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CORK Bibliography: Buphrenorphine

74 citations. January 2006 to present

Prepared: June 2007

Alford DP; Compton P; Samet JH. Acute pain management for patients receiving maintenance methadone or buprenorphine therapy. (review). Annals of Internal Medicine 144(2): 127-134, 2006. (103 refs.)

More patients with opioid addiction are receiving opioid agonist therapy (OAT) with methadone and buprenorphine. As a result, physicians will more frequently encounter patients receiving OAT who develop acutely painful conditions, requiring effective treatment strategies. Undertreatment of acute pain is suboptimal medical treatment, and patients receiving long-term OAT are at particular risk. This paper acknowledges the complex interplay among addictive disease, OAT, and acute pain management and describes 4 common misconceptions resulting in suboptimal treatment of acute pain. Clinical recommendations for providing analgesia for patients with acute pain who are receiving OAT are presented. Although challenging, acute pain in patients receiving this type of therapy can effectively be managed.

Altice FL; Sullivan LE; Smith-Rohrberg D; Basu S; Stancliff S; Eldred L. The potential role of buprenorphine in the treatment of opioid dependence in HIV-infected individuals and in HIV infection prevention. Clinical Infectious Diseases 43(Supplement 4): s178-s183, 2006. (80 refs.)

Untreated opioid dependence is a major obstacle to the successful treatment and prevention of human immunodeficiency virus (HIV) infection. In this review, we examine the interwoven epidemics of HIV infection and opioid dependence and the emerging role of buprenorphine in improving HIV treatment outcomes among infected individuals, as well as its role in primary and secondary prevention. This article addresses some of the emerging issues about integrating buprenorphine treatment into HIV clinical care settings and the various strategies that must be considered. Specifically, it addresses the role of buprenorphine in improving HIV treatment outcomes through engagement in care, access to antiretroviral therapy and preventive therapies for opportunistic infections, and the potential benefits of and pitfalls in integrating buprenorphine into HIV clinical care settings. We discuss the key research questions regarding buprenorphine in the area of improving HIV treatment outcomes and prevention, including a review of published studies of buprenorphine and antiretroviral treatment and currently ongoing studies, and provide insight into and models for integrating buprenorphine into HIV clinical care settings. Dialogue among practitioners and policy makers in the HIV care and substance abuse communities will facilitate an effective expansion of buprenorphine and ensure that these beneficial outcomes are achieved.

Andresz V; Marcantoni N; Binder F; Velten M; Alt M; Weber J-C et al. Puffy hand syndrome due to drug addiction: A case-control study of the pathogenesis. Addiction 101(9): 1347-1351, 2006. (20 refs.)

Aim: We studied the pathogenesis of puffy hand syndrome of intravenous drug use. We hypothesized that injections of high-dose sublingual buprenorphine, instead of the recommended sublingual administration, could play an important role in lymphatic obstruction and destruction. Design and participants: We set up a case-control study in substitution centres, recruiting intravenous drug addicts with and without puffy hands, respectively. The subjects were asked to answer anonymously a questionnaire of 40 items comprising social and demographic status, history of illicit drugs use, buprenorphine misuse and injection practices. Findings: We included 33 cases and 33 controls, mean age of 34 years. They were past heroin users, mainly methadone-substituted. In multivariate analysis, sex (women) (OR = 8.9, P = 0.03), injections in the hands (OR = 5.9, P = 0.03), injections in the feet (OR = 6.5, P = 0.01) and the absence of tourniquet (OR = 7.0, p = 0.02) were significant risk factors for puffy hand syndrome. In 69.7% of the cases and 59.4% of the controls, respectively, there was a high-dose sublingual buprenorphine misuse, although it appeared not to be a significant risk factor for puffy hand syndrome. Conclusions: Injection practices are likely to cause puffy hands syndrome, but buprenorphine misuse should not be considered as a significant risk factor. However, intravenous drug users must still be warned of local and systemic complications of intravenous drug misuse.

Basu S; Smith-Rohrberg D; Bruce RD; Altice FL. Models for integrating buprenorphine therapy into the primary HIV care setting. Clinical Infectious Diseases 42(5): 716-721, 2006. (29 refs.)

Opiate dependence among human immunodeficiency virus (HIV)-infected patients has been associated with negative clinical outcomes, yet few affected patients receive appropriate and coordinated treatment for both conditions. The introduction of buprenorphine maintenance therapy into HIV care settings provides an opportunity for providers to integrate treatment for opiate dependence into their practices. Buprenorphine maintenance therapy has been associated with reductions in opiate use, increased social stability, improved adherence to antiretroviral therapy, and lowered rates of injection drug use. We describe the following 4 models for the integration of buprenorphine maintenance therapy into HIV care: (1) a primary care model, in which the highly active antiretroviral therapy-administering clinician also prescribes buprenorphine; (2) a model that relies on an on-site specialist in addiction medicine or psychiatry to prescribe the buprenorphine; (3) a hybrid model, in which an on-site specialist provides the induction (with or without stabilization phases) and the HIV care provider provides the maintenance phase; and (4) a drug treatment model that provides buprenorphine maintenance therapy services with HIV services in the substance abuse clinic setting. The key barriers against effective integration of buprenorphine maintenance therapy and primary HIV services are discussed, and we suggest several mechanisms to overcome such obstacles.

Becker WC; Fiellin DA. Provider satisfaction with office-based treatment of opioid dependence: A systematic review. Substance Abuse 26(1): 15-22, 2006

Purpose: New federal regulations allow for office-based treatment of opioid dependent patients with opioid agonist medication (e.g., buprenorphine). We sought to evaluate the literature on office-based physicians' acceptance of this practice. Methods: We searched the MEDLINE database for original research examining office-based providers' acceptance or satisfaction with office-based treatment. Articles included in the analysis met the following criteria: (1) discussed the treatment of patients with substance abuse disorders, (2) focused on the treatment of opioid dependent patients, (3) discussed treatment with opioid agonist therapy, (4) discussed treatment by office-based physicians, (5) presented original research, and (6) provided data examining physician acceptance or satisfaction. Results: Eight studies met the criteria. Their heterogeneity precluded aggregate analysis. Four of 8 studies revealed that providers had a positive perception concerning the efficacy of opioid agonist treatment, 4/8 indicated that providers believed that opioid dependent patients were more complex than others in their practices, and 3/8 studies indicated the need for additional support services. Conclusions: There are few studies of provider satisfaction with office-based treatment of opioid dependence. This literature reveals overall provider acceptance of this practice but highlights the need for support services. Further research, designed to identify the barriers to provider satisfaction with office-based opioid agonist therapy, is needed to ensure that these barriers do not limit expansion of this practice.

Bell J; Burrell T. Retention and attendance with supervised buprenorphine treatment: A case-note review. Drug and Alcohol Review 25(2): 161-165, 2006. (16 refs.)

Since 2001, the Langton Centre has used supervised administration of buprenorphine in treating heroin dependence, without distinguishing between detoxification and maintenance; most people commencing treatment may remain on buprenorphine indefinitely. The aim of this study was to describe retention in treatment, reasons for leaving, re-entry and pattern of attendance, and compare retention in practice with results from research trials, using a file review of sequential presentations for buprenorphine treatment. Retention in treatment was 37% at 6 months, the same as in Australian research trials of buprenorphine maintenance (37%); most people dropped-out without consultation or dose tapering. Repeated episodes of treatment constituted 45% of all episodes; missed scheduled doses were common. Participation in buprenorphine treatment often involves repeated, short episodes and erratic attendance. Measures to improve retention in treatment could improve treatment efficacy.

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.

Bruce RD; McCance-Katz E; Kharasch ED; Moody DE; Morse GD. Pharmacokinetic interactions between buprenorphine and antiretroviral medications. Clinical Infectious Diseases 43(Supplement 4): s216-s223 , 2006. (66 refs.)

Buprenorphine is used for the treatment of opioid dependence. As the number of persons receiving buprenorphine treatment and antiretroviral therapy continues to grow, so too does the existence and clinical impact of drug interactions between buprenorphine and medications for treating human immunodeficiency virus (HIV) infection. Awareness that such interactions exist may deter some patients and physicians from initiating potentially lifesaving therapy or lead to complications among patients whose treatment is already under way. Complications include nonadherence to antiretroviral therapy and the development of viral resistance. Illicit drug use is a frequent consequence of adverse drug effects experienced by injection drug users. The occurrence of unrecognized drug interactions can lead to unsuccessful therapy for HIV infection and the treatment of substance dependence. The present review is organized to provide a working background of buprenorphine pharmacology. Review of the current state of knowledge regarding specific interactions between buprenorphine and antiretrovirals is followed by a review of the clinical applicability of these interactions.

