean (SD) RIII reflex threshold and subjective threshold at baseline were 31.6 (9.5) mA and 45.5 (22.3) m angstrom, respectively. The maximum increases (mean [SD]) were +14.1 (17.5) m angstrom for the RIII reflex (P = 0.02) and +24.2 (21.7) m angstrom for the subjective threshold (P = 0.02), corresponding to mean (SEM) percentages of 53.7% (20.2%) and 74.7% (20.4%) of the baseline values, respectively. The maximum increases were observed at 120 minutes for both measures. The effect of buprenorphine on pain tolerance peaked at 30 minutes. Mean (SEM) latency before withdrawal of the hand was 69 (10) seconds, corresponding to a mean increase of 63.8%) (14.4%) from baseline (P = 0.003). Buprenorphine had a significant effect on the DSST. The mean maximum decrease in the total number of symbols drawn was -6 (14.5%; P = 0.005) at 1 hour. The participants reported high levels of sedation: at peak effect (120 minutes), mean scores increased from 2.9 to 6.4 (SEM 0.7) (P = 0.005). Levels returned to baseline values by the end of the session, unlike for the nociceptive tests. The onset of effects occurred during the distribution phase for all the measures, and their duration was observed across a wide range of concentrations during the elimination phase. The most likely explanation for this finding is the high affinity of buprenorphine at mu-opiold receptors, and possibly distribution to the brain. Buprenorphine t(1/2),2 was 2.75 hours. A secondary peak in concentration was observed at 90 minutes, suggesting enterohepatic circulation of buprenorphine. A 2-compartment model adequately described buprenorphine pharmacokinetics. Conclusions: A clinically relevant analgesic dose of 0.002 mg/kg (0.15 mg/70 kg) of buprenorphine had a significant effect on nociception and psychomotor performance in these healthy male volunteers. A 2-compartment model satisfactorily characterized buprenorphine pharmacokinetics, and we found evidence of enterohepatic circulation.

Esses JL; Rosman J; Do LT; Schweitzer P; Hanon S. Successful transition to buprenorphine in a patient with methadone-induced torsades de pointes. Journal of Interventional Cardiac Electrophysiology 23(2): 117-119, 2008. (7 refs.)

A 56-year-old-man presented with syncope and torsades de pointes secondary to methadone-induced QT prolongation. After transition from methadone to buprenorphine, a partial mu-opiate-receptor agonist and a kappa-opiate-receptor antagonist, the QT normalized and ventricular arrhythmias resolved. Buprenorphine should be used for opiate dependence and chronic pain in patients with methadone-induced QT prolongation and as first line therapy in patients with risk factors for torsades de pointes.

Fiellin DA. The first three years of buprenorphine in the United States: Experience to date and future directions. Journal of Addiction Medicine 1(2): 62-67, 2007

Buprenorphine, primarily as the buprenorphine/naloxone combination, has been available in the United States for office and specialty treatment program-based care since 2003. The existing evidence, collected primarily from federal sources, indicates that access to this type of treatment has expanded, that more than 50% of the 12,000 physicians able to provide this care are not addiction specialists, that buprenorphine diversion is low, that physician scrutiny by federal agents is infrequent, and among those receiving treatment patient acceptance is high. Implementation has been slowed because of physician training and support needs, reimbursement, and limits on the number of patients each physician can treat. As a result there are geographic variations in access and unmet treatment needs. The United States Congress has moved twice to loosen numerical limitations, now allowing each physician to treat up to 100 patients. Future research and evaluation are needed to ensure that opioid-dependent patients receive optimal care with buprenorphine.

Fiellin DA; Moore BA; Sullivan LE; Becker WC; Pantalon MV; Chawarski MC et al. Long-term treatment with buprenorphine/naloxone in primary care: Results at 2-5 years. American Journal on Addictions 17(2): 116-120, 2008. (31 refs.)

To examine long-term outcomes with primary care office-based buprenorphine/naloxone treatment, we followed 53 opioid-dependent patients who had already demonstrated six months of documented clinical stability for 2-5 years. Primary outcomes were retention, illicit drug use, dose, satisfaction, serum transaminases. and adverse events. Thirty-eight percent of enrolled subjects were retained for two years. Ninety-one percent of urine samples had no evidence of opioid use, and patient satisfaction was high. Serum transaminases remained stable from baseline. No serious adverse events related to treatment occurred. We conclude that select opioid-dependent patients exhibit moderate levels of retention in primary care office-based treatment.

Finch JW; Kamien JB; Amass L. Two-year experience with buprenorphine-naloxone (Suboxone) for maintenance treatment of opioid dependence within a private practice setting. Journal of Addiction Medicine 1(2): 104-110, 2007. (27 refs.)

Office-based buprenorphine-naloxone (Suboxone) treatment in the United States has significantly improved access to safe and effective opioid-dependence therapy. Little data from physicians' experiences prescribing Suboxone in private offices have been available. This retrospective chart review describes a family practitioner's first 2 years of clinical experience prescribing Suboxone for opioid dependence to 71 patients in a private office. After directly observed rapid office dose induction, Suboxone prescriptions were given monthly after evidence of continued stability. Urine was screened regularly and patients were referred for counseling and other ancillary services. Patients averaged 32 years old, 4.3 years of opioid dependence, and were primarily white (93%) and employed (70%). Fifty-two percent used heroin primarily (most by injection), and 70% had no agonist substitution therapy history. Almost half (47%) paid for their own treatment. Compliance during dose induction was excellent. Suboxone maintenance doses averaged 10 (range, 2-24) mg per day. More than 80% of urine samples were opioid-negative after Suboxone treatment began, although urinalysis did not always include a test for oxycodone. Seventy-five percent had successful outcomes by remaining in Suboxone treatment (43%), tapering successfully (21%), transferring to methadone maintenance (7%), or inpatient treatment (4%). Fifty-eight percent reported receiving counseling. Almost all (85%) paid their fees on time. There were no safety, medication abuse, or diversion issues detected. Overall, office-based Suboxone therapy was easily implemented and the physician considered the experience excellent. Suboxone maintenance was associated with good treatment retention and significantly reduced opioid use, and it is helping to reach patients, including injection drug users, without histories of agonist substitution therapy.

Garcia CA; Correa GC; Viver ADH; Kinlock TW; Gordon MS; Avila CA et al. Buprenorphine-naloxone treatment for pre-release opioid-dependent inmates in Puerto Rico. Journal of Addiction Medicine 1(3): 126-132, 2007. (46 refs.)

The following study, conducted in Puerto Rico, examined the feasibility of providing daily buprenorphine-naloxone (bup-nx) in prison and on release to 45 male inmates with histories of heroin addiction. Participants were assessed at study entry and at 1 month after release (N = 42; 93.3% follow-up rate). Treatment completers compared with noncompleters had significantly greater reductions in self-reported heroin use, cocaine use, and crime and were less likely to be opioid-positive according to urine drug testing. Despite study limitations, the short-term outcomes of this study suggest that bup-nx may contribute to reductions in readdiction to heroin and in criminal activities among re-entering male prisoners.

Gardner T; Kosten T. Buprenorphine for dual dependency: Cocaine, alcohol and opiates. Heroin Addiction and Related Clinical Problems 9(2): 11-16, 2007. (22 refs.)

Dual-drug dependency is common in Europe and America and represents a complex management and treatment challenge. Most heroin addicts abuse stimulants or alcohol in addition to opiates. Cocaine pharmacotherapy remains a challenge, but there has been some success with Buprenorphine, Disulfiram, Modafinil and GABA agonists. A promising cocaine vaccine is also under development. Triple-dependency with alcohol or benzodiazepines is also common and can lead to serious dependence requiring detoxification. In addition to regular monitoring following alcohol detoxification, relapse prevention pharmacotherapy is essential. The following review will briefly describe concurrent-drug abuse with cocaine and opiates as well as describe current pharmacotherapies for multi-drug dependence. In addition, we will briefly discuss the implications for combining behavioral therapies with medications to improve treatment efficacy.

Gibson A; Degenhardt L; MattickRP; Ali R; White J; O'Brien S. Exposure to opioid maintenance treatment reduces long-term mortality. Addiction 103(3): 462-468, 2008. (31 refs.)

Aims To (i) examine the predictors of mortality in a randomized study of methadone versus buprenorphine maintenance treatment; (ii) compare the survival experience of the randomized subject groups; and (iii) describe the causes of death. Design Ten-year longitudinal follow-up of mortality among participants in a randomized trial of methadone versus buprenorphine maintenance treatment. Setting Recruitment through three clinics for a randomized trial of buprenorphine versus methadone maintenance. Participants A total of 405 heroin-dependent (DSM-IV) participants aged 18 years and above who consented to participate in original study. Measurements Baseline data from original randomized study; dates and causes of death through data linkage with Births, Deaths and Marriages registries; and longitudinal treatment exposure via State health departments. Predictors of mortality examined through survival analysis. Findings There was an overall mortality rate of 8.84 deaths per 1000 person-years of follow-up and causes of death were comparable with the literature. Increased exposure to episodes of opioid treatment longer than 7 days reduced the risk of mortality; there was no differential mortality among methadone versus buprenorphine participants. More dependent, heavier users of heroin at baseline had a lower risk of death, and also higher exposure to opioid treatment. Older participants randomized to buprenorphine treatment had significantly improved survival. Aboriginal or Torres Strait Islander participants had a higher risk of death. Conclusions: Increased exposure to opioid maintenance treatment reduces the risk of death in opioid-dependent people. There was no differential reduction between buprenorphine and methadone. Previous studies suggesting differential effects may have been affected by biases in patient selection.

Gibson AE; Degenhardt LJ. Mortality related to pharmacotherapies for opioid dependence: A comparative analysis of coronial records. Drug and Alcohol Review 26(4): 405-410, 2007. (47 refs.)

Introduction and Aims. The aim of this study was to compare the mortality associated with oral naltrexone, methadone and buprenorphine in opioid dependence treatment, employing a retrospective data analysis using coronial and prescription data. Design and Methods. The number of deaths were identified through national coronial data and number of treatment recipients were estimated from 2000 to 2003 prescriptions and restricted medications data. Mortality rates were expressed as deaths per number of treatment episodes and per person-years at high and low risk of fatal opioid overdose. Results. Thirty-two oral naltrexone, one buprenorphine and 282 methadone-related deaths were identified. Mortality rates in the highest risk period in deaths per 100 person-years were 22.1 (14.6-32.2) for oral naltrexone following treatment cessation and 3.0 (2.3-3.9) for methadone during treatment induction. Rates in the lowest risk period in deaths per 100 person-years were 1.0 (0.3-2.2) during oral naltrexone treatment and 0.34 (0.3-0.4) during post-induction methadone treatment. The relative risk of death for oral naltrexone subjects was 7.4 times (high-risk period, p < 0.0001) or 2.8 times (low-risk period, p = 0.055) that of methadone subjects. Discussion and Conclusions. This is the first comparison of mortality associated with these three pharmacotherapies for opioid dependence. The risk of death related to oral naltrexone appears higher than that related to methadone treatment.

Goodwin RS; Wilkins DG; Averin O; Choo RE; Schroeder JR; Jasinski DR et al. Buprenorphine and norbuprenorphine in hair of pregnant women and their infants after controlled buprenorphine administration. Clinical Chemistry 53(12): 2136-2143, 2007. (16 refs.)

Background: Buprenorphine is under investigation as a pharmacotherapeutic agent for treating opioid dependence in pregnant women. We hypothesized that there would be a relationship between the cumulative maternal dose. of buprenorphine during pregnancy and the concentration of buprenorphine and norbuprenorphine in maternal and infant hair. Methods: This study examined buprenorphine and norbuprenorphine concentrations in hair obtained from 9 buprenorphine-maintained pregnant women and 4 of their infants. Specimens were analyzed by liquid chromatography-tandem mass spectrometry with limits of quantification of 3.0 pg/mg. All maternal hair specimens Were washed with methylene chloride before analysis, and when sufficient amounts of maternal hair were available, specimens also were analyzed without washing, Infant hair specimens were not washed. Results: Buprenorphine concentrations were significantly greater in unwashed hair than washed hair (P = 0.031). Norbuprenorphine concentrations were significantly greater than buprenorphine concentrations in both maternal (P = 0.0097) and infant hair (P = 0.0033). There were statistically significant associations between the cumulative maternal dose of buprenorphine administered and the concentrations of buprenorphine (washed, P < 0.0001; unwashed, P = 0.0004), norbuprenorphine (washed, P < 0.0001; unwashed, P = 0.0005), and buprenorphine plus norbuprenorphine (washed, P < 0.0001; unwashed, P = 0.0005) for both washed and unwashed maternal hair specimens. There was a significant positive association between concentrations of buprenorphine and norbuprenorphine in maternal hair (washed, P < 0.0001; unwashed, P = 0.0003), a trend for this association in infant hair (P = 0.08), and an association between buprenorphine concentrations in maternal unwashed hair and infant hair (P = 0.0002). The buprenorphine:norbuprenorphine ratio increased in distal segments. Conclusion: Buprenorphine treatment during gestation provides an opportunity for monitoring drug disposition in maternal and fetal tissues under controlled conditions.

Gordon AJ; Trafton JA; Saxon AJ; Gifford AL; Goodman F; Calabrese VS; McNicholas L; Liberto J. Implementation of buprenorphine in the Veterans Health administration: Results of the first 3 years. Drug and Alcohol Dependence 90(2/3): 292-296, 2007. (17 refs.)

