buprenorphine and Heroin-Dependence

Deaths due to heroin overdoses are increasing and are the leading cause of death among intravenous heroin users. Although medication-assisted treatment (MAT) improves morbidity and mortality in patients with opioid use disorders, it is underutilized. Most efforts to expand access to MAT have focused on outpatient settings. Although the inpatient medical setting presents a critical opportunity to initiate treatment, general hospitals are often unfamiliar with MAT, creating a number of barriers to its use. In this report, we describe the case of a woman with heroin use disorder who was initiated on buprenorphine maintenance treatment while hospitalized for cardiac disease related to her intravenous heroin use. Barriers to initiating buprenorphine in this case included patient, practitioner, and organizational factors, and, ultimately, shared misperceptions about the feasibility of administering buprenorphine in a general medical hospital. These barriers were addressed, buprenorphine was initiated, and the patient demonstrated reduced craving, improved postoperative pain control, improved overall well-being, increased engagement in discharge planning, and acceptance of referral for addiction specialty aftercare. Our experience with this patient suggests that it is feasible to initiate buprenorphine in acute medical settings and that such treatment can improve patient outcomes. Our review of the literature reveals emerging evidence supporting the value of this practice.

Topics: Adult; Buprenorphine; Female; Heroin Dependence; Hospitals, General; Humans; Inpatients; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Referral and Consultation

Although counseling is a required part of office-based buprenorphine treatment of opioid use disorders, the nature of what constitutes appropriate counseling is unclear and controversial. The authors review the literature on the role, nature, and intensity of behavioral interventions in office-based buprenorphine treatment.. The authors conducted a review of randomized controlled studies testing the efficacy of adding a behavioral intervention to buprenorphine maintenance treatment.. Four key studies showed no benefit from adding a behavioral intervention to buprenorphine plus medical management, and four studies indicated some benefit for specific behavioral interventions, primarily contingency management. The authors examined the findings from the negative trials in the context of six questions: 1) Is buprenorphine that effective? 2) Is medical management that effective? 3) Are behavioral interventions that ineffective in this population? 4) How has research design affected the results of studies of buprenorphine plus behavioral treatment? 5) What do we know about subgroups of patients who do and those who do not seem to benefit from behavioral interventions? 6) What should clinicians aim for in terms of treatment outcome in buprenorphine maintenance?. High-quality medical management may suffice for some patients, but there are few data regarding the types of individuals for whom medical management is sufficient. Physicians should consider a stepped-care model in which patients may begin with relatively nonintensive treatment, with increased intensity for patients who struggle early in treatment. Finally, with 6-month retention rates seldom exceeding 50% and poor outcomes following dropout, we must explore innovative strategies for enhancing retention in buprenorphine treatment.

Topics: Behavior Therapy; Buprenorphine; Cocaine-Related Disorders; Combined Modality Therapy; Heroin Dependence; Humans; Long-Term Care; Methadone; Opioid-Related Disorders; Outcome and Process Assessment, Health Care; Patient Compliance; Patient Preference; Randomized Controlled Trials as Topic

Heroin addiction is one of the most devastating and expensive of public health problems. The most effective treatment is opioid replacement therapy. Replacement of heroin, a short-acting euphoriant with methadone or other opioids that have significantly longer duration of action provides a number of therapeutic benefits. Opioid detoxification has a role in both preventing acute withdrawal and maintaining long-term abstinence. Opioid-based detoxification is based on the principle of cross-tolerance, in which one opioid is replaced with another one that is slowly tapered. For the treatment of heroin addicts a wide range of psychosocial and pharmacotherapeutic treatments are available; of these, methadone maintenance therapy has the most evidence of benefit. Methadone maintenance reduces and/or eliminates the use of heroin, reduces the death rate and criminality associated with heroin use, and allows patients to improve their health and social productivity. In addition, enrollment in methadone maintenance has the potential to reduce the transmission of infectious diseases associated with heroin injection, such as hepatitis and HIV. The principal effects of methadone maintenance are to relieve narcotic craving, suppress the abstinence syndrome, and block the euphoric effects associated with heroin. There is growing interest in expanding treatment into primary care, allowing opioid addiction to be managed like other chronic illnesses. Buprenorphine which is a long-acting partial agonist was also approved as pharmacotherapy for opioid dependence. Opioid antagonists can reduce heroin self-administration and opioid craving in detoxified addicts. Naltrexone, which is a long-acting competitive antagonist at the opioid receptors, blocks the subjective and objective responses produced by intravenous opioids. Naltrexone is employed to accelerate opioid detoxification by displacing heroin and as a maintenance agent for detoxified formerly heroin-dependent patients who want to remain opioid-free.

Topics: Adrenergic alpha-2 Receptor Agonists; Analgesics, Opioid; Buprenorphine; Euphoria; Heroin; Heroin Dependence; Humans; Methadone; Naltrexone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment

The aim of this review was to update and summarize the scientific knowledge on the long term outcomes of the different pharmacological treatment options for opioid dependence currently available and to provide a critical discussion on the different treatment options based on these results. We performed a literature search using the PubMed databases and the reference lists of the identified articles. Data from research show that the three pharmacological options reviewed are effective treatments for opioid dependence with positive long term outcomes. However, each one has its specific target population and setting. While methadone and buprenorphine are first line options, heroin-assisted treatment is a second line option for those patients refractory to treatment with methadone with concomitant severe physical, mental, social and/or functional problems. Buprenorphine seems to be the best option for use in primary care offices. The field of opioid dependence treatment is poised to undergo a process of reinforcement and transformation. Further efforts from researchers, clinicians and authorities should be made to turn new pharmacological options into clinical reality and to overcome the structural and functional obstacles that maintenance programmes face in combatting opioid dependence.

Topics: Buprenorphine; Heroin; Heroin Dependence; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Time Factors; Treatment Outcome

For people seeking treatment, the course of heroin addiction tends to be chronic and relapsing, and longer duration of treatment is associated with better outcomes. Heroin addiction is strongly associated with deviant behaviour and crime, and the objectives in treating heroin addiction have been a blend of humane support, rehabilitation, public health intervention and crime control. Reduction in street heroin use is the foundation on which all these outcomes are based. The pharmacological basis of maintenance treatment of dependent individuals is to minimize withdrawal symptoms and attenuate the reinforcing effects of street heroin, leading to reduction or cessation of street heroin use. Opioid maintenance treatment can be moderately effective in suppressing heroin use, although deviations from evidence-based approaches, particularly the use of suboptimal doses, have meant that treatment as delivered in practice may have resulted in poorer outcomes than predicted by research. Methadone treatment has been 'programmatic', with a one-size-fits-all approach that in part reflects the perceived need to impose discipline on deviant individuals. However, differences in pharmacokinetics and in side-effects mean that many patients do not respond optimally to methadone. Injectable diamorphine (heroin) provides a more reinforcing medication for some 'nonresponders' and can be a valuable option in the rehabilitation of demoralized, socially excluded individuals. Buprenorphine, a partial agonist, is a less reinforcing medication with different side-effects and less risk of overdose. Not only is it a different medication, but also it can be used in a different paradigm of treatment, office-based opioid treatment, with less structure and offering greater patient autonomy.

Topics: Buprenorphine; Drug Overdose; Heroin; Heroin Dependence; Humans; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Reinforcement, Psychology; Substance Withdrawal Syndrome; Time Factors

To review evidence on the effectiveness of opioid maintenance treatment (OMT) in prison and post-release.. Systematic review of experimental and observational studies of prisoners receiving OMT regarding treatment retention, opioid use, risk behaviours, human immunodeficiency virus (HIV)/hepatitis C virus (HCV) incidence, criminality, re-incarceration and mortality. We searched electronic research databases, specialist journals and the EMCDDA library for relevant studies until January 2011. Review conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.. Twenty-one studies were identified: six experimental and 15 observational. OMT was associated significantly with reduced heroin use, injecting and syringe-sharing in prison if doses were adequate. Pre-release OMT was associated significantly with increased treatment entry and retention after release if arrangements existed to continue treatment. For other outcomes, associations with pre-release OMT were weaker. Four of five studies found post-release reductions in heroin use. Evidence regarding crime and re-incarceration was equivocal. There was insufficient evidence concerning HIV/HCV incidence. There was limited evidence that pre-release OMT reduces post-release mortality. Disruption of OMT continuity, especially due to brief periods of imprisonment, was associated with very significant increases in HCV incidence.. Benefits of prison OMT are similar to those in community settings. OMT presents an opportunity to recruit problem opioid users into treatment, to reduce illicit opioid use and risk behaviours in prison and potentially minimize overdose risks on release. If liaison with community-based programmes exists, prison OMT facilitates continuity of treatment and longer-term benefits can be achieved. For prisoners in OMT before imprisonment, prison OMT provides treatment continuity.

Topics: Buprenorphine; Cocaine-Related Disorders; Continuity of Patient Care; Crime; Epidemiologic Methods; Heroin Dependence; Humans; Illicit Drugs; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Compliance; Prisoners; Risk-Taking; Treatment Outcome

Heroin use in pregnancy is a worldwide problem. Methadone maintenance treatment has definite advantages for the mother and is currently recommended in the UK. There is, however, increasing evidence of adverse effects upon developing cortical and visual function in children of treated heroin-addicted mothers. The longer-term implications of this are not yet clear, and are confounded by poly-drug misuse and ongoing social deprivation. There is a paucity of evidence regarding outcome for infants who require pharmacological treatment for neonatal abstinence syndrome compared to those who have only mild symptoms. Well-controlled studies of the treatment of heroin misuse in pregnancy that take account of both neonatal and longer term outcomes for the child are urgently required.

Topics: Buprenorphine; Child, Preschool; Developmental Disabilities; Female; Heroin Dependence; Humans; Infant; Infant, Newborn; Maternal-Fetal Exchange; Methadone; Opiate Substitution Treatment; Pregnancy; Pregnancy Complications; Prenatal Care; Prenatal Exposure Delayed Effects

Dependence on opioids is a multifactorial condition involving genetic and psychosocial factors. There are three stages to treating opioid dependence. Stabilisation is usually by opioid substitution treatments, and aims to ensure that the drug use becomes independent of mental state (such as craving and mood) and independent of circumstances (such as finance and physical location). The next stage is to withdraw (detox) from opioids. The final stage is relapse prevention. This treatment process contributes to recovery of the individual, which also includes improved overall health and wellbeing, as well as engagement in society.. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for stabilisation (maintenance) in people with opioid dependence? What are the effects of drug treatments for withdrawal in people with opioid dependence? What are the effects of drug treatments for relapse prevention in people with opioid dependence? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).. We found 26 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.. In this systematic review, we present information relating to the effectiveness and safety of the following interventions: buprenorphine; clonidine; lofexidine; methadone; naltrexone; and ultra-rapid withdrawal regimens.

Topics: Analgesics, Opioid; Buprenorphine; Evidence-Based Medicine; Heroin Dependence; Humans; Incidence; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Treatment Outcome

Heroin craving is a trigger for relapse and dropping out of treatment. Methadone has been the standard medication for the management of heroin craving.. We explored the medication options other than methadone which may have heroin anticraving properties.. To be selected for the review, articles had to include outcome measures of the effect of the studied medication on subjective and/or objective opiate craving and be of the following two types: (1) randomized, controlled, and/or double-blind clinical trials (RCTs) examining the relationship between the studied medication and heroin craving; (2) nonrandomized and observational studies (NRSs) examining the relationship between the studied medication and heroin craving. Thirty-three articles were initially included in the review. Twenty-one were excluded because they did not meet the inclusion criteria. We present the results of 12 articles that met all the inclusion criteria.. Some new medications have been under investigation and seem promising for the treatment of opiate craving. Buprenorphine is the second most studied medication after methadone for its effect on opiate craving. At doses above 8 mg daily, it seems very promising and practical for managing opiate craving in patients receiving long-term opioid maintenance treatment.. In doses higher than 8 mg daily, buprenorphine is an appropriate treatment for opiate craving. More research with rigorous methodology is needed to study the effect of buprenorphine on heroin craving. Also more studies are needed to directly compare buprenorphine and methadone with regard to their effects on heroin craving.

Topics: Buprenorphine; Heroin; Heroin Dependence; Humans; Methadone; Naltrexone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome

Opioid substitution treatment (OST) is an effective treatment for heroin dependence. The World Health Organization has recommended that OST be implemented in prisons because of its role in reducing drug injection and associated problems such as HIV transmission. The aim of this paper was to examine the extent to which OST has been implemented in prisons internationally.. Literature review.. As of January 2008, OST had been implemented in prisons in at least 29 countries or territories. For 20 of those countries, the proportion of all prisoners in OST could be calculated, with results ranging from less than 1% to over 14%. At least 37 countries offer OST in community settings, but not prisons.. This study has identified an increase in the international implementation of OST in prisons. However, there remain large numbers of prisoners who are unable to access OST, even in countries that provide such programs. This raises issues of equivalence of care for prisoners and HIV prevention in prisons.

Topics: Buprenorphine; Heroin Dependence; HIV Infections; Humans; International Cooperation; Methadone; Naltrexone; Narcotic Antagonists; Patient Care; Prisoners; Prisons

Many studies have documented the safety, efficacy, and effectiveness of long-acting opioids (L-AOs), such as methadone and buprenorphine, in the treatment of heroin addiction. This article reviews the pharmacological differences between L-AO medications and short-acting opioids (heroin) in terms of reinforcing properties, pharmacokinetics, effects on the endocrine and immune systems. Given their specific pharmacological profile, L-AOs contribute to control addictive behavior, reduce craving, and restore the balance of disrupted endocrine function. The use of the term "substitution," referring to the fact that methadone or buprenorphine replace heroin in binding to brain opioid receptors, has been generalized to consider L-AOs as simple replacement of street drugs, thus contributing to the widespread misunderstanding of this treatment approach.

Topics: Arousal; Brain; Buprenorphine; Delayed-Action Preparations; Heroin; Heroin Dependence; Humans; Immunocompetence; Methadone; Motivation; Narcotics; Receptors, Opioid; Treatment Outcome

In spite of its seriousness, dependence on alcohol and benzodiazepines during substitution treatment are poorly documented. Its frequency is nonetheless significant. According to studies, between one and two thirds of patients are affected. This consumption is under verbalized by patients and underestimated by carers. In one study, where the average diazepam doses were from 40 to 45 mg per day, 30% of the patients were taking 70 to 300 mg per day, two thirds having experimented with a fixed dose of 100mg. Benzodiazepines, especially diazepam and flunitrazepam, were studied versus placebo. Thus, 10 to 20mg of diazepam gave rise to euphoria, a sensation of being drugged, sedation and lessening of cognitive performance. The aim of this consumption is to potentiate the euphoria induced by opioids, a "boost" effect during the hour after taking it, or the calming of the outward signs of withdrawal. The most sought after molecules are the most sedative, those with pronounced plasmatic peaks, and the most accessible.. In multidependant subjects, opioid dependence had been earlier in adolescence, with a number of therapeutic failures. They had been faced with repetitive rejection and separation during childhood, medicolegal and social problems. Somatization, depression, anxiety and psychotic disorders are frequent in this subgroup. Heavy drinkers under methadone treatment are highly vulnerable to cocaine. Their behaviour is at risk, with exchange of syringes; their survival rate is 10 years less than that of moderate consumers of alcohol. Most are single, with a previous prison, psychiatric or addictive cursus and they present significant psychological vulnerability. For some authors, benzodiazepines indicate a psychiatric comorbidity. Methadone significantly reduces the consumption of alcohol by nonalcoholic heroin addicts. Although alcohol is an enzymatic inductor of methadone catabolism, with bell-shaped methadone plasma curves over 24 hours, a substitution treatment is recommended. It has a minimum impact on care, in spite of efficiency and retention in therapeutical programs, allowing the subject's inclusion in the framework of a more regular and sustained medical follow-up. Treatment of benzodiazepine dependence by a progressive regression of doses has little efficacy in subjects which cannot control how much medication they are taking. Certain authors have suggested maintenance treatments of clonezepam. The most appropriate therapeutic propositions are: (1) maintenance of therapeutic links though a framework of deliverance from flexible substitution treatment; (2) prevention by cautious prescribing and control of dispensing medication; (3) parallel treatment of psychiatric comorbidities and related personality disorders; (4) individual psychiatric treatment, either institutional or in consistent networks.

Topics: Adolescent; Adult; Alcoholism; Benzodiazepines; Buprenorphine; Clonazepam; Clorazepate Dipotassium; Comorbidity; Controlled Clinical Trials as Topic; Diazepam; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Ethanol; Euphoria; Flunitrazepam; Heroin Dependence; Humans; Metabolic Clearance Rate; Methadone; Narcotics; Substance-Related Disorders; Young Adult

Dependence on opioids is a multifactorial condition involving genetic and psychosocial factors. There are three approaches to treating opioid dependence. Stabilisation is usually by opioid substitution treatments, and aims to ensure that the drug use becomes independent of mental state (such as craving and mood) and independent of circumstances (such as finance and physical location). The next stage is to withdraw (detox) from opioids. The final aim is relapse prevention.. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments for stabilisation (maintenance) in people with opioid dependence? What are the effects of drug treatments for withdrawal in people with opioid dependence? What are the effects of drug treatments for relapse prevention in people with opioid dependence? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).. We found 23 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.. In this systematic review, we present information relating to the effectiveness and safety of the following interventions: buprenorphine; clonidine; lofexidine; methadone; naltrexone; and ultra-rapid withdrawal regimes.

Topics: Analgesics, Opioid; Buprenorphine; Evidence-Based Medicine; Heroin Dependence; Humans; Incidence; Methadone; Naltrexone; Opioid-Related Disorders

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

Topics: Analgesics, Opioid; Buprenorphine; Cost-Benefit Analysis; Female; Heroin Dependence; Humans; Male; Methadone

In France, all registered medical doctors have been allowed to prescribe buprenorphine without any special education or licensing since 1995. This has led to a rapidly increasing number of opiate-dependent users under buprenorphine treatment in primary care. French physician compensation mechanisms, pharmacy services, and medical insurance funding all have contributed to minimizing barriers to buprenorphine treatment. Approximately 20% of all physicians in France are prescribing buprenorphine to treat more than one half of the estimated 180,000 problem heroin users. Intravenous diversion of buprenorphine may occur in up to 20% of buprenorphine patients and has led to relatively rare overdoses in combination with sedatives, whereas total opiate overdose deaths have declined substantially. In France, buprenorphine maintenance treatment for problem opiate users was feasible and safe through office-based prescriptions in a relaxed regulatory environment.

Topics: Buprenorphine; Cause of Death; Cross-Sectional Studies; Drug Approval; Drug Overdose; Drug Prescriptions; Drug Utilization; Feasibility Studies; France; Heroin Dependence; Humans; Long-Term Care; Narcotics; National Health Programs; Opioid-Related Disorders; Primary Health Care; Substance Abuse, Intravenous

Methadone has been the mainstay of pharmacological management of opioid dependence since the 1960s but buprenorphine is fast gaining acceptance among addiction specialists and patients. This article provides an overview of buprenorphine, its pharmacology, clinical efficacy and role in the treatment of opioid dependence.

Topics: Buprenorphine; Heroin Dependence; Humans; Methadone; Narcotic Antagonists; Treatment Outcome

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.

Topics: Acute Disease; Adult; Analgesics, Opioid; Buprenorphine; Female; Heroin Dependence; Humans; Methadone; Narcotic Antagonists; Pain; Recurrence; Ulna Fractures

To review buprenorphine and explore its role in the treatment of heroin dependence.. Articles were identified through a search of MEDLINE (1966-February 2005) using the key terms buprenorphine, heroin, opioid, addiction, and methadone.. Buprenorphine appears to provide potential advantages over methadone. Two Cochrane meta-analyses were evaluated on the use of buprenorphine in opioid dependence-one in the management of opioid dependence and the other in the management of opioid withdrawal.. Buprenorphine offers several advantages for the treatment of heroin addiction. As maintenance treatment, buprenorphine is effective, but not more effective than methadone. In the management of opioid withdrawal, buprenorphine may be better tolerated than clonidine or methadone.

Topics: Buprenorphine; Heroin Dependence; Humans; Narcotic Antagonists

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.

Topics: Australia; Buprenorphine; Cost-Benefit Analysis; Data Interpretation, Statistical; Evaluation Studies as Topic; Heroin Dependence; Humans; Methadone; Randomized Controlled Trials as Topic; Research Design

Our objective was to compare the effectiveness of buprenorphine (BUP) and methadone maintenance treatment in opiate-addicted patients in a clinical nonexperimental setting.. We used a naturalistic observational prospective study of 24 months' duration.. Subjects were enrolled and treated at a drug addiction outpatient clinic of the National Health System Local Unit in Milan, Italy.. Two hundred fifty-seven subjects meeting the DSM-IV criteria for opioid dependence and opioid-seeking substitutive pharmacological treatment participated in the study.. 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.. The main efficacy parameters were treatment retention rates and illicit substance abuse, as assessed by urinalysis.. Retention rates were comparable in both treatment groups, but BUP-treated subjects had significantly lower rates of illicit opiate consumption (p < .0001).. 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.

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Female; Heroin Dependence; Humans; Male; Methadone; Narcotics; Occupational Therapy; Psychiatric Status Rating Scales; Social Support; Substance Abuse Detection; Substance-Related Disorders; Treatment Outcome

Buprenorphine is an opioid agonist-antagonist with a 'ceiling effect' for respiratory depression. Compared with methadone, its unique pharmacology offers practical advantages and enhanced safety when prescribed as recommended and supervised by a physician. Buprenorphine has been approved in several countries as an efficient and safe maintenance therapy for heroin addiction. Its use resulted in a salutary effect with a reduction in heroin overdose-related deaths in countries that implemented office-based buprenorphine maintenance. In France, however, where high-dose buprenorphine has been marketed since 1996, several cases of asphyxic deaths were reported among addicts treated with buprenorphine. Death resulted from buprenorphine intravenous misuse or concomitant sedative drug ingestion, such as benzodiazepines. In these situations of abuse, misuse, or in association with elevated doses of psychotropic drugs, buprenorphine may cause severe respiratory depression. Unlike other opiates, the respiratory effects from buprenorphine are not responsive to naloxone. However, the exact mechanism of buprenorphine-induced effects on ventilation is still unknown. The role of norbuprenorphine, the main N-dealkylated buprenorphine metabolite with potent respiratory depressor activity, also remains unclear. Experimental studies investigating the respiratory effects of combinations of high doses of buprenorphine and benzodiazepines suggested that this drug-drug interaction may result from a pharmacodynamic interaction. A pharmacokinetic interaction between buprenorphine and flunitrazepam is also considered. As there are many questions regarding the possible dangers of death or respiratory depression associated with buprenorphine use, we aimed to present a comprehensive critical review of the published clinical and experimental studies on buprenorphine respiratory effects.