Caldiero RM; Parran TV; Adelman CL; Piche B. Inpatient initiation of buprenorphine maintenance vs. detoxification: Can retention of opioid-dependent patients in outpatient counseling be improved? American Journal on Addictions 15(1): 1-7, 2006. (23 refs.)

Buprenorphine-naloxone is an office-based opioid agonist released in 2003 in the United States for the maintenance of heroin-and other opioid-dependent patients. Concern has been raised that the medication will distract or otherwise inhibit patients from participating in a holistic recovery program or abstinence-based counseling. Using a retrospective chart review, the first thirty opioid-dependent patients induced on buprenorphine maintenance therapy in an inpatient detoxification unit were compared to thirty age- and gender-matched patients who underwent detoxification (with a tramadol taper) and referral to intensive outpatient treatment. The clinical outcomes were a comparison of completion rates for an intensive outpatient program (IOP) and retention in treatment after twelve weeks of aftercare therapy. Patients induced on buprenorphine maintenance over three days had similar relief of withdrawal symptoms to patients detoxified from opioids over five days with tramadol. Patients maintained on buprenorphine had a markedly increased initiation of IOP and remained in outpatient treatment longer than patients who were detoxified (8.5 wks vs. 0.4 wks, p < 0.001). This study indicates that induction and maintenance on buprenorphine may be more effective than detoxification for engaging and retaining patients in abstinence-based comprehensive outpatient addiction treatment.

Caplehorn J; Deeks JJ. A critical appraisal of the Australian comparative trial of methadone and buprenorphine maintenance. Drug and Alcohol Review 25(2): 157-160, 2006. (11 refs.)

While there are serious problems with the analyses and reports, the Australian comparative trial of methadone and buprenorphine maintenance has generated very useful data. Contrary to the triallists' conclusions, their study provides good evidence that methadone is better than buprenorphine at retaining addicts in programmes where clinicians can adjust their patients' daily doses. The trial also provides the first evidence that methadone is significantly cheaper than buprenorphine maintenance. The savings from less frequent clinic attendance were more than offset by the extra time spent dispensing buprenorphine and the greater cost of the buprenorphine itself. In cost-effectiveness terms, the trial's results show methadone 'dominates' buprenorphine as an opioid maintenance drug because it is not only more effective but also cheaper.

Carrieri MP; Amass L; Lucas GM; Vlahov D; Wodak A; Woody GE. Buprenorphine use: The international experience. Clinical Infectious Diseases 43(Supplement 4): s197-s215, 2006. (185 refs.)

The confluence of the heroin injection epidemic and the human immunodeficiency virus (HIV) infection epidemic has increased the call for expanded access to effective treatments for both conditions. Buprenorphine and methadone are now listed on the World Health Organization's Model Essential Drugs List. In France, which has the most extensive experience, buprenorphine has been associated with a dramatic decrease in deaths due to overdose, and buprenorphine diversion appears to be associated with inadequate dosage, social vulnerability, and prescriptions from multiple providers. Other treatment models (in the United States, Australia, Germany, and Italy) and buprenorphine use in specific populations are also reviewed in the present article. In countries experiencing a dual epidemic of heroin use and HIV infection, such as former states of the Soviet Union and other eastern European and Asian countries, access to buprenorphine and methadone may be one potential tool for reducing the spread of HIV infection among injection drug users and for better engaging them in medical care.

Chua SM; Lee TS. Abuse of prescription buprenorphine, regulatory controls and the role of the primary physician. Annals of Medicine (Singapore) 35(7): 492-495, 2006. (16 refs.)

Introduction: Buprenorphine is an opioid partial agonist approved in several countries for the treatment of opioid dependence. It was approved in Singapore in 2002 for this indication, and is more widely available in the primary care setting and can be prescribed by all licensed physicians who have undergone designated training. There is limited literature addressing the risk of its illicit abuse via intravenous self-ad ministration. Clinical Picture: We report 2 such cases of the abuse of prescription buprenorphine in the psychiatric consultation-liaison service of a general teaching hospital, the treatment approaches and outcomes. Conclusion: We also briefly review the indications, uses and abuses of buprenorphine in Singapore, and as reported in other countries, and the roles of primary care physicians, in order to stimulate greater awareness and understanding among specialists and general practitioners, who would encounter these patients in various settings.

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.

Coffin PO; Blaney S; Fuller C; Vadnai L; Miller S; Vlahov D. Support for buprenorphine and methadone prescription to heroin-dependent patients among New York City physicians. American Journal of Drug and Alcohol Abuse 32(1): 1-6, 2006. (8 refs.)

Methadone and bilprenorphine are treatments for heroin-dependent patients. Methadone is available through highly-regulated treatment centers while buprenorphine was approved in 2002 for prescription by certified physicians. Just prior to the approval of buprenorphine, we conducted a random postal survey of 770 physicians in New York City to determine willingness to prescribe methadone or buprenorphine for heroin-dependent patients to be picked up at a pharmacy. Among 247 respondents, 36.3% would consider prescribing methadone and 17.9% were unsure, while 25.8% would consider prescribing buprenorphine and 31.8% were unsure. Willingness to prescribe methadone or buprenorphine was associated with more recent year of licensure (p = 0.044; p = 0.033), working in a hospital or clinic as opposed to an office setting (p = 0.009; p = 0.024), and being the director of a clinic or program (p = 0.031; p = 0.008). This preliminary study suggests that a substantial proportion of New York City physicians would prescribe methadone or buprenorphine to heroin-dependent patients.

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; Moody D; Chiang N. Pharmacokinetics, bioavailability and opioid effects of liquid versus tablet buprenorphine. Drug and Alcohol Dependence 82(1): 25-31, 2006. (12 refs.)

Aims: Two tablet formulations of buprenorphine (a buprenorphine mono-product, subutex(R), and a buprenorphine/naloxone combination product, Suboxone(R)) are available for use in the treatment of opioid addiction; however, the bulk of the clinical studies supporting its approval by the US Food and Drug Administration (FDA) were conducted with a sublingual liquid preparation. To assist the clinician in interpreting the relevant literature in establishing dosing parameters for prescription of tablet buprenorphine, this Study was designed to compare the steady state: (1) pharmacokinetics and bioavailability, and (2) physiological, subjective and objective opiate effects of two 8 mg buprenorphine tablets (16 mg) to those of 1 ml (8 mg/ml) buprenorphine solution based upon early reports Suggesting that the bioavailability of the tablet was approximately 50% of that of the liquid. Design: Randomized, open-label, two-way crossover xtudy. Setting: Inpatient hospitalization for 21 days. Participants: Twenty-four male and females in general good health and meeting DSM-IV criteria for opiate dependence. Intervention: Subjects received one of the two buprenorphine formulations in the first 10-day period, and the other for the second 10-day period with no washout. Measurements: Pharmacokinetic analyses, opiate effects and adverse events. Findings: Drug steady state was reached by Day 7 of each 10-day period, area under the curve for 16 mg (two 8 mg) tablets was higher than the solution. The only non-kinetic statistically significant difference observed between the formulations was in changes in total opioid agonist score. Conclusions: The serum concentration achieved by 16 mg of tablet buprenorphine is higher than that of the 8 mg solution, although differences between physiologic, subjective and objective opioid effects were not noted. The relative bioavailability of tablet versus solution is estimated to be 0.71; thus, with respect to dosing parameters for the tablet, clinicians should consider using less than 16 mg to achieve bioequivalence to the 8 mg solution.

Cozzolino E; Guglielmino L; Vigezzi P; Marzorati P; Silenzio R; De Chiara M et al. Buprenorphine treatment: A three-year prospective study in opioid-addicted patients of a public out-patient addiction center in Milan. American Journal on Addictions 15(3): 246-251, 2006. (17 refs.)

The data shown here were collected with an open label prospective design from March 2001 to February 2004 while conducting routine recruitment and therapy of heroin-addicted patients. All of the data collected demonstrate the safety and efficacy of buprenorphine therapy and different characteristics observed in buprenorphine patients versus methadone patients.

Cunningham CO; Sohler NL; McCoy K; Kunins HV. Attending physicians' and residents' attitudes and beliefs about prescribing buprenorphine at an urban teaching hospital. Family Medicine 38(5): 336-340, 2006. (21 refs.)