Background: Compared to non-veterans, veterans are disproportionately diagnosed with opioid dependence. Sublingual buprenorphine provides greater access to opioid agonist therapy. To understand the diffusion of this innovative treatment within a large healthcare system, we describe the introduction of buprenorphine, within the Veterans Health Administration (VHA) during the first 3 years of its approval as a VHA non-formulary medication. Methods: Using VHA pharmacy databases, we examined the number of physicians who have prescribed buprenorphine and the number of veterans who have received office-based buprenorphine within VHA veterans integrated service networks (VISN) from fiscal years (FY) 2003 through FY 2005 (October 2002 through September 2005). Results: From FY2003 through FY2005 the number of veterans with opioid dependence increased from 25,031 to 26,859 (>7.3%) and the number of veterans prescribed office-based buprenorphine increased from 53 to 739. During this interval, 16 of 21 VISNs had prescribed buprenorphine. In FY2005, two VISNs accounted for 31% of buprenorphine prescriptions. The number of buprenorphine prescriptions varied widely by VISN, but increased from 212 to 7076 from FY2003 through FY2005. During this interval, prescriptions per patient increased from 4.0 to 9.6 and physicians prescribing buprenorphine increased from 14 to 170. The ratio of patients prescribed buprenorphine to providers prescribing buprenorphine increased from 3.8 to 4.3 with an average increase of 15.1-41.6 of prescriptions per provider. Conclusions: VHA increased, but not uniformly, the non-formulary use of office-based buprenorphine during the first 3 years of availability.

Gunderson EW; Fiellin DA; Levin FR; Sullivan LE; Kleber HD. Evaluation of a combined online and in person training in the use of buprenorphine. Substance Abuse 27(3): 39-45, 2007

To evaluate buprenorphine training methodology, we surveyed physicians who had completed a combined online and in person buprenorphine curriculum. Of 53/70 (76%) survey respondents, 57% were psychiatrists and 40% generalists. On a scale of 1 (very poor) to 7 (superlative), the overall training rated a mean of 5.8. The online course (5.0) rated lower than in person training components (p < .001) except for material that addressed the logistics of office practice. The in person patient interview received the highest rating (mean 6.3, p < .001). The 67% of physicians who intended to prescribe buprenorphine after the training were more likely than hesitant physicians to agree that the course provided enough information (p < .05) and that telephone access to experienced providers would improve their confidence (p < .05). Physicians hesitant to prescribe cited lack of experience as the main barrier (41%), with 24% concerned about induction difficulty and reimbursement. Overall, physicians preferred in person instruction and may benefit from additional experiential training and support after curriculum participation.

Hakansson A; Medvedeo A; Andersson M; Berglund M. Buprenorphine misuse among heroin and amphetamine users in Malmo, Sweden: Purpose of misuse and route of administration. European Addiction Research 13(4): 207-215, 2007. (35 refs.)

Buprenorphine misuse by injecting drug users was assessed in a survey of 350 needle exchangers, either amphetamine (57%) or heroin users (42%). 89% of heroin users and 24% of amphetamine users reported using buprenorphine at some time during the previous year. Most users reported illicit acquisition. Among illicit users, 87% of heroin users reported intake for withdrawal treatment or self-detoxification, and 11% for euphoria. Euphoria seeking was more common among amphetamine users (62%, p < 0.001). Intravenous misuse was reported by 43% of illicit users, and snorting by 29%. Sole sublingual intake was more common among heroin users than among amphetamine users (46 vs. 20%, p < 0.05), and less common among patients reporting euphoria seeking (20 vs. 46%, p < 0.05).

Hallinan R; Byrne A; Agho K; McMahon C; Tynan P; Attia J. Erectile dysfunction in men receiving methadone and buprenorphine maintenance treatment. Journal of Sexual Medicine 5(3): 684-692, 2008. (29 refs.)

Introduction. Use of opiates/opioids is associated with hypoactive sexual desire, erectile and orgasmic dysfunction. Aim. To determine prevalence and investigate etiology of sexual dysfunction in men on methadone or buprenorphine maintenance treatment (MMT, BMT). Main Outcome Measures. International Index of Erectile Function (IIEF), hormone assays, Beck Depression Inventory. Methods. A total of 103 men (mean age 37.6 +/- 7.9) on MMT (N = 84) or BMT (N = 19) were evaluated using the IIEF, hormone assays, Beck Depression Inventory, body mass index (BMI), demographic, and other substance use measures. Results. Mean total IIEF scores for partnered men were lower for MMT (50.4 +/- 18.2; N = 53) than reference groups (61.4 +/- 16.8; N = 415; P < 0.0001) or BMT (61.4 +/- 7.0; N = 14; P = 0.048). Among partnered men on MMT, 53% had erectile dysfunction (ED) compared with 24% of reference groups; 26% had moderate to severe ED, 12.1% in under 40s and 40.0% among those 40+ years. On multiple regression, depression, older age, and lower total testosterone were associated with lower IIEF and EF domain; on multivariate analysis, there were no significant associations between IIEF or EF and free testosterone, opioid dose, cannabis or other substance use, viral hepatitis, or BMI. Total testosterone accounted for 16% of IIEF and 15% of EF variance. Men without sexual partners had lower Desire and Erection Confidence scores and less recent sexual activity, suggesting potentially higher prevalence of sexual dysfunction in this group. Conclusion. Men on MMT, but not BMT, have high prevalence of ED, related to hypogonadism and depression. Practitioners should screen for sexual dysfunction in men receiving opioid replacement treatment. Future studies of sexual dysfunction in opioid-treated men should examine the potential benefits of dose reduction, androgen replacement, treatment of depression, and choice of opioid.

Hallinan R; Byrne A; Agho K; McMahon CG; Tynan P; Attia J. Hypogonadism in men receiving methadone and buprenorphine maintenance treatment. International Journal of Andrology 32(2): 131-139, 2009. (34 refs.)

The aim of this study was to determine the prevalence and investigate the aetiology of hypogonadism in men on methadone or buprenorphine maintenance treatment (MMT, BMT). 103 men (mean age 37.6 +/- 7.9) on MMT (n = 84) or BMT (n = 19) were evaluated using hormone assays, body mass index (BMI), serological, biochemical, demographic and substance use measures. Overall 54% of men (methadone 65%; buprenorphine 28%) had total testosterone (TT) < 12.0 nm; 34% (methadone 39%; buprenorphine 11%) had TT < 8.0 nm. Both methadone- and buprenorphine-treated men had lower free testosterone, luteinising hormone and estradiol than age-matched reference groups. Methadone-treated men had lower TT than buprenorphine-treated men and reference groups. Prolactin did not differ between methadone, buprenorphine groups, and reference groups. Primary testicular failure was an uncommon cause of hypogonadism. Yearly percentage fall in TT by age across the patient group was 2.3%, more than twice that expected normally. There were no associations between TT and opioid dose, cannabis, alcohol and tobacco consumption, or chronic hepatitis C viraemia. On multiple regression higher TT was associated with higher alanine aminotransferase and lower TT with higher BMI. Men on MMT have high prevalence of hypogonadotrophic hypogonadism. The extent of hormonal changes associated with buprenorphine needs to be explored further in larger studies. Men receiving long term opioid replacement treatment, especially methadone treatment, should be screened for hypogonadism. Wide interindividual differences in methadone metabolism and tolerance may in a cross-sectional study obscure a methadone dose relationship to testosterone in individuals. Future studies of hypogonadism in opioid-treated men should examine the potential benefits of dose reduction, choice of opioid medication, weight loss, and androgen replacement.

Hayes BD; Klein-Schwartz W; Doyon S. Toxicity of buprenorphine overdoses in children. Pediatrics 121(4): e782-e786, 2008. (21 refs.)

OBJECTIVE. There are few reports in children of overdoses of buprenorphine, a partial opioid agonist used in the treatment of opioid dependence and pain. The purpose of this study was to analyze buprenorphine overdoses in young children reported by US poison centers to the Researched Abuse, Diversion, and Addiction-Related Surveillance System. METHODS. A retrospective review of buprenorphine overdoses in children < 6 years of age reported to the Researched Abuse, Diversion, and Addiction-Related Surveillance System from November 2002 through December 2005 was performed. Patients lost to follow- up and those ingesting multiple substances were excluded. RESULTS. Eighty-six cases met inclusion criteria. In the 54 children who developed toxicity, the clinical effects included drowsiness or lethargy (55%), vomiting (21%), miosis (21%), respiratory depression (7%), agitation or irritability (5%), pallor (3%), and coma (2%). There were no fatalities. The mean time to onset of effects was 64.2 minutes, with a range of 20 minutes to 3 hours. Duration of clinical effects was under 2 hours in 11%, 2 to 8 hours in 59%, 8 to 24 hours in 26%, and > 24 hours in 4%. Children who ingested >= 2 mg of buprenorphine were more likely to experience clinical effects, and all of the children who ingested > 4 mg experienced some effect. No child ingesting > 4 mg experienced a severe effect. Of the 22 children administered naloxone, 67% had at least a partial response. CONCLUSIONS. Buprenorphine overdoses are generally well tolerated in children, with significant central nervous system and respiratory depression occurring in only 7%. Any child ingesting > 2 mg and children < 2 years of age ingesting more than a lick or taste should be referred to the emergency department for a minimum of 6 hours of observation. Naloxone can be used to reverse respiratory depression.

Horgan CM; Reif S; Hodgkin D; Garnick DW; Merrick EL. Availability of addiction medications in private health plans. Journal of Substance Abuse Treatment 34(2): 147-156, 2008. (31 refs.)

Health plans have implemented cost sharing and administrative controls to constrain escalating prescription expenditures. These policies may impact physicians' prescribing and patients' use of these medications. Important clinical advances in the pharmacological treatment of addiction highlight the need to examine how pharmacy benefits consider medications for substance dependence. The extent of restrictions influencing the availability of these medications to consumers is unknown. We use nationally representative survey data to examine the extent and stringency of private health plans' management of naltrexone and disulfiram for alcohol dependence, and buprenorphine for opiate dependence. Thirty-one percent of insurance products excluded buprenorphine from formularies, whereas 55% placed it on the highest cost-sharing tier. Generic naltrexone is the only substance dependence medication that is both rarely excluded from formularies and usually placed on a lower cost-sharing tier. These findings demonstrate that pharmacy benefits have an impact on access to medications for substance abuse.

Hytinantti T; Kahila H; Renlund M; Jarvenpaa AL; Halmesmaki E; Kivitie-Kallio S. Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero. Acta Paediatrica 97(8): 1040-1044, 2008. (14 refs.)

Aim: To study the neonatal outcome of infants exposed to buprenorphine in utero. Methods: We prospectively followed 54 buprenorphine-using pregnant women and their 58 infants. Urinary buprenorphine and norbuprenorphine concentrations in the mothers were measured prior to delivery, and in the infants during the first 3 days of life. The Finnegan score was used to evaluate neonatal abstinence syndrome. Other medical problems as well as social outcomes were recorded. Results: All infants had buprenorphine in their urine. A total of 38 infants required 20 +/- 10 days (range 7-48 days) of morphine treatment for neonatal abstinence syndrome. The length of hospital stay for all infants was 25 +/- 19 days (range 3-125 days). The infants' highest urinary norbuprenorphine concentrations across their first 3 days of life correlated with the length of hospital stay and duration of morphine treatment (both p < 0.05). The mean birth weight and mean head circumference (n = 58) were below average (mean -0.7 standard deviation [SD] and mean -0.5 SD, respectively). Eleven infants were discharged home, 19 infants were placed in foster care and 28 infants were discharged with their mothers to Mother and Child homes or to other institutions. Conclusion: Maternal buprenorphine use at the time of birth may cause neonatal abstinence syndrome, requiring long-term hospitalization. Multiple social problems require a multidisciplinary team approach.

Jakobovits SL; Mcdonough M; Chen RY. Buprenorphine-associated gastroparesis during in-patient heroin detoxification. Addiction 102(3): 490-491, 2007. (6 refs.)

Background: Buprenorphine is a partial mu receptor agonist used in opiate detoxification. It has been shown to cause delayed gastric emptying in healthy volunteers. Case description: We describe a case of clinically severe gastroparesis (delayed gastric emptying due to impaired contraction of the stomach) whose onset coincided with the commencement of buprenorphine-assisted detoxification. Conclusion: We review the literature on gastric effects of buprenorphine in healthy volunteers, providing proof of the concept that this was the most probable cause of this patient's gastroparesis.

Jones ES; Moore BA; Sindelar JL; O'Connor PG; Schottenfeld RS; Fiellin DA. Cost analysis of clinic and office-based treatment of opioid dependence: Results with methadone and buprenorphine in clinically stable patients. Drug and Alcohol Dependence 99(1-3): 132-140, 2009. (47 refs.)

The cost of providing and receiving treatment for opioid dependence can determine its adoption. To compare the cost of clinic-based methadone (MC, n = 23), office-based methadone (MO, it = 2 1), and office-based buprenorphine (130, it = 34) we performed an analysis of treatment and patient costs over 6 months of maintenance in patients who had previously been stabilized for at least I year. We performed statistical comparisons using ANOVA and chi-square tests and performed a sensitivity analysis varying cost estimates and intensity of clinical contact. The cost of providing I month of treatment per patient was $147 (MC), $220 (MO) and $336 (130) (p < 0.001). Mean monthly medication cost was $93 (MC), $86 (MO) and $257 (130) (1), < 0.001). The cost to patients was $92 (MC), $63 (MO) and $38 (130) (P = 0.102). Sensitivity analyses, varying cost estimates and clinical contact, result in total monthly costs of $117 to $183 (MC), $149 to $279 (MO), $292 to $499 (BO). Monthly patient costs were $84 to $133 (MC), $55 to $105 (MO) and $34 to $65 (130). We conclude that providing clinic-based methadone is least expensive. The price of buprenorphine accounts for a major portion of the difference in costs. For patients, office-based treatment may be less expensive.

Jones HE; Johnson RE; O'Grady KE; Jasinski DR; Tuten M; Milio L. Dosing adjustments in postpartum patients maintained on buprenorphine or methadone. Journal of Addiction Medicine 2(2): 103-107, 2008. (14 refs.)