Topics: Analgesics, Opioid; Anti-Anxiety Agents; Asphyxia; Benzodiazepines; Buprenorphine; Drug Interactions; Heroin Dependence; Humans; Respiratory Insufficiency

Despite the effectiveness of drug treatment and harm reduction programmes aimed at reducing illegal drug use, especially heroin use, situations at risk of transmitting HCV infection are still very frequent. Among routes of drug administration, injection appears as the most dangerous mean regarding the spread of HCV infection among drug users. This practice frequently occurs within a context of a group sharing climate (equipment, substance, housing, etc.) and mutual support. Risk of unsafe behaviour is increased at the time of their first injection or during the first steps of their experience as newly injectors. Public health interventions should target a reduction in the number of injections by modifying the pharmacological format of sublingual buprenorphine, by defining the cessation of injection as one of the main objectives of drug users care programs, by designing and implementing interventions and iniatives that target recreational multiple drug users at risk of initiating drug injection.

Topics: Administration, Sublingual; Adolescent; Adult; Buprenorphine; Clinical Trials as Topic; Cocaine-Related Disorders; Data Collection; Female; France; Hepatitis C; Heroin Dependence; Humans; Incidence; Male; Narcotic Antagonists; Prospective Studies; Public Health; Risk-Taking; Substance Abuse, Intravenous; Substance-Related Disorders; Time Factors

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.

Topics: Antiretroviral Therapy, Highly Active; Buprenorphine; Comorbidity; Female; Follow-Up Studies; Global Health; Heroin Dependence; HIV Infections; Humans; International Cooperation; Male; Methadone; Narcotic Antagonists; Patient Selection; Quality of Health Care; Risk Assessment; Substance Abuse, Intravenous; Treatment Outcome; World Health Organization

This overview of the March 2003 conference on the U.S. national buprenorphine implementation program is developed to inform the practitioner about the positive experience that has been accumulated worldwide on the use of buprenorphine for office-based practice. The first paper delineates the challenges for American psychiatry in moving buprenorphine forward into general practice. Most psychiatrists are unprepared to work with opiate-dependent patients or to use buprenorphine. The international successes with office-based buprenorphine from France and Australia are presented in the next papers, followed by presentations on several U.S. studies using buprenorphine in the community for detoxification and office-based maintenance. These experiences have thus far confirmed buprenorphine's utility and promise for opiate addiction treatment in the U.S. Finally, two national monitoring programs have been implemented to assess the public health impact of this new treatment opportunity. This opportunity has a three-year window, however, and a critical need will be to attract a sufficient number of physicians into prescribing buprenorphine/naloxone in order to allow our patients increased access to this treatment.

Topics: Attitude of Health Personnel; Buprenorphine; Community Health Services; Cross-Cultural Comparison; Diffusion of Innovation; Family Practice; Heroin Dependence; Humans; Narcotic Antagonists; Narcotics; Office Visits; Opioid-Related Disorders; Product Surveillance, Postmarketing; Psychiatry; Treatment Outcome; United States

Buprenorphine and buprenorphine/naloxone (BUP) are newly approved for office-based treatment of opioid dependence. Federal and non-federal regulatory and monitoring agencies, national and international researchers, national professional organizations, researchers involved in monitoring, opioid treatment programs and the pharmaceutical industry met to synthesize and disseminate practical information to guide training, practice, monitoring, regulation and evaluation efforts with these medications. We performed a review of the literature, training curricula and practice guidelines and commissioned manuscripts describing recently completed, or still in progress, studies or field experiences with BUP treatment. A consensus process generated fifteen statements: (1) The federal government should collect baseline data on opioid-related deaths and morbidity to assess the effect of BUP on public health, (2) the patient limit for group practices should apply to individual physicians rather than group practices, (3 and 4) telephone and Internet-based physician and pharmacist support is needed, (5) clinicians who provide psychosocial services to opioid dependent patients should be informed of the role of BUP, (6) opioid-dependent patients should be instructed to present for induction in mild withdrawal, (7) the existing Center for Substance Abuse Treatment guidelines provide a reasonable induction protocol, (8) physicians should be prepared to use ancillary medications with BUP induction, (9) a physician or nurse must be available to the patient during the induction period, (10) concurrent counseling and support services are necessary, (11) detoxification without appropriate followup addiction treatment leads to rapid relapse and is not as effective as maintenance, (12) pregnant opioid-dependent women should be treated using good clinical practice including specialist addiction care and prenatal care, (13) BUP induction and withdrawal treatment may benefit from different designations for payment, (14) take-home medication options should be tailored to patients' needs, (15) there is a need for clinical and policy research in unique patient populations.

Topics: Ambulatory Care; Buprenorphine; Heroin Dependence; Humans; Narcotic Antagonists; Opioid-Related Disorders; Practice Guidelines as Topic; United States

Given the difficulty of achieving sustained recovery, pharmacotherapy of opioid and cocaine addiction is more effective when combined with behavioral and psychosocial approaches. Effective pharmacotherapies for opioid dependence and withdrawal include methadone, L-alpha acetylmethadol (LAAM), naltrexone, buprenorphine, and clonidine. Treatment of cocaine addiction includes anti-craving agents, dopamine agonists or blocking agents, antidepressants, and treatment of co-morbid psychiatric disorders, but all with mixed results. In this paper, we discuss the use of medication in the context of general principles of opioid and cocaine addiction treatment. Both established medications and promising directions in pharmacotherapy will be addressed.

Topics: Buprenorphine; Clonidine; Cocaine-Related Disorders; Comorbidity; Heroin Dependence; Humans; Mental Disorders; Methadone; Methadyl Acetate; Naltrexone; Narcotic Antagonists; Narcotics

In France, so called "substitution treatments" for addiction are nicotine substitutes for tobacco dependence and buprenorphine, and methadone for opiate dependence. The word "substitution" participates to the uncertainty as to the objective of such treatments. From an addiction psychiatry perspective, these treatments are of interest as pharmacological treatments for maintenance of abstinence. In such a perspective they are not changing one substance of dependence for another. The goal is to reduce craving by low potential reinforcement medications. Conditions for success are a clarification of treatment goal with the patients, adequate dosing, and time. All medical doctors may prescribe buprenorphine for treatment of opiate dependence. Supervised daily dispensing in pharmacies is useful to increase compliance and collaboration, and avoid misuse and diversion. For tobacco dependence, nicotine patch must be clearly differentiated from other nicotine substitutes like gums and inhalers that have significant reinforcing effects. Because the patch is accessible without medical prescription, many patients are not sufficiently medically supervised and dropout frequently. For patients that cannot initially accept the behavioral changes associated to the goal of abstinence, it is legitimate to truly substitute them with less dangerous reinforcing substances. This possibility exists in France only for tobacco use that can be substituted to inhaled or chewed nicotine. It is possible that some reported misuse of buprenorphine and methadone are inadequate attempts to increase the reinforcing effects of these medications.

Topics: Buprenorphine; Ganglionic Stimulants; Heroin Dependence; Humans; Methadone; Narcotics; Nicotine; Prognosis; Substance-Related Disorders; Tobacco Use Disorder; Treatment Outcome

Buprenorphine is used for maintenance treatment of opiate abusers.. A literature review was carried out in order to describe buprenorphine's pharmacology, its clinical use in maintenance treatment, and its efficacy when compared to methadone.. Buprenorphine is a partial agonist to the opiate mu-receptor and is therefore safer in overdose. The distress of abstinence is reduced compared to methadone. The potential for abuse is, however, considerable. Some patients may not be maintained well enough on buprenorphine.. Buprenorphine should be subject to the same considerations in maintenance treatment as methadone.

Topics: Buprenorphine; Dose-Response Relationship, Drug; Heroin Dependence; Humans; Methadone; Narcotics; Receptors, Opioid

Topics: Buprenorphine; Heroin Dependence; Humans; Methadone; Narcotics; Opioid-Related Disorders

Heroin abuse is an international problem with which all countries must continually cope. Many countries have implemented heroin substitution therapy as an effective means of decreasing illicit heroin use, crime, HIV risk, and death, and in improving employment and social adjustment. Although methadone is the most commonly used medication for heroin substitution, other agonists in current use include levomethadyl acetate (LAAM), buprenorphine, and pharmaceutical-grade heroin. This report reviews toxicologic issues that arise in these programs. A broad array of testing methodologies are available that allow selection of on-site testing or laboratory-based methodology. Urine specimens may be monitored for nonprescribed drugs on a qualitative or semiquantitative basis. Methods for differentiating opiate sources by urinalysis have been proposed to distinguish poppy seed consumption from heroin abuse and for distinguishing pharmaceutical-grade heroin from illicit heroin. Therapeutic drug monitoring for methadone in plasma continues to be evaluated for use in establishing adequate dosing and detecting diversion, and new methods have been devised for measurement of the optical isomers of methadone in plasma. Biologic specimens, in addition to plasma and urine, have been evaluated for use in drug monitoring, including sweat, hair, and oral fluid, with promising results. Overall, the many recent developments in testing methodology provide more effective means to assess patients in heroin substitution programs and should contribute to improvements in public health.

Topics: Buprenorphine; Hair; Heroin Dependence; Humans; Methadone; Methadyl Acetate; Narcotics; Saliva; Sweat

Patients with heroin dependence frequently present to internists and other physicians for heroin-related medical, psychiatric, and behavioral health problems and often seek help with reducing their heroin use. Thus, physicians should be familiar with the identification and diagnosis of heroin dependence in their patients and be able to initiate treatment of heroin dependence both directly and by referral. Recent research has provided much information concerning effective pharmacologically based treatment approaches for managing opioid withdrawal and helping patients to remain abstinent Methadone maintenance and newer approaches using L-alpha acetylmethadol and buprenorphine seem to be particularly effective in promoting relapse prevention. Although these treatments are currently provided in special drug treatment settings, recent and ongoing research indicates that the physician's office may be an effective alternative site for these treatments.

Topics: Analgesics, Opioid; Buprenorphine; Counseling; Heroin Dependence; Humans; Mental Disorders; Methadone; Methadyl Acetate; Naltrexone; Narcotic Antagonists; Physician's Role; Substance Withdrawal Syndrome

The pharmacology of buprenorphine is unique because of its partial agonist profile at the mu-opioid receptor (ie, high affinity, low intrinsic activity and slow dissociation). This unique profile results in greater safety, less physical dependence, and greater flexibility in dose scheduling. Buprenorphine has been investigated in combination with the opioid antagonist, naloxone, with the goal of decreasing abuse, misuse, and diversion. When combined with naloxone in a sublingual tablet, buprenorphine has been shown to be effective 1) in retaining patients in treatment, 2) in reducing opioid use and craving, and 3) when dosed less-than-daily. The pharmacologic effects of buprenorphine are not altered by the addition of naloxone when administered to the population in an appropriate combination ratio. However, if taken intravenously by individuals dependent on short- or long-acting opioids a precipitated withdrawal syndrome is observed, which should reduce its abuse potential. This review discusses the rationale for development and evidence supporting the use of a buprenorphine/naloxone combination product. The buprenorphine/naloxone combination product should be considered for use in primary care office-based settings as a safe and effective treatment that is likely to increase the availability of agonist treatment for opioid dependence.

Topics: Buprenorphine; Clinical Trials as Topic; Heroin Dependence; Humans; Naloxone; Narcotic Antagonists

In this review, we present methods of pharmacotherapy in opiate dependence currently used in Poland and worldwide. As problems associated with drug abuse increase in severity, it is particularly important to bring these methods to the attention of medical professionals, governmental agencies and the general public. Here we describe pharmacotherapeutic approaches used in detoxification as well as relapse prevention. The presented methods of detoxification include classical treatments with clonidine and methadone as well as newer methods of rapid and ultrarapid detoxification. Agonists, partial agonists, and antagonists can be used in preventing relapse in detoxified patients. Experimental therapeutic approaches in the treatment of drug dependence are also presented. Psychotherapy and psychiatric care, central to the successful treatment of opiate dependence, are reviewed as well.

Topics: Adrenergic alpha-Agonists; Buprenorphine; Clonidine; Heroin Dependence; Humans; Inactivation, Metabolic; Methadone; Naltrexone; Narcotic Antagonists; Narcotics

Topics: Acquired Immunodeficiency Syndrome; Buprenorphine; Codeine; Female; Heroin Dependence; HIV Infections; HIV Seropositivity; HIV Seroprevalence; Humans; Incidence; Male; Methadone; Prospective Studies; Risk Factors; Self Medication; Sex Work; Sexual Behavior; Substance Abuse, Intravenous

Topics: Animals; Buprenorphine; Cocaine; Heroin Dependence; Humans; Opioid-Related Disorders

Topics: Analgesics, Opioid; Animals; Buprenorphine; Heroin Dependence; Humans; Nausea; Opioid-Related Disorders; Substance Withdrawal Syndrome

Topics: Buprenorphine; Cocaine; Desipramine; Female; Heroin Dependence; Humans; Male; Naltrexone; Opioid-Related Disorders; Sex Factors; Substance-Related Disorders

Buprenorphine is an opioid mixed agonist-antagonist that has potential usefulness as a pharmacotherapy for opiate addiction. Buprenorphine significantly suppressed opiate self-administration by heroin addicts. Buprenorphine also suppressed opiate self-administration in a primate model. Although buprenorphine is a positive reinforcer in rhesus monkey, it is less reinforcing than other opioids and some opioid mixed agonist-antagonists as evaluated in progressive ratio and drug substitution procedures. These data suggest that the abuse liability of buprenorphine should be less than that of other opioid drugs. The safety and potential therapeutic benefits of buprenorphine relative to other currently available pharmacotherapies probably overweigh the possible risks of abuse.

Topics: Adult; Animals; Buprenorphine; Conditioning, Operant; Eating; Heroin Dependence; Humans; Macaca; Male; Methadone; Morphinans; Naltrexone; Opioid-Related Disorders; Reinforcement, Psychology; Self Administration

Buprenorphine and methadone are two substances widely used in the substitution treatment of patients who are addicted to opioids. Although it is known that they partly act efficiently towards this direction, there is no evidence regarding their effects on the redox status of patients, a mechanism that could potentially improve their action. Therefore, the aim of the present investigation was to examine the impact of buprenorphine and methadone, which are administered as substitutes to heroin-dependent patients on specific redox biomarkers in the blood. From the results obtained, both the buprenorphine (

Topics: Adult; Analgesics, Opioid; Antioxidants; Biomarkers; Buprenorphine; Case-Control Studies; Catalase; Female; Glutathione; Heroin Dependence; Humans; Male; Methadone; Oxidation-Reduction; Oxidative Stress; Protein Carbonylation; Thiobarbituric Acid Reactive Substances

There are approximately 256,000 heroin and other opiate users in England of whom 155,000 are in treatment for heroin (or opiate) addiction. The majority of people in treatment receive opiate substitution treatment (OST) (methadone and buprenorphine). However, OST suffers from high attrition and persistent heroin use even whilst in treatment. Contingency management (CM) is a psychological intervention based on the principles of operant conditioning. It is delivered as an adjunct to existing evidence based treatments to amplify patient benefit and involves the systematic application of positive reinforcement (financial or material incentives) to promote behaviours consistent with treatment goals. With an international evidence base for CM, NICE recommended that CM be implemented in UK drug treatment settings alongside OST to target attendance and the reduction of illicit drug use. While there was a growing evidence base for CM, there had been no examination of its delivery in UK NHS addiction services. The PRAISe trial evaluates the feasibility, acceptability, clinical and cost effectiveness of CM in UK addiction services. It is a cluster randomised controlled effectiveness trial of CM (praise and financial incentives) targeted at either abstinence from opiates or attendance at treatment sessions versus no CM among individuals receiving OST. The trial includes an economic evaluation which explores the relative costs and cost effectiveness of the two CM intervention strategies compared to TAU and an embedded process evaluation to identify contextual factors and causal mechanisms associated with variations in outcome. This study will inform UK drug treatment policy and practice. Trial registration ISRCTN 01591254.

Topics: Adult; Behavior Therapy; Buprenorphine; Cluster Analysis; Drug Misuse; Female; Heroin Dependence; Humans; Male; Medication Therapy Management; Mental Health Services; Methadone; Narcotic Antagonists; Opioid-Related Disorders; Quality Improvement; Reinforcement, Psychology; United Kingdom

This study examined whether starting buprenorphine treatment prior to prison and after release from prison would be associated with better drug treatment outcomes and whether males and females responded differently to the combination of in-prison treatment and post-release service setting.. Study design was a 2 (In-Prison Treatment: Condition: Buprenorphine Treatment: vs. Counseling Only)×2 [Post-Release Service Setting Condition: Opioid Treatment: Program (OTP) vs. Community Health Center (CHC)]×2 (Gender) factorial design. The trial was conducted between September 2008 and July 2012. Follow-up assessments were completed in 2014. Participants were recruited from two Baltimore pre-release prisons (one for men and one for women). Adult pre-release prisoners who were heroin-dependent during the year prior to incarceration were eligible. Post-release assessments were conducted at 1, 3, 6, and 12-month following prison release.. Participants (N=211) in the in-prison treatment condition effect had a higher mean number of days of community buprenorphine treatment compared to the condition in which participants initiated medication after release (P=0.005). However, there were no statistically significant hypothesized effects for the in-prison treatment condition in terms of: days of heroin use and crime, and opioid and cocaine positive urine screening test results (all Ps>0.14) and no statistically significant hypothesized gender effects (all Ps>0.18).. Although initiating buprenorphine treatment in prison compared to after-release was associated with more days receiving buprenorphine treatment in the designated community treatment program during the 12-months post-release assessment, it was not associated with superior outcomes in terms of heroin and cocaine use and criminal behavior.

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Counseling; Crime; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Prisoners; Recurrence; Sex Characteristics; Treatment Outcome; Young Adult

Syringe exchange has been suggested as a potential conduit to treatment for drug dependence, but this has never been documented in Europe. The primary aim was to compare the effectiveness of strength-based case management intervention (CMI) against referral only to facilitate treatment attendance in a syringe exchange programme. We also assessed the effectiveness of a syringe exchange programme for referral of heroin-dependent patients to evidence-based treatment with methadone or buprenorphine (buprenorphine-naloxone).. Single-site, two-group randomized controlled trial.. The syringe exchange programme in Malmö, Sweden and an out-patient clinic (research treatment facility) for maintenance treatment, situated outside the hospital area and run by Malmö Addiction Centre.. Heroin-dependent patients willing to participate (n = 75) were referred to maintenance treatment and randomized to either a strength-based case management intervention aiming to facilitate referral (n = 36) or to referral-only (n = 39).. The intervention group received an appointment for maintenance treatment and a CMI adjusted to individual patient needs. The CMI was semi-structured, assessing the patients' strengths and needs and identifying what practical help they might need to get to the appointment for maintenance treatment. The control group received an appointment for maintenance treatment.. The primary outcome was treatment entry.. Among patients who turned up for recruitment interview and randomization, the percentage of patients who started treatment was 95% in the intervention group and 94% in the control group. Treatment entry was unrelated to intervention status [unadjusted odds ratio (OR) = 0.92 (0.12–6.89), P = 1.00 and adjusted OR = 0.96 (0.12–7.83)].. A randomized controlled trial in a syringe exchange programme showed no evidence that a strength-based case management intervention improved attendance for treatment over referral alone. Attendance rates were high in both groups.

Topics: Adult; Aged; Analgesics, Opioid; Buprenorphine; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Needle-Exchange Programs; Patient Acceptance of Health Care; Pilot Projects; Referral and Consultation; Sweden; Young Adult

Addiction is often conceptualized as a behavioral strategy for avoiding negative experiences. In rodents, opioid intake has been associated with abnormal acquisition and extinction of avoidance behavior. Here, we tested the hypothesis that these findings would generalize to human opioid-dependent subjects.. Adults meeting DSM-IV criteria for heroin dependence and treated with opioid medication (n = 27) and healthy controls (n = 26) were recruited between March 2013 and October 2013 and given a computer-based task to assess avoidance behavior. For this task, subjects controlled a spaceship and could either gain points by shooting an enemy spaceship or hide in safe areas to avoid on-screen aversive events. Hiding duration during different periods of the task was used to measure avoidance behavior.. While groups did not differ on escape responding (hiding) during the aversive event, heroin-dependent men (but not women) made more avoidance responses during a warning signal that predicted the aversive event (analysis of variance, sex × group interaction, P = .007). Heroin-dependent men were also slower to extinguish the avoidance response when the aversive event no longer followed the warning signal (P = .011). This behavioral pattern resulted in reduced opportunity to obtain reward without reducing risk of punishment. Results suggest that, in male patients, differences in avoidance behavior cannot be easily explained by impaired task performance or by exaggerated motor activity.. This study provides evidence for abnormal acquisition and extinction of avoidance behavior in opioid-dependent patients. Interestingly, data suggest that abnormal avoidance is demonstrated only by male patients. Findings shed light on cognitive and behavioral manifestations of opioid addiction and may facilitate development of therapeutic approaches to help affected individuals.