Background and Objectives: Opioid abuse and dependence are increasing pharmacotherapy with an opioid agonist reduces adverse consequences of opioid dependency. Physicians can now prescribe buprenorphine for opioid dependency in the primary care setting. This study assessed primary care providers' attitudes and beliefs about opioid addiction treatment with buprenorphine. Methods: Ninety-nine resident and attending physicians from six ambulatory clinics associated with a university hospital were interviewed with on adapted questionnaire eliciting attitudes and beliefs about opioid addiction treatment options, including buprenorphine. Results: While only 37.8% of respondents believed primary care providers should prescribe buprenorphine, and 35.7% reported interest in prescribing buprenorphine, 72.1% were willing to prescribe it with training and support. Common training/support needs were buprenorphine education/training (83.8%), available consultation (19.2%), and on-site counselors (18.2%). The most frequent reasons for not prescribing buprenorphine were lack of knowledge or training (47.5%) and lack of time (25.3%). Physicians involved in primary care-oriented programs (versus non-primary care programs) were more likely to have positive attitudes regarding buprenorphine. Conclusions: Most physicians would be willing to prescribe buprenorphine with proper training and support. Barriers and training/support needy must be addressed to develop effective opioid addiction treatment programs in the primary care setting.

Digiusto E; Shakeshaft AP; Ritter A; Mattick RP; White J; Lintzeris N et al. Effects of pharmacotherapies for opioid dependence on participants' criminal behaviour and expenditure on illicit drugs: An Australian National Evaluation (NEPOD). Australian and New Zealand Journal of Criminology 39(2): 171-189, 2006. (53 refs.)

Data regarding criminal behaviour and expenditure on illicit drugs by 300 methadone patients and 997 heroin users who participated in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD) were analysed to measure the effects of pharmacotherapy and to identify predictor variables. At baseline, more heroin users than methadone patients reported recent involvement in any crime (39%, 13% respectively), and in each of four subtypes of crime (property, drug dealing, fraud, violence). Heroin users spent more on heroin than methadone patients (means of $3148, $617 in the past month, respectively). Younger age at first use of heroin was associated with higher reported levels of all four crime types, males reported more drug dealing and violent crime than females, lower employment status was associated with more property crime and drug dealing, lower educational status was associated with more property crime, and younger participants reported more violent crime. For participants who were heroin users at baseline and who were still in treatment at 3 months, mean monthly expenditure on heroin dropped from $2345 to $230. Involvement in any crime dropped from 39% to 20%, and also dropped in three of the four crime subtypes. There were no significant differences between the effects of methadone, buprenorphine, LAAM, and naltrexone treatment on criminal behaviour or expenditure on most types of illicit drug, although the pharmacotherapies did differ in terms of their effects on heroin expenditure. Improving treatment retention and expanding treatment availability to increase participation by heroin users would be likely to reduce drug-related crime, and would be a good social investment.

Fiellin DA; Pantalon MV; Chawarski MC; Moore BA; Sullivan LE; O'Connor PG et al. Counseling plus buprenorphine-naloxone maintenance therapy for opioid dependence. New England Journal of Medicine 355(4): 365-374, 2006. (30 refs.)

Background: The optimal level of counseling and frequency of attendance for medication distribution has not been established for the primary care, office-based buprenorphine-naloxone treatment of opioid dependence. Methods: We conducted a 24-week randomized, controlled clinical trial with 166 patients assigned to one of three treatments: standard medical management and either once-weekly or thrice-weekly medication dispensing or enhanced medical management and thrice-weekly medication dispensing. Standard medical management was brief, manual-guided, medically focused counseling; enhanced management was similar, but each session was extended. The primary outcomes were the self-reported frequency of illicit opioid use, the percentage of opioid-negative urine specimens, and the maximum number of consecutive weeks of abstinence from illicit opioids. Results: The three treatments had similar efficacies with respect to the mean percentage of opioid-negative urine specimens (standard medical management and once-weekly medication dispensing, 44 percent; standard medical management and thrice-weekly medication dispensing, 40 percent; and enhanced medical management and thrice-weekly medication dispensing, 40 percent; P=0.82) and the maximum number of consecutive weeks during which patients were abstinent from illicit opioids. All three treatments were associated with significant reductions from baseline in the frequency of illicit opioid use, but there were no significant differences among the treatments. The proportion of patients remaining in the study at 24 weeks did not differ significantly among the patients receiving standard medical management and once-weekly medication dispensing (48 percent) or thrice-weekly medication dispensing (43 percent) or enhanced medical management and thrice-weekly medication dispensing (39 percent) (P=0.64). Adherence to buprenorphine-naloxone treatment varied; increased adherence was associated with improved treatment outcomes. Conclusions: Among patients receiving buprenorphine-naloxone in primary care for opioid dependence, the efficacy of brief weekly counseling and once-weekly medication dispensing did not differ significantly from that of extended weekly counseling and thrice-weekly dispensing. Strategies to improve buprenorphine-naloxone adherence are needed. (ClinicalTrials.gov number, NCT00023283.)

Fischer G; Ortner R; Rohrmeister K; Jagsch R; Baewert A; Langer M et al. Methadone versus buprenorphine in pregnant addicts: A double-blind, double-dummy comparison study. Addiction 101(2): 275-281, 2006. (33 refs.)

Aims: To evaluate the efficacy and safety of methadone versus buprenorphine treatment in pregnant opioid-dependent women. Design: Randomized, double-dummy, double-blind, flexible-dosing comparison study. Setting Addiction Clinic at the Medical University of Vienna, Austria. Participants: Eighteen women were assigned randomly to receive either methadone (n = 9) or buprenorphine (n = 9) during weeks 24-29 of pregnancy. After dropouts, data were available from 14 cases (six in the methadone and eight in the buprenorphine group). Intervention Sublingual buprenorphine tablets (8-24 mg/day) or oral methadone solution (40-100 mg/day), with matched placebos. Measurements: Mothers: retention in treatment, urine toxicology and nicotine use. Neonates: Routine birth data, neonatal abstinence syndrome (NAS) in severity and duration. Findings There was somewhat greater retention in the buprenorphine group but significantly lowered use of additional opioids in the methadone group (P = 0.047). Neonates: There was earlier onset of NAS in neonates born to the methadone (mean 60 hours) than to the buprenorphine groups (mean 72 hours after last medication); 43% did not require NAS-treatment with short treatment duration in both groups (mean 5 days). Conclusion: This preliminary study had limited power to detect differences but the trends observed suggest this kind of research is practicable and that further studies are warranted.

Fornili K; Burda-Cohee C. Buprenorphine products for the pharmacologic management of opioid addiction: Why shouldn't advanced practice nurses prescribe? (editorial). Journal of Addictions Nursing 17(2): 139-145, 2006. (22 refs.)

This paper describes the current legislative authority that permits office-based prescribing of buprenorphine products for the pharmacological treatment of opioid addiction by physicians with certain qualifications. It outlines ways prescribers can improve the quality of care, ensure safety, prevent diversion and abuse of the medications, and improve treatment outcomes. It advances the concept of enabling advanced practice nurses with prescriptive authority (nurse practitioners) to prescribe buprenorphine products for the treatment of opioid addiction, so as to improve access to this treatment and reduce the treatment capacity gap.

Geib AJ; Babu K; Ewald MB; Boyer EW. Adverse effects in children after unintentional buprenorphine exposure. Pediatrics 118(4): 1746-1751, 2006. (39 refs.)

Buprenorphine in sublingual formulation was recently introduced to the American market for treatment of opioid dependence. We report a series of 5 toddlers with respiratory and mental-status depression after unintentional buprenorphine exposure. Despite buprenorphine's partial agonist activity and ceiling effect on respiratory depression, all children required hospital admission and either opioid-antagonist therapy or mechanical ventilation. Results of routine urine toxicology screening for opioids were negative in all cases. Confirmatory testing was sent for 1 child and returned with a positive result. The increasing use of buprenorphine as a home-based therapy for opioid addiction in the United States raises public health concerns for the pediatric population.

Giacomuzzi S; Kemmler G; Ertl M; Riemer Y. Opioid addicts at admission vs. slow-release oral morphine, methadone, and sublingual buprenorphine maintenance treatment participants. (review). Substance Use & Misuse 41(2): 223-244, 2006. (110 refs.)