Scant scientific attention has been given to examining the need for agonist medication dose changes in the postpartum period. Study objectives were: 1) to determine the need for medication dose adjustments in participants stabilized on buprenorphine or methadone 3 weeks before and 4 weeks after delivery, and 2) to evaluate the need for methadone dose adjustments during the first 7 days in participants transferred from buprenorphine to methadone at 5 weeks postpartum. Participants were opioid-dependent pregnant women who had completed a randomized, double-blind, double-dummy, flexible dosing comparison of buprenorphine to methadone. Participants received a stable dose of methadone (N = 10) or buprenorpbine (N = 8) before and 4 weeks after delivery. Buprenorphine-maintained participants were transferred to methadone at 5 weeks postpartum. There were no significant differences predelivery and/or postdelivery between the buprenorphine and methadone conditions in the mean ratings of dose adequacy, "liking," "hooked," and "craving" of heroin or cocaine. Patient response to the conversion from buprenorphine to methadone seems variable. Buprenorphine-maintained participants required dose changes postpartum only after they transferred to methadone. Regardless of type of medication, postpartum patients should be monitored for signs of overmedication.

Kacinko SL; Jones HE; Johnson RE; Choo RE; Huestis MA. Correlations of maternal buprenorphine dose, buprenorphine, and metabolite concentrations in meconium With neonatal outcomes. Clinical Pharmacology & Therapeutics 84(5): 604-612, 2008. (39 refs.)

For the first time, relationships among maternal buprenorphine dose, meconium buprenorphine and metabolite concentrations, and neonatal outcomes are reported. Free and total buprenorphine and norbuprenorphine, nicotine, opiates, cocaine, benzodiazepines, and metabolites were quantified in meconium from 10 infants born to women who had received buprenorphine during pregnancy. Neither cumulative nor total third-trimester maternal buprenorphine dose predicted meconium concentrations or neonatal outcomes. Total buprenorphine meconium concentrations and buprenorphine/norbuprenorphine ratios were significantly related to neonatal abstinence syndrome (NAS) scores >4. As free buprenorphine concentration and percentage free buprenorphine increased, head circumference decreased. Thrice-weekly urine tests for opiates, cocaine, and benzodiazepines and self-reported smoking data from the mother were compared with data from analysis of the meconium to estimate in utero exposure. Time of last drug use and frequency of use during the third trimester were important factors associated with drug-positive meconium specimens. The results suggest that buprenorphine and metabolite concentrations in the meconium may predict the onset and frequency of NAS.

Kahila H; Kivitie-Kallio S; Halmesmaki E; Valanne L; Autti T. Brain magnetic resonance imaging of infants exposed prenatally to buprenorphine. Acta Radiologica 48(2): 228-231, 2007. (16 refs.)

Purpose: To evaluate the brains of newborns exposed to buprenorphine prenatally. Material and Methods: Seven neonates followed up antenatally in connection with their mothers' buprenorphine replacement therapy underwent 1.5T magnetic resonance imaging (MRI) of the brain before the age of 2 months. The infants were born to heavy drug abusers. Four mothers were hepatitis C positive, and all were HIV negative. All mothers smoked tobacco and used benzodiazepines. All pregnancies were full term, and no perinatal asphyxia occurred. All but one neonate had abstinence syndrome and needed morphine replacement therapy. Results: Neither structural abnormalities nor abnormalities in signal intensity were recorded. Conclusion: Buprenorphine replacement therapy does not seem to cause any major structural abnormalities of the brain, and it may prevent known hypoxic-ischemic brain changes resulting from uncontrolled drug abuse. Longitudinal studies are needed to assess possible abnormalities in the brain maturation process.

Kahila H; Saisto T; Kivitie-Kallio S; Haukkamaa M; Halmesmaki E. A prospective study on buprenorphine use during pregnancy: Effects on maternal and neonatal outcome. Acta Obstetricia et Gynecologica Scandinavica 86(2): 185-190, 2007. (24 refs.)

Background. Exposure to illicit drugs in utero is associated with low birth weight and premature birth. Therefore, maintenance therapy for opioid dependence during pregnancy has been recommended to help withdrawal from street drugs, in order to improve maternal health and decrease risks to the fetus. Methods. In 2002-2005, 67 pregnancies of 66 buprenorphine users were followed prospectively in an outpatient multidisciplinary antenatal setting by an obstetrician, a midwife, a psychiatric nurse and a social worker. Decreasing doses or even abstinence from buprenorphine was encouraged. Outcome measures were daily buprenorphine dose, fetal growth, gestational age at birth, mode of delivery, birth weight, Apgar scores, umbilical pH values, and occurrence of neonatal abstinence syndrome [NAS]. National statistics were used as reference values. Results. The daily dose of buprenorphine decreased by 2.3 mg (median, range increase of 8 mg to decrease of 24 mg). There were no more incidences of premature birth, cesarean section, low Apgar scores (<= 6) or umbilical artery pH <7.05 at birth than in the national register, despite the lower birth weight. A total of 91% of the infants needed treatment in a neonatal care unit, 76% had NAS, and 57% needed morphine replacement therapy. Seven infants were taken into care directly from the maternity hospital. Two sudden infant deaths occurred later. Conclusions. The pregnancies and deliveries of buprenorphine-using women were uneventful, but severe NAS and need for morphine replacement therapy was seen in 57% of the buprenorphine-exposed newborns. A high number of sudden infant deaths occurred.

Kakko J; Gronbladh L; Svanborg KD; von Wachenfeldt J; Ruck C; Rawlings B et al. A stepped care strategy using buprenorphine and methadone versus conventional methadone maintenance in heroin dependence: A randomized controlled trial. American Journal of Psychiatry 164(5): 797-803, 2007. (34 refs.)

Objective: Both methadone and buprenorphine are effective therapy for heroin dependence. Efficacy is best documented for methadone maintenance therapy, but safety concerns limit its use. Buprenorphine offers lower overdose risk and improved access, but efficacy may be lower. The authors compared adaptive, buprenorphine-based stepped care to optimal methadone maintenance treatment. Method: This randomized controlled trial was undertaken 2004-2006. It consisted of a 24-day uniform double-blind induction phase followed by single-blind flexible dosing based on structured clinical criteria, for a total of 6 months. Ninety-six self-referred subjects with heroin dependence were randomly assigned to methadone or to stepped treatment initiated with buprenorphine/naloxone and escalated to methadone if needed. All subjects received intensive behavioral treatment. Primary outcome was retention in treatment. Secondary outcomes were completer analyses of problem severity (Addiction Severity Index) and proportion of urine samples free of illicit drugs. Results: Overall, 6-month retention was 78%. Stepped treatment and methadone maintenance therapy outcomes were virtually identical. Among completers of stepped therapy, 46% remained on buprenorphine/naloxone. Proportion of urine samples free of illicit opiates increased over time and ultimately reached approximately 80% in both arms. Problem severity decreased significantly and uniformly in both arms. Conclusions: A stepped treatment of heroin dependence as described here appears equally efficacious compared to optimally delivered methadone maintenance therapy. Together with prior data on the advantageous safety of buprenorphine, this suggests that broad implementation of strategies using buprenorphine as first-line treatment should be considered.

Kakko J; Heilig M; Sarman I. Buprenorphine and methadone treatment of opiate dependence during pregnancy: Comparison of fetal growth and neonatal outcomes in two consecutive case series. Drug and Alcohol Dependence 96(1-2): 69-78, 2008. (31 refs.)

Aim: To compare the effects of fetal buprenorphine and methadone exposure during maintenance treatment of pregnant heroin dependent subjects. Design and setting: A population based comparison of consecutive, prospectively followed buprenorphine-exposed pregnancies in Stockholm County, Sweden, to retrospectively analyzed consecutive methadone-exposed pregnancies. Participants: All 47 pregnancies in 39 women with opiate dependence and buprenorphine maintenance treatment 2001-2006, and all 35 methadone-exposed pregnancies (26 women) 1982-2006 in Stockholm County. Measurements: Intrauterine growth, birth outcome, malformations, neonatal adaptation, withdrawal syndrome and infant mortality. Findings: Buprenorphine-exposed pregnancies resulted in 47 uneventful live births (2 twin pairs), 1 stillbirth (for which no explanation was found) and 1 miscarriage. The birth weight of the infants was normal. Neonatal abstinence syndrome (NAS) occurred in 19 cases (40.4%), the majority mild in nature and only 7 (14.9%) needing withdrawal treatment. Compared to 35 infants born after intrauterine methadone exposure at the same hospital since 1982 (77.8% of them exhibiting NAS and 52.8% needing withdrawal treatment), there were significant advantages with buprenorphine treatment: birth weight was higher, due to longer gestation. Incidence of NAS of any intensity, as well as incidence of NAS that required pharmacological treatment was lower, while length of hospital stay was shorter. When buprenorphine treatment started pre-conception, NAS at any level was significantly less frequent than in subjects with post-conception initiated treatment (7/27, 26%; 12/20, 60%, respectively). Conclusions: Data from this non-randomized comparison suggest that buprenorphine may offer advantages for treatment of opiate dependence during pregnancy.

Kamien JB; Branstetter SA; Amass L. Buprenorphine-naloxone versus methadone maintenance therapy: A randomised double-blind trial with opioid-dependent patients. Heroin Addiction and Related Clinical Problems 10(4): 5-18, 2008. (66 refs.)

This is the first randomised study comparing buprenorphine-naloxone with methadone for maintenance treatment of opioid dependence. A 17-week, double-blind, double-dummy trial of daily dosing compared buprenorphine-naloxone (8/2 mg and 16/4 mg) with methadone (45 mg and 90 mg) in 268 participants. The percentage of opioid-free urine samples over time did not differ by drug or dosage. The percentage of patients with >= 12 consecutive opioid-negative urine samples did not differ by drug and was significantly greater for patients receiving higher doses of either agent. Induction success, compliance, nonopioid drug use, retention and Addiction Severity Index scores did not differ among groups. Buprenorphine-naloxone is a viable alternative to methadone in clinical practice.

Katz EC; Schwartz RP; King S; Highfield DA; O'Grady KE; Billings T et al. Brief vs. extended buprenorphine detoxification in a community treatment program: Engagement and short-term outcomes. American Journal of Drug and Alcohol Abuse 35(2): 63-67, 2009. (27 refs.)

Background: Despite evidence supporting the efficacy of buprenorphine relative to established detoxification agents such as clonidine, little research has examined: 1) how best to implement buprenorphine detoxification in outpatient settings; and 2) whether extending the length of buprenorphine detoxification improves treatment engagement and outcomes. Objectives: The current study examined the impact on 1) successful detoxification completion; 2) transition to longer-term treatment; and 3) treatment engagement of two different length opioid detoxifications using buprenorphine. Methods: The study compared data obtained from two consecutive studies of early treatment engagement strategies. In one study (n = 364), opioid-addicted participants entered treatment through a Brief (5-day) buprenorphine detoxification. In the other study (n = 146), participants entered treatment through an Extended (i.e., 30-day) buprenorphine detoxification. Results: Results indicated a greater likelihood of successful completion and of transition among participants who received the Extended as compared to the Brief detoxification. Extended detoxification participants attended more counseling sessions and submitted fewer drug-positive urine specimens during the first 30 days of treatment, inclusive of detoxification, than did Brief detoxification participants. Conclusions: Results demonstrate that longer periods of detoxification improve participant engagement in treatment and early treatment outcomes. Scientific Significance: Current findings demonstrate the feasibility of implementing an extended buprenorphine detoxification within a community-based treatment clinic.

Knudsen HK; Ducharme LJ; Roman PM. Research network involvement and addiction treatment center staff: Counselor attitudes toward buprenorphine. American Journal on Addictions 16(5): 365-371, 2007. (37 refs.)

The National Institute on Drug Abuse's Clinical Trials Network (CTN) aims to improve addiction treatment in the United States in part through technology transfer. Given the importance of clinicians in the technology transfer process, this research compares 561 CTN-affiliated and 1,745 non-CTN counselors' ratings of buprenorphine acceptability. CTN-affiliated counselors reported significantly greater acceptability than non-CTN counselors. This difference was not explained by controlling for counselor characteristics, but was completely attenuated by measures of buprenorphine-specific training and buprenorphine implementation. These data suggest that the CTN's impact on counselor attitudes may be attributed to the greater exposure to buprenorphine received by CTN-affiliated counselors.

Kornor H; Waal H; Sandvik L. Time-limited buprenorphine replacement therapy for opioid dependence: 2-year follow-up outcomes in relation to programme completion and current agonist therapy status. Drug and Alcohol Review 26(2): 135-141, 2007. (33 refs.)

Programme completion is predictive of post-treatment abstinence and other improvements in persons with opioid dependence, while continued agonist treatment is associated with better outcomes than no agonist treatment. This study aimed to assess relationships between follow-up outcomes of a 9-month buprenorphine programme, completion and current agonist therapy status. Sixty-eight of 75 opioid-dependent former participants were assessed at study entry and 24 months thereafter. Outcome measures were opioid abstinence, substance use and psychosocial performance. Group comparisons were made between buprenorphine programme completers (n = 38) and non-completers (n = 30), and between participants who were currently in agonist therapy (n = 37) and those who were not. Performance at follow- up was compared to that at study entry. Nine people were abstinent from all opioids at follow-up. Completers and non-completers were similar in follow-up performance and patterns of change, while participants' current agonist therapy status was related to both substance use and psychosocial outcomes. Reductions in street opioid use and injecting were seen regardless of completion and agonist therapy status. Retaining patients in agonist replacement therapy over time is more likely than completion of a time-limited programme to influence long-term outcomes. Time-limited buprenorphine replacement therapy appears to be inappropriate for persons with opioid dependence.