Topics: Adult; Analgesics, Opioid; Avoidance Learning; Buprenorphine; Case-Control Studies; Extinction, Psychological; Female; Heroin Dependence; Humans; Male; Methadone; Video Games; Young Adult

In spite of the clinical utility of buprenorphine, parenteral abuse of this medication has been reported in several laboratory investigations and in the real world. Studies have demonstrated lower abuse liability of the buprenorphine/naloxone combination relative to buprenorphine alone. However, clinical research has not yet examined the utility of the combined formulation to deter intranasal use in a buprenorphine-maintained population. Heroin-using volunteers (n = 12) lived in the hospital for 8-9 weeks and were maintained on each of three sublingual buprenorphine doses (2, 8, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intranasal doses of buprenorphine (8, 16 mg), buprenorphine/naloxone (8/2, 8/8, 8/16, 16/4 mg) and controls (placebo, heroin 100 mg, naloxone 4 mg) were assessed. Intranasal buprenorphine alone typically produced increases in positive subjective effects and the 8 mg dose was self-administered above the level of placebo. The addition of naloxone dose dependently reduced positive subjective effects and increased aversive effects. No buprenorphine/naloxone combination dose was self-administered significantly more than placebo. These data suggest that within a buprenorphine-dependent population, intranasal buprenorphine/naloxone has reduced abuse potential in comparison to buprenorphine alone. These data strongly argue in favor of buprenorphine/naloxone rather than buprenorphine alone as the more reasonable option for managing the risk of buprenorphine misuse.

Topics: Administration, Intranasal; Administration, Sublingual; Adult; Analysis of Variance; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Psychomotor Performance; Reinforcement, Psychology; Self Administration; Surveys and Questionnaires; Treatment Outcome; Young Adult

Most research examining buprenorphine has been conducted with heroin users. Few studies have examined buprenorphine pharmacotherapy for prescription opioid users. Data were from a randomized controlled trial of behavioral treatment provided for 16weeks on a platform of buprenorphine pharmacotherapy and medication management. We compared heroin (H, n=54), prescription opioid (PO, n=54) and combination heroin+prescription opioid (POH, n=71) users to test the hypothesis that PO users will have better treatment outcomes compared with heroin users. The PO group provided more opioid-negative urine drug screens over the combined treatment period (PO:70%, POH:40%, H:38%, p<0.001) and at the end of the combined treatment period (PO:65%, POH:31%, H:33%, p<0.001). Retention was lowest in the H group (PO:80%, POH:65%, H:57%, p=0.039). There was no significant difference in buprenorphine dose between the groups. PO users appear to have better outcomes in buprenorphine pharmacotherapy compared to those reporting any heroin use, confirming that buprenorphine pharmacotherapy is effective in PO users.

Topics: Adult; Analgesics, Opioid; Behavior Therapy; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Heroin Dependence; Humans; Male; Middle Aged; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drug Misuse; Treatment Outcome

Buprenorphine (BUP) is effective for treating opioid use disorder. Individuals' heroin-use characteristics may predict their responses to BUP, which could differ during maintenance and dose-taper phases. If so, treatment providers could use pre-treatment characteristics to personalize level of individual care and possibly improve treatment outcomes.. Non-treatment-seeking heroin-dependent volunteers (N=34) initiated outpatient BUP maintenance (8-mg/day) and submitted urine samples thrice weekly tested for opioids (non-contingent result). After completing three programmatically-related inpatient behavioral pharmacology experiments (while maintained on 8-mg/day BUP), participants were discharged and underwent a double-blind BUP dose taper (4-mg/day, 2-mg/day and 0-mg/day during weeks 1-3, respectively) with an opioid-abstinence incentive ($30 per consecutive opioid-negative urine specimen, obtained thrice weekly).. Participants who reported less pre-study (past-month) heroin use and shorter lifetime duration of heroin use were more likely to submit an opioid-negative urine sample during initial outpatient BUP maintenance. Participants who reported more lifetime heroin-quit attempts and provided any opioid-free urine sample during initial outpatient maintenance sustained longer continuous opioid-abstinence during the BUP dose taper. Participants who reported >3 lifetime quit attempts abstained from opioid use nearly one week longer (14 days vs. 8 days to opioid-lapse) and nearly half (46.7%) refrained from opioid use during dose taper.. Number of prior heroin quit attempts may predict BUP dose taper response and provide a metric for stratifying heroin-dependent individuals by relative risk for opioid lapse. This metric may inform personalized relapse prevention care and improve treatment outcomes.

Topics: Adolescent; Adult; Buprenorphine; Double-Blind Method; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Middle Aged; Motivation; Narcotic Antagonists; Opiate Substitution Treatment; Outpatients; Treatment Outcome; Volunteers; Young Adult

While research suggests primary prescription opioid (PO) abusers may exhibit less severe demographic and drug use characteristics than primary heroin abusers, less is known about whether a lifetime history of heroin use confers greater severity among PO abusers.. In this secondary analysis, we examined demographic and drug use characteristics as a function of lifetime heroin use among 89 PO-dependent adults screened for a trial evaluating the relative efficacy of buprenorphine taper durations. Exploratory analyses also examined contribution of lifetime heroin use to treatment response among a subset of participants who received a uniform set of study procedures.. Baseline characteristics were compared between participants reporting lifetime heroin use ≥5 (H(+); n=41) vs. <5 (H(-); n=48) times. Treatment response (i.e., illicit opioid abstinence and treatment retention at end of study) was examined in the subset of H(+) and H(-) participants randomized to receive the 4-week taper condition (N=22).. H(+) participants were significantly older and more likely to be male. They reported longer durations of illicit opioid use, greater alcohol-related problems, more past-month cocaine use, greater lifetime IV drug use, and greater lifetime use of cigarettes, amphetamines and hallucinogens. H(+) participants also had lower scores on the Positive Symptom Distress and Depression subscales of the Brief Symptom Inventory. Finally, there was a trend toward poorer treatment outcomes among H(+) participants.. A lifetime history of heroin use may be associated with elevated drug severity and unique treatment needs among treatment-seeking PO abusers.

Topics: Adult; Behavior Therapy; Buprenorphine; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Female; Heroin Dependence; Humans; Male; Naltrexone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drug Misuse

To investigate the efficacy and safety of Ji-Tai tablet and Ji-Tai tablet combined with buprenorphine in the treatment of patients with acute withdrawal syndrome of mild heroin dependence.. A total of 150 patients with mild heroin dependence were recruited, and were randomly assigned to a Ji-Tai tablet group (n=50), a Ji-Tai tablet combined with buprenorphine group (n=50) and a control group (n=50) during a 10-day clinical trial. Opiate withdrawal scale (OWS) was used to measure the severity of withdrawal symptoms. Anxiety symptoms assessments were made at 0 day (baseline), the day 5 (middle), and the day 10 (end) by the Hamilton anxiety scale (HAMA). Symptoms were assessed before and 1 h or 2 h after medication each day. The total withdrawal symptoms scores and the daily reduction rate were used to measure the effect of Ji-Tai tablet vs Ji- Tai tablet plus buprenorphine. Safety evaluation was carried out by the following measures: baseline of treatment, drug side effects after the treatment, vital signs (blood pressure, heart rate, and respiration rate), laboratory examination (routine blood and urine tests and the liver and kidney function tests), and electrocardiograms.. A total of 142 mild heroin dependence patients performed the experiments (including 48 in the Ji-Tai tablet group, 48 in the Ji-Tai tablet with buprenorphine group and 46 in the control group). The scores of baseline withdrawal symptoms were 43.520±19.786, 42.640±17.648 and 47.100±24.450, respectively, with no significant differences among the 3 groups (all P>0.05 ). During the 10-day treatment, the reduction rate of acute withdrawal symptoms scores increased daily, the acute withdrawal syndrome scores and the anxiety symptoms scores declined from day 0 to day 10, there was also no significant difference among the 3 groups (all P>0.05). Ji-Tai tablet did not affect vital signs such as blood pressure, heart rate, and respiration rate.. Ji-Tai tablet or Ji-Tai tablet combined with buprenorphine had no effect on acute withdrawal symptoms of mild heroin dependence.

Topics: Anxiety; Buprenorphine; Double-Blind Method; Drugs, Chinese Herbal; Heroin Dependence; Humans; Substance Withdrawal Syndrome; Tablets

Extended-release (XR) injection naltrexone has proved promising in the treatment of opioid dependence. Induction onto naltrexone is often accomplished with a procedure known as rapid naltrexone induction. The purpose of this study was to evaluate pre-treatment patient characteristics as predictors of successful completion of a rapid naltrexone induction procedure prior to XR naltrexone treatment.. A chart review of 150 consecutive research participants (N = 84 completers and N = 66 non-completers) undergoing a rapid naltrexone induction with the buprenorphone-clonidine procedure were compared on a number of baseline demographic, clinical and psychosocial factors. Logistic regression was used to identify client characteristics that may predict successful initiation of naltrexone after a rapid induction-detoxification.. Patients who failed to successfully initiate naltrexone were younger (AOR: 1.040, CI: 1.006, 1.075), and using 10 or more bags of heroin (or equivalent) per day (AOR: 0.881, CI: 0.820, 0.946). Drug use other than opioids was also predictive of failure to initiate naltrexone in simple bivariate analyses, but was no longer significant when controlling for age and opioid use level.. Younger age, and indicators of greater substance dependence severity (more current opioid use, other substance use) predict difficulty completing a rapid naltrexone induction procedure. Such patients might require a longer period of stabilization and/or more gradual detoxification prior to initiating naltrexone.. Our study findings identify specific characteristics of patients who responded positively to rapid naltrexone induction.

Topics: Administration, Oral; Adult; Buprenorphine; Clonidine; Delayed-Action Preparations; Drug Therapy, Combination; Female; Heroin Dependence; Humans; Injections, Intramuscular; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Patient Selection; Prognosis

Abuse of buprenorphine (BUP) by the intravenous (IV) route has been documented in several studies, and reports of intranasal (IN) abuse are increasing. However, no studies have directly compared the effects of BUP when it is administered intranasally and intravenously. The present secondary analysis used data from two separate studies to compare the reinforcing and subjective effects of IV and IN buprenorphine. One study evaluated IV buprenorphine (N=13) and the other evaluated IN buprenorphine (N=12). Participants were maintained on 2 mg sublingual (SL) BUP and tested with each intranasal or intravenous buprenorphine test dose (0 mg, 2 mg, 4 mg, 8 mg, and 16 mg). During morning laboratory sessions, participants received money (US $20) and sample doses of IN or IV BUP, and then completed subjective effects questionnaires. Later that day, they completed a self-administration task to receive 10% portions of the drug and/or money they previously sampled. In general, positive subjective ratings for both IV and IN BUP were significantly greater than placebo, with IV BUP having a greater effect than IN BUP. All active BUP doses (IV and IN) maintained significantly higher progressive ratio breakpoint values than placebo, but breakpoint values for IV BUP were greater than for IN BUP. Buprenorphine is an effective maintenance treatment for opioid dependence, valued for its ability to reduce the positive subjective effects of other opioids. Nevertheless, the present data demonstrate that in participants maintained on a low dose of SL BUP, the medication itself has abuse liability when used intravenously or intranasally.

Topics: Administration, Intranasal; Adult; Buprenorphine; Female; Heroin Dependence; Humans; Injections, Intravenous; Male; Opiate Substitution Treatment; Photic Stimulation; Psychomotor Performance; Reinforcement, Psychology

Buprenorphine is a promising treatment for heroin addiction. However, little is known regarding its provision to pre-release prisoners with heroin dependence histories who were not opioid-tolerant, the relative effectiveness of the post-release setting in which it is provided, and gender differences in treatment outcome in this population.. This is the first randomized clinical trial of prison-initiated buprenorphine provided to male and female inmates in the US who were previously heroin-dependent prior to incarceration. A total of 211 participants with 3-9 months remaining in prison were randomized to one of four conditions formed by crossing In-Prison Treatment Condition (received buprenorphine vs. counseling only) and Post-release Service Setting (at an opioid treatment center vs. a community health center). Outcome measures were: entered prison treatment; completed prison treatment; and entered community treatment 10 days post-release.. There was a significant main effect (p=.006) for entering prison treatment favoring the In-Prison buprenorphine Treatment Condition (99.0% vs. 80.4%). Regarding completing prison treatment, the only significant effect was Gender, with women significantly (p<.001) more likely to complete than men (85.7% vs. 52.7%). There was a significant main effect (p=.012) for community treatment entry, favoring the In-Prison buprenorphine Treatment Condition (47.5% vs. 33.7%).. Buprenorphine appears feasible and acceptable to prisoners who were not opioid-tolerant and can facilitate community treatment entry. However, concerns remain with in-prison treatment termination due to attempted diversion of medication.

Topics: Adult; Buprenorphine; Combined Modality Therapy; Counseling; Female; Heroin Dependence; Humans; Male; Middle Aged; Narcotics; Prisoners; Prisons; Treatment Outcome

Opioid substitution treatment (OST) has multiple benefits for heroin injectors and is an evidence-based major component of international treatment. The current qualitative study sought to explore participants' attitudes to and reasons for participating in a feasibility randomised trial in primary care offering 'same day' OST (methadone) for injecting heroin users compared to usual care.. Twenty injecting heroin users (8 intervention and 12 controls; 16 males and 4 females) were interviewed; purposive sampling was used to select a maximum variation sample from those who agreed; and analysis used thematic methods.. Motivation to join the trial included the need to secure treatment set against some ambivalence due to previous negative experiences of trying to obtain OST. Positive effects of securing methadone via the trial, included self-reported improvements in health and self-care; reduction in crime, stress and drug use. Completing the baseline questionnaires at recruitment appeared to enhance motivation for treatment for all participants. For some control participants, this motivation seemed to increase a sense of self-efficacy and cognitive dissonance generated was resolved by seeking treatment from their GP. Self-determination theory suggests that behaviour change may have been initiated during the recruitment appointment, resulting in an increased determination to seek treatment amongst control participants.. Taking part in the 'script in a day' trial enabled participants in the intervention arm to gain same-day access to methadone and reduce their drug use. For those in the control arm, completing the baseline questionnaires at recruitment appeared to create cognitive dissonance between their current health state and own aspirations, so increasing motivation for treatment. Over 50% obtained and were still in receipt of OST (methadone or buprenorphine) at the 3 month follow-up. We suggest that a regular 'health evaluation' for injecting heroin users not in treatment, paired with low-barrier access to treatment, may be a way of exploring this and encouraging more into obtaining OST more quickly and at the best time for them. This intervention should be delivered without pressure for change.. This trial is registered with International Standard Randomised Controlled Trial Number Register: SCript In a Day for injecting drug users: feasibility trial: ISRCTN16846554.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cognitive Dissonance; England; Feasibility Studies; Female; Harm Reduction; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Motivation; Motivational Interviewing; Narcotics; Opiate Substitution Treatment; Patient Satisfaction; Program Evaluation; Qualitative Research; Substance Abuse, Intravenous; Time-to-Treatment; Young Adult

The objective of this secondary analysis was to explore differences in baseline clinical characteristics and opioid replacement therapy treatment outcomes by type (heroin, opioid analgesic [OA], or combined [heroin and OA]) and route (injector or non-injector) of opioid use.. A total of 1,269 participants (32.2% female) were randomized to receive one of two study medications (methadone or buprenorphine/naloxone [BUP]). Of these, 731 participants completed the 24-week active medication phase. Treatment outcomes were opioid use during the final 30 days of treatment (among treatment completers) and treatment attrition.. Non-opioid substance dependence diagnoses and injecting differentiated heroin and combined users from OA users. Non-opioid substance dependence diagnoses and greater heroin use differentiated injectors from non-injectors. Further, injectors were more likely to be using at end of treatment compared with non-injectors. OA users were more likely to complete treatment compared with heroin users and combined users. Non-injectors were more likely than injectors to complete treatment. There were no interactions between type of opioid used or injection status and treatment assignment (methadone or BUP) on either opioid use or treatment attrition.. Findings indicate that substance use severity differentiates heroin users from OA users and injectors from non-injectors. Irrespective of medication, heroin use and injecting are associated with treatment attrition and opioid misuse during treatment. These results have particular clinical interest, as there is no evidence of superiority of BUP over methadone for treating OA users versus heroin users.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Severity of Illness Index; Substance Abuse, Intravenous; Treatment Outcome; Young Adult

This study examined associations between substance use behaviors and self-reported health among hospitalized heroin users. Of the 112 participants, 53 (47%) reported good or better health. In multivariable logistic regression models, each day of heroin use in the last month was associated with an 8% lower odds of reporting health as good or better (OR=.92; 95% CI 0.87, 0.97, p<.05). Cocaine, cannabis, cigarettes, alcohol use, unintentional overdose, nor injection drug use was associated with health status.

Topics: Adult; Buprenorphine; Diagnostic Self Evaluation; Female; Health Status; Heroin Dependence; HIV Infections; Hospitalization; Humans; Male; Narcotics; Opiate Substitution Treatment; Prognosis; Quality of Life; Self Report; Urban Health

The focus of drug policy in the UK has shifted markedly in the past 5 years to move beyond merely emphasising drug abstinence towards maximising individuals' opportunities for recovery. The UK government continues to recognise the prescribing of narcotic medications indicated for opiate dependence as a key element of these individuals' recovery journey. This article describes a small, naturalistic comparison of the efficacy of the two most commonly prescribed opiate substitute medications in the UK--methadone hydrochloride (methadone oral solution) and Suboxone (buprenorphine-naloxone sublingual tablets)--for reducing current heroin users' (n = 34) days of heroin use, and preventing short-term abstainers (n = 37) from relapsing to regular heroin use. All patients had been prescribed either methadone or Suboxone for maintenance for 6 months prior to intake. Results showed that when controlling for a number of patient-level covariates, both methadone and Suboxone significantly reduced current users' days of heroin use between the 90 days prior to intake and at the 8-month follow-up, with Suboxone yielding a significantly larger magnitude reduction in heroin use days than methadone. Methadone and Suboxone were highly and equally effective for preventing relapse to regular heroin use, with all but 3 of 37 (91.9%) patients who were abstinent at intake reporting past 90-day point prevalence heroin abstinence at the 8-month follow-up. Overall, prescribing methadone or Suboxone for eight continuous months was highly effective for initiating abstinence from heroin use, and for converting short-term abstinence to long-term abstinence. However, the study design, which was based on a relatively small sample size and was not able randomise patients to medication and so could not control for the effects of potential prognostic factors inherent within each patient group, means that these conclusions can only be made tentatively. These positive but preliminary indications of the comparative efficacy of methadone and Suboxone for treating opiate dependence now require replication in a well-powered, randomised controlled trial.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Follow-Up Studies; Health Policy; Heroin Dependence; Humans; Male; Methadone; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Recurrence; Time Factors; Treatment Outcome; United Kingdom

High doses of opiate substitution pharmacotherapy are associated with greater treatment retention and lower illicit drug consumption, although the neurobiological bases of these benefits are poorly understood. Dysfunction of the anterior cingulate cortex (ACC) is associated with greater addiction severity and mood dysregulation in opiate users, such that the beneficial effects of substitution pharmacotherapy may relate to normalisation of ACC function. This study aimed to investigate the differential impact of methadone compared with buprenorphine on dorsal ACC biochemistry. A secondary aim was to explore the differential effects of methadone and buprenorphine on dorsal ACC biochemistry in relation to depressive symptoms.. Twenty-four heroin-dependent individuals stabilised on methadone (n=10) or buprenorphine (n=14) and 24 healthy controls were scanned using proton Magnetic Resonance Spectroscopy and compared for metabolite concentrations of N-acetylaspartate, glutamate/glutamine, and myo-inositol.. (1) Methadone was associated with normalisation of dorsal ACC biochemistry (increased N-acetylaspartate and glutamate/glutamine levels, and decreased myo-inositol levels) in a dose-dependent manner; (2) buprenorphine-treated individuals had higher myo-inositol and glutamate/glutamine levels than methadone-treated patients in the right dorsal ACC; and (3) myo-inositol levels were positively correlated with depressive symptoms in participants stabilised on buprenorphine.. These findings point to a beneficial role of high-dose methadone on dorsal ACC biochemistry, and suggest a link between elevated myo-inositol levels and depressive symptoms in the context of buprenorphine treatment.

Topics: Adult; Aspartic Acid; Buprenorphine; Depression; Dose-Response Relationship, Drug; Female; Functional Neuroimaging; Glutamic Acid; Glutamine; Gyrus Cinguli; Heroin Dependence; Humans; Inositol; Male; Methadone; Opiate Substitution Treatment

In laboratory animals, the biological stressor yohimbine (α(2)-noradrenergic autoreceptor antagonist) promotes drug seeking. Human laboratory studies have demonstrated that psychological stressors can increase drug craving but not that stressors alter drug seeking.. This clinical study tested whether yohimbine increases opioid-seeking behavior.. Ten heroin-dependent, buprenorphine-stabilized (8 mg/day) volunteers sampled two doses of hydromorphone [12 and 24 mg IM in counterbalanced order, labeled drug A (session 1) and drug B (session 2)]. During each of six later sessions (within-subject, double-blind, randomized crossover design), volunteers could respond on a 12-trial choice progressive ratio task to earn units (1 or 2 mg) of the sampled hydromorphone dose (drug A or B) vs money ($2) following different oral yohimbine pretreatment doses (0, 16.2, and 32.4 mg).. Behavioral economic demand intensity and peak responding (O (max)) were significantly higher for hydromorphone 2 than 1 mg. Relative to placebo, yohimbine significantly increased hydromorphone demand inelasticity, more so for hydromorphone 1-mg units (P (max) = 909, 3,647, and 3,225 for placebo, 16.2, and 32.4 mg yohimbine doses, respectively) than hydromorphone 2-mg units (P (max) = 2,656, 3,193, and 3,615, respectively). Yohimbine produced significant but clinically modest dose-dependent increases in blood pressure (systolic ≈ 15 and diastolic ≈ 10 mmHg) and opioid withdrawal symptoms, and decreased opioid agonist symptoms and elated mood.. These findings concur with preclinical data by demonstrating that yohimbine increases drug seeking; in this study, these effects occurred without clinically significant subjective distress or elevated craving, and partly depended on opioid unit dose.