With rise of a randomized study design, quality of life (QOL) and physical symptoms of opioid addicts at admission were compared with slow-release oral morphine, methadone, and sublingual buprenorphine maintenance program participants after 6 months of treatment. The study was conducted from February to July 2004 in the outpatient drug user treatment center at University Department of Psychiatry at Innsbruck, providing maintenance treatment programs and detoxification in Tyrol, Austria. One hundred twenty opioid users seeking treatment were compared with 120 opioid-dependent patients retained for 6 months on a slow-release oral morphine, methadone, or sublingual buprenorphine maintenance program. The German version ("Berlin Quality of Life Profile") of the Lancashire Quality of Life Profile was used, and illicit opioid use was determined by urinalysis. Physical symptoms were measured by using the Opioid Withdrawal Scale. Urinalyses revealed a significantly lower consumption of cocaine and opioids in all three substitution groups than in patients at admission (p < 0.001 and p <= 0.004, respectively). Both the buprenorphine and the methadone maintenance group showed significantly more favorable values than opioid clients at admission for stomach cramps (p <= 0.002), muscular tension (p <= 0.027), general pain (p <= 0.001), feelings of coldness (p <= 0.000), heartpounding (p <= 0.008), runny eyes (p <= 0.047), and aggressions (p <= 0.009). Patients who received slow-release oral morphine treatment generally showed the least favorable QOL scores compared with patients at admission or sublingual buttrenorphine and methadone clients. Patients in the sublingual buprenorphine or methadone program showed nearly the same QOL scores. The buprenorphine and the methadone maintenance group showed significantly more favorable values than opioid clients at admission regarding leisure time (p <= 0.019), finances (p <= 0.014), mental health (p <= 0.010), and overall satisfaction (p <= 0.010). Slow-release oral morphine is a well-established treatment for pain, but more research is required to evaluate it as a treatmentfor heroin dependence. The present data indicate that slow-release oral morphine could have some disadvantages compared with sublingual buprenorphine and methadone in QOL, physical symptoms, and additional consumption. The results further suggest that buprenorphine treatment is as effective as methadone in effects on quality of life and physical symptoms.

Gorelick DA. Counseling plus buprenorphine-naloxone for opioid dependence. (letter). New England Journal of Medicine 355(16): 1736-1736, 2006. (4 refs.)

Gowing L; Ali R; White J. Buprenorphine for the management of opioid withdrawal. Cochrane Database of Systemic Reviews 2006(2): article CD002025, 2006. (141 refs.)

Background: Managed withdrawal is a necessary step prior to drug-free treatment. It may also represent the end point of maintenance treatment. Objectives: To assess the effectiveness of interventions involving the use of buprenorphine to manage opioid withdrawal, for withdrawal signs and symptoms, completion of withdrawal and adverse effects. Search strategy: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, including the Cochrane Drugs and Alcohol Group trials register, Issue 3, 2005), MEDLINE (January 1966 to August 2005), EMBASE (January 1985 to August 2005), PsycINFO (1967 to August 2005), CINAHL(1982 to July 2005) and reference lists of articles. Selection criteria: Experimental interventions involved the use of buprenorphine to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. Comparison interventions involved reducing doses of methadone, alpha2 adrenergic agonists, symptomatic medications or placebo, or different buprenorphine-based regimes. Data collection and analysis: One reviewer assessed studies for inclusion and methodological quality, and undertook data extraction. Inclusion decisions and the overall process was confirmed by consultation between all three reviewers. Main results: Eighteen studies (14 randomised controlled trials), involving 1356 participants, were included. Ten studies compared buprenorphine with clonidine; four compared buprenorphine with methadone; one compared buprenorphine with oxazepam; three compared different rates of buprenorphine dose reduction; two compared different starting doses of buprenorphine. (Two studies included more than one comparison.) Relative to clonidine, buprenorphine is more effective in ameliorating the symptoms of withdrawal, patients treated with buprenorphine stay in treatment for longer, particularly in an outpatient setting (SMD 0.82, 95% CI 0.57 to 1.06, P < 0.001), and are more likely to complete withdrawal treatment (RR 1.73, 95% CI 1.21 to 2.47, P = 0.003). At the same time there is no significant difference in the incidence of adverse effects, but drop-out due to adverse effects may be more likely with clonidine. Severity of withdrawal is similar for withdrawal managed with buprenorphine and withdrawal managed with methadone, but withdrawal symptoms may resolve more quickly with buprenorphine. There is a trend towards completion of withdrawal treatment being more likely with buprenorphine relative to methadone (RR 1.30, 95% CI 0.97 to 1.73, P = 0.08). Authors' conclusions: Buprenorphine is more effective than clonidine for the management of opioid withdrawal. There appears to be no significant difference between buprenorphine and methadone in terms of completion of treatment, but withdrawal symptoms may resolve more quickly with buprenorphine.

Gowing LR; Ali RL. The place of detoxification in treatment of opioid dependence. Current Opinion in Psychiatry 19(3): 266-270, 2006. (22 refs.)

Purpose of review: This review summarizes current research on the management of opioid withdrawal and considers the selection of the approach in different situations. Recent findings: The recent publication of three controlled trials makes firm conclusions about the relative effectiveness of newer approaches (antagonist-induced withdrawal under anaesthesia or with minimal sedation; buprenorphine) to the management of opioid withdrawal possible. Summary: Antagonist-induced withdrawal under anaesthesia should not be pursued as it has an increased risk of life-threatening adverse events and has no additional benefits relative to antagonist-induced withdrawal under minimal sedation. Antagonist-induced withdrawal with minimal sedation is feasible and may be suitable for those who intend to enter antagonist-maintenance treatment with a clear commitment to abstinence and good support. Buprenorphine is suitable for quick withdrawal, supports transition to naltrexone maintenance treatment, is safe and effective in outpatient settings and can be extended into maintenance treatment if the detoxification attempt is unsuccessful. Adrenergic agonists (clonidine and lofexidine) remain an effective option for those who do not want to use an opioid and do not intend to transfer to naltrexone maintenance treatment, with lofexidine being preferable for outpatient settings. Through appropriate choice of approach, detoxification can be a gateway to multiple, long-term treatment options.

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 HE; Jasinski D; Johnson RE. Response to "transferring methadone-stabilized pregnant patients to buprenorphine" (letter). American Journal on Addictions 15(5): 401-402, 2006. (4 refs.)

This article presents a response to Dr Newman's commentary on "Transferring Methadone--Stabilized Pregnant Patients to Buprenorphine Using and Immediate Release Morphine Transition: An Open-Label Exploratory Study."

Jones HE; Suess P; Jasinski DR; Johnson RE. Transferring methadone-stabilized pregnant patients to buprenorphine using an immediate release morphine transition: An open-label exploratory study. American Journal on Addictions 15(1): 61-70, 2006. (19 refs.)

A transition from methadone to buprenorphine without intervening withdrawal symptoms is critical for advancing the treatment of opioid-dependent patients. Four pregnant inpatients were transferred from methadone (65-85 mg) to five days of immediate release morphine (IRM) and then to buprenorphine (12-28 mg). Withdrawal scores decreased during the five days of IRM and subsequently increased over the first three days on buprenorphine. The transitional use of IRM appears safe for both mother and fetus. Withdrawal symptoms appeared during buprenorphine induction; however, these data suggest that the intensity of withdrawal symptoms may be lessened by the dose and frequency of buprenorphine administration.

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.

Khalsa J; Vocci F; Altice F; Fiellin D; Miller V. Buprenorphine and HIV primary care: New opportunities for integrated treatment. Introduction. (editorial). Clinical Infectious Diseases 43(Supplement 4): s169-s172, 2006. (15 refs.)

Drug abuse and infection with human immunodeficiency virus (HIV) are associated with high rates of morbidity and mortality, but, because of medical, social, and legal factors, opiate addiction/dependence is a major obstacle to successful treatment of disease-for example, treatment of acquired immunodeficiency syndrome (AIDS) with highly active antiretroviral therapy. In an effort to improve the opportunity for treatment of drug abuse and HIV infection, the Forum for Collaborative HIV Research, in collaboration with the Substance Abuse and Mental Health Services Administration, the National Institute on Drug Abuse, the Centers for Disease Control and Prevention, and other agencies, presented a workshop entitled "Buprenorphine in the Primary HIV Care Setting." Participants reviewed and discussed current issues, such as the introduction of and sources for the provision of buprenorphine in HIV primary care settings and strategies for integrating treatment of HIV-infected drug abusers, all of which are covered in this supplement.

Khalsa J; Vocci F; Altice F; Fiellin D; Miller V. Introduction: Buprenorphine and HIV primary care: New ppportunities for integrated treatment. Clinical Infectious Diseases 43(Supplement 4): s169-s172, 2006. (15 refs.)

Kissin W; McLeod C; Sonnefeld J; Stanton A. Experiences of a national sample of qualified addiction specialists who have and have not prescribed buprenorphine for opioid dependence. Journal of Addictive Diseases 25(4): 91-103, 2006. (34 refs.)