Kovas AE; McFarland BH; McCarty DJ; Boverman JF; Thayer JA. Buprenorphine for acute heroin detoxification: Diffusion of research into practice. Journal of Substance Abuse Treatment 32(2): 199-206, 2007. (48 refs.)

Buprenorphinc has been approved for heroin detoxification, but little is known about its impact on everyday practice. Concerns about buprenorphine include expense, limited knowledge about its use, patient limits, and social and clinical attitudes regarding opioid treatment for heroin dependence. On the other hand, randomized clinical trials suggest that buprenorphine is superior to clonidine with regard to withdrawal symptom relief In June 2004, a community-based residential medical detoxification center switched from clonidine to buprenorphine treatment for all new and returning heroin clients. This study is a retrospective chart review of subject outcomes with clonidine (n = 100) versus buprenorphine (n = 100). Bivariate analysis suggested few cohort differences in pretreatment demographics and client characteristics. In contrast, buprenorphine was significantly associated with increased length of stay and treatment completion. The positive associations between buprenorphine and both treatment completion and length of stay persisted and were slightly enhanced after regression analysis adjusted for potential confounders. Additionally, clinical staff reported better subject engagement in treatment and psychosocial group sessions. This single-site study is an example of successful integration of an evidence-based treatment into community-based practice.

Kraft WK; Gibson E; Dysart K; Damle VS; LaRusso JL; Greenspan JS et al. Sublingual buprenorphine for treatment of neonatal abstinence syndrome: A randomized trial. Pediatrics 122(3): e601-e607, 2008. (38 refs.)

OBJECTIVE. In utero exposure to drugs of abuse can lead to neonatal abstinence syndrome, a condition that is associated with prolonged hospitalization. Buprenorphine is a partial mu-opioid agonist used for treatment of adult detoxification and maintenance but has never been administered to neonates with opioid abstinence syndrome. The primary objective of this study was to demonstrate the feasibility and, to the extent possible in this size of study, the safety of sublingual buprenorphine in the treatment of neonatal abstinence syndrome. Secondary goals were to evaluate efficacy relative to standard therapy and to characterize buprenorphine pharmacokinetics when sublingually administered. METHODS. We conducted a randomized, open-label, active-control study of sublingual buprenorphine for the treatment of opiate withdrawal. Thirteen term infants were allocated to receive sublingual buprenorphine 13.2 to 39.0 mu g/kg per day administered in 3 divided doses and 13 to receive standard-of-care oral neonatal opium solution. Dose decisions were made by using a modified Finnegan scoring system. RESULTS. Sublingual buprenorphine was largely effective in controlling neonatal abstinence syndrome. Greater than 98% of plasma concentrations ranged from undetectable to similar to 0.60 ng/mL, which is less than needed to control abstinence symptoms in adults. The ratio of buprenorphine to norbuprenorphine was larger than that seen in adults, suggesting a relative impairment of N-dealkylation. Three infants who received buprenorphine and 1 infant who received standard of care reached protocol-specified maximum doses and required adjuvant therapy with phenobarbital. The mean length of treatment for those in the neonatal-opium-solution group was 32 compared with 22 days for the buprenorphine group. The mean length of stay for the neonatal-opium-solution group was 38 days compared with 27 days for those in the buprenorphine group. Treatment with buprenorphine was well tolerated. CONCLUSIONS. Buprenorphine administered via the sublingual route is feasible and apparently safe and may represent a novel treatment for neonatal abstinence syndrome.

Kress HG. Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine. (review). European Journal of Pain 13(3): 219-230, 2009. (109 refs.)

Buprenorphine was not used widely in clinical practice over many years, mainly due to analgesic potency and clinical safety concerns based on misinterpreted animal data. Contrary to previous concerns, however, no analgesic ceiling effect and no antagonism of combined pure p-opioid receptor agonists is seen within the therapeutic dose range. In recent studies, buprenorphine could be effectively and safely combined with full mu-agonists, and switching between buprenorphine and another opioid provided comparable pain relief based on equianalgesic doses. Moreover, buprenorphine exerts an anti hyperalgesic effect, which is due-at least in part-to antagonistic activity at K-opioid receptors. Buprenorphine pharmacokinetics are not altered by advanced age or renal dysfunction. In addition, the risk of respiratory depression is lower than with other opioids including morphine, hydromorphone, methadone and fentanyl. Unlike morphine and fentanyl, there is no immunosuppressive activity with buprenorphine at therapeutic analgesic doses, Transdermal buprenorphine has significantly improved the clinical use of the drug, providing continuous buprenorphine release for Lip to 96 h. In clinical trials, patients receiving transdermal buprenorphine experienced significantly greater pain relief, better sleep, and a reduced need for rescue therapy, compared to placebo. Large-scale post-marketing studies have confirmed the effectiveness of transdermal buprenorphine in treating moderate-to-severe cancer and non-cancer pain including neuropathic syndromes. Finally, the comparably low incidence of CNS adverse events and constipation, and the possibility of use in severe renal dysfunction without a need for dose adjustment make buprenorphine well suited for chronic pain management in at-risk patients, such as diabetics, elderly or renally impaired individuals including those requiring haemodialysis.

Lanier RK; Umbricht A; Harrison JA; Nuwayser ES; Bigelow GE. Evaluation of a transdermal buprenorphine formulation in opioid detoxification. Addiction 102(10): 1648-1656, 2007. (31 refs.)

Aims: Buprenorphine is marketed in a sublingual formulation for treatment of opioid dependence. A transdermal formulation has been developed that may provide extended relief from opioid withdrawal, reduce required clinic visits and improve adherence, while having less potential for diversion and abuse. This study evaluated the safety and biodelivery (blood levels) of this transdermal buprenorphine formulation (i.e. buprenorphine patch), and its apparent efficacy in suppressing the opioid withdrawal syndrome. Design Open-label, first-in-humans trial. Setting A residential research facility. Participants Nine physically dependent opioid-users completed the 10-day opioid detoxification study. Interventions Each volunteer received a single patch application that remained in place for 3 days. The formulation has shown an average delivery of 1.9 mg/day of buprenorphine over 3 days in pre-clinical evaluation. Measures Physiological, behavioral, subjective and observer ratings of opioid withdrawal and opioid agonist effects were collected. Findings Overall, the patch appeared safe and well tolerated. There were no serious adverse events, and no opioid intoxication following patch application. Oxygen saturation, heart rate, blood pressure, skin temperature and pupil diameter remained well within normal ranges. Buprenorphine blood levels peaked 48 hours after patch application at a concentration of 0.60 ng/ml. Volunteers' self-reports of the presence and severity of withdrawal symptoms were reduced by approximately 50% on the 3 days of patch application. Withdrawal symptoms increased marginally upon patch removal. Administration of opioid rescue medication was eliminated within 6 hours of patch application, and increased slightly upon patch removal. Conclusions The significant biodelivery of buprenorphine and the suppression of the opioid withdrawal syndrome during patch application and its reappearance after patch removal indicate clinically useful pharmacodynamic activity. Transdermal buprenorphine may be a useful opioid detoxification treatment that reduces compliance concerns, and delivers buprenorphine in a formulation less likely to be diverted to illicit use.

Lavie E; Fatseas M; Denis C; Auriacombe M. Benzodiazepine use among opiate-dependent subjects in buprenorphine maintenance treatment: Correlates of use, abuse and dependence. Drug and Alcohol Dependence 99(1-3): 338-344, 2009. (34 refs.)

Background: Previous studies from North America, Europe and Australia have reported high levels of benzodiazepine use among opiate-dependent patients in opiate maintenance treatment. However, to date, there are no available data on patterns of abuse and dependence on benzodiazepines according to DSM criteria among these patients. Aims: To describe the independent correlates of use, abuse and dependence on benzodiazepines among buprenorphine patients selected from standard treatment settings. Methods: Cross-sectional study in France between June 2001 and June 2004. Buprenorphine patients treated for over 3 months were recruited via physicians prescribing buprenorphine. Patients answered a self-administered questionnaire, the DSM-IV criteria for benzodiazepine abuse and dependence, the Beck Anxiety and Depression Inventories (BAI, BDI) and the Nottingham Health Profile (NHP). Main outcome was modalities of benzodiazepine use: no use vs. simple use vs. problematic use (abuse or dependence according to DSM-IV). Results: 170 patients were recruited. 54% did not use benzodiazepines during the previous month, 15% were simple users and 31% were problematic users. Benzodiazepine use (all modalities) was associated with poly-use of psychotropics. Simple users of benzodiazepines were not statistically different from non-users for the other factors explored. Problematic users of benzodiazepines had higher depression and anxiety levels, correlated with quality of life impairment and precariousness. They used higher dosages of benzodiazepines than simple users. Conclusions: Characteristics of simple benzodiazepine users were distinct from problematic users but not from non-users in this sample of buprenorphine patients. This should be taken into account in the clinical management of benzodiazepine use among buprenorphine patients.

Leonardi C; Hanna N; Laurenzi P; Fagetti R. Multi-centre observational study of buprenorphine use in 32 Italian drug addiction centres. Drug and Alcohol Dependence 94(1/3): 125-132, 2008. (38 refs.)

Aim: To examine how buprenorphine is currently being used across Italy, and to identify simultaneously best practice protocols to guide physicians in optimising the safety and efficacy of this treatment option. Design: Retrospective, observational, multi-centre study. Participants: A total of 979 opioid-dependent patients were included from 32 centres involving the initiation of 1122 treatments. Findings: During the study period 33.4% of patients relapsed during the induction phase. Lower induction doses resulted in markedly higher relapse rates (51.2% of those who received 2 mg versus 20.6% of those who received 10 mg of buprenorphine relapsed). Over 89% of patients who received 16 mg of buprenorphine during the induction phase successfully went on to maintenance treatment. The percentage of drug-positive urines also decreased over time on buprenorphine treatment (cocaine-positive urines decreased from 25.8% at study entrance to 0% at 24 months). Psychosocial support in addition to buprenorphine pharmacotherapy further decreased the risk of relapse and was associated with lower levels of heroin craving. Retention in treatment was increased by less-than-daily dosing of buprenorphine. Conclusions: Higher induction doses of buprenorphine significantly decreased relapse rates and increased the percentage of patients achieving maintenance treatment. Psychosocial support and/or less-than-daily dosing also appeared to promote positive treatment outcomes.

Levy S; Vaughan BL; Angulo M; Knight JR. Buprenorphine replacement therapy for adolescents with opioid dependence: Early experience from a children's hospital-based outpatient treatment program. Journal of Adolescent Health 40(5): 477-482, 2007. (20 refs.)

Opioid use by adolescents is on the rise and replacement therapy is an effective treatment. Methadone replacement has been used safely and effectively with adults, but methadone programs are often unattractive to teenagers. Buprenorphine is a new replacement therapy that has been shown to be as effective as high dose methadone and may be better suited for the treatment of younger patients. We describe the experiences of several adolescent patients who received treatment from an outpatient adolescent substance abuse program that operates within a children's hospital, with an emphasis on issues of adolescent development.

Ling W. Why we do what we do: Delivery of buprenorphine and the treatment of opioid addiction. (editorial). Addiction 102(12): 1908-1909, 2007. (9 refs.)

Magura S; Lee JD; Hershberger J; Joseph H; Marsch L; Shronshire C; Rosenblum A. Buprenorphine and methadone maintenance in jail and post-release: A randomized clinical trial. Drug and Alcohol Dependence 99(1-3): 222-230, 2009. (53 refs.)

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. Hero in-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. Boprenorphine 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.

Magura S; Lee SJ; Salsitz EA; Kolodny A; Whitley SD; Taubes T et al. Outcomes of buprenorphine maintenance in office-based practice. Journal of Addictive Diseases 26(2): 13-23, 2007. (37 refs.)

Buprenorphine is an efficacious treatment for opioid dependence recently approved for office-based medical practice. The purpose of the study was to describe the background characteristics, treatment process, outcomes and correlates of outcomes for patients receiving buprenorphine maintenance in "real world" office-based settings in New York City, without employing the many patient exclusion criteria characterizing clinical research studies of buprenorphine, including absence of co-occurring psychiatric and non-opioid substance use disorders. A convenience sample of six physicians completed anonymous chart abstraction forms for all patients who began buprenorphine induction or who transferred to these practices during 2003-2005 (N = 86). The endpoint was the patient's current status or status at discharge from the index practice, presented in an intent-to-treat analysis. The results were: male (74%); median age (38 yrs); White, non-Hispanic (82%); employed full-time, (58%); HCV+ (15%); substance use at intake: prescription opioids (50%), heroin (35%), non-opioids (49%); median length of treatment (8 months); median maintenance dose (15 mg/day); prescribed psychiatric medication (63%). The most frequent psychiatric disorders were: major depression, obsessive-compulsive and other anxiety, bipolar. At the endpoint: retained in the index practice (55%); transferred to other buprenorphine practice (6%); transferred to other treatment (7%); lost to contact or out of any treatment (32%). Outcomes were positive, in that 2/3 of patients remained in the index practice or transferred to other treatment. Patients living in their own home or misusing prescription opioids (rather than heroin) were more likely, and those employed part-time were less likely, to be retained in the index practice. At the endpoint, 24% of patients were misusing drugs or alcohol. Co-occurring psychiatric disorders and polysubstance abuse at intake were common, but received clinical attention, which may explain why their effect on outcomes was minimal.

Maremmani I. When a new drug promotes the integration of treatment modalities: Suboxone and harm reduction. Heroin Addiction and Related Clinical Problems 10(3): 5-11, 2008. (51 refs.)