Topics: Adult; Behavior, Addictive; Buprenorphine; Choice Behavior; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Yohimbine

To provide controlled data on direct induction with buprenorphine/naloxone (BNX) versus indirect buprenorphine (BPN)-to-BNX induction.. Phase 4, prospective, randomized, active-drug controlled, parallel-group trial consisting of a 2-day, double-blind, double-dummy induction phase followed by 26 days of open-label treatment with BNX.. Nineteen sites in 10 European countries from March 2008 to December 2009.. A total of 187 opioid-dependent men and women ≥ 15 years of age.. The primary objective was assessment of patient response to direct and indirect BNX induction [proportion of patients receiving the scheduled 16-mg BNX dose on day 3 (i.e. first day post-induction)]. Secondary assessments included illicit drug use, treatment retention and compliance, withdrawal scale scores, and safety.. Patient response to direct- versus indirect-BNX induction was similar [direct 91.4% (85/93) versus indirect 90.4% (85/94); 95% confidence interval (CI): -7.3%, 9.2%]. Rapid dose induction (16 mg of BPN equivalent on day 2) was acceptable and 72% of patients completed treatment (day 28). There were no significant differences in secondary measures across groups. An average BNX maintenance dose of 15.3 mg across groups was associated with substantial reductions in illicit opioid use and no self-reported intravenous misuse. Treatment compliance and retention rates were similar (98.5% and 81.3%, respectively). Treatment-emergent adverse event rates were comparable: 75% versus 74% for direct- versus indirect-induction groups, respectively.. Direct buprenorphine/naloxone induction was a safe and effective strategy for maintenance treatment of opioid dependence. Response to high-dose direct buprenorphine/naloxone induction appears to be similar to indirect buprenorphine-to-buprenorphine/naloxone induction and was not associated with reports of intravenous buprenorphine/naloxone misuse.

Topics: Administration, Sublingual; Adolescent; Adult; Buprenorphine; Drug Combinations; Europe; Female; Heroin Dependence; Humans; Induction Chemotherapy; Intention to Treat Analysis; Maintenance Chemotherapy; Male; Middle Aged; Naloxone; Narcotic Antagonists; Patient Compliance; Prospective Studies; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Treatment Outcome; Young Adult

Prescription opioid (PO)-dependent treatment presentations are becoming increasingly common; however, most research on the treatment of opioid-dependent populations has been conducted in heroin users. The aim of this secondary data analysis was to compare the buprenorphine induction experience of 167 heroin and 61 PO users. Results demonstrate that although the groups differed on some baseline characteristics, many of the key induction experience variables were comparable between the groups. Heroin users were found to have significantly higher preinduction Clinical Opiate Withdrawal Scale (COWS) scores (p = .014) and postinduction COWS score (p = .008) compared with the PO users. No differences between groups were found for self-reported craving and withdrawal scores, mean buprenorphine dose on Day 1, or retention at the end of the first week. The findings of this study suggest that existing buprenorphine induction practices developed for heroin users appear to be equally effective with PO users.

Topics: Adult; Aged; Buprenorphine; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Prescription Drugs; Substance Withdrawal Syndrome; Treatment Outcome

To aid public health policymaking, we studied the cost-effectiveness of buprenorphine, naltrexone, and placebo interventions for heroin dependence in Malaysia.. We estimated the cost-effectiveness ratios of three treatments for heroin dependence. We used a microcosting methodology to determine fixed, variable, and societal costs of each intervention. Cost data were collected from investigators, staff, and project records on the number and type of resources used and unit costs; societal costs for participants' time were estimated using Malaysia's minimum wage. Costs were estimated from a provider and societal perspective and reported in 2004 US dollars.. Muar, Malaysia.. 126 patients enrolled in a randomized, double-blind, placebo-controlled clinical trial in Malaysia (2003-2005) receiving counseling and buprenorphine, naltrexone, or placebo for treatment of heroin dependence.. Primary outcome measures included days in treatment, maximum consecutive days of heroin abstinence, days to first heroin use, and days to heroin relapse. Secondary outcome measures included treatment retention, injection drug use, illicit opiate use, AIDS Risk Inventory total score, and drug risk and sex risk subscores.. Buprenorphine was more effective and more costly than naltrexone for all primary and most secondary outcomes. Incremental cost-effectiveness ratios were below $50 for primary outcomes, mostly below $350 for secondary outcomes. Naltrexone was dominated by placebo for all secondary outcomes at almost all endpoints. Incremental treatment costs were driven mainly by medication costs, especially the price of buprenorphine.. Buprenorphine appears to be a cost-effective alternative to naltrexone that might enhance economic productivity and reduce drug use over a longer term.

Topics: Acquired Immunodeficiency Syndrome; Buprenorphine; Cost-Benefit Analysis; Heroin Dependence; Humans; Malaysia; Naltrexone; Risk Factors; Risk-Taking; Treatment Outcome

In order to investigate the effects of exposure to buprenorphine compared with methadone during pregnancy, a prospective multicenter study was conducted in collaboration with maternity hospitals, maintenance therapy centers, and general practitioners involved in addiction care. Ninety pregnant women exposed to buprenorphine and 45 to metadone were selected for the study.. During pregnancy, some women were exposed to illicit agents: cannabis (42% in the buprenorphine group vs. 58% in the methadone-treated group), heroin (17% vs. 44%), or cocaine (3% vs. 11%). Pregnancies ended in 85 vs. 40 live births, one vs. two stillbirths, two vs. one spontaneous abortion, two vs. one voluntary termination, and one vs. one medical termination in the buprenorphine and the methadone groups, respectively. Newborns had a birth weight of 2,892 ± 506 g (buprenorphine) vs. 2,731 ± 634 g (methadone) and a body length of 47.6 ± 2.5 cm vs. 47.1 ± 3 cm. 18.8% vs. 10% of newborns were delivered before 37 weeks of amenorrhea. Neonatal withdrawal syndrome occurred more frequently in the methadone group (62.5% vs. 41.2, p = 0.03). After adjustment for heroin exposure in late pregnancy, rates of neonatal withdrawal were no longer different between the methadone and buprenorphine groups. Twenty-one babies (84%) in the methadone group and 20 (57%) in the buprenorphine group (p = 0.03) required opiate treatment.. We did not observe more frequent malformations or cases of withdrawal syndrome in the buprenorphine group than in the methadone-treated group. Buprenorphine appears to be as safe as the currently approved substitute methadone considered to date as the reference treatment for pregnant opioid-dependent women.

Topics: Adult; Analgesics, Opioid; Birth Weight; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Infant, Newborn; Methadone; Narcotics; Neonatal Abstinence Syndrome; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prospective Studies

Environmental stimuli associated with drug taking have been known to elicit drug craving and physiologic arousal, as well as hypothalamic-pituitary-adrenal axis activation. However, the relationship between these responses and substance use outcomes in heroin-dependent subjects has not been previously studied. We investigated the relationship among subjective and physiologic reactivity, biological stress response evoked in the laboratory, and relapse to substance use in treated opiate-dependent individuals.. Eighteen opiate-abstinent methadone- or buprenorphine-treated patients and 13 control subjects were exposed to neutral- and drug-cue exposure laboratory sessions with a 3-month follow-up period. Exposure to cues involved both videotapes and handling during a 100-min session. Subjective craving, agonistic effects, withdrawal feelings, galvanic skin resistance, and salivary cortisol were assessed. Substance use outcome among patients was examined during the follow-up phase. Differences between relapsers, nonrelapsers, and controls were analyzed with respect to the data on drug-cue responsivity and on cortisol responses using repeated-measures analysis of variance. The association with substance use outcome was assessed using a nominal logistic model.. Relapsers experienced greater drug-cue induced subjective responses and an increased cortisol response compared with both nonrelapsers and control subjects. After adjusting on covariates, cue-induced cortisol response was associated with the relapser group and was highly correlated with self-reports of "high.". Subjects defined as relapsers presented a higher cue-induced reactivity during the drug-cue exposure as well as an increased cortisol response to drug cues. Higher cortisol response to drug cues may increase relapse vulnerability in stable-dose buprenorphine or methadone-maintained subjects.

Topics: Adult; Buprenorphine; Cues; Drug-Seeking Behavior; Female; Galvanic Skin Response; Heroin Dependence; Humans; Hydrocortisone; Logistic Models; Male; Methadone; Opiate Substitution Treatment; Recurrence; Saliva

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

Topics: Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; National Institute on Drug Abuse (U.S.); Opiate Substitution Treatment; Opioid-Related Disorders; United States

Sublingual buprenorphine is an effective maintenance treatment for opioid dependence, yet intravenous buprenorphine misuse occurs. A buprenorphine/naloxone formulation was developed to mitigate this misuse risk. This randomized, double-blind, cross-over study was conducted to assess the intravenous abuse potential of buprenorphine/naloxone compared with buprenorphine in buprenorphine-maintained injection drug users (IDUs).. Intravenous heroin users (n = 12) lived in the hospital for 8-9 weeks and were maintained on each of three different sublingual buprenorphine doses (2 mg, 8 mg, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intravenous placebo, naloxone, heroin and low and high doses of buprenorphine and buprenorphine/naloxone were examined. Every participant received each test dose under the three buprenorphine maintenance dose conditions.. Intravenous buprenorphine/naloxone was self-administered less frequently than buprenorphine or heroin (P < 0.0005). Participants were most likely to self-administer drug intravenously when maintained on the lowest sublingual buprenorphine dose. Subjective ratings of 'drug liking' and 'desire to take the drug again' were lower for buprenorphine/naloxone than for buprenorphine or heroin (P = 0.0001). Participants reported that they would pay significantly less money for buprenorphine/naloxone than for buprenorphine or heroin (P < 0.05). Seven adverse events were reported; most were mild and transient.. These data suggest that although the buprenorphine/naloxone combination has intravenous abuse potential, that potential is lower than it is for buprenorphine alone, particularly when participants received higher maintenance doses and lower buprenorphine/naloxone challenge doses. Buprenorphine/naloxone may be a reasonable option for managing the risk for buprenorphine misuse during opioid dependence treatment.

Topics: Administration, Sublingual; Adult; Analysis of Variance; Behavior, Addictive; Buprenorphine; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Female; Heroin Dependence; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Patient Preference; Self Administration; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Young Adult

This study investigated the extent to which hydromorphone (HYD) choice and behavioral economic demand differed during experimental analogs of Unemployment (Drug Only: HYD and no money alternative), Employment (Drug or Money: HYD and $4 alternative), and Punishment (Drug Only+Money Loss: HYD only and $4 subtracted for each HYD choice), in the context of anticipated high vs. low post-session drug availability (HYD 24 mg vs. placebo). Eleven heroin-dependent, buprenorphine-stabilized (8 mg/day) volunteers first sampled two HYD doses (0 and 24 mg IM in randomized, counterbalanced order, labeled Drug A [session 1] and Drug B [session 2]). In each of the final six sessions, volunteers were given access to a 12-trial choice progressive ratio (PR) task and could work to receive HYD unit doses (2mg each); cumulative dose units earned were administered in a bolus injection after the work session. Before the PR task, volunteers were told which HYD dose (Drug A or B) would be available 3h after the PR-contingent injection. Relative to Unemployment (Drug Only), Employment (Drug or Money) and Punishment (Drug Only+Money Loss) each significantly suppressed HYD seeking (e.g., breakpoints). Employment and Punishment also reduced HYD behavioral economic demand, but via different mechanisms: Employment increased HYD price-elasticity, whereas Punishment decreased HYD demand intensity. Adjusting for the initial level difference (i.e., normalized demand), Employment significantly decreased P(max) (i.e., lower "essential value" of HYD) and O(max) (maximum HYD responding) compared to Punishment or Unemployment. These effects were not significantly altered by post-session drug availability.

Topics: Adult; Analgesics, Opioid; Analysis of Variance; Buprenorphine; Choice Behavior; Double-Blind Method; Drug-Seeking Behavior; Employment; Female; Games, Experimental; Heroin Dependence; Humans; Hydromorphone; Male; Middle Aged; Narcotics; Punishment; Reinforcement, Psychology

Replacement therapy with buprenorphine is clinically effective in reducing withdrawal and craving for heroin during detoxification but not in decreasing the probability of relapse after detoxification. This study examined the acute effects of buprenorphine on brain responses to heroin-related cues to reveal the neurobiological and therapeutic mechanisms of addiction and relapse. Fifteen heroin addicts at a very early period of abstinence, were studied in two separate periods 10-15 min apart: an early period (5-45 min) and a later period (60-105 min) after sublingual buprenorphine, roughly covering the onset and peak of buprenorphine plasma level. During both periods, fMRI scanning with heroin-related visual stimuli were performed followed by questionnaires. Under effect of buprenorphine, brain responses to heroin-related cues showed decrease in amygdala, hippocampus, ventral tegmental area (VTA) and thalamus but no changes in ventral striatum and orbital-prefrontal-parietal cortices. As an uncontrolled trial, these preliminary results suggest that buprenorphine has specific brain targets in reducing withdrawal and craving during early abstinence, and that ventral striatum and orbital-prefrontal-parietal cortices may be the key targets in developing therapy for drug addiction and relapse.

Topics: Administration, Sublingual; Adult; Brain; Buprenorphine; Cues; Female; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Narcotic Antagonists; Photic Stimulation; Psychomotor Performance

Few studies in community settings have evaluated predictors, mediators, and moderators of treatment success for medically supervised opioid withdrawal treatment. This report presents new findings about these factors from a study of 344 opioid-dependent men and women prospectively randomized to either buprenorphine-naloxone or clonidine in an open-label 13-day medically supervised withdrawal study. Subjects were either inpatient or outpatient in community treatment settings; however not randomized by treatment setting. Medication type (buprenorphine-naloxone versus clonidine) was the single best predictor of treatment retention and treatment success, regardless of treatment setting. Compared to the outpatient setting, the inpatient setting was associated with higher abstinence rates but similar retention rates when adjusting for medication type. Early opioid withdrawal severity mediated the relationship between medication type and treatment outcome with buprenorphine-naloxone being superior to clonidine at relieving early withdrawal symptoms. Inpatient subjects on clonidine with lower withdrawal scores at baseline did better than those with higher withdrawal scores; inpatient subjects receiving buprenorphine-naloxone did better with higher withdrawal scores at baseline than those with lower withdrawal scores. No relationship was found between treatment outcome and age, gender, race, education, employment, marital status, legal problems, baseline depression, or length/severity of drug use. Tobacco use was associated with worse opioid treatment outcomes. Severe baseline anxiety symptoms doubled treatment success. Medication type (buprenorphine-naloxone) was the most important predictor of positive outcome; however the paper also considers other clinical and policy implications of other results, including that inpatient setting predicted better outcomes and moderated medication outcomes.

Topics: Adrenergic alpha-Agonists; Adult; Aged; Anxiety; Buprenorphine; Clonidine; Data Interpretation, Statistical; Depression; Drug Therapy, Combination; Female; Heroin Dependence; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; National Institute on Alcohol Abuse and Alcoholism (U.S.); Opioid-Related Disorders; Prognosis; Smoking; Socioeconomic Factors; Substance Abuse Detection; Substance Withdrawal Syndrome; Treatment Outcome; United States; Young Adult

Buprenorphine, a mu-opioid receptor partial agonist, has been shown to be safe and effective for treatment of opioid dependence. A novel implantable formulation of buprenorphine (Probuphine), using a polymer matrix sustained-release technology, has been developed to offer treatment for opioid dependence while minimizing risks of patient noncompliance and illicit diversion. The goal of the current study was to conduct an initial, open-label, evaluation of the safety, pharmacokinetics, and efficacy of two doses of Probuphine in subjects with opioid dependence maintained on sublingual buprenorphine. Two doses of Probuphine were evaluated in 12 heroin-dependent volunteers switched from daily sublingual buprenorphine dosing to either two or four Probuphine implants based upon their buprenorphine daily maintenance dose of 8 mg or 16 mg respectively, and were monitored for 6 months. Probuphine implants provided continuous steady state delivery of buprenorphine until their removal at 6 months. Withdrawal symptoms and craving remained low throughout the 6 months. For the 12 subjects, an average of 59% of urines were opioid-negative across the 6 month treatment period. Injection site reactions were present in half of patients, but none were serious. No safety concerns were evident. These results suggest that Probuphine implants offer significant promise for enhancing delivery of effective opioid substitution treatment while minimizing risk for abuse of medication.

Topics: Administration, Sublingual; Adolescent; Adult; Buprenorphine; Drug Implants; Female; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Patient Selection; Safety; Substance Withdrawal Syndrome; Young Adult

Methadone and buprenorphine are among the most widely employed pharmacological treatments currently available for opioid addiction. Cognitive effects of buprenorphine in abstinent heroin abusers are nevertheless far from being understood.. Neuropsychological performance of 18 buprenorphine-maintained patients (BMP) was evaluated relative to that of 32 currently abstinent heroin abusers on naltrexone hydrochloride therapy (FHAN), and 34 non-drug dependent controls. The three groups were demographically balanced. Clinical groups reported histories of similar patterns of drug use and had increased periods of abstinence from any illicit substance use including heroin.. The BMP group performed poorer than controls on the RAVLT (encoding and delayed recall of verbal information), CTT (conceptual flexibility, executive functions) and the RBANS figure copy (visual perception) and delayed recall of visual information. There were no significant differences in any of the cognitive measures between the BMP and FHAN groups or between the FHAN group and controls. Furthermore, the non-differing percentage of abnormal cases between the two patient groups led us to infer that treatment with either BPM or FHAN is not accompanied by qualitative differences in the cognitive profiles of these patients.. Overall, results suggest that treatment with naltrexone in abstinent heroin abusers may result in less impairment of cognitive functions compared to treatment with buprenorphine. These findings are relevant for improved prognosis and treatment strategies in opioid dependence.

Topics: Adult; Buprenorphine; Cognition Disorders; Female; Heroin Dependence; Humans; Male; Mental Recall; Middle Aged; Naltrexone; Narcotic Antagonists; Neuropsychological Tests; Psychomotor Performance; Verbal Learning

Expansion of access to effective treatments for heroin dependence is a worldwide health priority that will also reduce HIV transmission. We compared the efficacy of naltrexone, buprenorphine, and no additional treatment, in patients receiving detoxification and subsequent drug counselling, for maintenance of heroin abstinence, prevention of relapse, and reduction of HIV risk behaviours.. 126 detoxified heroin-dependent patients, from an outpatient research clinic and detoxification programme in Malaysia, were randomly assigned by a computer-generated randomisation sequence to 24 weeks of manual-guided drug counselling and maintenance with naltrexone (n=43), buprenorphine (n=44), or placebo (n=39). Medications were administered on a double-blind and double-dummy basis. Primary outcomes, assessed by urine testing three times per week, were days to first heroin use, days to heroin relapse (three consecutive opioid-positive urine tests), maximum consecutive days of heroin abstinence, and reductions in HIV risk behaviours over 6 months. The study was terminated after 22 months of enrolment because buprenorphine was shown to have greater efficacy in an interim safety analysis. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00383045.. We observed consistent, linear contrasts in days to first heroin use (p=0.0009), days to heroin relapse (p=0.009), and maximum consecutive days abstinent (p=0.0007), with all results best for buprenorphine and worst for placebo. Buprenorphine was associated with greater time to first heroin use than were naltrexone (hazard ratio 1.87 [95% CI 1.21-2.88]) or placebo (2.02 [1.29-3.16]). With buprenorphine, we also recorded significantly greater time to heroin relapse (2.17 [1.38-3.42]), and maximum consecutive days abstinent than with placebo (mean days 59 [95% CI 43-76] vs 24 [13-35]; p=0.003); however, for these outcomes, differences between buprenorphine and naltrexone were not significant. Differences between naltrexone and placebo were not significant for any outcomes. HIV risk behaviours were significantly reduced from baseline across all three treatments (p=0.003), but the reductions did not differ significantly between the three groups.. Our findings lend support to the widespread dissemination of maintenance treatment with buprenorphine as an effective public-health approach to reduce problems associated with heroin dependence.

Topics: Adult; Buprenorphine; Counseling; Double-Blind Method; Heroin Dependence; HIV Infections; Humans; Malaysia; Naltrexone; Narcotic Antagonists; Recurrence; Risk-Taking; Treatment Outcome

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

Topics: Adult; Alcohol Drinking; Alcoholism; Analysis of Variance; Buprenorphine; Dose-Response Relationship, Drug; Drug Evaluation; Female; Heroin Dependence; Humans; Male; Methadone; Narcotics; Prospective Studies; Young Adult

A positive reinforcement contingency increased opioid abstinence during outpatient dose tapering (4, 2, then 0 mg/day during Weeks 1 through 3) in non-treatment-seeking heroin-dependent volunteers who had been maintained on buprenorphine (8 mg/day) during an inpatient research protocol. The control group (n=12) received $4.00 for completing assessments at each thrice-weekly visit during dose tapering; 10 of 12 lapsed to heroin use 1 day after discharge. The abstinence reinforcement group (n=10) received $30.00 for each consecutive opioid-free urine sample; this significantly delayed heroin lapse (median, 15 days).

Topics: Adult; Ambulatory Care; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Middle Aged; Motivation; Narcotics; Patient Discharge; Reinforcement Schedule; Secondary Prevention; Substance Abuse Detection; Substance Abuse, Intravenous; Token Economy

Abuse of prescription opioid medications has increased dramatically in the United States during the past decade, as indicated by a variety of epidemiological sources. However, few studies have systematically examined the relative reinforcing effects of commonly abused opioid medications. The current double-blind, placebo-controlled in-patient study was designed to compare the effects of intravenously delivered fentanyl (0, 0.0625, 0.125, 0.187, and 0.250 mg/70 kg), oxycodone (0, 6.25, 12.5, 25, and 50 mg/70 kg), morphine (0, 6.25, 12.5, 25, and 50 mg/70 kg), buprenorphine (0, 0.125, 0.5, 2, and 8 mg/70 kg), and heroin (0, 3.125, 6.25, 12.5, and 25 mg/70 kg) in morphine-maintained heroin abusers (N=8 completers maintained on 120 mg per day oral morphine in divided doses (30 mg q.i.d.)). All of the participants received all of the drugs tested; drugs and doses were administered in non-systematic order. All of the drugs produced statistically significant, dose-related increases in positive subjective ratings, such as 'I feel a good drug effect' and 'I like the drug.' In general, the order of potency in producing these effects, from most to least potent, was fentanyl>buprenorphine>or=heroin >morphine=oxycodone. In contrast, buprenorphine was the only drug that produced statistically significant increases in ratings of 'I feel a bad drug effect' and it was the only drug that was not self-administered above placebo levels at any dose tested. These data suggest that the abuse liability of buprenorphine in heroin-dependent individuals may be low, despite the fact that it produces increases in positive subjective ratings. The abuse liabilities of fentanyl, morphine, oxycodone, and heroin, however, appear to be similar under these experimental conditions.