The limited availability of medication-assisted treatment has created a treatment gap leaving many opioid dependent individuals without access to appropriate treatment. Survey data from a national random sample of 545 addictions physicians with waivers to provide buprenorphine treatment under The Drug Addiction Treatment Act of 2000 are presented. During the first year, an estimated 63,204 opioid dependent patients were treated with buprenorphine; many were dependent on prescription opioids and were new to drug treatment. Prescribing physicians reported high treatment effectiveness and patient satisfaction, with minimal adverse reactions or evidence of diversion. However, many waivered physicians had not provided buprenorphine treatment. Prescribers identified challenges such as induction logistics, recordkeeping requirements, the 30-patient limit, DEA involvement, and limited patient compliance. Buprenorphine treatment could potentially reduce the treatment gap by providing safe and effective treatment for opioid dependence and by attracting patients who do not typically seek care at opioid treatment programs.

Knudsen HK; Ducharme LJ; Roman PM. Early adoption of buprenorphine in substance abuse treatment centers: Data from the private and public sectors. (review). Journal of Substance Abuse Treatment 30(4): 363-373, 2006. (50 refs.)

The recent approval of buprenorphine for the treatment of opiate dependence offers an opportunity to analyze innovation adoption in community-based treatment. Using data collected from national samples of 299 privately funded and 277 publicly funded treatment centers, this research examines buprenorphine adoption using baseline data collected between 2002 and 2004 as well as follow-up data collected 12 months later. Private centers were significantly more likely than public centers to report current use of buprenorphine. The baseline data indicated that early adoption was positively associated with center accreditation, physician services, availability of detoxification services, current use of naltrexone, and the percentage of opiate-dependent clients. Multivariate analyses of follow-up data suggest that adoption was greater in accredited centers, for-profit facilities, organizations offering detoxification services, and naltrexone-using centers. Future research should continue to monitor the extent to which buprenorphine is adopted in these settings.

Koch AL; Arfken CL; Schuster CR. Characteristics of U.S. substance abuse treatment facilities adopting buprenorphine in its initial stage of availability. Drug and Alcohol Dependence 83(3): 274-278, 2006. (5 refs.)

This study examined the adoption of buprenorphine for the treatment of opiate dependence among U.S. substance abuse treatment facilities and their characteristics at the time of the initial availability of the medication. Data come from a 2003 national survey of all substance abuse treatment facilities in the U.S. Out of our sample of 13,060 facilities, 5.5% of facilities reported they offered buprenorphine. Not unexpectedly, the prevalence was higher in certified opioid treatment programs (11.3%) compared to other facilities (4.6%). For opioid treatment programs, offering Naltrexone (OR = 8.34, 95% CI = 5.53, 12.58) and offering medically supervised withdrawal (OR = 2.76, 95% CI = 1.38, 5.52) were independent and robust predictors of offering buprenorphine. These same variables were independent predictors for the non-opioid treatment programs as well (Naltrexone, OR = 14.32, 95% CI = 7.85, 26.10; and medically supervised withdrawal services, OR = 4.42, 95% CI = 3.01, 6.49). Our results suggest that the adoption of buprenorphine soon after the Food and Drug Administration approved its use for treatment of opioid dependence and the shipping of the medication commenced was associated with facilities already offering pharmacotherapies such as Naltrexone and medically assisted withdrawal. These findings provide baseline data to track the adoption of buprenorphine by substance abuse treatment programs in future years.

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.

Lai SH; Yao YJ; Lob DST. A survey of buprenorphine related deaths in Singapore. Forensic Science International 162(1/3): 80-86, 2006. (9 refs.)

Buprenorphine is available in Singapore as substitution treatment for opioid dependence since 2002. This study surveys buprenorphine related deaths in Singapore between September 2003 and December 2004. The aims are to establish the autopsy prevalence of buprenorphine related deaths and the demographical and toxicological profile of the cases. Toxicological screening was performed for all unnatural deaths, deaths involving known drug addicts, as well as when autopsy revealed no obvious cause of death. Twenty-one cases had buprenorphine detected in postmortem blood and/or urine samples. Eighteen were sudden deaths. There were two fatal falls from height and one death by hanging. All subjects were male. The age range was 24-48 years. Fourteen subjects were between 30 and 39 years of age. The mean age was 35 years. The majority (62%) were Chinese. Eleven (52%) were known drug abusers. For sudden deaths, two groups were identified. Six cases died from natural causes. Blood buprenorphine levels ranged from undetected (detected in urine) to 3.2 ng/mL (mean 1.4 ng/mL). Twelve cases were attributed directly and indirectly to mixed drug poisoning. Blood buprenorphine levels ranged from undetected (detected in urine) to 17 ng/mL (mean 3.2 ng/mL). Nineteen cases showed concurrent abuse of buprenorphine and benzodiazepine, diazepam being the most frequently detected, followed by nitrazepam and midazolam. The availability of buprenorphine as substitution therapy is associated with an increase in buprenorphine related deaths. The danger of co-abuse of buprenorphine and benzodiazepines is highlighted.

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.

Liu KS; Lin CN; Shieh JP; Chu CC; Kuei CH; Wang JJ. The novel depot of buprenorphine propionate has a long-acting effect on physical dependence on morphine. Drug Development Research 67(5): 462-469, 2006. (29 refs.)

Buprenorphine is a promising drug for the treatment of physical dependence on opioids. The aim of the present study was to evaluate the efficacy and duration of action of a novel depot form of a buprenorphine prodrug, buprenorphine propionate, on physical dependence on morphine. Following intramuscular injection in morphine-dependent mice, the efficacy and duration of action of buprenorphine propionate in sesame oil were evaluated. Two other dosage forms of buprenorphine were used as controls. Intramuscular injection of buprenorphine HCl (0.1 mu mol/kg in saline) attenuated the severity of morphine dependence (P < 0.05) with a 9-h duration of action. However, a further increase in dose up to 60-fold could not further increase its duration of action. On the other hand, buprenorphine base and propionate when prepared in sesame oil produced longer durations of action than did buprenorphine HCl in saline under an equimolar basis of 6 mu mol/kg (P < 0.05, for each comparison). Among dosage forms, buprenorphine propionate in sesame oil produced the longest duration of action, 11.3-fold longer than that of buprenorphine HCl in saline and 2-fold longer than buprenorphine base in oil. In conclusion, the novel depot of buprenorphine propionate produced a dose-related long-acting effect on physical dependence on morphine in mice.

Lott DC; Strain EC; Brooner RK; Bigelow GE; Johnson RE. HIV risk behaviors during pharmacologic treatment for opioid dependence: A comparison of levomethadyl acetate hydrochloride, buprenorphine, and methadone. Journal of Substance Abuse Treatment 31(2): 187-194, 2006. (32 refs.)

The efficacies of three opioid substitution medications for reducing HIV risk behaviors in opioid-dependent patients were assessed in a randomized double-blind clinical trial comparing levomethadyl acetate hydrochloride (LAAM), buprenorphine, and methadone. Individually optimized flexible dosing was used for each group, with weekly possible doses of 255-391 mg of LAAM, 56-112 mg of buprenorphine, and 420-700 mg of methadone. An interview regarding specific HIV risk behaviors, including injecting, equipment sharing, and sexual activity, yielded data for pretreatment and four in-study time points for 137 subjects. Declines in risk behaviors during treatment were evident in all groups for most measures of injecting and equipment sharing. Only the methadone group showed consistent declines in measures of sexual behaviors. These results demonstrate that all three medications can be highly effective in decreasing HIV risk behaviors when the dose is optimized. Reductions in sexual behaviors for the METH group are consistent with known methadone side effects. [Note: correction published in following issue, 31(3): 317.]

Loxterkamp D. Helping 'them': Our role in recovery from opioid dependence. (editorial). Annals of Family Medicine 4(2): 168-171, 2006. (4 refs.)

The crisis of opioid addiction in America has been fueled by the diversion of prescription pain pills and the emergence of pure and inexpensive heroin. Until recently, benefits of and access to therapy were limited. This situation changed in 2003 with Food and Drug Administration approval of buprenorphine for the office-based treatment of opioid dependence. Now armed with a potent drug, primary care physicians can treat addicted patients in their own practice and from their own neighborhood, but first we must overcome deficiencies in our training and personal biases about addicts and what they need. This a report of one doctor's progress.

McCance-Katz EF; Moody DE; Morse GD; Friedland G; Pade P; Baker J et al. Interactions between buprenorphine and antiretrovirals. I. The nonnucleoside reverse-transcriptase inhibitors efavirenz and delavirdine. Clinical Infectious Diseases 43(Supplement 4): s224-s234, 2006. (28 refs.)