In medicine, the introduction of a new drug is often associated with an overall enhanced understanding of the clinical issues that originally stimulated its own development. Sometimes newer drugs must be introduced to counter the improper use of existing drugs. In this paper, we discuss some concepts regarding the pharmacotherapy of heroin addiction (regarding blocking dosages and stabilization dosages), the advantages and disadvantages of opioid agonists in the pharmacotherapy of heroin addiction, the role of motivation for harm reduction strategies, the difficulties of methadone, buprenorphine, naltrexone and naloxone use in harm reduction strategies, and the possible use of buprenorphine-naloxone combination in harm reduction strategies. A buprenorphine-naloxone combination is not only a clinical improvement over pre-existing treatments, but it also represents a good example of a drug designed to limit the misuse of another resulting in the integration of different modalities of intervention, previously believed to be in opposition.

Maremmani I; Pani PP; Pacini M; Perugi G. Substance use and quality of life over 12 months among buprenorphine maintenance-treated and methadone maintenance-treated heroin-addicted patients. Journal of Substance Abuse Treatment 33(1): 91-98, 2007. (64 refs.)

The purpose of this study was to investigate the effects of methadone treatment and buprenorphine treatment on retention in treatment, urine drug testing results, psychiatric status, social adjustment, and quality of life among patients involved in long-term treatment with the cited medications. Two hundred thirteen patients (106 on buprenorphine treatment and 107 on methadone treatment) were enrolled in this open study at the 3rd month of their treatment and followed up until the 12th month; those who left the program before the end of the 3rd month of their treatment were not included in the study sample. The results of this study show statistically significant improvements in opioid use, psychiatric status, and quality of life between the 3rd and 12th months for both medications. This study suggests the long-term efficacy of methadone treatment and buprenorphine treatment on symptoms of opioid addiction and quality of life.

Marermmani I; Pani PP; Popovic D; Pacini M; Deltito J; Perugi G. Improvement in the Quality of Life in heroin addicts: Differences between methadone and buprenorphine treatment. Heroin Addiction and Related Clinical Problems 10(1): 39-46, 2008. (22 refs.)

The main goals of opioid treatment in heroin addiction are to eliminate or reduce the use of heroin and other substances of abuse, to promote patients' social rehabilitation and to improve their quality of life. The purpose of this study is to evaluate the efficacy of buprenorphine and methadone on the quality of life of patients. These subjects were sampled on the basis of the same severity of illness and the same impairment of quality of life at the start of treatment. 50 patients (41 male and 9 female) in buprenorphine treatment and 83 patients (63 males and 20 females) in methadone treatment, were evaluated regarding their retention in treatment, the use of substances, their clinical improvement and their quality of life over a one year period. In markedly ill patients buprenorphine and methadone both successfully and similarly reduce substance abuse and the severity of illness. Patients treated with buprenorphine show a better improvement of quality of life especially regarding improvements in jobs, leisure activities, income and self-acceptance. We conclude that buprenorphine is a good choice for markedly ill patients with severe impairment in their quality of life parameters.

Mark TL; Kassed CA; Vandivort-Warren R; Levit KR; Kranzler HR. Alcohol and opioid dependence medications: Prescription trends, overall and by physician specialty. Drug and Alcohol Dependence 99(1-3): 345-349, 2009. (18 refs.)

Over the past decade, advances in addiction neurobiology have led to the approval of new medications to treat alcohol and opioid dependence. This study examined data from the IMS National Prescription Audit (NPA) Plus (TM) database of retail pharmacy transactions to evaluate trends in U.S. retail sales and prescriptions of FDA-approved medications to treat substance use disorders. Data reveal that prescriptions for alcoholism medications grew from 393,000 in 2003 ($30 million in sales) to an estimated 720,000 ($78 million in sales) in 2007. The growth was largely driven by the introduction of acamprosate in 2005, which soon became the market leader ($35 million in sales). Prescriptions for the two buprenorphine formulations increased from 48,000 prescriptions ($5 million in sales) in the year of their introduction (2003) to 1.9 million prescriptions ($327 million in sales) in 2007. While acamprosate and buprenorphine grew rapidly after market entry, overall substance abuse retail medication sales remain small relative to the size of the population that could benefit from treatment and relative to sales for other medications, such as antidepressants. The extent to which substance dependence medications will be adopted by physicians and patients, and marketed by industry, remains uncertain.

Meier BR; Patkar AA. Buprenorphine treatment: Factors and first-hand experiences for providers to consider. Journal of Addictive Diseases 26(1): 3-14, 2007. (40 refs.)

The viability of using buprenorphine to treat opiate dependence was well documented prior to federal approval in October 2002. What has been lacking in the literature is "hands-on" experience of providers from a clinical management and practice management perspective. This article adds to the knowledge base by providing information about buprenorphine treatment as well as anecdotes from patients treated by the authors, leading to a detailed list of factors worth considering for the treatment provider contemplating adding an opiate-addicted population to an existing treatment base.

Mendelson J; Flower K; Pletcher MJ; Galloway GP. Addiction to prescription opioids: Characteristics of the emerging epidemic and treatment with buprenorphine. Experimental and Clinical Psychopharmacology 16(5): 435-441, 2008. (49 refs.)

Dependence on and abuse of prescription opioid drugs is now a major health problem, with initiation of prescription opioid abuse exceeding cocaine in young people. Coincident with the emergence of abuse and dependence on prescription opioids, there has been an increased emphasis on the treatment of pain. Pain is now the "5th vital sign" and physicians face disciplinary action for failure to adequately relieve pain. Thus, physicians are whipsawed between the imperative to treat pain with opioids and the fear of producing addiction in some patients. In this article, the authors characterize the emerging epidemic of prescription opioid abuse, discuss the utility of buprenorphine in the treatment of addiction to prescription opioids, and present illustrative case histories of successful treatment with buprenorphine.

Mercadante S; Ferrera P; Villari P. Is there a ceiling effect of transdermal buprenorphine? Preliminary data in cancer patients. Supportive Care in Cancer 15(4): 441-444, 2007. (13 refs.)

Objective: The aim of this preliminary study was to explore the possibility of using higher doses of transdermal buprenorphine (TD-BUP) than those commonly used and available as manufactured patches, which are based on the assumption that BUP may have a ceiling effect that has never been determined yet. Materials and methods: Ten patients who were already receiving TD-BUP (70 mu g/h, which is about 1.6 mg/day) and were no longer responsive to this dosage were administered higher doses up to a maximum of 140 mu g/h within 6 days, when the study was completed. Results: In six patients, dose increments of TD-BUP were effective, and patients achieved adequate analgesia within 6 days. Four patients discontinued the treatment due to inefficacy of TD-BUP 140 mu g/ h and were switched to other opiolds until achieving stabilization (oxycodone 320 and 400 mg/day, methadone 120 mg/day, transdermal fentanyl 200 mu g/h). This group of patients required higher doses than those chosen for TD-BUP, underlying the need to escalate the dose rapidly, a modality not accomplished with transdermal drugs. Adverse effects did not change and were similar to those observed before increasing the dose of TD-BUP. On the basis of these preliminary data, patients requiring doses higher than 70 mu g/h of TD-BUP, in the range of 105-140 mu g/h, may still have an analgesic benefit without important consequences in terms of adverse effects. It cannot be excluded that even higher doses may be effective, as some patients required rapid titration with higher morphine equivalent doses, and according to the protocol, other opioids were provided to facilitate this process. Further studies should clarify the role and the benefit of TD-BUP in specific clinical circumstances.

Mintzer MZ. Effects of opioid pharmacotherapy on psychomotor and cognitive performance: A review of human laboratory studies of methadone and buprenorphine. (review). Heroin Addiction and Related Clinical Problems 9(1): 5-24, 2007

Opioid pharmacotherapy can provide the stability necessary to initiate lifestyle changes, obtain steady employment and function in society. Thus, a critical question is the extent to which pharmacotherapy is associated with impairment in psychomotor and cognitive performance that might affect functioning. In this article, I review human laboratory studies of the effects of the most common opioid pharmacotherapies, methadone and buprenorphine, on psychomotor and cognitive performance (both observational group comparison and experimental drug administration studies) and the effects of withdrawal from opioid pharmacotherapy on performance. I then outline some recommendations for further study in this area.

Mooney ME; Poling J; Gonzalez G; Gonsai K; Kosten T; Sofuoglu M. Preliminary study of buprenorphine and bupropion for opioid-dependent smokers. American Journal on Addictions 17(4): 287-292, 2008. (39 refs.)

In this double-blind, placebo-controlled trial, bupropion (BUPRO, 300 mg/day) was compared to placebo (PBO) for the concurrent treatment of opioid and tobacco addiction in 40 opioid-dependent smokers stabilized on buprenorphine (BUPRE, 24 mg/day). Participants received contingent, monetary reinforcement for abstinence from smoking, illicit opioids, and cocaine. Significant differences in treatment retention were observed (BUPRE+BUPRO, 58%; BUPRE+PBO, 90%). BUPRO treatment was not more effective than placebo for abstinence from tobacco, opioids, or cocaine in BUPRE-stabilized patients. These preliminary findings do not support the efficacy of BUPRO, in combination with BUPRE, for the concurrent treatment of opioid and tobacco addiction.

Moore BA; Fiellin DA; Barry DT; Sullivan LE; Chawarski MC; O'Connor PG et al. Primary care office-based buprenorphine treatment: Comparison of heroin and prescription opioid dependent patients. Journal of General Internal Medicine 22(4): 527-530, 2007. (19 refs.)

BACKGROUND: Prescription opioid dependence is increasing, but treatment outcomes with office-based buprenorphine/naloxone among these patients have not been described. METHODS: We compared demographic, clinical characteristics and treatment outcomes among 200 patients evaluated for entry into a trial of primary care office-based buprenorphine/naloxone treatment stratifying on those who reported exclusive heroin use (n = 124), heroin and prescription opioid use (n = 47), or only prescription opioid use (n = 29). RESULTS: Compared to heroin-only patients, prescription-opioid-only patients were younger, had fewer years of opioid use, and less drug treatment history. They were also more likely to be white, earned more income, and were less likely to have Hepatitis C antibodies. Prescription-opioid-only patients were more likely to complete treatment (59% vs. 30%), remained in treatment longer (21.0 vs. 14.2 weeks), and had a higher percent of opioid-negative urine samples than heroin only patients (56.3% vs. 39.8%), all p values <.05. Patients who used both heroin and prescription opioids had outcomes that were intermediate between heroin only and prescription-opioid-only patients. CONCLUSIONS: Individuals dependent on prescription opioids have an improved treatment response to buprenorphine/naloxone maintenance in an office-based setting compared to those who exclusively or episodically use heroin.

Motamed M; Marsch LA; Solhkhah R; Bickel WK; Badger GJ. Differences in treatment outcomes between prescription opioid-dependent and heroin-dependent adolescents. Journal of Addiction Medicine 2(3): 158-164, 2008. (24 refs.)

Objective: This Study was designed to examine the extent to which heroin-dependent and prescription opioid-dependent adolescents experienced differential outcomes during a clinical trial designed to evaluate combined behavioral-pharmacological treatment. Methods: Participants were a volunteer sample of 36 adolescents who met DSM-IV criteria for opioid-dependence (ages 13-18 years eligible) 53% of which were heroin-dependent and 47% of which were dependent on prescription opioids used for nonmedical put-poses. Participants received a 28-day, outpatient, medication-assisted withdrawal with the partial opioid agonist, buprenorphine, or the centrally active A-adrenergic blocker, clonidine, along with behavioral counseling and incentives contingent on opioid abstinence. Heroin-dependent and prescription opioid-dependent participants were compared on baseline characteristics and treatment Outcomes, which included retention, opioid abstinence, HIV risk behavior, opioid withdrawal, and medication effects. Results: Heroin-dependent and prescription opioid-dependent youth had similar characteristics at intake. Heroin-dependent youth had higher baseline rates of drug-related HIV risk, behavior and greater opioid withdrawal before receiving medication during treatment; however, this same group showed markedly greater improvements on these domains during treatment relative to prescription opioid-dependent youth. Both participant groups showed comparable outcomes based on clinically meaningful measures of treatment retention and opioid abstinence. Both heroin-dependent and prescription opioid-dependent youth who received buprenorphine experienced markedly better treatment outcomes relative to those who received clonidine. Conclusions: These results demonstrate that combined behavioral and buprenorphine treatment seems safe and efficacious in the treatment of both heroin-dependent and prescription opioid-dependent adolescents and provide novel information relating to treatment outcomes for these subgroups of opioid-dependent youth.

Musshoff F; Lachenmeier K; Trafkowski J; Madea B; Nauck F; Stamer U. Determination of opioid analgesics in hair samples using liquid chromatography/tandem mass spectrometry and application to patients under palliative care. Therapeutic Drug Monitoring 29(5): 655-661, 2007. (32 refs.)

Hair testing procedures allow a cumulative reflection of long-term drug abuse and are useful as a test for compliance in clinical toxicology. In the present study, liquid chromatography coupled with tandem mass spectrometry was used to determine analgesic opioid drugs in hair samples. The procedure used a simple methanolic extraction, and the evaporated extract was analyzed directly. A selective and sensitive. procedure for the simultaneous determination of bisnortilidine, nortilidine, tilidine, buprenorphine, codeine, oxycodone, fentanyl, norfentanyl, hydromorphone, morphine, normorphine, oxymorphone, methadone, piritramide, and tramadol was developed and fully validated. The method fulfilled validation criteria and was shown to be sensitive, with limits of detection ranging from 0.008 to 0.017 ng/mg hair matrix, and precision ranging between 3.1% and 14.9 %. The applicability of the method was shown by analysis of authentic hair samples from patients receiving opioids for the treatment of cancer pain (eg, fentanyl was detected in concentrations up to 0.292 ng/mg, tramadol in concentrations up to 0.612 ng/mg of hair of 1 patient). Hair analysis was shown to be a complementary and useful tool in monitoring the drug-taking behavior of patients consuming opioid analgesics for the treatment of pain. In self-reports and medical records especially, the ingestion of tramadol and methadone was found to be dramatically underreported. In summary, hair analyses gave important additional information for the medical treatment of patients, the results often coming as a surprise to even the attending physicians.