Topics: Adult; Analysis of Variance; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Prescriptions; Female; Heroin Dependence; Humans; Male; Morphine Dependence; Narcotic Antagonists; Narcotics; Pain Measurement; Pupil; Reinforcement, Psychology; Respiration

This study examined how having a history of sexual, physical, or emotional abuse is related to overall functioning as assessed by the Addiction Severity Index during short-term opioid maintenance treatment with either buprenorphine/naloxone or methadone. Furthermore, the relation between abuse history and overall functioning by sex was explored. Participants (N = 268) were opioid-dependent adults entering an outpatient randomized clinical trial with buprenorphine/naloxone and methadone. Latent growth modeling indicated that females with an abuse history entered treatment with more problems in the psychiatric and family domains as compared with females without an abuse history. Over the course of treatment, a history of abuse predicted problems in the psychiatric and alcohol domains. Furthermore, a history of abuse predicted slower recovery times and less recovery overall for females in some domains. Males with an abuse history entered treatment with more severe psychiatric and family problems as compared with males with no history of abuse. Victims of abuse may present to substance abuse treatment with weaknesses in the areas of family relations, psychiatric status, and alcohol use. The nature of these problems and their trajectory over time differed by sex.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Buprenorphine; Domestic Violence; Double-Blind Method; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Psychiatric Status Rating Scales; Severity of Illness Index; Sex Factors; Sex Offenses; Social Adjustment; Time Factors; Treatment Outcome

Heroin dependence is associated with a hyperactive hypothalamic-pituitary-adrenal (HPA) axis, proposed as a biological correlate of craving. Maintenance treatment with methadone normalizes HPA axis activity. Here, we examined HPA axis activity under maintenance treatment with the increasingly utilized partial opiate agonist buprenorphine.. Responses to a metyrapone challenge were compared in 20 buprenorphine-maintained heroin addicts and 20 healthy volunteers (10 received a single 50 mg naltrexone dose [NTX+] and 10 received no naltrexone [NTX-]). Patients were 16 male subjects and 4 female subjects, aged 30 to 38 years, heroin-dependent and relapse-free under buprenorphine maintenance (BUP) for a minimum of 6 months. Healthy volunteers were 9 male subjects and 11 female subjects, aged 36 to 49 years, with no history of dependence. Serial measures were obtained of plasma adrenocorticotropic hormone (ACTH) and cortisol and Profile of Mood States (POMS) ratings over time. Subjects were genotyped for the OPRM1 118A/G polymorphism.. Buprenorphine maintenance showed a dampened HPA axis response to metyrapone, with OPRM1 118G carriers showing a significantly attenuated response compared with 118A carriers. The response of the NTX+ group was markedly increased. In contrast, negative affect was elevated in the BUP group but did not differ between NTX- and NTX+. Buprenorphine maintenance and NTX- groups did not differ in positive affect, whereas the NTX+ group was lower.. In contrast to exaggerated HPA axis responsiveness reported in untreated heroin dependence, response to metyrapone was subnormal in heroin addicts maintained on buprenorphine. Despite this, increased measures of negative affect were seen in this group. This implies a dissociation of HPA axis responsiveness and affect in heroin dependence.

Topics: Adult; Affect; Asparagine; Buprenorphine; DNA Mutational Analysis; Drug Interactions; Enzyme Inhibitors; Female; Heroin Dependence; Humans; Hypothalamo-Hypophyseal System; Male; Metyrapone; Middle Aged; Naltrexone; Narcotic Antagonists; Pituitary-Adrenal System; Polymorphism, Single Nucleotide; Receptors, Opioid, mu; Time Factors

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

Topics: Adolescent; Adult; Buprenorphine; Counseling; Diagnostic and Statistical Manual of Mental Disorders; Female; Heroin Dependence; HIV Infections; Home Care Services; Humans; Male; Middle Aged; Narcotics; Patient Acceptance of Health Care; Pilot Projects; Risk Reduction Behavior

The aim of the study was to evaluate the effect of substitution therapy in heroin addicted pregnant women on the course of pregnancy, perinatal outcomes and course of the neonatal abstinence syndrome.. A five-year randomised prospective comparative study. The study was carried out in the period of 2002-2007. The group of patients included 147 i.v. heroin-addicted pregnant women. All of them were outpatients of our Perinatal Care Unit. Their daily dose of heroin was approximately lg. Later, 30 women were disqualified from the study for breaking the randomised criteria engagement. The substitution therapy in women who agreed to undergo it, started during the I. trimester of pregnancy. Finally, 47 heroin, 32 methadone and 38 buprenorphine addicted women were enrolled in the study. Birthweight of newborns was compared with the national birthweight tables. Severity and duration of neonatal abstinence syndrome (NAS) were evaluated by Finnegan s score scale.. None of the women delivered before the end of 34th gestational week. We did not encounter any perinatal death or developmental defect. The lowest birthweight, the highest number of newborns with IUGR and the most numerous placental changes were found in the group of heroin-addicted women. The differences compared to the two groups receiving substitution therapy were statistically significant (p < 0.05). The severity and course of NAS were the most severe (p < 0.001) in newborns of women from the methadone group.. Comparison of the groups of outpatients is in many ways questionable because of the restricted possibility of the patients' control. The lifestyle of addicted women has the same impact as the drug use alone. This is probably the main reason for differences in some of the monitored parameters between individual groups. Based on our results we can state that substitution therapy provides pregnant women with the possibility of social stabilization and adequate prenatal care. substitution therapy decreases the street heroin consumption. Methadone notably protracts the newborn's abstinence syndrome. With regard to this fact, attention has been recently focused on substitution with buprenorphine that seems to be from this viewpoint a more considerate option.

Topics: Adult; Birth Weight; Buprenorphine; Female; Fetal Growth Retardation; Heroin; Heroin Dependence; Humans; Infant, Newborn; Life Style; Methadone; Narcotics; Neonatal Abstinence Syndrome; Outpatients; Postpartum Period; Pregnancy; Pregnancy Outcome; Prospective Studies; Severity of Illness Index

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

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Heroin Dependence; Humans; Immune System; Immunocompetence; Interferon-gamma; Interleukin-2; Interleukin-4; Male; Methadone; T-Lymphocytes; Tumor Necrosis Factor-alpha

Buprenorphine has considerable abuse potential. Patients who are maintained on buprenorphine (for opioid dependence) further use additional doses besides its maintenance dose. Subjective effects of the additional doses of buprenorphine in patients on buprenorphine maintenance patients is focused in this study.. Nineteen subjects who were maintained on buprenorphine 4mg, s/l per day for at least 1month were admitted and given three additional doses of buprenorphine 2mg, s/l at the interval of 2h each and subjective effects were assessed with the help of standard tools after 2h of each dose and the next day also. Drug was given in a cumulative dose design in the inpatient unit of a de-addiction centre.. Dysphoria and sleepiness increased while euphoria and drug liking decreased with additional doses of buprenorphine. These changes were statistically significant and were highest at maximum cumulative dose of 10mg.. Results suggest that abuse liability of buprenorphine in these subjects is low in higher doses. However, these findings need to be replicated in this group of patients to make a comment on clinical implication.

Topics: Adult; Buprenorphine; Chi-Square Distribution; Drug Administration Schedule; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Surveys and Questionnaires

Objective measures of experimentally induced aggressiveness were evaluated in heroin-dependent patients (HDP), 15 receiving buprenorphine (BUP) and 15 receiving methadone (METH) treatment. HDP were randomly assigned to BUP and METH groups. Fifteen healthy subjects (CONT) were included in the study as controls. During a laboratory task, the Point Subtraction Aggression Paradigm, subjects earned monetary reinforcement and could respond by ostensibly subtracting money from a fictitious subject (the aggressive response). Money-earning (points maintained) responses did not differ in BUP patients and in controls. In contrast, point-maintained responses were significantly lower in the group of HDP treated with METH than in both the BUP and CONT groups. Aggressive responses were significantly higher in the HDP group than in the CONT group. No significant differences in aggressive responses were found between the BUP and METH groups. Baseline concentrations of plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) were higher in HDP than in CONT. During the experimental task, ACTH and CORT increased significantly less in METH patients than in BUP patients and CONT. Norepinephrine (NE) and epinephrine (EPI) levels increased significantly more in HDP than in CONT, without any difference between the METH and BUP patients. PSAP aggressive responses positively correlated with NE and EPI changes, as well as with Buss-Durkee Hostility Inventory (BDHI) scores in both METH and BUP patients and also in CONT subjects. No correlation was found between the extent of heroin exposure, drug doses and aggressiveness levels. BUP, similarly to METH, does not seem to affect outward-directed aggressiveness, as aggressive responses related more to monoamine levels and personality traits than to the action of opioid agonists. Money-earning responses seemed to be unimpaired in BUP patients.

Topics: Adrenocorticotropic Hormone; Adult; Aggression; Blood Pressure; Buprenorphine; Epinephrine; Heart Rate; Heroin Dependence; Humans; Hydrocortisone; Male; Methadone; Monoamine Oxidase; Narcotic Antagonists; Norepinephrine; Psychometrics; Surveys and Questionnaires

To determine annual patterns and correlates of nonfatal heroin overdose across 3 years, data were analyzed on 387 heroin users recruited for the Australian Treatment Outcome Study (ATOS), interviewed at 12, 24, and 36 months. A heroin overdose across follow-up was reported by 18.6%, and naloxone had been administered to 11.9%. Annual rates of overdose declined between baseline and 12 months and then remained stable. Previous overdose experience was strongly related to subsequent overdose. Those with a history of overdose before ATOS were significantly more likely to overdose during the study period. In particular, there was a strong association between overdose experience in any 1 year and increased overdose risk in the subsequent year. This is the first study to examine long-term annual trends in nonfatal heroin overdose. While overdose rates declined after extensive treatment, substantial proportions continued to overdose in each year, and this was strongly associated with overdose history.

Topics: Adolescent; Adult; Buprenorphine; Cohort Studies; Drug Overdose; Episode of Care; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Inactivation, Metabolic; Incidence; Interviews as Topic; Male; Methadone; Middle Aged; Naloxone; Needle-Exchange Programs; New South Wales; Substance Abuse Treatment Centers; Treatment Outcome

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

Topics: Adult; Behavior Therapy; Buprenorphine; Combined Modality Therapy; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Heroin; Heroin Dependence; Humans; Longitudinal Studies; Male; Methadone; Naloxone; Patient Compliance; Patient Dropouts; Severity of Illness Index; Single-Blind Method; Substance Abuse Detection; Treatment Outcome

To compare the effectiveness and cost-effectiveness of unobserved versus observed dosing of patients seeking treatment of heroin dependence.. Randomized controlled trial and cost-effectiveness analysis. Setting Specialist out-patient drug treatment centres in Australia.. Heroin users seeking maintenance treatment.. Participants were allocated randomly to observed or unobserved dosing for 3 months. All subjects received buprenorphine-naloxone and weekly clinical reviews.. Primary end-points were retention in treatment and heroin use at 3 months. Costs of treatment were measured (in Australian dollars, AU$) and cost-effectiveness compared. Secondary outcomes included quality of life, psychological symptoms and use of non-opioid drugs.. A total of 119 subjects were randomized and analysed. At 3 months, 33/58 (57%) randomized to unobserved treatment, and 37/61 (61%) observed were retained (log-rank chi2 = 0.04, df = 1, P = 0.84). On an intention-to-treat analysis, reductions in days of heroin use in the preceding month, from baseline to 3 months, did not differ significantly; 18.5 days (95% CI: 21.8-15.3) and 22.0 days (95% CI: 24.3-19.7), respectively (Mann-Whitney U = 807.5, P = 0.13). The mean cost for the unobserved group was AU$1,663 (95% CI 1308-2017) per treatment episode, significantly less than the mean cost for the observed group at AU$2,138 (95% CI 1713-2562).. Retention and heroin use was not significantly different between observed and unobserved dosing groups. Attendance for observed dosing was not associated with worse retention. Treatment with close clinical monitoring, but no observation of dosing, was significantly cheaper and therefore significantly more cost-effective.

Topics: Adult; Australia; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cost-Benefit Analysis; Directly Observed Therapy; Drug Combinations; Health Care Costs; Heroin Dependence; Humans; Male; Naloxone; Narcotic Antagonists; Patient Compliance; Self Administration; Statistics as Topic

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

Topics: Administration, Cutaneous; Adult; Buprenorphine; Dose-Response Relationship, Drug; Female; Heroin Dependence; Humans; Inactivation, Metabolic; Male; Middle Aged; Narcotic Antagonists; Substance Withdrawal Syndrome

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

Topics: Adult; Buprenorphine; Chromatography, Liquid; Female; Hair; Heroin Dependence; Humans; Infant; Infant, Newborn; Pregnancy; Pregnancy Complications; Receptors, Opioid, kappa; Receptors, Opioid, mu; Tandem Mass Spectrometry; Tissue Distribution

The present study compared retrospectively in a clinical non-experimental setting the efficacy of buprenorphine (BUP) in different subgroups of dually diagnosed and non-dually diagnosed opioid-dependent patients: all the subjects included in the study showed severe long-lasting heroin addiction and 68.4% were affected by psychiatric comorbidity. Participants (206) (mean age 32.2+/-8.9, 177 males-29 females) were applicants to a long-term buprenorphine treatment program (mean doses 7.9+/-0.42 mg). Aim of the study was to evaluate dual diagnosis variables possibly influencing retention rate and abstinence from illicit drugs. The patients were divided into 5 subgroups on the basis of dual diagnosis: group 1: major depression (MD) 29.61%; group 2: generalized anxiety (GAD) (11.2%); group 3: personality disorders (PD), antisocial-borderline (21.84%); group 4: schizophrenia (SC)(6.3%); group 5: substance use disorder without overt psychiatric comorbidity (SUD) (31.1%). Group 1 patients affected by MD showed the highest retention rate at 12 months (72.1%) in comparison with the other groups of patients: group 2 GAD (39.1%), group 3 PD (17.8%), group 4 SC (7.7%) and group 5 SUD, without comorbidity (45.3%) (p=0.006, p<0.001, p<0.001, p=0.002). Similarly, at 12 months, the patients affected by MD showed less risk of illicit opioid use (16.4%) than those affected by GAD (34.8%), PD (42.2%), SC (53.8%) and SUD without comorbidity (34.4%) (p=0.06, p=0.003, p=0.008, p=0.017). When evaluated on the whole sample, retention rate was not influenced by dose. In contrast, the higher BUP doses were associated with less risk of illicit opioid use, than lower doses (p<0.001). Multivariate analysis and factor analysis showed a greater association of outcome measures (retention rate and negative urines rate) with comorbid diagnosis (depression) (respectively 0.64) than with buprenorphine doses (respectively 0.54). Our data need to be interpreted with caution because of the retrospective methodology applied to a clinical non-experimental setting. BUP seems to be more effective in opioid-dependent patients affected by depression, probably due to the kappa opioid-receptors antagonist action, counteracting dysphoria, negativism and anxiety. High doses of BUP appear to predict a better outcome, in terms of negative urines, but not in terms of retention.

Topics: Adult; Anxiety; Buprenorphine; Depressive Disorder, Major; Dose-Response Relationship, Drug; Female; Heroin Dependence; Humans; Male; Multivariate Analysis; Narcotics; Personality Disorders; Retrospective Studies; Schizophrenia; Time Factors; Treatment Outcome

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 10days followed by 11days 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.

Topics: Adolescent; Adult; Analgesics; Analgesics, Opioid; Buprenorphine; Clonidine; Cross-Sectional Studies; Female; Health Status; Heroin Dependence; Humans; Male; Middle Aged; Self Efficacy; Social Support; Substance Withdrawal Syndrome

Behavioral economic analysis has been used to investigate factors underlying drug consumption in laboratory animals and, increasingly, in human drug abusers. However, there are few studies in heroin abusers, especially those who are not in treatment; such studies may be valuable for understanding the mechanisms of persistent drug use. This study investigated effects of unit price (UP) and pre-session supply of hydromorphone (HYD) on choice and consumption of HYD. Heroin-dependent research volunteers (n=13) stabilized on buprenorphine 8 mg/day completed this eight-session inpatient study. In sessions 1-2, participants sampled two total HYD doses (12 and 24 mg IM) that could be earned in later sessions. In each of the final six sessions, volunteers were given access to a 12-trial choice progressive ratio schedule lasting 3h. On each trial, volunteers could earn a HYD unit dose (1 or 2 mg, for a maximum of 12 or 24 mg, respectively) or money (US dollars 2, for a maximum of US dollars 24). Fixed ratio requirements increased exponentially, generating 24 unit prices for behavioral economic analysis. Before some choice sessions, volunteers could choose (FR 1) to receive extra HYD (12 or 24 mg; at 0915), whereas on other days no supplement was available. HYD choice and peak responding (breakpoint, O(max)) measures increased with unit dose, decreased with pre-session supplements, and were greater among volunteers who used cocaine prior to the experiment. Taking pre-session supplements decreased P(max) and made group-percent HYD consumption more demand-elastic. Consumption was functionally equivalent at differing FR/unit dose combinations. Thus, opioid demand in heroin-dependent individuals not in treatment is a function of drug supply, unit price, and cocaine use.

Topics: Adolescent; Adult; Behavior, Addictive; Buprenorphine; Choice Behavior; Commerce; Costs and Cost Analysis; Drug Administration Schedule; Female; Heroin Dependence; Humans; Hydromorphone; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Urinalysis

Benzodiazepine use by patients in methadone and buprenorphine substitution treatment is common, despite safety concerns regarding these drug interactions. The relative safety of diazepam use by methadone- or buprenorphine-treated patients has not been systematically examined. This study aimed to examine the effect of single diazepam doses, within normal therapeutic range (doses: 0, 10, and 20 mg), upon physiological, subjective, and performance measures in stable methadone and buprenorphine-treated patients. In a double-blind, randomized crossover design, methadone- or buprenorphine-treated patients were administered their normal opioid dose and either placebo, 10-, or 20-mg diazepam, in balanced order over 3 sessions. Eight methadone- and 8 buprenorphine-prescribed patients with no concurrent benzodiazepine dependence or significant comorbidity were recruited from an outpatient addiction clinic in London. Measures were taken at baseline and for 6 hours after dosing, and included physiological responses (pulse rate, blood pressure, pupil size, respiratory rate, and peripheral pO2), subjective drug effects (Addiction Research Center Inventory subscales, visual analog scales of strength of drug effect, drug-liking, and sedation), and performance measures (simple reaction time, cancellation task, digit symbol substitution task, and balance). The 10- and 20-mg diazepam doses resulted in comparable subjective experiences of greater sedation and strength of drug effects in both patient groups, and had minimal impact on physiological parameters. However, diazepam had greater peak effects on performance measures (simple reaction time, digit symbol substitution task, and cancellation time) in methadone-treated than in buprenorphine-treated patients. Diazepam may significantly alter the response to opioid substitution treatment with methadone or buprenorphine.

Topics: Adolescent; Adult; Buprenorphine; Diazepam; Double-Blind Method; Drug Interactions; Female; Heroin Dependence; Humans; Hypnotics and Sedatives; Male; Methadone; Narcotics; Oxygen Consumption; Psychomotor Performance; Reaction Time; Substance-Related Disorders; Treatment Outcome

Twelve-month treatment of heroin addicts with methadone or buprenorphine normalized plasma cortisol levels, and controlled withdrawal symptoms as well as craving. During treatment, the time course of plasma cortisol levels and craving was not strictly correlated: heroin craving was more elevated at 12 than at 3 months. The results suggest a correlation between hypercortisolism, withdrawal symptoms and heroin use and suppose a more complex role for craving and its components in drug-taking behaviour. The main goal of the pharmacological treatment of opioid-dependence should be addressed at the normalization of hypothalamic-pituitary-adrenocortical (HPA) axis more than at the control of craving.

Topics: Adult; Buprenorphine; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Methadone; Motivation; Narcotics; Pituitary-Adrenal System; Statistics as Topic; Substance Withdrawal Syndrome

The optimum dose of buprenorphine for acute inpatient heroin detoxification has not been determined. This randomized, double-blind, double-dummy, pilot study compares two buprenorphine sublingual tablet dosing schedules to oral clonidine. Heroin users (N = 30) who met DSM-IV criteria for opioid dependence and achieved a Clinical Opiate Withdrawal Scale (COWS) score of 13 (moderate withdrawal), were randomized to receive higher dose buprenorphine (HD, 8-8-8-4-2 mg/day on days 1-5), lower dose buprenorphine (LD, 2-4-8-4-2 mg/day on days 1-5), or clonidine (C, 0.2-0.3-0.3-0.2-0.1 mg QID on days 1-5). COWS scores were obtained QID. Twenty-four hours after randomization, the percentages of subjects who achieved suppression of withdrawal, as defined by four consecutive COWS scores <12, were: C = 11%, LD = 40%, and HD = 60%. Generalized estimating equation regression models, controlling for baseline COWS and time, indicated that COWS scores over the course of 5 days were lower in both LD and HD compared to C (chi(2)(2) = 13.28, P = 0.001). Similar analyses examining scores over time on the Adjective Rating Scale for Withdrawal (ARSW) and on a Visual Analog Scale of Opiate Craving (VAS) indicated an overall treatment effect on the VAS accounted for by a significant difference between HD and C, but no overall treatment effect on the ARSW. There were no discontinuations due to treatment-related adverse events. Both HD and LD regimens are safe and efficacious treatment for opioid detoxification, but HD demonstrated superiority to C on a greater number of measures.