This study examined drug interactions between buprenorphine, an opioid partial agonist medication used in the treatment of opioid dependence, and the nonnucleoside reverse-transcriptase inhibitors (NNRTIs) efavirenz (EFV) and delavirdine (DLV). Opioid-dependent, buprenorphine/ naloxone-maintained, human immunodeficiency virus (HIV)-negative volunteers (n = 10 per NNRTI) participated in 24-h sessions to determine pharmacokinetics of buprenorphine and of buprenorphine with either EFV or DLV after administration of standard doses of either antiretroviral for 15 or 7 days, respectively. Opiate withdrawal symptoms, cognitive effects, and adverse events were determined before and after antiretroviral administration in opioid-dependent participants. The pharmacokinetics of NNRTIs in healthy control participants were used to determine the effect of buprenorphine on NNRTIs. EFV decreased the buprenorphine area under the concentration-time curve (P < .001). DLV increased buprenorphine concentrations (P < .001). Clinically significant consequences of these interactions were not observed. Buprenorphine did not alter antiretroviral pharmacokinetics. Adjustments of doses of either buprenorphine or EFV or DLV are not likely to be necessary when these drugs are administered for the treatment of opiate dependence and HIV disease.

McCance-Katz EF; Moody DE; Smith PF; Morse GD; Friedland G; Pade P et al. Interactions between buprenorphine and antiretrovirals. II. The protease inhibitors nelfinavir, lopinavir/ritonavir, and ritonavir. Clinical Infectious Diseases 43(Supplement 4): s235-s253, 2006. (33 refs.)

We examined drug interactions between buprenorphine, an opioid partial agonist available by prescription for treatment of opioid dependence, and the protease inhibitors (PIs) nelfinavir (NFV), ritonavir (RTV), and lopinavir/ ritonavir (LPV/R). Opioid-dependent, buprenorphine/naloxone-maintained, human immunodeficiency virus (HIV)-negative volunteers (n = 10 per PI) participated in 24-h pharmacokinetic studies, before and after administration of each PI. Symptoms of opiate withdrawal and excess were determined before and after PI administration. PI pharmacokinetics were determined and compared between opiate-dependent participants and healthy control participants (n = 15 per PI). Administration of RTV, but not of NFV or LPV/R, resulted in a significant increase in the buprenorphine area under the concentration-time curve (AUC). Symptoms of opiate excess, however, were not observed. Buprenorphine had no significant effects on PI AUC. Adjustments of doses of either buprenorphine or NFV, LPV/R, or RTV are not likely to be necessary when these drugs are administered for the treatment of opioid dependence and HIV disease.

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.

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.

Miller V; Forum for Collaborative HIV Research. Buprenorphine and HIV primary care: Report of a forum for collaborative HIV research workshop. (editorial). Clinical Infectious Diseases 43(Supplement 4): s254+, 2006

On 3-4 June 2004, in Washington, DC, the Forum for Collaborative HIV Research convened experts from academia, community and private practices, US government agencies, and industry to develop recommendations for increased uptake of buprenorphine integrated into human immunodeficiency virus (HIV) primary care, with special emphasis on Ryan White CARE Act-funded programs. Workshop participants evaluated knowledge gaps requiring research; barriers to integration at the patient, clinic, and systems level; policy and financing issues; and program impacts. Recommendations were developed for training, including medical school and post-medical school training of clinical teams as well as training of patients; for improving programs and services, including integration of opioid dependence and HIV infection into chronic disease models, providing flexible access to core and support services, and monitoring and evaluation of programs; for changes in policy supportive of program and services goals; for financing buprenorphine treatment by use of existing models of integrated treatment and merging funding streams at the local level; and for addressing research gaps, including cost-effectiveness research.

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.

Newman RG. Response to "transferring methadone-stabilized pregnant patients to buprenorphine". (letter). American Journal on Addictions 15(5): 400-400, 2006. (2 refs.)

This article concerns transferring methadone stabilized pregnant patients to buprenorphines. During pregnancy, the risk of inducing withdrawal when dosages are changed in the course of opiate addiction treatment should be avoided. All patients returned to methadone from buprenorphines. The transitional use of immediate release morphine (IRM) appears safe for both mother and fetus. Withdrawal symptoms appeared during buprenorphine induction and the severity of these symptoms may be lessened by the dose and frequency of buprenorphine administration.

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.

O'Brien S; Mattick RP; White J; Breen C; Kimber J; Ritter A et al. Maintenance pharmacotherapy for opioid dependence and SF-36 health status: A comparison with general population norms and other chronic disorders. Addictive Disorders and their Treatment 5(4): 155-164, 2006. (31 refs.)

OBJECTIVES: To assess the health status of heroin users starting and following 3 months of pharmacotherapy for opioid dependence, and to compare outcomes to a range of other chronic medical illnesses treated with maintenance medication. METHODS: The study uses pooled data from 6 clinical trials included in an Australian National Evaluation of Pharmacotherapies for Opioid Dependence. Participants received maintenance pharmacotherapy (oral naltrexone treatment, methadone, or buprenorphine) for the treatment of heroin dependence. Participants' health status was measured using the Short Form 36 health survey completed before treatment and at 3-month follow-up. Baseline data from 326 heroin-dependent participants starting maintenance treatment, and 3-month follow-up data for the 117 participants retained in trial treatment are presented. RESULTS: Heroin users at entry into pharmacotherapy for opioid dependence were in very poor psychological and physical health in relation to Australian population norms. For the 117 participants retained in treatment, clinically and statistically significant improvements in physical health, and emotional and social health were observed in just 3 months. Importantly, the health status of treated heroin users improves to a comparable or greater degree than that observed with other chronic illnesses treated with maintenance medication. CONCLUSIONS: Existing, evidence-based pharmacotherapies should be used in the treatment of heroin dependence with the same long-term care and medical monitoring strategies currently used in the treatment of other chronic illnesses.

Peh ALH; Ng BY. Medicalising the treatment of opioid dependence. (editorial). Annals of Medicine (Singapore) 35(7): 447-449, 2006. (14 refs.)

Pirastu R; Fais R; Messina M; Bini V; Spiga S; Falconieri D; Diana M. Impaired decision-making in opiate-dependent subjects: Effect of pharmacological therapies. Drug and Alcohol Dependence 83(2): 163-168, 2006. (45 refs.)

Cognitive dysfunction is a major feature of drug addiction. In the present paper, we compared the decision-making ability using the Iowa gambling task of methadone- and buprenorphine-maintained individuals to non opiate-dependent drug-free controls. Buprenorphine-maintained individuals performed better than methadone-maintained individuals, and not differently than non opiate-dependent controls. In addition, methadone-maintained individuals had more perseverative errors on the Wisconsin card sorting task (WCST) as compared with non opiate-dependent drug-free controls whereas buprenorphine-maintained individuals had intermediate scores. Scores on Weschler adult intelligence scale (WAIS-R) were similar for methadone- and buprenorphine-maintained individuals whereas drug-free controls had significantly higher scores. In addition, both opiate-dependent groups performed more poorly than drug-free controls on the Benton visual retention test (BVRT). The results suggest that buprenorphine in contrast to methadone improves decision-making, and thus may be more effective in rehabilitation programs of opiate-dependent subjects and this improvement may be related to its distinct pharmacological action as a k antagonist.

Ponizovsky AM; Grinshpoon A; Margolis A; Cohen R; Rosca P. Well-being, psychosocial factors, and side-effects among heroin-dependent inpatients after detoxification using buprenorphine versus clonidine. Addictive Behaviors 31(11): 2002-2013, 2006. (57 refs.)

Previous studies comparing buprenorphine and clonidine provided little information about subjective factors associated with the effective management of opioid withdrawal. This study sought to compare detoxification programs using these medications with regard to side-effects and related distress, general well-being, perceived self-efficacy and social support. A total of 200 treatment-seeking heroin-dependent patients, aged 18-50, were randomly assigned to buprenorphine or clonidine inpatient withdrawal treatments over 10 days followed by 11 days of relapse prevention measures. A semi-structured interview and a battery of self-rating scales assessing parameters of the interest were administered to the patients who completed the 10-day detoxification protocol with buprenorphine (n = 90) and clonidine (n = 50). Chi-square statistics and analysis of covariance were performed to examine between-group differences. Compared with patients treated with clonidine, patients who received buprenorphine developed significantly less side-effects and related distress, and had higher senses of well-being, self-efficacy and social support. The findings suggest that buprenorphine is preferable for inpatient detoxification due to its side-effects profile and positive effects on well-being and psychosocial variables. These early benefits of buprenorphine could enable consequent maintenance 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.

Robinson SE. Buprenorphine-containing treatments: Place in the management of opioid addiction. (review). CNS Drugs 20(9): 697-712, 2006. (154 refs.)