Nava F; Manzato E; Leonardi C; Lucchini A. Opioid maintenance therapy suppresses alcohol intake in heroin addicts with alcohol dependence: Preliminary results of an open randomized study. (review). Progress in Neuro-Psychopharmacology & Biological Psychiatry 32(8): 1867-1872, 2008. (16 refs.)

An open randomized study lasting 12 months was performed to evaluate the efficacy of methadone or buprenorphine to suppress alcohol use in two hundred and eighteen heroin addicts with alcohol dependence. Daily maintenance doses of methadone were 80, 120, 160, and 200 mg/day, while doses of buprenorphine were 8,16, 24, and 32 mg/day. As expected. both treatments were able to reduce both heroin use and addiction severity (measured with ASI interview). However, although both medications were able to suppress alcohol use, the highest dose of buprenorphine was better than the highest dose of methadone, in reducing alcohol craving, ethanol intake (measured as daily number of drinks), and the ASI subscale of alcohol use. The mechanism underlying the effects of the opioid maintenance therapy on the reduction of alcohol intake is still unclear. The results of the present study may represent the first clinical evidence of the potential effective use of the highest doses of buprenorphine for the suppression of ethanol intake in heroin addicts with alcohol dependence.

Nielsen S; Dietze P; Cantwell K; Lee N; Taylor D. Methadone- and buprenorphine-related ambulance attendances: A population-based indicator of adverse events. Journal of Substance Abuse Treatment 35(4): 457-461, 2008. (19 refs.)

This study examined the nature and extent of methadone- and buprenorphine-related morbidity through a retrospective analysis of ambulance service records (N = 243) in Melbourne, Australia. Cases in which methadone and buprenorphine were implicated are examined. Demographic and presenting characteristics, transport outcomes, and other Substance use were explored. There were 84 buprenorphine-related attendances and 159 methadone-related attendances recorded on the database over the 4-year period. Presenting signs (respiratory rate and Glasgow Coma Scale score) were lower in the methadone-related attendances. Most of the attendances resulted in transport to hospital. Most presentations did not involve traditional signs of opioid overdose, a finding that warrants further investigation. This is the first article to describe characteristics of methadone- and buprenorphine-related ambulance attendances, with results suggesting this may be a useful way to monitor harms associated with these medications in the future.

Nielsen S; Dietze P; Dunlop A; Muhleisen P; Lee N; Taylor D. Buprenorphine supply by community pharmacists in Victoria, Australia: Perceptions, experiences and key issues identified. Drug and Alcohol Review 26(2): 143-151, 2007. (23 refs.)

Buprenorphine is dispensed primarily in community pharmacies in Victoria, with buprenorphine prescribing expanding nationally. The aim of this paper was to examine issues that affect the delivery of buprenorphine in the community setting. A cross- sectional survey was conducted of 282 pharmacies participating in the methadone and buprenorphine programme across Victoria. Dispensing pharmacists completed the survey, designed to canvass issues around buprenorphine diversion and other issues related to the programme. Themes from the results indicated that there was concern from the majority of pharmacies with the issue of the supervision of buprenorphine and diversion of dispensed doses. The rate of suspected diversion was 1.5 times per 100 doses per month or 33 times per 100 clients per month. Seventy-four per cent of pharmacists indicated that this was a negative aspect of buprenorphine treatment. Frequency of suspected and confirmed diversion was associated with the number of pharmacy clients. Pharmacists' perceptions of issues related to buprenorphine appeared to affect opinions of buprenorphine clients and the buprenorphine programme more generally. Pharmacists believe that a significant level of diversion is occurring. This finding warrants serious attention, particularly in light of the increasing use of buprenorphine nationally and internationally.

Nielsen S; Dietze P; Lee N; Dunlop A; Taylor D. Concurrent buprenorphine and benzodiazepines use and self-reported opioid toxicity in opioid substitution treatment. Addiction 102(4): 616-622, 2007. (33 refs.)

Aims To examine concurrent buprenorphine and benzodiazepine consumption and to compare opioid toxicity symptoms induced by methadone and buprenorphine, examining factors associated with the reporting of these symptoms. Design Self-report cross-sectional survey. Setting Five needle syringe programmes and five opioid substitution treatment services in Melbourne, Australia. Participants A total of 250 people who had experience with methadone or buprenorphine. Eligibility criteria were current or previous methadone or buprenorphine use. Measurements Structured questionnaire covering: demographic characteristics; current treatment and drug use; concurrent use of buprenorphine and benzodiazepines, including route of administration and source of medications; and opioid toxicity symptoms reported in association with methadone and buprenorphine consumption. Findings Of those reporting buprenorphine use, two-thirds reported concurrent benzodiazepine use, with a median dose reported of 30 mg diazepam equivalents. A greater number of opioid toxicity symptoms were reported in relation to methadone consumption compared with buprenorphine. Those reporting opioid toxicity with buprenorphine were more likely to report intravenous use compared with those reporting opioid toxicity with methadone. Conclusions The risk of opioid toxicity appeared greater with methadone compared with buprenorphine, despite high levels of benzodiazepine consumption and injection being reported in relation to buprenorphine use. The prevalence of buprenorphine injection and the normalization of methadone-induced sedation are two findings that merit further investigation. Establishing recommendations as to the safest and most effective way to manage benzodiazepine-using people in opioid substitution treatment is necessary for the optimization of treatment for opioid dependence in polydrug-using individuals.

Ponizovsky AM; Grinshpoon A. Quality of life among heroin users on buprenorphine versus methadone maintenance. American Journal of Drug and Alcohol Abuse 33(5): 631-642, 2007. (23 refs.)

Objectives: To assess the quality of life (QoL) of heroin users starting and following 4 and 8 months of maintenance treatment program using buprenorphine vs. methadone. Methods: Participants received maintenance treatment with oral methadone or sublingual buprenorphine for the treatment of heroin dependence. Participants' QoL was measured using the Quality of Life Enjoyment and Satisfaction Questionnaire completed before treatment and at 1-, 4-, and 8-month follow-up. Baseline data from 304 heroin-dependent participants starting maintenance treatment, and 4- month and 8-month follow-up data for the 180 and 129 participants, respectively, retained in trial treatment are presented. Results: For the participants retained in treatment, statistically significant improvements in QoL and all specific life domains were observed in 4 and 8 months. However, for users who were maintained on methadone, this improvement was observed during the first month of treatment. Conclusions: The results show the beneficial effects of the maintenance treatment programs using both buprenorphine and methadone with regard to satisfaction with QoL and all specific life domains among heroin-dependent outpatients, with methadone having an earlier onset than buprenorphine. Further studies are needed to identify the factors linked to these benefits and their time course.

Quaglio G; Lugoboni F; Pattaro C; Melara B; Mezzelani P; Jarlais DCD. Erectile dysfunction in male heroin users, receiving methadone and buprenorphine maintenance treatment. Drug and Alcohol Dependence 94(1/3): 12-18, 2008. (39 refs.)

Erectile dysfunction (ED) is common among people in treatment for heroin addiction. The purpose of the study was to examine the frequency of ED among methadone and buprenorphine maintenance therapy patients, and to identify factors associated with ED. Patients - recruited from 7 centres in Italy - underwent: (i) a structured interview on socio-demographic characteristics, drug use and sexual behaviour; (h) IIEF-15 test, a test of sexual function; (iii) Zung test for depression. The study included 201 males: 42% were on methadone maintenance, 58% were on buprenorphine. Overall, 58% reported no ED, 24% reported mild to moderate ED, and 18% severe ED, In univariate analysis buprenorphine patients had less ED than methadone patients (p = 0.0135). Subjects living with a partner had less ED than others (p = 0.0018). More depressed subjects had more ED (p < 0.001). Heterosexual patients reported less ED than homo/bisexual patients (p = 0.0427), and partner's use of heroin was associated with more ED (p = 0.0078). The significant univariate predictors were entered into a cumulative logit model. Living with a sexual partner was associated with a lower likelihood of ED, while depression, having a sexual partner with a history of drug use and not having a steady partner were associated with a greater likelihood of ED. The significant association between treatment and ED which appeared in univariate analysis (with buprenorphine patients reporting less ED than methadone patients) was not confirmed by the multivariate analysis. Both psychological and social factors were associated with ED which is an important problem for many males in methadone and buprenorphine treatment.

Reed LJ; Glasper A; de Wet CJ; Bearn J; Gossop M. Comparison of buprenorphine and methadone in the treatment of opiate withdrawal: Possible advantages of buprenorphine for the treatment of opiate-benzodiazepine codependent patients? Journal of Clinical Psychopharmacology 27(2): 188-192, 2007. (35 refs.)

The study is a preliminary investigation to compare the effectiveness of buprenorphine and methadone as opiate detoxification treatments. The sample comprised 123 drug misusers who were dependent upon opiates only or who were codependent upon opiates and benzodiazepines. Drug misusers dependent upon methadone doses up to 70 mg were eligible for the study. Detoxification took place within a specialist inpatient drug-dependence unit. Withdrawal symptom severity was assessed on a daily basis by means of the Short Opiate Withdrawal Scale. Outcome was assessed for reductions in severity of withdrawal symptoms, treatment retention, and treatment completion. Buprenorphine detoxification was associated with less severe opiate withdrawal symptoms than methadone. Opiate/Benzodiazepine codependent patients reported less severe withdrawal symptoms during treatment with buprenorphine than with methadone and were also more likely to complete detoxification when treated with buprenorphine.

Rieckmann T; Daley M; Fuller BE; Thomas CP; McCarty D. Client and counselor attitudes toward the use of medications for treatment of opioid dependence. Journal of Substance Abuse Treatment 32(2): 207-215, 2007. (32 refs.)

Attitudes, perceived social nonns, and intentions were assessed for 376 counselors and 1,083 clients from outpatient, methadone, and residential drug treatment programs regarding four medications used to treat opiate dependence: methadone, louprenorphine, clonidine, and ibogaine. Attitudes, social norms, and intentions to use varied by treatment modality. Methadone clients and counselors had more positive attitudes toward the use of methadone, whereas their counterparts in residential and outpatient settings had neutral or negative assessments. Across modalities, attitudes, perceived social norms, and intentions toward the use of buprenorphine were relatively neutral. Assessments of clonidine and ibogame were negative for clients and counselors in all settings. Social normative influences were dominant across settings and medications in determining counselor and client intentions to use medications, Suggesting that perceptions about beliefs of peers may play a critical role in use of medications to treat opiate dependence.

Roose RJ; Kunins HV; Sohler NL; Elam RT; Cunningham CO. Nurse practitioner and physician assistant interest in prescribing buprenorphine. Journal of Substance Abuse Treatment 34(4): 456-459, 2008. (16 refs.)

Office-based buprenorphine places health care providers in a unique position to combine HIV and drug treatment in the primary care setting. However, federal legislation restricts nurse practitioners (NPs) and physician assistants (PAs) from prescribing buprenorphine, which may limit its potential for uptake and inhibit the role of these nonphysician providers in delivering drug addiction treatment to patients with HIV This study aimed to examine the level of interest in prescribing buprenorphine among nonphysician providers. We anonymously surveyed providers attending HIV educational conferences in six large U.S. cities about their interest in prescribing buprenorphine. Overall, 48.6% (n = 92) of nonphysician providers were interested in prescribing buprenorphine. Compared to infectious disease specialists, nonphysician providers (adjusted odds ratio [AOR] = 2.89, 95% confidence interval [CI] = 1.22-6.83) and generalist physicians (AOR = 2.04, 95% CI = 1.09-3.84) were significantly more likely to be interested in prescribing buprenorphine. NPs and PAs are interested in prescribing buprenorphine. To improve uptake of buprenorphine in HIV settings, the implications of permitting nonphysician providers to prescribe buprenorphine should be further explored.

Rosado J; Walsh SL; Bigelow GE; Strain EC. Sublingual buprenorphine/naloxone precipitated withdrawal in subjects maintained on 100 mg of daily methadone. Drug and Alcohol Dependence 90(2/3): 261-269, 2007. (33 refs.)

Rationale: Acute doses of buprenorphine can precipitate withdrawal in opioid dependent persons. The likelihood of this withdrawal increases as a function of the level of physical dependence. Objectives: To test the acute effects of sublingual buprenorphine/naloxone tablets in volunteers with a higher level of physical dependence. The goal was to identify a dose that would precipitate withdrawal (Phase 1), then determine if withdrawal could be attenuated by splitting this dose (Phase 2). Methods: Residential laboratory study; subjects (N=16) maintained on 100 mg per day of methadone. Phase 1: randomized, double blind, triple dummy, within Subject study. Conditions were sublingual buprenorphine/naloxone (4/1, 8/2, 16/4, 32 mg/8 rug), intramuscular naloxone (0.2 mg), oral methadone (100 mg), or placebo. Medication conditions were randomized, but buprenorphine/naloxone doses were ascending within the randomization. Phase 2: Conditions were methadone, placebo, naloxone, 100% of the bulprenorphine/naloxone dose that precipitated withdrawal in Phase I (full dose), and 50% of this dose administered twice in a session (split dose). Analyses covaried by trough methadone serum levels. Results: Six subjects did not complete the study. Of the 10 who completed, 3 tolerated up to 32 mg/8 mg of buprenorphine/naloxone without evidence of precipitated withdrawal. For the seven completing both phases, split doses generally produced less precipitated withdrawal compared to full doses. Conclusions: There is considerable between subject variability insensitivity to buprenorphine's antagonist effects. Low, repeated doses of buprenorphine/naloxone (e.g., 2 mg/0.5 mg) may be an effective mechanism for safely dosing this medication in persons with higher levels of physical dependence.