Topics: Adult; Analgesics, Opioid; Analysis of Variance; Buprenorphine; Clonidine; Double-Blind Method; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Middle Aged; Pilot Projects; Prospective Studies; Receptors, Opioid, mu; Time Factors

Buprenorphine offers an alternative to methadone in the treatment of heroin dependence, and has the advantage of allowing alternate-day dosing. This study is the first to examine the cost effectiveness of buprenorphine as maintenance treatment for heroin dependence in a primary care setting using economic and clinical data collected within a randomised trial.. The study was a randomised, open-label, 12-month trial of 139 heroin-dependent patients in a community setting receiving individualised treatment regimens of buprenorphine or methadone. Those who were currently on a methadone program (n = 57; continuing therapy subgroup) were analysed separately from new treatment recipients (n = 82; initial therapy subgroup). The study took a broad societal perspective and included health, crime and personal costs. Data on resource use and outcomes were a combination of clinical records and self report at interview. The main outcomes were incremental cost per additional day free of heroin use and per QALY. An analysis of uncertainty calculated the likelihood of net benefits for a range of acceptable money values of outcomes. All costs were in 1999 Australian dollars (DollarA).. The estimated mean number of heroin-free days did not differ significantly between those randomised to methadone (225 [95% CI 91, 266]), or buprenorphine (222 [95% CI 194, 250]) over the year of the trial. Buprenorphine was associated with an average 0.03 greater QALYs over 52 weeks (not significant). The total cost was DollarA 17,736 (95% CI -DollarA 2981, DollarA 38,364) with methadone and DollarA 11,916 (95% CI DollarA 7697, DollarA 16,135) with buprenorphine; costs excluding crime were DollarA 4513 (95% CI DollarA 3495, DollarA 5531) and DollarA 5651 (95% CI DollarA 4202, DollarA 7100). With additional heroin-free days as the outcome, and crime costs included buprenorphine has a lower cost but less heroin-free days. If crime costs are excluded buprenorphine has a higher cost and worse outcome than methadone. With additional QALYs as the outcome, the cost effectiveness of buprenorphine is DollarA 39,404 if crime is excluded, but buprenorphine is dominant if crime is included.. The trial found no significant differences in costs or outcomes between methadone and buprenorphine maintenance in this particular setting. Although some of the results suggest that methadone may have a cost advantage, it is difficult to infer from the trial data that offering buprenorphine as an alternative would have a significant effect on total costs or outcomes. The point estimates of costs and outcomes suggest that buprenorphine may have an advantage in those initiating therapy. The confidence intervals were wide, however, and the likelihood of net benefits from substituting one treatment for another was close to 50%.

Topics: Adolescent; Adult; Aged; Buprenorphine; Cost-Benefit Analysis; Disease-Free Survival; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Primary Health Care; Quality-Adjusted Life Years; Treatment Outcome

This study was designed to compare the neonatal abstinence syndrome (NAS) in neonates of methadone and buprenorphine maintained pregnant opioid-dependent women and to provide preliminary safety and efficacy data for a larger multi-center trial. This randomized, double-blind, double-dummy, flexible dosing, parallel-group controlled trial was conducted in a comprehensive drug-treatment facility that included residential and ambulatory care. Participants were opioid-dependent pregnant women and their neonates. Treatment involved daily administration of either sublingual buprenorphine or oral methadone using flexible dosing of 4-24 mg or 20-100 mg, respectively. Primary a priori outcome measures were: (1) number of neonates treated for NAS; (2) amount of opioid agonist medication used to treat NAS; (3) length of neonatal hospitalization; and (4) peak NAS score. Two of 10 (20%) buprenorphine-exposed and 5 of 11 (45.5%) methadone-exposed neonates were treated for NAS (p=.23). Total amount of opioid-agonist medication administered to treat NAS in methadone-exposed neonates was three times greater than for buprenorphine-exposed neonates (93.1 versus 23.6; p=.13). Length of hospitalization was shorter for buprenorphine-exposed than for methadone-exposed neonates (p=.021). Peak NAS total scores did not significantly differ between groups (p=.25). Results suggest that buprenorphine is not inferior to methadone on outcome measures assessing NAS and maternal and neonatal safety when administered starting in the second trimester of pregnancy.

Topics: Administration, Sublingual; Adult; Buprenorphine; Double-Blind Method; Female; Heroin Dependence; Humans; Infant, Newborn; Methadone; Narcotic Antagonists; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications; Severity of Illness Index

Although buprenorphine is effective in treating opioid dependence, optimal maintenance doses of buprenorphine or the buprenorphine/naloxone combination have not yet been established.. The present study was designed to evaluate the effects of buprenorphine/naloxone maintenance (2/0.5, 8/2, 32/8 mg sublingual) on the reinforcing and subjective effects of heroin (0, 12.5, 25, 50, and 100 mg intranasal) in heroin-dependent individuals.. During test weeks, participants (N=7) first sampled a dose of heroin and 20 dollars. During subsequent choice sessions, participants could choose to self-administer heroin and/or money. Participants responded under a modified progressive-ratio schedule (PR 50, ..., 2,800) during a ten-trial self-administration task.. Heroin break point values and subjective responses were significantly lower under 8/2 and 32/8 mg buprenorphine/naloxone compared to 2/0.5 mg. The self-administration and subjective effects data for heroin in the presence of buprenorphine/naloxone were compared to a separate control group of recently detoxified participants (N=8) in order to obtain estimates for the apparent in vivo dissociation constant (K(A)), the efficacy estimate (tau), and the estimated fraction of receptors remaining after buprenorphine/naloxone treatment (q). The apparent in vivo dissociation constant for heroin ranged from 50 to 126 mg (K(A)) and the efficacy estimate ranged from 13 to 20 (tau). In addition, 2/0.5, 8/2, and 32/8 mg buprenorphine/naloxone dose-dependently reduced the receptor population by 74, 83, and 91%, respectively.. These data demonstrate that both 8/2 and 32/8 mg buprenorphine/naloxone were well tolerated and effective in reducing the reinforcing and subjective effects of heroin, relative to the 2/0.5-mg dose. The data also show for the first time in humans that it is possible to quantify the efficacy and affinity of heroin for mu opioid receptors, and that 80-90% of mu receptors need to be inactivated in order to obtain significant reductions in heroin-induced effects. These results have important implications for future studies in which it will be possible to obtain estimates of relative affinity and efficacy of different agonists at mu opioid receptors.

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Heroin; Heroin Dependence; Humans; Male; Middle Aged; Motivation; Naloxone; Narcotics; Reinforcement, Psychology; Substance Withdrawal Syndrome; Treatment Outcome

Rapid opioid detoxification with opioid antagonist induction using general anesthesia has emerged as an expensive, potentially dangerous, unproven approach to treat opioid dependence.. To determine how anesthesia-assisted detoxification with rapid antagonist induction for heroin dependence compared with 2 alternative detoxification and antagonist induction methods.. A total of 106 treatment-seeking heroin-dependent patients, aged 21 through 50 years, were randomly assigned to 1 of 3 inpatient withdrawal treatments over 72 hours followed by 12 weeks of outpatient naltrexone maintenance with relapse prevention psychotherapy. This randomized trial was conducted between 2000 and 2003 at Columbia University Medical Center's Clinical Research Center. Outpatient treatment occurred at the Columbia University research service for substance use disorders. Patients were included if they had an American Society of Anesthesiologists physical status of I or II, were without major comorbid psychiatric illness, and were not dependent on other drugs or alcohol.. Anesthesia-assisted rapid opioid detoxification with naltrexone induction, buprenorphine-assisted rapid opioid detoxification with naltrexone induction, and clonidine-assisted opioid detoxification with delayed naltrexone induction.. Withdrawal severity scores on objective and subjective scales; proportions of patients receiving naltrexone, completing inpatient detoxification, and retained in treatment; proportion of opioid-positive urine specimens.. Mean withdrawal severities were comparable across the 3 treatments. Compared with clonidine-assisted detoxification, the anesthesia- and buprenorphine-assisted detoxification interventions had significantly greater rates of naltrexone induction (94% anesthesia, 97% buprenorphine, and 21% clonidine), but the groups did not differ in rates of completion of inpatient detoxification. Treatment retention over 12 weeks was not significantly different among groups with 7 of 35 (20%) retained in the anesthesia-assisted group, 9 of 37 (24%) in the buprenorphine-assisted group, and 3 of 34 (9%) in the clonidine-assisted group. Induction with 50 mg of naltrexone significantly reduced the risk of dropping out (odds ratio, 0.28; 95% confidence interval, 0.15-0.51). There were no significant group differences in proportions of opioid-positive urine specimens. The anesthesia procedure was associated with 3 potentially life-threatening adverse events.. These data do not support the use of general anesthesia for heroin detoxification and rapid opioid antagonist induction.

Topics: Adult; Anesthesia, General; Buprenorphine; Clonidine; Drug Therapy, Combination; Female; Heroin Dependence; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Substance Withdrawal Syndrome

Buprenorphine, a partial mu-opioid agonist, has been shown effective for treatment of opioid dependence but also has some abuse potential. A novel formulation of buprenorphine, using a polymer microcapsule depot sustained-release technology, has been developed which may offer effective treatment of opioid dependence while also minimizing risks of patient noncompliance and illicit diversion. This open-label, first-in-human study evaluated the safety and pharmacokinetics of a single-dose buprenorphine depot in physically dependent opioid abusers. The present study also examined the efficacy of depot buprenorphine in suppressing symptoms of opioid withdrawal, attenuating the effects of exogenous opioid challenge, and providing clinical detoxification. Five opioid-dependent volunteers each received a single subcutaneous depot injection containing 58 mg of buprenorphine and were assessed for at least four weeks for signs and symptoms of opioid withdrawal, first residentially and then as outpatients. Depot buprenorphine appeared to provide effective relief from opioid withdrawal, with no participant requiring additional medication for withdrawal relief following depot administration. The depot was safe and well-tolerated, with no significant side effects, signs of intoxication, or respiratory depression. In the opioid challenge sessions, depot buprenorphine appeared to produce substantial opioid blockade that persisted for 6 weeks post-depot administration. Results from the present study suggest that depot buprenorphine offers significant promise for enhancing the delivery of effective opioid agonist treatment while minimizing risk for abuse of the medication.

Topics: Administration, Oral; Adult; Ambulatory Care; Buprenorphine; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heroin Dependence; Humans; Hydromorphone; Injections, Subcutaneous; Male; Metabolic Clearance Rate; Narcotics; Neurologic Examination; Patient Acceptance of Health Care; Rehabilitation Centers; Substance Withdrawal Syndrome

In France, high-dosage buprenorphine (HDB) is the main substitution treatment for narcotic addiction. Few data have been published concerning clinical factors predicting a good response to this treatment in a daily practice. A hospital-based multicenter clinical research program (PHRC) was undertaken in heroin-addicted patients, diagnosed according to DSM-III-R, to detect clinical criteria susceptible of predicting a good response to HDB administered during a 3-month treatment period. At the inclusion time in the study, a diagnostic structured interview (DIGS) was performed, and the Addiction Severity Index (ASI), Zuckerman scale, depression scale from Jouvent, and CGI were scored. MMPI was also administered. Good response was defined as an ongoing participation in the study, with absence of opiate detected in 75% of urine collected during the last month of treatment. Only subjects treated for at least 1 month were eligible for analyses. One hundred fifteen patients were recruited and 73 were analyzed. Patients received 8.5+/-2.6 mg (m+/-S.D.) of buprenorphine for 1 to 3 months. A forward stepwise logistic regression showed that six clinical parameters may predict a good response to treatment: probability to respond to buprenorphine was higher in subjects having a high psychopathology (ASI) subscore, low disinhibition and boredom susceptibility factor scores (Zuckerman scale), no alcohol dependence, no family history of addiction or mood disorder, and duration of opiate dependence less than 10 years. Only the MMPI D subscale was a psychological pattern correlated to a good response to substitution treatment. These findings are important to consider when making the decision to prescribe HDB substitution treatment in opiate addiction.

Topics: Buprenorphine; Chi-Square Distribution; Diagnostic and Statistical Manual of Mental Disorders; Drug Administration Schedule; Female; Follow-Up Studies; Heroin Dependence; Humans; Interviews as Topic; Male; Multivariate Analysis; Narcotic Antagonists; Personality Tests; Prospective Studies; Psychological Tests; Treatment Outcome

Heroin is a synthetic opioid with an extensive illicit market leading to large numbers of people becoming addicted. Heroin users often present to community treatment services requesting detoxification and in the UK various agents are used to control symptoms of withdrawal. Dissatisfaction with methadone detoxification 8 has lead to the use of clonidine, lofexidine, buprenorphine and dihydrocodeine; however, there remains limited evaluative research. In Leeds, a city of 700,000 people in the North of England, dihydrocodeine is the detoxification agent of choice. Sublingual buprenorphine, however, is being introduced. The comparative value of these two drugs for helping people successfully and comfortably withdraw from heroin has never been compared in a randomised trial. Additionally, there is a paucity of research evaluating interventions among drug users in the primary care setting. This study seeks to address this by randomising drug users presenting in primary care to receive either dihydrocodeine or buprenorphine.. The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) project is a pragmatic randomised trial which will compare the open use of buprenorphine with dihydrocodeine for illicit opiate detoxification, in the UK primary care setting. The LEEDS project will involve consenting adults and will be run in specialist general practice surgeries throughout Leeds. The primary outcome will be the results of a urine opiate screening at the end of the detoxification regimen. Adverse effects and limited data to three and six months will be acquired.

Topics: Adolescent; Adult; Buprenorphine; Codeine; England; Follow-Up Studies; Health Services Research; Heroin Dependence; Humans; Methadone; Narcotic Antagonists; Opioid-Related Disorders; Primary Health Care; State Medicine; Substance Abuse Detection; Treatment Outcome

Network therapy (NT) employs family members and/or friends to support compliance with an addiction treatment carried out in office practice. This study was designed to ascertain whether NT is a useful psychosocial adjunct, relative to a control treatment, for achieving diminished illicit heroin use for patients on buprenorphine maintenance. Patients agreeing to randomization to either NT (N = 33) or medication management (MM, N = 33) were inducted onto short-term buprenorphine maintenance and then tapered to zero dose. NT resulted in significantly more urine toxicologies negative for opioids than MM (65% vs. 45%) and more NT than MM patients (50% vs. 23%) experienced a positive outcome relative to secondary heroin use by the end of treatment. The use of NT in office practice may therefore improve the effectiveness of eliminating secondary heroin use during buprenorphine maintenance. It may also be useful in enhancing compliance with an addiction treatment regimen in other contexts.

Topics: Adult; Buprenorphine; Combined Modality Therapy; Female; Heroin Dependence; Humans; Male; Narcotic Antagonists; New York City; Patient Compliance; Psychotherapy; Social Support

The present study compared in a clinical non-experimental setting the efficacy of buprenorphine (BUP) and methadone (METH) in the treatment of opioid dependence: all the subjects included in the study showed severe long-lasting heroin addiction. Participants (154) were applicants to a 12 weeks treatment program, who were assigned to either METH (78) (mean doses 81.5 +/- 36.4 mg) or BUP (76) (mean doses 9.2 +/- 3.4 mg) treatment. Aim of the study was to evaluate patient/treatment variables possibly influencing retention rate, abstinence from illicit drugs and mood changes. METH patients showed a higher retention rate at week 4 (78.2 versus 65.8) (P < 0.05), but BUP and METH were equally effective in sustaining retention in treatment and compliance with medication at week 12 (61.5 versus 59.2). Retention rate was influenced by dose, psychosocial functioning and not by psychiatric comorbidity in METH patients. In contrast, BUP maintained patients who completed the observational period showed a significantly higher rate of depression than those who dropped out (P < 0.01) and the intention to treat sample (P < 0.05). No relationship between retention and dose, or retention and psychosocial functioning was evidenced for BUP patients. The risk of positive urine testing was similar between METH and BUP, as expression of illicit drug use in general. At week 12, the patients treated with METH showed more risk of illicit opioid use than those treated with BUP (32.1% versus 25.6%) (P < 0.05). Negative urines were associated with higher doses in both METH and BUP patients. As evidenced for retention, substance abuse history and psychosocial functioning appear unable to influence urinalyses results in BUP patients. Buprenorphine maintained patients who showed negative urines presented a significantly higher rate of depression than those with positive urines (P < 0.05). Alternatively, psychiatric comorbidity was found unrelated to urinalyses results in METH patients. Our data need to be interpreted with caution because of the observational clinical methodology and non-random procedure. The present findings provide further support for the utility of BUP in the treatment of opioid dependency and demonstrate efficacy equivalent to that of METH during a clinical procedure. BUP seems to be more effective than METH in patients affected by depressive traits and dysphoria, probably due to antagonist action on kappa-opioid receptors. Psychosocial functioning and addiction severi

Topics: Adult; Analysis of Variance; Buprenorphine; Female; Heroin Dependence; Humans; Male; Methadone; Opioid-Related Disorders; Predictive Value of Tests; Treatment Outcome

Sublingual buprenorphine, a long-acting, partial mu-opioid agonist, is as effective as methadone in the treatment of heroin dependence, with a better safety profile due to its antagonist activity. However, the safety of therapeutic doses (8 to 16 mg) that might be diverted for intravenous (i.v.) use has not been demonstrated. To evaluate the safety and possible ceiling effects of buprenorphine administered i.v. to experienced opioid users, buprenorphine was administered to 6 nondependent opioid abusers residing on a research unit; the doses tested, in separate sessions, were 12 mg buprenorphine sublingual, i.v./sublingual placebo, and escalating i.v. buprenorphine (2, 4, 8, 12, and 16 mg). Physiologic and subjective measures were collected for 72 hours post-drug administration. Buprenorphine minimally but significantly increased systolic blood pressure. Changes in heart rate or oxygen saturation among the 7 drug conditions were not statistically significant. The mean maximum decrease in oxygen saturation from baseline was greatest for the 8-mg i.v. dose. Buprenorphine produced positive mood effects, although with substantial variability among participants. Onset and peak effects occurred earlier following i.v. administration: peak i.v. effects occurred between 0.25 and 3 hours; peak sublingual effects occurred at 3 to 7 hours. Duration of effects varied among the outcome measures. The dose-response curves were flat for most parameters, particularly subjective measures. Side effects were mild except in one participant who experienced severe nausea and vomiting after the 12-mg i.v. dose. Buprenorphine appears to have a ceiling for cardiorespiratory and subjective effects and a high safety margin even when taken by the i.v. route.

Topics: Administration, Sublingual; Adult; Arousal; Attention; Blood Pressure; Buprenorphine; Cocaine-Related Disorders; Dose-Response Relationship, Drug; Female; Heart Rate; Heroin Dependence; Humans; Infusions, Intravenous; Male; Narcotic Antagonists; Narcotics; Pain Measurement; Reflex, Pupillary; Substance Abuse, Intravenous

The partial opiate-receptor agonist buprenorphine has been suggested for treatment of heroin dependence, but there are few long-term and placebo-controlled studies of its effectiveness. We aimed to assess the 1-year efficacy of buprenorphine in combination with intensive psychosocial therapy for treatment of heroin dependence.. 40 individuals aged older than 20 years, who met DSM-IV criteria for opiate dependence for at least 1 year, but did not fulfil Swedish legal criteria for methadone maintenance treatment were randomly allocated either to daily buprenorphine (fixed dose 16 mg sublingually for 12 months; supervised daily administration for a least 6 months, possible take-home doses thereafter) or a tapered 6 day regimen of buprenorphine, thereafter followed by placebo. All patients participated in cognitive-behavioural group therapy to prevent relapse, received weekly individual counselling sessions, and submitted thrice weekly supervised urine samples for analysis to detect illicit drug use. Our primary endpoint was 1-year retention in treatment and analysis was by intention to treat.. 1-year retention in treatment was 75% and 0% in the buprenorphine and placebo groups, respectively (p=0.0001; risk ratio 58.7 [95% CI 7.4-467.4]). Urine screens were about 75% negative for illicit opiates, central stimulants, cannabinoids, and benzodiazepines in the patients remaining in treatment.. The combination of buprenorphine and intensive psychosocial treatment is safe and highly efficacious, and should be added to the treatment options available for individuals who are dependent on heroin.

Topics: Adult; Buprenorphine; Counseling; Female; Heroin Dependence; Humans; Male; Narcotic Antagonists; Psychotherapy, Group; Severity of Illness Index; Sweden; Treatment Outcome

With the growing role of intravenous drug use in the transmission of HIV infection, HIV-infected patients frequently present with comorbid opioid dependence. Yet, few empirical evaluations of the efficacy and consequences of opioid detoxification medications in medically ill HIV-infected patients have been reported. In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine (n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medication taper. There were no significant differences of pain decline and other measures of withdrawal between the three treatment groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine, clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients.

Topics: Administration, Oral; Adrenergic alpha-Agonists; Adult; Buprenorphine; Clonidine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Heroin Dependence; HIV Infections; Hospitalization; Humans; Injections, Intramuscular; Male; Methadone; Middle Aged; Narcotics; Pain Measurement; Receptors, Opioid; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Treatment Outcome

This study examines the outcomes at 1, 3 and 6 months after a very brief outpatient detoxification with buprenorphine in 18-25-year-old heroin users.. Prospective follow-up study.. Outpatient drug treatment clinic, providing brief detoxification in downtown Baltimore, Maryland, USA.. One hundred and twenty-three subjects between 18 and 25 years old; 56% male; 95% Caucasian; seeking detoxification; living in Baltimore City and five surrounding counties.. Detoxification with buprenorphine over 3 days. Follow-up at 1, 3 and 6 months.. Drug use history, the Addiction Severity Index at baseline and follow-up, urine drug screens, evaluation of the detoxification experience.. By self-report, 37% of the total sample were not currently using heroin at 1 month, 32% at 3 months and 29% at 6 months, and 6.7%, 10.1% and 11.8% had an opioid negative urine test at 1, 3 and 6 months, respectively. There was a significant reduction from the baseline in mean Addiction Severity Index drug use composite score, as well as the mean number of days of heroin and cocaine use during past 30 days, that was sustained over the three follow-up points. Engagement in aftercare was generally poor.. The findings show a reduced frequency and intensity of drug use, suggesting a possible role for brief outpatient detoxification in reducing the severity of dependence for some younger heroin users who may not yet be ready to engage in long-term abstinence-oriented or opioid substitution treatments.