Although the synthetic opioid buprenorphine has been available clinically for almost 30 years, its use has only recently become much more widespread for the treatment of opioid addiction. The pharmacodynamic and pharmacokinetic profiles of buprenorphine make it unique in the armamentarium of drugs for the treatment of opioid addiction. Buprenorphine has partial g-opioid receptor agonist activity and is a kappa-opioid receptor antagonist; hence, it can substitute for other mu-opioid receptor agonists, yet is less apt to produce overdose reactions or dysphoria. On the other hand, buprenorphine can block the effects of opioids such as heroin (diamorphine) and morphine, and can even precipitate withdrawal in individuals physically dependent upon these drugs. Buprenorphine has significant sublingual bioavailability and a long half-life, making administration on a less than daily basis possible. Furthermore, its discontinuation is associated with only a mild withdrawal syndrome. Clinical trials have demonstrated that sublingual buprenorphine is effective in both maintenance therapy and detoxification of individuals addicted to opioids. The introduction of a sublingual formulation combining naloxone with buprenorphine further reduces the risk of diversion to illicit intravenous use. Because of its relative safety and lower risk of illegal diversion, buprenorphine has been made available in several countries for treating opioid addiction in the private office setting, greatly enhancing treatment options for this condition.

Schackman BR; Merrill JO; McCarty D; Levi J; Lubinski C. Overcoming policy and financing barriers to integrated buprenorphine and HIV primary care. Clinical Infectious Diseases 43(Supplement 4): s247-s253, 2006. (27 refs.)

Treatment for substance abuse and human immunodeficiency virus (HIV) infection historically have come from different providers, often in separate locations, and have been reimbursed through separate funding streams. We describe policy and financing challenges faced by health care providers seeking to integrate buprenorphine, a new treatment for opioid dependence, into HIV primary care. Regulatory challenges include licensing and training restrictions imposed by the Drug Addiction Treatment Act of 2000 and confidentiality regulations for alcohol and drug treatment records. Potential responses include the development of local training programs and electronic medical records. Addressing the complexity of funding sources for integrated care will require administrative support, up-front investments, and federal and state leadership. A policy and financing research agenda should address evidence gaps in the rationales for regulatory restrictions and should include cost-effectiveness studies that quantify the "value for money" of investments in integrated care to improve health outcomes for HIV-infected patients with opioid dependence.

Selzer J. Buprenorphine: Reflections of an addictions psychiatrist. (editorial). Journal of Clinical Psychiatry 67(9): 1466-1467, 2006. (5 refs.)

Sigmon SC; Moody DE; Nuwayser ES; Bigelow GE. An injection depot formulation of buprenorphine: Extended biodelivery and effects. Addiction 101(3): 420-432, 2006. (54 refs.)

Buprenorphine is an effective medication for treatment of opioid dependence. An injectable depot formulation of buprenorphine has been developed using biodegradable polymer microcapsule technology. This formulation may offer effective treatment of opioid dependence and enhance treatment delivery while minimizing risks of patient non-adherence or illicit diversion of the medication. This report provides a characterization of the biodelivery of this injectable depot in humans and of the relationship of drug blood levels to pharmacodynamic indices. The data are from two studies in which 11 opioid-dependent volunteers each received a single depot injection containing 58 mg of buprenorphine, and include previously unreported detailed plasma concentration data over a 6-week time-course following depot administration and examination of their relationship to pharmacodynamic indices. Mean plasma buprenorphine increased gradually following depot administration, peaked at 2-3 days with a mean concentration of 1.25 ng/ml and then decreased gradually, approaching undetectable levels (< 0.10 ng/mL) by 6 weeks. There was substantial between-subject consistency in several aspects of buprenorphine biodelivery, including time to first detectable blood level (4 hours), peak blood level (2 days) and undetectable blood level (6-6.5 weeks). In contrast, there was marked between-subject variability in the magnitude of peak buprenorphine concentrations, ranging from 0.17 to 3.47 ng/ml. Extent of opioid blockade was tested by weekly opioid challenges with 3 mg subcutaneous hydromorphone; subjective response and pupillary constriction were related inversely to both buprenorphine and norbuprenorphine plasma concentrations (r = 0.84-0.95). The data document that this depot formulation provides effective buprenorphine delivery for several weeks and that effects persist even at fairly low buprenorphine plasma concentrations. Suggestions are offered for further research needed to develop this formulation for clinical use as a detoxification and/or maintenance pharmacotherapy for opioid dependence.

Srivastava A; Kahan M. Buprenorphine: A potential new treatment option for opioid dependence. (editorial). Canadian Medical Association Journal 174(13): 1835-1836, 2006. (5 refs.)

Strain EC. Clinical use of buprenorphine. IN: Strain EC; Stitzer ML, eds. The Treatment of Opioid Dependence. Baltimore: Johns Hopkins University Press, 2006. pp. 230-252. (81 refs.)

In 1996, buprenorphine became available in the U.S. as an alternative to methadone in the management of opiate dependence. This chapter discusses the efficacy and safety of buprenorphine. There is a review of the studies comparing methadone and buprenorphine, and research on buprenorphine compared to placebo. Alternative-day dosing schedules are discussed, an approach developed to decrease the likelihood of diversion. Also addressed are the use of buprenorphine for opioid withdrawal, its use with cocaine disorders, and potential side effects. The chapter concludes with discussion of starting a patient on buprenorphine, use for medically supervised opioid withdrawal.

Strain EC. Pharmacology of buprenorphine. IN: Strain EC; Stitzer ML, eds. The Treatment of Opioid Dependence. Baltimore: Johns Hopkins University Press, 2006. pp. 213-229. (66 refs.)

Buprenorphine is a mixed agonist-antagonist opioid. The chapter reviews the pharmacology of buprenorphine, its actions at different opioid receptors, its absorption, metabolism, and excretion, half-life and duration of effects. The clinical features are summarized in terms of withdrawal suppression, analgesic effects, respiratory depression, cross tolerance, plus its subjective and cognitive/psychomotor effects. Also there is discussion of the pharmacologic rationale for combining buprenorphine and naloxone.

Sullivan LE; Barry D; Moore BA; Chawarski MC; Tetrault JM; Pantalon MV et al. A trial of integrated buprenorphine/naloxone and HIV clinical care. Clinical Infectious Diseases 43(Supplement 4): s184-s190 , 2006. (37 refs.)

Background. Untreated opioid dependence adversely affects the care of human immunodeficiency virus (HIV) positive patients. Buprenorphine, a partial opioid agonist, is available for maintenance treatment of opioid dependence in HIV specialty settings. We investigated the feasibility and efficacy of integrating buprenorphine, along with 2 levels of counseling, into HIV clinical care. Methods. HIV-positive, opioid-dependent patients were enrolled in a 12-week pilot study and randomized to receive daily buprenorphine/naloxone treatment along with either brief physician management or physician management combined with nurse-administered drug counseling and adherence management. Primary outcomes included treatment retention; illicit drug use, assessed by urine toxicology test and self-report; CD4 lymphocyte counts; and log 10 HIV type 1 (HIV-1) RNA levels. Results. Of the 16 patients who received at least 1 dose of buprenorphine, 13 (81%) completed 12 weeks of treatment. The proportion of opioid-positive weekly urine test results decreased from 100% at baseline to 32% (month 1), 20% (month 2), and 16% (month 3). Only 4 patients reported any opioid use (in the prior 7 days) during the 12-week study. CD4 lymphocyte counts remained stable over the course of the study. The mean log 10 HIV-1 RNA level (+/- standard deviation) declined significantly, from 3.66 +/- 1.06 log(10) HIV-1 RNA copies/mL at baseline to log 10 HIV-1 RNA copies/mL at month 3 (P < .05). No significant differences based on counseling intervention were detected. All 13 patients who completed the study continued to receive treatment in an extension phase of at least 0-15 months' duration. Conclusions. We conclude that it is feasible to integrate buprenorphine into HIV clinical care for the treatment of opioid dependence. Patients experienced good treatment retention and reductions in their opioid use. HIV biological markers remained stable or improved during buprenorphine/naloxone treatment.

Sullivan LE; Bruce RD; Haltiwanger D; Lucas GM; Eldred L; Finkelstein R; . Initial strategies for integrating buprenorphine into HIV care settings in the United States. Clinical Infectious Diseases 43(Supplement 4): s191-s196, 2006. (30 refs.)