Roux P; Villes V; Bry D; Spire B; Feroni I; Marcellin F et al. Buprenorphine sniffing as a response to inadequate care in substituted patients: Results from the Subazur survey in south-eastern France. Addictive Behaviors 33(12): 1625-1629, 2008. (22 refs.)

Background: Despite the safety profile of buprenorphine, which makes this treatment highly acceptable for many countries, the risk of its diversion raises several public health and drug policy concerns. Although buprenorphine injection has been investigated quite extensively, diversion by sniffing has been overlooked. The Subazur survey gave us the opportunity to identify factors associated with buprenorphine sniffing in patients receiving buprenorphine in primary care. Methods: We studied a population of 111 stabilized patients receiving office-based buprenorphine in south-eastern France. The design of the study consisted of two longitudinal assessments by phone interviews (at enrollment and 6 months later) detailing patients' socio-demographic characteristics, addictive behaviors, treatment experience and general health status. We used a logistic regression based on generalized estimating equations (GEE) to identify factors associated with buprenorphine sniffing at any interview. Results: Among the Ill interviewed subjects, 33 (30%) patients reported sniffing buprenorphine after having initiated treatment. After multivariate analysis, 4 variables remained significantly associated with buprenorphine sniffing: not living in a stable relationship, having had only one or no parents during childhood, a history of drug sniffing and dissatisfaction with buprenorphine treatment. Conclusions: Our findings underline the need to address these patients to appropriate social and mental services as well as diversifying therapeutic options, in order to provide them with adequate care and minimize diversion. The issues highlighted in the study reflect the need for recommendations for physicians prescribing OST in primary care to consider buprenorphine diversion during treatment more as non-adherence behavior than an abuse.

Sacerdote P; Franchi S; Gerra G; Leccese V; Panerai AE; Somaini L. Buprenorphine and methadone maintenance treatment of heroin addicts preserves immune function. Brain, Behavior and Immunity 22(4): 606-613, 2008. (69 refs.)

Opiate addiction influences many physiological functions including immune responses. The objective of this study was to investigate the immune system function in heroin addicted patients submitted to methadone or buprenorphine maintenance treatment compared to untreated heroin addicts and healthy controls. Four groups were studied: group A included nine heroin addicted subjects, who were still injecting heroin; groups B and C were composed of 12 patients previously addicted to heroin, being treated with methadone (mean dosage 58 +/- 12.7 mg/day) or buprenorphine (mean dose 9.3 +/- 2.3 mg/day) since at least 6 months; group D was composed of 15 sex and age matched healthy controls. Lymphoproliferation and peripheral mononuclear cell cultures production of the Th1 cytokines IL-2 and IFN-gamma, the Th2 cytokine IL-4, and of the pro-inflammatory cytokine TNF-alpha were evaluated in all the patients and controls. PHA-lymphoproliferation was lower in untreated heroin addicts than in controls, while it was normal in methadone and buprenorphine treated patients. An altered Th1/Th2 balance, characterized by reduced IL-4, IFN-gamma and TNF-alpha but normal IL-2 levels, was present in untreated heroin addicted subjects, while the Th1/Th2 balance was well conserved in the methadone and buprenorphine groups. These findings suggest that the immune system abnormalities in heroin addicted patients can be restored to almost normal values by controlled treatment with methadone and buprenorphine.

Sansone RA; Whitecar P; Wiederman MW. The prevalence of childhood trauma among those seeking buprenorphine treatment. Journal of Addictive Diseases 28(1): 64-67, 2009. (12 refs.)

In this study, the authors examined the prevalence of five types of childhood trauma among a sample of adult patients who were addicted to opioids and seeking treatment with buprenorphine. Using a survey methodology, the authors examined a consecutive sample of 113 participants and found that 20.4% reported having experienced sexual abuse, 39.8% reported having experienced physical abuse, 60.2% reported having experienced emotional abuse, 23.0% reported having experienced physical neglect, and 65.5% reported having witnessed violence. Only 19.5% of the sample denied having experienced any of the five forms of childhood trauma. Most respondents (60.2%) reported having experienced one, two, or three different forms of childhood trauma. A minority reported having experienced four (13.3%) or all five (7.1%) forms of childhood trauma. These data indicate that among individuals with opioid dependence who are seeking treatment with buprenorphine, the prevalence rates of various types of childhood trauma are quite high.

Schottenfeld RS; Chawarski MC; Mazlan M. Maintenance treatment with buprenorphine and naltrexone for heroin dependence in Malaysia: a randomised, double-blind, placebo-controlled trial. Lancet 371(9631): 2192-2200, 2008. (41 refs.)

Background: Expansion of access to effective treatments for heroin dependence is a worldwide health priority that will also reduce HIV transmission. We compared the efficacy of naltrexone, buprenorphine, and no additional treatment I in patients receiving detoxification and subsequent drug counselling, for maintenance of heroin abstinence, prevention of relapse, and reduction of HIV risk behaviours. Methods: 126 detoxified heroin-dependent patients, from an outpatient research clinic and detoxification programme in Malaysia, were randomly assigned by a computer-generated randomisation sequence to 24 weeks of manual-guided drug counselling and maintenance with naltrexone (n=43), buprenorphine (n=44), or placebo (n=39). Medications were administered on a double-blind and double-dummy basis. Primary outcomes, assessed by urine testing three times per week, were days to first heroin use, days to heroin relapse (three consecutive opioid-positive urine tests), maximum consecutive days of heroin abstinence, and reductions in HIV risk behaviours over 6 months. The study was terminated after 22 months of enrolment because buprenorphine was shown to have greater efficacy in an interim safety analysis. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00383045. Findings: We observed consistent, linear contrasts in days to first heroin use (p=0 . 0009), days to heroin relapse (p=0 . 009), and maximum consecutive days abstinent (p=0.0007), with all results best for buprenorphine and worst for placebo. Buprenorphine was associated with greater time to first heroin use than were naltrexone (hazard ratio 1.87 [95% CI 1.21-2.88]) or placebo (2.02 [1.29-3.16]). With buprenorphine, we also recorded significantly greater time to heroin relapse (2.7 [1.38-3.42]), and maximum consecutive days abstinent than with placebo (mean days 59 [95% CI 43-76] vs 24 [13-35]; p=0. 003); however, for these outcomes, differences between buprenorphine and naltrexone were not significant. Differences between naltrexone and placebo were not significant for any outcomes. HIV risk behaviours were significantly reduced from baseline across all three treatments (p=0.003), but the reductions did not differ significantly between the three groups. Interpretation: Our findings lend support to the widespread dissemination of maintenance treatment with buprenorphine as an effective public-health approach to reduce problems associated with heroin dependence.

Schwartz RP; Kelly SM; O'Grady KE; Mitchell SG; Peterson JA; Reisinger HS et al. Attitudes toward buprenorphine and methadone among opioid-dependent individuals. American Journal on Addictions 17(5): 396-401, 2008. (22 refs.)

Attitudes and beliefs about drug abuse treatment have long been known to shape response to that treatment. Two major pharmacological alternatives are available for opioid dependence: methadone, which has been available for the past 40 years, and buprenorphine, a recently introduced medication. This mixed-methods study examined the attitudes of opioid-dependent individuals toward methadone and buprenorphine. A total of 195 participants (n = 140 who were enrolling in one of six Baltimore area methadone programs and n = 55 who were out-of-treatment) were administered the Attitudes toward Methadone and toward Buprenorphine Scales, and a subset (n = 46) received an ethnographic interview. The in-treatment group had significantly more positive attitudes toward methadone than did the out-of-treatment group (p < .001), while they did not differ in their attitudes toward buprenorphine. Both groups had significantly more positive attitudes toward buprenorphine than methadone. Addressing these attitudes may increase treatment entry and retention.

Sigmon SC; Dunn KE; Badger GJ; Heil SH; Higgins ST. Brief buprenorphine detoxification for the treatment of prescription opioid dependence: A pilot study. Addictive Behaviors 34(3): 304-311, 2009. (73 refs.)

We examined the feasibility of brief outpatient detoxification as a treatment for prescription opioid (PO) abusers. Fifteen PO-dependent adults were enrolled to receive buprenorphine stabilization, a 2-week buprenorphine taper, and subsequent naltrexone for those who completed the taper. Subjects also received behavioral therapy, urinalysis monitoring, and double-blind drug administration. Subjects provided 83.8%. 91.7% and 31.2% opioid-negative samples during stabilization. taper and naltrexone phases, respectively. Inspection of individual subject data revealed systematic differences in whether subjects successfully completed the taper without resumption of illicit opioid use. Post-hoc analyses were used to examine the characteristics of subjects who successfully completed the taper (Responders, n = 5 ) vs. those who failed to do so (Nonresponders, n = 9). These pilot data suggest a subset of PO abusers may respond to brief buprenorphine detoxification, though future efforts should aim to improve outcomes, investigate individual differences in treatment response and identify characteristics that may predict those for whom longer-term agonist treatment is warranted.

Simmat-Durand L; Lejeune C; Gourarier L. Pregnancy under high-dose buprenorphine. European Journal of Obstetrics & Gynecology and Reproductive Biology 142(2): 119-123, 2009. (21 refs.)

Objective: This study was first conducted to compare the consequences of the use of methadone and high-dose buprenorphine in pregnancy in France and secondly to describe the heterogeneity of women under high-dose buprenorphine. This paper focuses on the second point only. Study design: From October 1998 to September 1999, data on pregnancy, delivery outcomes and neonatal parameters were collected for 251 addicted women on methadone or high-dose buprenorphine (HDB) substitution followed in 35 hospitals and clinics in continental France. Then the data of 159 women who had been taking HDB during pregnancy and had delivered 160 live infants were analyzed. Results: Most of these women were treated as outpatients by general practitioners. 43% of them belong to what we considered a "hidden population" of drug users: most of them were native French citizens, who lived with the future fathers in their own homes, had at least some secondary education, and were usually not followed in specialized centers for drug addicts. Almost all the women smoked every day during their pregnancies; 20% used heroin during the last 4 weeks preceding delivery; 16% admitted having injected HDB at least once. Notably. neither the severity nor the duration of the neonatal abstinence syndrome (NAS) seemed to be related to the daily doses of the substitution agent. Half of the newborns were treated for NAS, mainly with morphine hydrochloride. Conclusion: Although two different populations of women were clearly identified, 64 with no social disadvantage and 95 socially disadvantaged, there was no difference between the groups as for the severity of NAS which was only related to the mothers' compliance with a programme of treatment against addiction.

Singhal A; Tripathi BM; Pal HR; Jena R; Jain R. Subjective effects of additional doses of buprenorphine in patients on buprenorphine maintenance. Addictive Behaviors 32(2): 320-331, 2007. (28 refs.)

Objectives: Buprenorphine has considerable abuse potential. Patients who are maintained on buprenorphine (for opioid dependence) further use additional doses besides its maintenance dose. Subjective effects of the additional doses of buprenorphine in patients on buprenorphine maintenance patients is focused in this study. Methods: Nineteen subjects who were maintained on buprenorphine 4mg, s/l per day for at least I month were admitted and given three additional doses of buprenorphine 2mg, s/l at the interval of 2h each and subjective effects were assessed with the help of standard tools after 2h of each dose and the next day also. Drug was given in a cumulative dose design in the inpatient unit of a de-addiction centre. Results: Dysphoria and sleepiness increased while euphoria and drug liking decreased with additional doses of buprenorphine. These changes were statistically significant and were highest at maximum cumulative dose of 10mg. Conclusion: Results suggest that abuse liability of buprenorphine in these subjects is low in higher doses. However, these findings need to be replicated in this group of patients to make a comment on clinical implication.

Stimmel B. Buprenorphine misuse, abuse, and diversion: When will we ever learn? (editorial). Journal of Addictive Diseases 26(3): 1-3, 2007. (15 refs.)

Sullivan LE; Fiellin DA. Narrative review: Buprenorphine for opioid-dependent patients in office practice. (review). Annals of Internal Medicine 148(9): 662-670, 2008. (85 refs.)

The profile of opioid dependence in the United States is changing. Abuse of prescription opioids is more common than that of illicit opioids: Recent data indicate that approximately 1.6 million persons abuse or are dependent on prescription opioids, whereas 323 000 abuse or are dependent on heroin. Despite this prevalence, nearly 80% of opioid-dependent persons remain untreated. One option for expanding treatment is the use of buprenorphine and the buprenorphine-naloxone combination. Buprenorphine is a partial opioid agonist that can be prescribed by trained physicians and dispensed at pharmacies. This article addresses the clinical presentation of a patient with opioid dependence and describes the relatively new practice of office-based treatment with buprenorphine-naloxone. The different components of treatment; the role of the physician who provides this treatment; and the logistics of treating this growing, multifaceted patient, population are also examined.

Sullivan LE; Moore BA; Chawarski MC; Pantalon MV; Barry D; O'Connor PG et al. Buprenorphine/naloxone treatment in primary care is associated with decreased human immunodeficiency virus risk behaviors. Journal of Substance Abuse Treatment 35(1): 87-92, 2008. (29 refs.)