Topics: Adolescent; Adult; Ambulatory Care; Buprenorphine; Drug Administration Schedule; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Narcotic Antagonists; Patient Satisfaction; Treatment Outcome

To compare outcomes, costs and incremental cost-effectiveness of heroin detoxification performed in a specialist clinic and in general practice.. Randomised controlled trial set in a specialist outpatient drug treatment centre and six office-based general practices in inner city Sydney, Australia.. 115 people seeking treatment for heroin dependence, of whom 97 (84%) were reinterviewed at Day 8, and 78 (68%) at Day 91.. Participants were randomly allocated to primary care or a specialist clinic, and received buprenorphine for 5 days for detoxification, then were offered either maintenance therapy with methadone or buprenorphine, relapse prevention with naltrexone, or counselling alone.. Completion of detoxification, engagement in post-detoxification treatment, and heroin use assessed at Days 8 and 91. Costs relevant to providing treatment, including staff time, medication use and diagnostic procedures, with abstinence from heroin use on Day 8 as the primary outcome measure.. There were no significant differences in the proportions completing detoxification (40/56 [71%] primary care v 46/59 [78%] clinic), participating in postwithdrawal treatment (28/56 [50%] primary care v 36/59 [61%] clinic), reporting no opiate use during the withdrawal period (13/56 [23%] primary care v 13/59 [22%] clinic), and in duration of postwithdrawal treatment by survival analysis. Most participants in both groups entered postwithdrawal buprenorphine maintenance. On an intention-to-treat basis, self-reported heroin use in the month before the Day 91 interview was significantly lower than at baseline (27 days/month at baseline, 14 days/month at Day 91; P < 0.001) and did not differ between groups. Buprenorphine detoxification in primary care was estimated to be $24 more expensive per patient than treatment at the clinic. The incremental cost-effectiveness ratio reveals that, in this context, it costs $20 to achieve a 1% improvement in outcome in primary care.. Buprenorphine-assisted detoxification from heroin in specialist clinic and primary care settings had similar efficacy and cost-effectiveness. Buprenorphine treatment can be initiated safely in primary care settings by trained GPs.

Topics: Adolescent; Adult; Ambulatory Care Facilities; Buprenorphine; Cost-Benefit Analysis; Family Practice; Female; Health Care Costs; Heroin Dependence; Humans; Male; Middle Aged; New South Wales; Outcome and Process Assessment, Health Care; Primary Health Care; Treatment Outcome

Fifty-two heroin addicts were inducted onto buprenorphine under the care of psychiatric residents in a setting modeled on office practice. Subjects were maintained on a protocol of six weeks of 16 mg daily dosing, then tapered to zero dose up to week 16, and maintained on placebo through week 18. Of 44 subjects who continued after the first induction dose, 11 terminated during maintenance, 17 during taper; and 16 while on zero dose. Twice weekly urine toxicologies showed significant successive declines in samples positive for heroin use across these three periods: 70%, 41%, and 20%, respectively. Among historical variables, only prior AA attendance distinguished subjects who achieved zero dose from those who did not. A comparison with recent studies suggests that relatively inexperienced office-based physicians can maintain patients on buprenorphine at a level comparable to that reported for research clinic settings, but with comparable rates of heroin abstinence. These findings are discussed in light of potential options for office-based opioid maintenance.

Topics: Adult; Alcoholics Anonymous; Appointments and Schedules; Buprenorphine; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Heroin Dependence; Humans; Internship and Residency; Male; Naloxone; Narcotic Antagonists; Narcotics; Outcome and Process Assessment, Health Care; Patient Dropouts; Substance Abuse Detection; Substance Withdrawal Syndrome; Treatment Outcome

Various drugs have been used for the treatment of opioid withdrawal, e.g., methadone, buprenorphine, and clonidine. Tramadol is a centrally acting synthetic analgesic agent with opiate activity due to low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabolite M1 to mu opioid receptors. As a consequence, there may be a role for the use of tramadol in the treatment of opiate withdrawal. We attempt to assess the efficacy of tramadol in treating moderate heroin withdrawal through a retrospective cohort control study, conducted in a detoxification unit in a community teaching hospital. Out of 100 heroin abusers admitted for detoxification during the review period, 64 patients who were treated either with buprenorphine or tramadol, were included in this study, with 20 participants in the buprenorphine group and 44 in the tramadol group. Both groups were matched for age, sex, and self-reported average quantity of heroin used per day. In the tramadol group, the average CINA maximum was 9.0, and in the buprenorphine group it was 11.2 (P = 0.07). The use of oral clonidine per patient in the tramadol group was 1.6 tablets, and in the buprenorphine group 0.1 tablets (P = 0.002). The length of stay was 3.7 days in the tramadol group and 4.1 days in the buprenorphine group (P = 0.5). Four participants in the tramadol group received three or more doses of buprenorphine because their symptoms were not controlled, and were considered as treatment failures. These preliminary data suggest that tramadol may be comparable to buprenorphine in the management of mild to moderately severe heroin withdrawal. These findings, if reproduced in larger studies with stronger research designs, have potentially great implications for the management of opioid withdrawal in both the inpatient and outpatient setting.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cohort Studies; Female; Heroin Dependence; Humans; Male; Narcotic Antagonists; Retrospective Studies; Substance Withdrawal Syndrome; Tramadol

Buprenorphine is a partial mu-opioid agonist and kappa-opioid antagonist currently under development as a maintenance medication for heroin dependence. Because of concerns about illicit diversion of buprenorphine, a combination tablet containing buprenorphine and naloxone has been developed. The present study evaluated the reinforcing effects of intravenously administered placebo, buprenorphine alone (BUP; 2 and 8 mg), and the buprenorphine/naloxone combination (BUP/NX; 2 mg of buprenorphine plus 0.5 mg of naloxone, and 8 mg of buprenorphine plus 2 mg of naloxone) in recently detoxified heroin abusers during a 6-week inpatient study. Participants (n = 6) were detoxified from heroin over approximately 1 week immediately after admission. During the next 5 weeks, the reinforcing effects of placebo, BUP, and BUP/NX were evaluated. Participants first received a dose of drug and $20 and then were given the opportunity to self-administer either the dose or $20 during choice sessions. Progressive ratio break point values were significantly higher after active drug, compared with placebo, but they did not significantly differ as a function of dose or drug. In contrast, positive subjective ratings were higher after administration of BUP compared with BUP/NX, and these ratings increased in a dose-dependent manner. BUP and the combination had few effects on performance. Relative to placebo, both BUP and BUP/NX decreased pupil diameter, but there were no significant differences in pupil diameter as a function of drug or dose. These results demonstrate that both BUP and BUP/NX served as reinforcers under these conditions and that they may have similar abuse liability in recently detoxified individuals who abuse heroin.

Topics: Administration, Oral; Adult; Blood Pressure; Buprenorphine; Dose-Response Relationship, Drug; Drug Combinations; Female; Heroin Dependence; Humans; Male; Naloxone; Narcotic Antagonists; Narcotics; Psychomotor Performance; Pupil; Reinforcement, Psychology; Self Administration; Surveys and Questionnaires

The purpose of this open-label, uncontrolled study was to evaluate the feasibility of administering off-label buprenorphine in combination with ancillary medications for inpatient short-term detoxification of heroin-dependent patients at a psychiatric facility. A sample of 20 heroin-dependent patients admitted to an urban psychiatric hospital was administered buprenorphine 6, 4, and 2 mg/day during the first, second, and third day of detoxification, respectively, and then observed during the fourth and fifth day. Eighty-five percent of the subjects abused other substances, 75% reported cocaine abuse/dependence, 75% had comorbid mood disorders. All subjects completed the medication phase of the study. No clinically significant adverse events were reported. There was a significant decrease in the Clinical Investigation Narcotic Assessment (CINA) total score between baseline and days 2 through 5. The results suggest that buprenorphine is well tolerated and may be beneficial for medically supervised short-term withdrawal from heroin for hospitalized psychiatric patients.

Topics: Adult; Analgesics, Opioid; Baltimore; Buprenorphine; Cocaine-Related Disorders; Comorbidity; Emergency Services, Psychiatric; Female; Heroin Dependence; Humans; Male; Middle Aged; Mood Disorders; Narcotic Antagonists; Patient Satisfaction; Pilot Projects; Substance Withdrawal Syndrome

To determine whether buprenorphine is more effective than clonidine and other symptomatic medications in managing ambulatory heroin withdrawal.. Open label, prospective randomized controlled trial examining withdrawal and 4-week postwithdrawal outcomes on intention-to-treat.. Two specialist, out-patient drug treatment centres in inner city Melbourne and Sydney, Australia.. One hundred and fourteen dependent heroin users were recruited. Participants were 18 years or over, and with no significant other drug dependence, medical or psychiatric conditions or recent methadone treatment. One hundred and one (89%) participants completed a day 8 research interview examining withdrawal outcomes, and 92 (81%) completed day 35 research interview examining postwithdrawal outcomes.. Participants randomized to control (n = 56) (up to 8 days of clonidine and other symptomatic medications) or experimental (n = 58) (up to 5 days of buprenorphine) withdrawal groups. Following the 8-day withdrawal episode, participants could self-select from range of postwithdrawal options (naltrexone, substitution maintenance, or counselling).. Retention in withdrawal; heroin use during withdrawal; and retention in drug treatment 4 weeks after withdrawal.. Withdrawal severity; adverse events, and heroin use in the postwithdrawal period.. The experimental group had better treatment retention at day 8 (86% versus 57%, P = 0.001, 95% CI for numbers needed to treat (NNT) = 3-8) and day 35 (62% versus 39%, P = 0.02, 95% CI for NNT = 4-18); used heroin on fewer days during the withdrawal programme (2.6 +/- 2.5 versus 4.5 +/- 2.3, P < 0.001, 95% CI = 1-2.5 days) and in the postwithdrawal period (9.0 +/- 8.2 versus 14.6 +/- 10, P < 0.01, 95% CI = 1.8-9.4); and reported less withdrawal severity. No severe adverse events reported.. Buprenorphine is effective for short-term ambulatory heroin withdrawal, with greater retention, less heroin use and less withdrawal discomfort during withdrawal; and increased postwithdrawal treatment retention than symptomatic medications.

Topics: Adult; Ambulatory Care; Buprenorphine; Clonidine; Female; Heroin Dependence; Humans; Male; Narcotics; Patient Compliance; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome; Sympatholytics

Several sources indicate that intravenously administered buprenorphine may have significant abuse liability in humans. The present study evaluated the reinforcing effects of intravenously administered buprenorphine (0, 2, and 8 mg) in detoxified heroin-dependent participants during a 7.5-week inpatient study. Participants (n = 6) were detoxified from heroin over a 1.5-week period immediately after admission. Testing subsequently occurred in three 2-week blocks. During the first week of each 2-week block, the reinforcing effects of buprenorphine were evaluated. Participants first received a dose of buprenorphine and $20 and then were given either the opportunity to self-administer the dose or $20 during choice sessions. During the second week of each 2-week block, the direct effects of heroin were measured to evaluate potential long-lasting antagonist effects of buprenorphine. Progressive ratio break-point values were significantly higher after 2 and 8 mg of buprenorphine compared with placebo. Correspondingly, several positive subjective ratings increased after administration of active buprenorphine relative to placebo. Although there were few differences in peak effects produced by 2 versus 8 mg of buprenorphine, the higher buprenorphine dose generally produced longer-lasting effects. Heroin also produced dose-related increases in several subjective effects. Peak ratings produced by heroin were generally higher than peak ratings produced by buprenorphine. There was little evidence of residual antagonism produced by buprenorphine. These results demonstrate that buprenorphine served as a reinforcer under these conditions, and that it may have abuse liability in nonopioid-dependent individuals who abuse heroin.

Topics: Adult; Attention; Blood Pressure; Buprenorphine; Dose-Response Relationship, Drug; Heroin; Heroin Dependence; Humans; Male; Narcotics; Psychomotor Performance; Pupil; Reinforcement, Psychology; Substance Abuse, Intravenous; Time Factors

Buprenorphine can decrease opioid self-administration by humans and animals, but its ability to decrease drug-seeking behavior and craving (i.e. motivational measures) among outpatient volunteers using clinically relevant dosing schedules has not been extensively studied.. We investigated whether daily versus alternating-day administration of high versus low buprenorphine doses influenced choice of, and operant responding for, hydromorphone versus money.. Fourteen heroin-dependent outpatients were maintained under four buprenorphine sublingual tablet (double blind) dose conditions using a within-subject, randomized crossover design. All participants received, for 2 weeks each, buprenorphine doses of 2 mg daily, 4 mg/placebo on alternating days, 16 mg daily, and 32 mg/placebo on alternating days. In each laboratory test session, participants chose between money ($2/choice) and drug (1/8 of total hydromorphone, 4 or 24 mg IM in different sessions) alternatives using an eight-trial non-independent progressive ratio schedule (FR 100, 200,.12,800). The drug dose and money amount earned was delivered after the end of the 2.5-h work period.. Hydromorphone 24 mg was more reinforcing than 4 mg. Higher versus lower average buprenorphine doses (regardless of daily versus alternate-day schedule) significantly decreased hydromorphone 24 mg choice and increased money choice. Baseline heroin craving questionnaire scores predicted drug choice, and craving scores were significantly decreased by high-dose buprenorphine.. High-dose buprenorphine attenuated opioid drug-seeking behavior, heroin craving self-reports and increased sensitivity to alternative reinforcement. These beneficial effects were retained when high-dose buprenorphine was administered on alternate days.

Topics: Administration, Sublingual; Adolescent; Adult; Analysis of Variance; Behavior, Addictive; Buprenorphine; Cross-Over Studies; Female; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Tablets

The aim of this study was to assess the safety of buprenorphine administered intravenously for the treatment of opioid withdrawal in medically ill hospitalized patients. Data regarding demographic information, number of doses of buprenorphine, and measures of buprenorphine's effects were collected via chart reviews for 30 heroin-dependent patients who received buprenorphine intravenously during their hospitalization for an acute medical problem. No respiratory depression was observed, and no patients reported feeling "high." All patients reported that buprenorphine decreased withdrawal symptoms. Thus, intravenous administration of buprenorphine appears to be safe for the treatment of opioid withdrawal.

Topics: Acute Disease; Adult; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Male; Middle Aged; Narcotic Antagonists; Substance Withdrawal Syndrome

The aim of this study was to assess the efficacy of 1-, 2-, and 4-mg-per-day sublingual doses of buprenorphine in the maintenance treatment of heroin-dependent patients over a 17-week treatment period. Subjects were randomized to three dosage groups. Participants consisted of 105 heroin addicts (102 men and 3 women) who met the DSM-IV criteria for opioid dependence and were seeking treatment. Subjects received buprenorphine at a dose of 1, 2, or 4 mg per day and were treated in an urban outpatient clinic, including a weekly 1-hour individual counseling session. Days retained in treatment were measured. Overall, 49 patients (46.7%) completed the 17-week study. Completion rates by dosage group were 34.3% for the 1 mg dose group, 42.9% for the 2 mg dose group, and 62.9% for the 4 mg dose group. Retention in the 4 mg dose group was significantly better than in the 1 mg dose group (P = .017). None of the other comparisons was significant. The results support the efficacy and safety of buprenorphine for outpatient treatment of heroin dependence and seem to indicate that the highest dose (4 mg) of buprenorphine was the best of the three doses for Iranian heroin addicts to increase their retention in treatment.

Topics: Adolescent; Adult; Ambulatory Care Facilities; Buprenorphine; Female; Heroin Dependence; Humans; Iran; Male; Middle Aged; Narcotic Antagonists; Patient Dropouts; Treatment Outcome

This study compared the safety and efficacy of sublingual buprenorphine tablets with oral methadone in a population of opioid-dependent individuals in a double-blind, randomized, 6-week trial using a flexible dosing procedure. Fifty-eight patients seeking treatment for opioid dependence were recruited in three outpatient facilities and randomly assigned to substitution with buprenorphine or methadone. The retention rate was significantly better in the methadone maintained group (90 vs. 56%; P<0.001). Subjects completing the study in both the treatment groups had similar proportions of opioid positive urine samples (buprenorphine 62%; methadone 59%) and positive urine specimens, as well as mean heroin craving scores decreased significantly over time (P=0.035 and P<0.001). The proportion of cocaine-positive toxicology results did not differ between groups. At week six mean stabilization doses were 10.5 mg per day for the sublingual buprenorphine tablet, and 69.8 mg per day for methadone, respectively. Patient performance during maintenance was similar in both the groups. The high attrition rate in the buprenorphine group during the induction phase might reflect inadequate induction doses. Thus, buprenorphine is a viable alternative for methadone in short-term maintenance treatment for heroin dependence if treatment induction is done with adequate dosages.

Topics: Adult; Analysis of Variance; Behavior, Addictive; Buprenorphine; Chi-Square Distribution; Double-Blind Method; Female; Heroin Dependence; Humans; Male; Methadone; Narcotic Antagonists; Opioid-Related Disorders; Patient Compliance

Studies have shown that buprenorphine, a partial mu opioid agonist, effectively reduces heroin taking. While previous research with buprenorphine utilized a liquid formulation, a tablet formulation is proposed for clinical use. However, because recent research suggests that the liquid and tablet differ in bio-availability, it is unclear what dose of the buprenorphine tablet effectively antagonizes the reinforcing effects of heroin.. The present study was designed to compare the effects of two sublingual doses of buprenorphine maintenance on heroin self-administration.. Eight heroin-dependent men participated in a 6-week, double-blind, placebo-controlled inpatient study to evaluate the reinforcing effects of intravenous heroin (0, 6.25, 12.5, 25 mg) during maintenance on 8 or 16 mg sublingual buprenorphine. Participants first sampled the available dose of heroin, and then were allowed to respond under a progressive ratio schedule for either heroin or $20. For each heroin dose, one sample session and three choice sessions occurred. Two sessions per day were conducted. A sample session was followed by the first choice session on one day, and the second and third choice sessions occurred on the following day. These sessions were conducted while participants were maintained on daily doses of 8 or 16 mg buprenorphine (3 weeks each).. Relative to placebo, 12.5 and 25 mg heroin produced significant increases in break point values under both maintenance dose conditions. The mean break point value for 12.5 mg heroin was significantly lower under 16 mg buprenorphine, compared to 8 mg.. These results demonstrate that the reinforcing effects of heroin were not fully antagonized by these doses of the tablet formulation of buprenorphine, and that 16 mg buprenorphine reduced heroin self-administration relative to 8 mg.

Topics: Administration, Sublingual; Adult; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Male; Narcotic Antagonists; Narcotics; Psychomotor Performance; Pupil; Self Administration; Tablets

Buprenorphine has a partial morphine-agonist pharmacological profile. It is proposed as alternative to methadone in opiate drug addicts with greater safety of use and less cost in terms of public health. The aim of this study was to determine the clinical factors of response to this molecule.. The study was conducted in 73 patients treated for 3 months with adaptable doses. Mean dose was 8.5 mg/d (range: 3 to 16 mg/d). Response to treatment was defined as: still in the study at 3 months and absence of opiates in 75% of urinary samples over the past month.. Forty-eight patients responded and 25 did not. The determinating clinical variables of response were: opiate drug addiction less than 10 years, high score on the Addiction Severity Index (ASI), absence of depression according to the Minnesota Multiphasic Personality Inventory (MMPI) and low rate of disinhibition on Zukerman's sensation seeking scale. Conversely, the dose of buprenorphine within the limits specified in the Marketing Authorisation did not intervene in the response.. In view of its partial agonist effect, administration of buprenorphine must be reserved for patients addicted to opiates for less than 10 years, non-depressive and with low disinhibition on Zukerman's scale.

Topics: Adult; Buprenorphine; Female; Heroin Dependence; Humans; Male; Narcotics; Prognosis; Prospective Studies

Several lines of evidence, including the well-established observation that kappa opiate agonists produce dysphoria and psychotomimetic effects in humans, suggest that dysfunction of the endogenous kappa opioid system may contribute to opioid and cocaine addiction. The objective of this open-label study was to determine the effectiveness of a functional kappa antagonist as a treatment for opioid dependence. This was accomplished by combining a partial mu agonist/kappa antagonist (buprenorphine, 4 mg, sublingual) with a mu antagonist (naltrexone, 50 mg by mouth), theoretically leaving kappa antagonism as the major medication effect. Subjects were treatment-seeking heroin-dependent (as per Diagnostic and Statistical Manual of Mental Disorders, 4th ed.) men (41 +/- 7 years old; 19 +/- 8 years heroin use) eligible for methadone maintenance. After inpatient detoxification and a naloxone-challenge test to verify that they were not physically dependent on opioids, subjects received naltrexone. Starting on the fourth day, patients also received liquid buprenorphine. All patients received medication at the clinic 6 days per week and a full program of psychosocial treatment. The major endpoints of the study were: pupil diameter to determine if the mu agonist effects of buprenorphine were blocked by naltrexone, urine toxicology, and retention in treatment. Five patients (33%) completed the 3-month study. Four were abstinent from opioids and cocaine for the entire study, and one was abstinent from opioids and cocaine for the last 9 weeks. Six subjects dropped out due to either minor side effects or disliking the sensation of sublingual buprenorphine. There were no significant changes in pupillary diameter. The positive response to treatment exceeds that expected from naltrexone alone (90% dropout). These promising results suggest that controlled studies of this medication combination should be conducted.

Topics: Administration, Sublingual; Adult; Affect; Buprenorphine; Drug Therapy, Combination; Heroin Dependence; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Patient Dropouts; Psychiatric Status Rating Scales; Pupil; Receptors, Opioid, kappa; Recurrence; Substance Abuse Detection; Treatment Outcome

This study targeted poly-drug (cocaine plus heroin) abstinence among buprenorphine-maintained participants with a 12-week voucher-based reinforcement therapy (VBRT) phase versus a yoked control condition. Baseline levels of cocaine and heroin use were significant predictors of treatment outcome, regardless of treatment assignment. Overall, there were no significant group differences on treatment outcome. However, among the subsample that produced one or more poly-drug-free urine results, VBRT participants had significantly increased cocaine-but not heroin and poly-drug-abstinence, although all results were in the predicted direction. Results suggest that for those who achieve poly-drug abstinence, VBRT may enhance treatment outcome. However, improved interventions, perhaps targeting single-drug abstinence, increasing reinforcement magnitude, or both, may be necessary to promote initial poly-drug abstinence in this population.