The Centers for Disease Control and Prevention's HIV Prevention Strategic Plan Through 2005 advocated for increasing the proportion of persons with human immunodeficiency virus (HIV) infection and in need of substance abuse treatment who are successfully linked to services for these 2 conditions. There is evidence that integrating care for HIV infection and substance abuse optimizes outcomes for patients with both disorders. Buprenorphine, a recently approved medication for the treatment of opioid dependence in physicians' offices, provides the opportunity to integrate the treatment of HIV infection and substance abuse in one clinical setting, yet little information exists on the models of care that will most successfully facilitate this integration. To promote the uptake of this type of integrated care, the current review provides a description of 4 recently implemented models for combining buprenorphine treatment with HIV primary care: (1) an on-site addiction/HIV specialist treatment model; (2) a HIV primary care physician model; (3) a nonphysician health professional model; and (4) a community outreach model.

Threlkeld M; Parran TV; Adelman CA; Grey SF; Yu JH. Tramadol versus buprenorphine for the management of acute heroin withdrawal: A retrospective matched cohort controlled study. American Journal on Addictions 15(2): 186-191, 2006. (13 refs.)

Many medications have been used over the past thirty years for the treatment of opioid withdrawal, including propoxyphene, methadone, clonidine, parenteral buprenorphine, and, more recently, sublingual buprenorphine. Each has been found to have clinical strengths and limitations. Tramadol is a centrally acting synthetic analgesic with opiate activity primarily due to the binding of a metabolite to the m receptor. Despite this m receptor activity, tramadol appears to have low abuse potential and is a non-scheduled analgesic. The pharmacologic profile of tramadol makes it a candidate for opiate withdrawal treatment. A chart review was undertaken to retrospectively compare treatment outcomes of heroin-dependent patients when detoxified with parenteral buprenorphine ( 1996-1997) versus tramadol ( 1999-2000). Inclusion criteria for this study were heroin as drug of choice, current opioid physical dependence ( ie, withdrawal symptoms), no current abuse of oral opioid analgesics, and no alcohol or benzodiazepine withdrawal symptoms. Patient cases that met inclusion criteria were group-matched between buprenorphine and tramadol on the basis of age, sex, and amount of heroin used ( bags/day). Charts were audited for patient demographics, daily heroin use at admission, withdrawal symptoms, and discharge status. In total, 129 patient charts were reviewed, and 115 met all inclusion criteria and were group-matched ( 45 patients in the buprenorphine group, seventy in the tramadol group). There were no differences in demographics between the two groups of patients. Fifty-six percent of the buprenorphine group and 71% of the tramadol group completed detoxification; tramadol-treated patients had significantly higher average withdrawal symptoms when compared to the buprenorphine group and a greater reduction in withdrawal symptoms over time. Finally, the number of side effects was small and did not differ between the groups. The results of this study are consistent with previous pilot reports that indicated few clinical differences between parenteral buprenorphine and oral tramadol protocols when used in the management of acute heroin withdrawal. As a consequence, tramadol shows some promise as an opioid withdrawal management medication.

Vigezz P; Guglielmino L; Marzorati P; Silenzio R; De Chiara M; Corrado F et al. Multimodal drug addiction treatment: A field comparison of methadone and buprenorphine among heroin- and cocaine-dependent patients. Journal of Substance Abuse Treatment 31(1): 3-7, 2006. (18 refs.)

Aims: Our objective was to compare the effectiveness of buprenorphine (BUP) and methadone maintenance treatment in opiate-addicted patients in a clinical nonexperimental setting. Design: We used a naturalistic observational prospective study of 24 months' duration. Setting: Subjects were enrolled and treated at a drug addiction outpatient clinic of the National Health System Local Unit in Milan, Italy. Participants: Two hundred fifty-seven subjects meeting the DSM-IV criteria for opioid dependence and opioid-seeking substitutive pharmacological treatment participated in the study. Intervention: One hundred twenty-one subjects received BUP at a mean daily dose of 11 � 6 mg (median = 8; range = 2-30) for a mean duration of 249 days. One hundred thirty-six subjects received methadone at a mean daily dose of 54 � 29 mg (median = 50; range = 4-140) for a mean duration of 267 days. Measurements: The main efficacy parameters were treatment retention rates and illicit substance abuse, as assessed by urinalysis. Findings: Retention rates were comparable in both treatment groups, but BUP-treated subjects had significantly lower rates of illicit opiate consumption (p < .0001). Conclusions: The results confirm that, in a nonexperimental clinical practice setting, BUP is as effective as methadone in the treatment of heroin dependence, with significantly better opiate abuse control, thus possibly allowing longer and more effective treatment programs with reduced relapse rates.

Wallen MC; Lorman WJ; Gosciniak JL. Combined buprenorphine and clonidine for short-term opiate detoxification: Patient perspectives. Journal of Addictive Diseases 25(1): 23-31, 2006. (21 refs.)

The approval in 2003 for the use of buprenorphine in opiate addiction treatment has provided physicians with a new pharmacological tool to combat opiate addiction. We surveyed a sample of 100 inpatients who completed short-term opiate detoxification treatment utilizing, a combination of buprenorphine and clonidine to assess patient perspectives regarding the usefulness and tolerability of this medication regimen and to compare it to their past opiate detox experiences, if any. Patients identified pain (63%), sleep problems (57%), and anxiety (56%) as the symptoms they perceived to be most helped with buprenorphine. Over 90% of patients with past detoxification treatments rated buprenorphine treatment to be as good as or better than their past treatments. Reports of a euphoric effect were minimal (7%) and no patients reported any generalized worsening of their opiate withdrawal symptoms. We conclude that based upon patient perspectives that combining buprenorphine with clonidine is a useful and well-tolerated medication regimen for the treatment of opiate withdrawal.

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.

Winslow M; Ng WL; Mythily S; Song G; Yiong HC. Socio-demographic profile and help-seeking behaviour of buprenorphine abusers in Singapore. Annals of Medicine (Singapore) 35(7): 451-456, 2006. (31 refs.)

Introduction: The US Food and Drug Administration (FDA) approved buprenorphine or Subutex for the treatment of opiate dependence in October 2002. Buprenorphine is a partial agonist of the mu-opioid receptor; although initial animal research suggested a low abuse potential for buprenorphine, it was subsequently shown to have an abuse potential similar to that of morphine or hydromorphone. The objectives of this study were to establish the sociodemographic profile and help-seeking behaviour of buprenorphine abusers attending the de-addiction treatment clinics of the Community Addictions Management Programme. Materials and Methods: One hundred and twenty subjects, all buprenorphine abusers fulfilling the diagnostic criteria for opiate dependence, who consented to the study, completed an interviewer-administered questionnaire. Results: The mean age of those participating in the study was 39.2 [standard deviation (SD) 8.0] years. The majority of the participants were male (90%), 52.5% were currently employed and 98% had at least primary education. A family history of drug abuse was reported by 27% of the subjects. Illicit drug abuse occurred at an early age with mean age of onset of illicit drug abuse being 16.9 (SD 4.8) years with gateway drugs like marijuana and glue. Conclusions: It is vital for our medical profession to be aware of the trend in the local population to move from the abuse of illicit substances, to the abuse of prescriptive medications. It makes it necessary to increase the understanding of addictions both amongst our practising medical fraternity, and amongst those training to enter the profession. At the hospital level, it necessitates a higher level of vigilance among our emergency room physicians and those treating infectious diseases.

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.

Yeo AKS; Chan CY; Chia KH. Complications relating to intravenous buprenorphine abuse: A single institution case series. Annals of Medicine (Singapore) 35(7): 487-491, 2006. (11 refs.)

Introduction: We present a retrospective descriptive study of cases admitted to Tan Tock Seng Hospitalital from March 2005 to October 2005 with complications of Subutex abuse. Clinical Picture: A total of 8 patients were studied. Of the 8, 7 were male and one was female. Their complications consist of the following: arterial pseudoaneurysm (2), arterial pseudoaneurysm with infective venous thrombus (1), infective venous thrombus (1), venous thrombus (2), end arterial spasms (1) and sympathetic dystrophy (1). Treatment: For the patient who presented with buprenorphine-associated neuropathy, non-operative treatment with analgesics was given. Conservative medical therapy involving deep venous thrombosis treatment was instituted for the patient with deep venous thrombosis. Repair, restorative bypass and embolectomy surgery were performed for patients who had severe embolic/thrombotic complications. One of the patients who received the above surgery required amputation of his lower limb. Outcome: Of the 8 patients, 4 were treated medically, 3 required surgery and 1 required amputation. Their recoveries were uneventful. Of the 8, 1 absconded and was not followed up with. Conclusion: Parenteral injection of buprenorphine can cause a wide range of vascular complications from simple vascular irritation to severe infective thrombosis and pseudoaneurysms requiring limb amputations. Non-sterile preparation of an injected substance or non-sterile injection sites and the repeated punctures of major vessels are possible culprits in those who are seen to have acute infection of injection sites.