Methadone treatment reduces human immunodeficiency virus (HIV) risk, but the effects of primary-care-based buprenorphine/naloxone on HIV risk are unknown. The purpose of this study was to determine whether primary-care-based buprenorphine/naloxone was associated with decreased HIV risk behavior. We conducted a longitudinal analysis of 166 opioid-dependent persons (129 men and 37 women) receiving buprenorphine/naloxone treatment in a primary care clinic. We compared baseline and 12- and 24-week overall, drug-related, and sex-related HIV risk behaviors using the AIDS/HIV Risk Inventory (ARI). Buprenorphine/naloxone treatment was associated with significant reductions in overall and drug-related ARI scores from baseline to 12 and 24 weeks. Intravenous drug use in the past 3 months was endorsed by 37%, 12%, and 7% of patients at baseline and at 12 and 24 weeks, respectively (p <.001). Sex while you or your partner were "high" was endorsed by 64%, 13%, and 15% of patients at baseline and at 12 and 24 weeks, respectively (p <.001). Inconsistent condom use during sex with a steady partner was high at baseline and did not change over time. We conclude that primary-care-based buprenorphine/naloxone treatment is associated with decreased drug-related HIV risk, but additional efforts may be needed to address sex-related HIV risk when present (ClinicalTrials.gov number, NCT00023283).

Sullivan LE; Tetrault J; Bangalore D; Fiellin DA. Training HIV physicians to prescribe buprenorphine for opioid dependence. Substance Abuse 27(3): 13-18, 2007

Few HIV physicians are trained to provide buprenorphine treatment. We conducted a cross-sectional survey to assess the impact of an eight-hour course on the treatment of opioid dependence on HIV physicians� preparedness to prescribe buprenorphine. 113 of 257 trained physicians (44%) provided HIV care. Post-course, the majority of both HIV physicians and non-HIV physicians (66% vs. 67%, P = .8) planned to pursue a registration to prescribe buprenorphine. The most common reason for not planning to do so was lack of experience (9% vs. 15%, P = .19). 52 of the 113 (46%) HIV physicians had concerns about prescribing buprenorphine. 30 of the 52 (58%) indicated that interactions between buprenorphine and HAART was their primary concern. Following training, most physicians feel prepared and plan to obtain a registration to prescribe buprenorphine. HIV physicians' concerns regarding interactions between buprenorphine and HAART need to be addressed in future training efforts.

Thomas CP; Reif S; Haq S; Wallack SS; Hoyt A; Ritter GA. Use of buprenorphine for addiction treatment: Perspectives of addiction specialists and general psychiatrists. Psychiatric Services 59(8): 909-916, 2008. (18 refs.)

Objective: In 2002 buprenorphine (Suboxone or Subutex) was approved by the U. S. Food and Drug Administration for office-based treatment of opioid addiction. The goal of office-based pharmacotherapy is to bring more opiate-dependent people into treatment and to have more physicians address this problem. This study examined prescribing practices for buprenorphine, including facilitators and barriers, and the organizational settings that facilitate its being incorporated into treatment. Methods: Addiction specialists and other psychiatrists in four market areas were surveyed by mail and Internet in fall 2005 to examine prescribing practices for buprenorphine. Respondents included 271 addiction specialists (72% response rate) and 224 psychiatrists who were not listed as addiction specialists but who had patients with addictions in their practice (57% response rate). Results: Three years after approval of buprenorphine for office-based addiction treatment, nearly 90% of addiction specialists had been approved to prescribe it and two-thirds treated patients with buprenorphine. However, fewer than 10% of non-addiction specialist psychiatrists prescribed it. Regression-adjusted factors predicting prescribing of buprenorphine included support of training and use of buprenorphine by the physician's main affiliated organization, less time in general psychiatry compared with addictions treatment, more time in group practice rather than solo, ten or more opiate-dependent patients, belief that drugs play a large role in addiction treatment, and patient demand. Conclusions: Office-based pharmacotherapy offers a promising path to improved access to addictions treatment, but prescribing has expanded little beyond the addiction specialist community.

Walley AY; Alperen JK; Cheng DM; Botticelli M; Castro-Donlan C; Samet JH et al. Office-based management of opioid dependence with buprenorphine: Clinical practices and barriers. Journal of General Internal Medicine 23(9): 1393-1398, 2008. (21 refs.)

BACKGROUND: Buprenorphine is a safe, effective and underutilized treatment for opioid dependence that requires special credentialing, known as a waiver, to prescribe in the United States. OBJECTIVE: To describe buprenorphine clinical practices and barriers among office-based physicians. DESIGN: Cross-sectional survey. PARTICIPANTS: Two hundred thirty-five office-based physicians waivered to prescribe buprenorphine in Massachusetts. MEASUREMENTS: Questionnaires mailed to all waivered physicians in Massachusetts in October and November 2005 included questions on medical specialty, practice setting, clinical practices, and barriers to prescribing. Logistic regression analyses were used to identify factors associated with prescribing. RESULTS: Prescribers were 66% of respondents and prescribed to a median of ten patients. Clinical practices included mandatory counseling (79%), drug screening (82%), observed induction (57%), linkage to methadone maintenance (40%), and storing buprenorphine notes separate from other medical records (33%). Most non-prescribers (54%) reported they would prescribe if barriers were reduced. Being a primary care physician compared to a psychiatrist (AOR: 3.02; 95% CI: 1.48-6.18) and solo practice only compared to group practice (AOR: 3.01; 95% CI: 1.23-7.35) were associated with prescribing, while reporting low patient demand (AOR: 0.043, 95% CI: 0.009-0.21) and insufficient institutional support (AOR: 0.37; 95% CI: 0.15-0.89) were associated with not prescribing. CONCLUSIONS: Capacity for increased buprenorphine prescribing exists among physicians who have already obtained a waiver to prescribe. Increased efforts to link waivered physicians with opioid-dependent patients and initiatives to improve institutional support may mitigate barriers to buprenorphine treatment. Several guideline-driven practices have been widely adopted, such as adjunctive counseling and monitoring patients with drug screening.

White JM; Lopatko OV. Opioid maintenance: A comparative review of pharmacological strategies. (review). Expert Opinion on Pharmacotherapy 8(1): 1-11, 2007. (100 refs.)

The use of opioids outside of medical practice is a significant health problem with important social and political implications. Although treatment of opioid dependence is traditionally focused on heroin users, there is increasing recognition that a large number of people become dependent through the use of prescription opioids. The necessity for long-term treatment has also been increasingly recognised. At present, there are several pharmacotherapies available for maintenance treatment, including drugs that are full agonists at the opioid receptor (e.g., methadone, slow-release oral morphine), a partial agonist (buprenorphine) and an opioid antagonist (naltrexone). This review examines the existing strategies, highlights problems associated with their use and discusses the opportunities for new treatment approaches, particularly the use of long-acting formulations.

Whitley SD; Kunins HV; Amsten JH; Gourevitch MN. Colocating buprenorphine with methadone maintenance and outpatient chemical dependency services. Journal of Substance Abuse Treatment 33(1): 85-90, 2007. (21 refs.)

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 benzodiazepme 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, Cl = 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.

Winstock AR; Lea T; Jackson AP. Methods and motivations for buprenorphine diversion from public opioid substitution treatment clinics. Journal of Addictive Diseases 28(1): 57-63, 2009. (22 refs.)

This study aimed to develop a better understanding of the motives for suspected buprenorphine diversion during supervised dosing. Structured interviews were conducted with clients after 71 episodes of diversion at 3 opioid substitution treatment clinics in Sydney, Australia. Interviews were conducted by the clinic manager. An equivalent number of suspected episodes involved diversion via removal of buprenorphine from the mouth (n = 35), and secretion of buprenorphine in the mouth (n = 32). Denial of diversion occurred in 45% of suspected episodes and was significantly associated with secretion of buprenorphine in the mouth (P .0001), suggesting a possible misunderstanding between clinicians and clients to what constitutes diversion. Motivations for diversion included stockpiling for later sublingual use (n = 15), discarding buprenorphine (n = 11), and giving it to another person (n = 5). A consistent definition of diversion of supervised dosed of buprenorphine is required. Diversion of supervised doses may represent a single episode of nonadherence to dosing instructions or more significant ambivalence over treatment. Responses to suspected diversion should aim to minimise harm and maximise treatment outcomes.

Winstock AR; Lea T; Ritter A. The impact of community pharmacy dispensing fees on the introduction of buprenorphine: Naloxone in Australia. Drug and Alcohol Review 26(4): 411-416, 2007. (24 refs.)

Introduction and Aims. The introduction of buprenorphine-naloxone in Australia in April 2006 has permitted the revision of takeaway policies in many states and has introduced the possibility of unsupervised treatment. This study explored the implications of the introduction of buprenorphine-naloxone in terms of cost to patients through a survey of pharmacists' intended pricing practices. The aim of the research was to examine the intentions of pharmacists in relation to fees for buprenorphine-naloxone and study the potential implications to patients when compared with the existing fee structure for methadone and for buprenorphine alone. Design and Methods. A self-complete questionnaire was mailed to every community pharmacy in New South Wales (NSW) (n = 593) dispensing methadone or buprenorphine to people with opioid dependence. A response rate of 68.6% (n = 407) was achieved after three mailouts. Results. The majority of pharmacies charged a flat weekly fee for methadone (92.2%; mean = $31.90) and buprenorphine (74.8%; mean = $31.00). The mean intended fees for buprenorphine-naloxone according to different dosing and takeaway regimens ranged from $19.19 per week for no supervised doses and fortnightly takeaways to a $30.88 per week flat fee. There appeared to be little variation in fee structure irrespective of the takeaway regimen, until reaching the 2 weeks' unsupervised dose regimen. Discussion and Conclusions. This study highlights the importance of the early dissemination of unambiguous information regarding the introduction of a new medication, especially where supervised dispensing through community pharmacies is essential to the provision of treatment. The potential impact upon the successful rollout of a new treatment paradigm that was developed to benefit stable patients in the community may be jeopardised when such processes are not followed.

Winstock AR; Lea T; Sheridan J. Patients' help-seeking behaviours for health problems associated with methadone and buprenorphine treatment. Drug and Alcohol Review 27(4): 393-397, 2008. (27 refs.)

Introduction and Aims. Clients in opioid substitution therapy often have considerable unmet health-care needs. The current study aimed to explore health problems related to opioid substitution therapy among clients on methadone and buprenorphine treatment. Design and Methods. A self-complete, cross-sectional survey conducted among 508 patients receiving methadone and buprenorphine treatment at community pharmacies in New South Wales (NSW), Australia. Results. The most common problems for which participants had ever sought help were dental (29.9%), constipation (25.0%) and headache (24.0%). The most common problems for which participants would currently like help were dental (41.1%), sweating (26.4%) and reduced sexual enjoyment (24.2%). There were no significant differences between those currently on methadone and those currently on buprenorphine for any of the health problems explored, nor differences for gender or treatment duration. Participants on methadone doses 100mg or above were significantly more likely to want help currently for sedation. Discussion and Conclusions. The considerable unmet health care needs among participants in this study suggest that treatment providers should consider improving the detection and response to common health problems related to opioid substitution therapy.

Winstock AR; Lea T; Sheridan J. Prevalence of diversion and injection of methadone and buprenorphine among clients receiving opioid treatment at community pharmacies in New South Wales, Australia. International Journal of Drug Policy 19(6): 450-458, 2008. (52 refs.)

Background: This study aimed to investigate the prevalence of diversion and injection of methadone and buprenorphine among clients receiving opioid pharmacotherapy treatment at community pharmacies in New South Wales (NSW), Australia. Methods: A multi-site cross-sectional survey design was Utilised using a self-complete questionnaire. Participants were 508 clients receiving supervised methadone (n = 442) and buprenorphine (n = 66) at 50 community pharmacies. Participants were surveyed about whether they had diverted their currently prescribed pharmacotherapy, whether they had injected methadone or buprenorphine, the frequency, desirability and duration of action of injecting. and the ease of availability of street-purchased pharmacotherapies. Results: The prevalence of recent diversion was more than 10 times higher among those receiving buprenorphine compared to methadone, with 23.8% of buprenorphine-maintained participants reporting diverting their dose in the preceding 12 months. Seventeen percent of methadone clients had injected methadone in the preceding 12 months compared with 9.1% of buprenorphine clients over the same time period. Conclusion: The higher prevalence of buprenorphine diversion compared to methadone diversion is likely to be due to its sublingual tablet formulation and difficulty associated with supervising its consumption compared to that of an oral liquid. Methadone diversion is also less prevalent likely due to the high levels of methadone takeaway provision, which also helps to explain the higher levels of recent methadone injecting compared to buprenorphine injecting. A clearer understanding of the motivations for diversion and injection of opioid pharmacotherapies, and the relationship between them is required.

Wright NMJ; Sheard L; Tompkins CNE; Adams CE; Allgar VL; Oldham NS. Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial. BMC Family Practice 8: article 3, 2007. (43 refs.)

Background: Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with dihydrocodeine for detoxification from illicit opiates in primary care. Methods: Open label randomised controlled trial in NHS Primary Care (General Practices), Leeds, UK. Sixty consenting adults using illicit opiates received either daily sublingual buprenorphine or daily oral dihydrocodeine. Reducing regimens for both interventions were at the discretion of prescribing doctor within a standard regimen of not more than 15 days. Primary outcome was abstinence from illicit opiates at final prescription as indicated by a urine sample. Secondary outcomes during detoxification period and at three and six months post detoxification were recorded. Results: Only 23% completed the prescribed course of detoxification medication and gave a urine sample on collection of their final prescription. Risk of non-completion of detoxification was reduced if allocated buprenorphine (68% vs 88%, RR 0.58 CI 0.35-0.96, p = 0.065). A higher proportion of people allocated to buprenorphine provided a clean urine sample compared with those who received dihydrocodeine (21% vs 3%, RR 2.06 CI 1.33-3.21, p = 0.028). People allocated to buprenorphine had fewer visits to professional carers during detoxification and more were abstinent at three months (10 vs 4, RR 1.55 CI 0.96-2.52) and six months post detoxification (7 vs 3, RR 1.45 CI 0.84-2.49). Conclusion: Informative randomised trials evaluating routine care within the primary care setting are possible amongst drug using populations. This small study generates unique data on commonly used treatment regimens.