Topics: Adolescent; Adult; Breath Tests; Buprenorphine; Cocaine-Related Disorders; Cognitive Behavioral Therapy; Combined Modality Therapy; Female; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Psychiatric Status Rating Scales; Substance Abuse Detection; Substance-Related Disorders; Time Factors; Treatment Outcome

Buprenorphine is a promising alternative to methadone or levo-acetyl alpha methadol for opioid agonist maintenance treatment, and thrice-weekly dosing would facilitate its use for this purpose.. After a 3-day induction, opioid-dependent patients (n = 92) were randomly assigned to daily clinic attendance and 12-weeks maintenance treatment with sublingual buprenorphine administered double blind either daily (n = 45; 16 mg/70 kg) or thrice weekly (n = 47; 34 mg/70 kg on Fridays and Sundays and 44 mg/70 kg on Tuesdays). Outcome measures include retention, results of 3x/week urine toxicology tests, and weekly self-reported illicit drug use.. There were no significant differences at baseline in important social, demographic, and drug-use features. Retention was 71% in the daily and 77% in the 3x/week conditions. The proportion of opioid-positive urine tests decreased significantly from baseline in both groups and averaged 57% (daily) and 58% in 3x/week. There were no significant differences between groups in self-reported number of bags of heroin used for any day of the week, including Thursdays (48-72 hours following the last buprenorphine dose for subjects in the 3x/week condition), or in medication compliance (92%, 91%) and counseling attendance (82%, 82%).. At an equivalent weekly dose of 112 mg/70 kg, thrice-weekly and daily sublingual buprenorphine appear comparable in efficacy with regard to retention and reductions in illicit opioid and other drug use. These findings support the potential for utilizing thrice-weekly buprenorphine dosing in novel settings.

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Double-Blind Method; Female; Heroin Dependence; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Psychiatric Status Rating Scales

We examined the effects of disulfiram versus placebo on cocaine dependence in buprenorphine-maintained subjects.. Opioid and cocaine dependent subjects (n = 20) were induced onto buprenorphine maintenance, then randomized to disulfiram (250 mg q.d. ; n = 11) or placebo (n = 9) treatment for 12 weeks.. Groups were comparable at baseline on demographic measures and on baseline measures of drug-use severity. Fifteen subjects completed the study, including 8 subjects randomized to disulfiram (72.7%) and 7 subjects randomized to placebo (77.8%). The total number of weeks abstinent from cocaine was significantly greater on disulfiram versus placebo (mean +/- SD: 7.8 +/- 2.6 vs. 3.3 +/- 0.5, p <.05) and the number of days to achieving 3 weeks (24.6 +/- 15.1 vs. 57.8 +/- 7.7, p <.01) of continuous cocaine abstinence was significantly lower in disulfiram compared with placebo. The number of cocaine-negative urine tests during the trial were also higher on disulfiram (14.7) than on placebo (8.6); furthermore, subjects in the disulfiram group achieved consistently higher rates of cocaine-negative urine tests in each 3-week interval and the increase over time was faster in the disulfiram compared with placebo.. This preliminary study suggests the potential efficacy of disulfiram versus placebo for treatment of cocaine dependence in buprenorphine-maintained patients.

Topics: Adult; Alcohol Deterrents; Buprenorphine; Chi-Square Distribution; Cocaine-Related Disorders; Disulfiram; Female; Heroin Dependence; Humans; Male; Narcotic Antagonists; Substance Abuse Detection; Time Factors

A principle of opioid pharmacotherapy is that high medication doses should occupy fractionally more opioid receptors that mediate heroin effects. In this preliminary study we examined in vivo mu opioid receptor (muOR) binding in three healthy opioid-dependent volunteers during maintenance on 2 and 16 mg sublingual buprenorphine (BUP) liquid, and after detoxification (0 mg) under double-blind, placebo-controlled conditions, and once in matched controls. Binding measures were obtained with the muOR-selective radioligand [11C]carfentanil (CFN) and PET 4 hrs after BUP administration. BUP induced dose-dependent reductions in muOR availability, 36-50% at 2 mg and 79-95% at 16 mg relative to placebo. Heroin abusers also had greater muOR binding potential in the inferofrontal cortex and anterior cingulate regions during placebo, compared to matched controls. Further studies are warranted to examine the relationship of muOR availability with BUP therapeutic actions, and the clinical implications of increased muOR binding during withdrawal.

Topics: Adult; Analgesics, Opioid; Brain; Brain Chemistry; Buprenorphine; Double-Blind Method; Fentanyl; Heroin Dependence; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Narcotics; Receptors, Opioid, mu; Tomography, Emission-Computed

Cocaine abuse occurs in 40% to 60% of patients entering opioid maintenance treatment, and effective pharmacotherapies are needed for this combined dependence.. This 13-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of desipramine hydrochloride (0 or 150 mg/d) plus buprenorphine hydrochloride (12 mg/d) or methadone hydrochloride (65 mg/d) in 180 opioid-dependent cocaine abusers (124 men, 56 women). Supervised urine samples were obtained thrice weekly, and self-reported cocaine and heroin use was reported once weekly. Desipramine plasma levels were determined at weeks 4 and 10.. In men, opioid abstinence was increased more rapidly over time when treated with methadone than with buprenorphine, whereas cocaine abstinence was increased more with buprenorphine than with methadone. In women, opioid abstinence was increased the least rapidly when treated with buprenorphine plus placebo, while cocaine abstinence was increased more rapidly over time when treated with methadone than with buprenorphine. Regardless of sex or opioid medication, desipramine increased opioid and cocaine abstinence more rapidly over time than placebo. Self-reported opioid use confirmed these findings. Desipramine plasma levels were higher in women than in men, particularly those on buprenorphine maintenance. Higher desipramine plasma levels were associated with greater opioid, but not cocaine, abstinence.. Desipramine may be a useful adjunctive medication in facilitating opioid and cocaine abstinence in opioid-maintained patients. The efficacy of opioid medications to treat opioid or cocaine dependence may differ by sex. These findings highlight the importance of including sex as a factor when examining treatment outcome in these types of trials.

Topics: Adult; Analgesics, Opioid; Antidepressive Agents, Tricyclic; Buprenorphine; Cocaine-Related Disorders; Comorbidity; Desipramine; Drug Administration Schedule; Drug Therapy, Combination; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Sex Factors; Treatment Outcome

This double-blind, randomized, placebo-controlled clinical trial evaluated the impact on withdrawal symptoms of (i) combining naltrexone with a 4-day buprenorphine taper for short opioid detoxification (NB Group), compared to (ii) using a 4-day buprenorphine taper alone, followed by naltrexone on day 8 (PB Group). Sublingual buprenorphine was administered on days 1-4 (26 mg total). For the NB Group (n = 32) escalating doses of oral naltrexone were given on days 2-8 (placebo day 1). For the PB Group (n = 28) placebo was given on days 1-7 and naltrexone on day 8. Main outcome measures were Observed Opioid Withdrawal scores (OOW, 0-30) and use of medications to treat opioid withdrawal. Of 32 patients in the NB group, 59% experienced clinically relevant withdrawal (defined as OOW > or = 5) on day 2, but, after day 5, none experienced withdrawal. In the PB group, the number of patients experiencing withdrawal increased over time. The first naltrexone dose induced comparable withdrawal in both groups: peak OOW scores were (mean +/- SD) 5.2 +/- 3.3 on day 2 for the NB group, and 4.0 +/- 3.9 on day 8 for the PB group (NS), though, on day 2, 7 patients dropped out in the NB group and none in the PB group, while only one patient dropped out in the PB group on day 8. Throughout the 8-day study, patients in both groups received similar amount of adjunct medication: 0.64 +/- 0.07 mg (NB group) of clonidine vs 0.73 +/- 0.15 mg (PB group; NS). Only 25% of patients required use of sedatives (up to 20 mg diazepam). Starting naltrexone on day 2 appeared to abolish withdrawal symptoms after day 5 and, thus, to shorten the duration of withdrawal symptoms. Peak withdrawal symptoms after naltrexone were of moderate intensity, suggesting that naltrexone combined with buprenorphine is an acceptable and safe treatment for shortened opioid detoxification and induction of naltrexone maintenance.

Topics: Adult; Analgesics; Area Under Curve; Buprenorphine; Clonidine; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Female; Heroin; Heroin Dependence; Humans; Male; Naltrexone; Narcotic Antagonists; Substance Withdrawal Syndrome

This study examined the reinforcing effects of hydromorphone (HYD) (0, 4, 8, and 16 mg/70 kg i.m.) in heroin-dependent outpatient volunteers maintained on buprenorphine (BUP) at doses of 2, 4, and 8 mg, each for 2 weeks. Following a week of maintenance at each dose, volunteers received injections of one of the four HYD doses under double-blind conditions. Eight volunteers (abstainers) were heroin-free during HYD test weeks, whereas six volunteers remained heroin-positive (nonabstainers). Among abstainers, HYD had minimal reinforcing value, whereas in nonabstainers there were marked dose-related increases in HYD reinforcing value, which were not attenuated by increasing doses of BUP. A similar pattern was found for HYD subjective agonist effects. Heroin craving among nonabstainers was significantly higher compared with abstainers, and was reduced in a dose-related manner by HYD. Although BUP and HYD produced dose-related miosis, abstinence status had no differential effect. In summary, BUP effects on opioid reinforcement were consistent from outpatient setting (heroin abstinence) to laboratory setting (decreased HYD reinforcement), supporting the validity of this laboratory model.

Topics: Adult; Analysis of Variance; Behavior, Addictive; Buprenorphine; Double-Blind Method; Drug Synergism; Female; Heroin Dependence; Humans; Hydromorphone; Male; Middle Aged; Narcotic Antagonists; Narcotics; Outpatients; Pupil; Reinforcement, Psychology; Surveys and Questionnaires

Six male post-detoxified opiate dependent subjects were evaluated for abuse liability of buprenorphine (0.6 mg), morphine (16 mg), pentazocine (30 mg) and distilled water (placebo) intramuscular injection in a single blind cross-over random order. Subjective states, drug discrimination, drug linking, sedation and euphoria were assessed at pre-injection, 30 min and 4 hrs post-injection. Buprenorphine caused significant euphoria and was identified as heroin. On all parameters, buprenorphine resembled morphine rather than pentazocine and placebo. The data suggest that abuse liability of buprenorphine is similar to morphine i.e. moderate rather than low.

Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Child; Euphoria; Heroin Dependence; Humans; Male; Substance-Related Disorders; Surveys and Questionnaires

Positively reinforcing appropriate behaviors improved verbal behaviors of opioid-dependent patients in a buprenorphine treatment clinic. During B phases of an ABAB design, clients received stickers for engaging in appropriate verbal or nonverbal behaviors. Each sticker provided a chance of winning $25. No reinforcement was provided during the A phases. Appropriate verbal behaviors increased during reinforcement periods, and inappropriate verbal behaviors decreased.

Topics: Adult; Behavior Therapy; Buprenorphine; Cooperative Behavior; Female; Heroin Dependence; Humans; Male; Narcotic Antagonists; Token Economy; Verbal Behavior

Examine the relationship between buprenorphine and norbuprenorphine plasma concentrations with subject-reported withdrawal symptomatology during buprenorphine dose induction, maintenance treatments (daily and alternate-day dosing) and withdrawal.. Two groups of randomly assigned subjects inducted onto buprenorphine and maintained on 8 mg daily by the sublingual route for 18 days. Group 1 continued to receive daily buprenorphine to day 36. Group 2 subjects received alternate-day dosing of buprenorphine and placebo on days 19 to 36. Both groups received placebo on days 37 to 52.. Inpatient facilities at the Addiction Research Center, Intramural Research Center, NIDA, Baltimore, MD.. Eleven male, heroin-dependent volunteers participating in a research study.. Medications for treatment of withdrawal symptoms were prescribed as needed after day 39 (72 hours after the last dose of buprenorphine).. Plasma concentrations of buprenorphine and norbuprenorphine, withdrawal symptomatology and pupil diameter.. The mean steady-state buprenorphine plasma concentration (24 hours) after daily administrations of sublingual buprenorphine for study days 21-35 was 0.80 ng/ml, and the mean alternate day steady-state buprenorphine plasma concentration (24 hours) was 0.77 ng/ml. Daily and alternate day steady-state norbuprenorphine plasma concentrations were 1.10 and 0.90 ng/ml, respectively. Predicted alternate day steady-state buprenorphine and norbuprenorphine plasma concentrations at 48 hours were 0.49 ng/ml and 0.57 ng/ml, respectively. Withdrawal scores varied inversely with plasma concentration. There were no significant differences between Groups 1 and 2 during steady-state (days 21-35) with regard to withdrawal scale scores or pupillary diameter. The overall, mean terminal elimination half-lives for buprenorphine and norbuprenorphine were 42 and 57 hours, respectively.. during daily buprenorphine maintenance, plasma concentrations greater than 0.7 ng/ml of buprenorphine and norbuprenorphine were associated with minimal withdrawal symptoms. The long elimination half-life of buprenorphine suggested that increasing the buprenorphine dose with alternate-day administration may provide an effective, flexible therapy regimen for the treatment of opioid dependence.

Topics: Administration, Sublingual; Buprenorphine; Heroin Dependence; Humans; Male; Narcotic Antagonists; Substance Withdrawal Syndrome; Time Factors

Buprenorphine is an alternative to methadone for the maintenance treatment of heroine dependence and may be effective on a thrice weekly basis. Our objective was to evaluate the effect of thrice weekly buprenorphine maintenance for the treatment of heroin dependence in a primary care clinic on retention in treatment and illicit opioid use.. Opioid-dependent patients were randomly assigned to receive thrice weekly buprenorphine maintenance in a primary care clinic that was affiliated with a drug treatment program (n = 23) or in a traditional drug treatment program (n = 23) in a 12-week clinical trial. Primary outcomes were retention in treatment and urine toxicology for opioids; secondary outcomes were opioid withdrawal symptoms and toxicology for cocaine.. Retention during the 12-week study was higher in the primary care setting (78%, 18 of 23) than in the drug treatment setting (52%, 12 of 23; P = 0.06). Patients admitted to primary care had lower rates of opioid use based on overall urine toxicology (63% versus 85%, P < 0.01) and were more likely to achieve 3 or more consecutive weeks of abstinence (43% versus 13%, P = 0.02). Cocaine use was similar in both settings.. Buprenorphine maintenance is an effective treatment for heroin dependence in a primary care setting.

Topics: Adult; Ambulatory Care Facilities; Buprenorphine; Chi-Square Distribution; Cocaine; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Narcotic Antagonists; Patient Dropouts; Primary Health Care; Statistics, Nonparametric; Substance-Related Disorders; Treatment Outcome; United States

Opioid detoxification in a primary care setting followed by ongoing substance abuse treatment may be appropriate for selected opioid-dependent patients.. To compare three pharmacologic protocols for opioid detoxification in a primary care setting.. Randomized, double-blind clinical trial with random assignment to treatment protocols.. A free-standing primary care clinic affiliated with drug treatment programs.. 162 heroin-dependent patients.. Three detoxification protocols: donidine, combined donidine and naltrexone, and buprenorphine.. Successful detoxification (that is, when study participants received a full opioid-blocking dose [50 mg] of naltrexone), treatment retention (8 days), and withdrawal symptoms.. Overall, 65% of participants (36 of 55) who received clonidine, 81% (44 of 54) who received combined clonidine and naltrexone, and 81% (43 of 53) who received buprenorphine were successfully detoxified. Retention did not differ significantly across the groups: 65% of participants (36 of 55) who received clonidine, 54% (29 of 54) who received combined clonidine and naltrexone, and 60% (32 of 53) who received buprenorphine. Participants who received buprenorphine had a significantly lower mean withdrawal symptom score than those who received clonidine or combined clonidine and naltrexone.. Participants in the combined clonidine and naltrexone group and those in the buprenorphine group were more likely to complete detoxification, although retention at 8 days did not differ among the groups. Participants who were assigned to the buprenorphine group experienced less severe withdrawal symptoms than those assigned to the other two groups.

Topics: Adolescent; Adrenergic alpha-Agonists; Adult; Buprenorphine; Clonidine; Double-Blind Method; Drug Therapy, Combination; Female; Heroin; Heroin Dependence; Humans; Inactivation, Metabolic; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Primary Health Care; Substance Withdrawal Syndrome

Buprenorphine is a partial agonist at the mu-opioid receptor that has been proposed as an alternative to traditional full agonist maintenance therapy for the treatment of opioid addiction. We report on a clinical trial in which the relative safety and efficacy of long-term fixed-dose buprenorphine maintenance was examined in comparison to low- and high-dose methadone maintenance.. Two hundred twenty-five treatment-seeking opioid addicts (46 women, 179 men) were randomly assigned to receive, in a double-blind manner, either 8 mg/d of buprenorphine, 30 mg/d of methadone, or 80 mg/d of methadone maintenance over a 1-year period. Objective and subjective measures of efficacy (urine toxicology, retention, craving, and withdrawal symptoms) were examined at the study midpoint and at termination, and safety data were tabulated over the entire 52-week study period.. Patients assigned to high-dose methadone maintenance performed significantly better on measures of retention, opioid use, and opioid craving than either the low-dose methadone or the buprenorphine group at both 26-week and 52-week time points. Performance on these measures was virtually identical between the latter two groups. No serious adverse health effects attributable to buprenorphine were noted.. Buprenorphine maintenance at 8 mg/d appears to be less than optimally efficacious under the conditions of the present study. Continued research is needed to reconcile these findings with the more positive results reported by other investigative groups. There are no apparent health risks associated with long-term buprenorphine maintenance at this dosage.

Topics: Adult; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Methadone; Opioid-Related Disorders; Placebos; Substance Abuse Detection; Substance-Related Disorders; Treatment Outcome

This article reports results for patients who completed the 16-week maintenance phase of a double-blind clinical trial comparing buprenorphine (N = 43; average dose = 9.0 mg/day sublingually) with methadone (N = 43; average dose = 54 mg/day orally) in the outpatient treatment of opioid dependence. In addition to pharmacotherapy, treatment during the clinical trial included individual counseling, weekly group therapy, and on-site medical services. Patients in both medication groups showed significant and substantial improvements over time in areas of psychosocial functioning, as assessed by the Addiction Severity Index, rates of urinalysis tests positive for opioids, and self-reports of opioid withdrawal symptoms, illicit opioid use, and cocaine use. Buprenorphine and methadone produced very similar outcomes on the wide array of outcome measures assessed, and improvements for both groups were large and occurred rapidly after treatment entry. A trend toward continued improvement in opioid-positive urines over time was noted for the buprenorphine but not the methadone group. These results provide further evidence of the efficacy of buprenorphine in the treatment of opioid dependence and provide a characterization of the time course of effects for buprenorphine and methadone. In addition, these results demonstrate the benefits of drug abuse treatment, both for drug and alcohol use and in other areas of psychosocial functioning.

Topics: Adolescent; Adult; Alcoholism; Buprenorphine; Cocaine; Double-Blind Method; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Substance Abuse Detection; Substance Withdrawal Syndrome; Treatment Outcome

We assessed cognitive function following heroin and cocaine detoxification and investigated whether buprenorphine treatment improves the disruptive effects of detoxification. Three groups of male volunteers meeting DSM-III-R criteria for concurrent opiate and cocaine dependence were tested using an auditory oddball paradigm before and after detoxification, and again on the 15th day of either buprenorphine or placebo treatment. There were no significant differences in P300 amplitude, latency, or topographic distribution between drug-dependent subjects and controls on admission day. Following detoxification there was a significant decrease in P300 amplitude in the drug-dependent group at a time when self-reported signs of withdrawal were minimal. Buprenorphine treatment significantly reversed the P300 amplitude decrement following detoxification, whereas placebo-treated subjects continued to show depressed P300 amplitudes. These data demonstrate that buprenorphine treatment is effective in eliminating detoxification-induced impairments in one measure of cognitive ability.

Topics: Adult; Arousal; Attention; Brain Mapping; Buprenorphine; Cerebral Cortex; Cocaine; Event-Related Potentials, P300; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Reaction Time; Substance Withdrawal Syndrome

For many years, toxicologists have detected the presence of drugs of abuse in biological materials using blood or urine. In recent years, remarkable advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional samples such as sweat. In a study conducted in a detoxification center, sweat patches were applied to 20 known heroin abusers. Subjects wore the patch with minimal discomfort for five days. During the same period, two urine specimens were also collected. Target drugs analyzed either by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS) included opiates (heroin, 6-monoacetylmorphine, morphine, codeine), cocaine (cocaine, benzoylecgonine, ecgonine methyl ester), delta 9-tetrahydrocannabinol, benzodiazepines (nordiazepam, oxazepam), amphetamines (amphetamine, methamphetamine, methylenedioxyamphetamine [MDA], methylenedioxymethamphetamine [MDMA], methylenedioxyethylamphetamine [MDEA]), and buprenorphine. Patches were positive for opiates in 12 cases. Heroin (37-175 ng/patch) and/or 6-acetylmorphine (60-2386 ng/patch) were identified in eight cases, and codeine exposure (67-4018 ng/patch) was determined in four cases. When detected, heroin was always present in lower concentrations than 6-acetylmorphine, which was the major analyte found in sweat. Cocaine (324 ng/patch) and metabolites were found in only one case. delta 9-Tetrahydrocannabinol (4-38 ng/patch) was identified in nine cases. Benzodiazepine concentrations were very low, ranging from 2 to 44 and from 2 to 15 ng/patch for nordiazepam and oxazepam, respectively. MDEA (121 ng/patch) and its metabolite, MDA (22 ng/patch), were detected in one case. Buprenorphine, which was administered as therapy under close medical supervision, was detected in the range 1.3-153.2 ng/patch with no apparent relationship between the daily dose and amount excreted in sweat. All the urine tests were consistent with the sweat findings, but to identify the same drugs it was necessary to test two urine specimens along with only one sweat specimen. It was concluded that sweat testing appears to offer the advantage of being a relatively noninvasive means of obtaining a cumulative estimate of drug exposure over the period of a week. This new technology may find useful applications in the treatment and monitoring of substance abusers, as the patch provides a long-term continuous monitor of drug exposure or noncompliance.

Topics: Amphetamines; Benzodiazepines; Buprenorphine; Cannabinoids; Chromatography, High Pressure Liquid; Cocaine; Codeine; Dose-Response Relationship, Drug; Gas Chromatography-Mass Spectrometry; Heroin; Heroin Dependence; Humans; Illicit Drugs; Morphine; Morphine Derivatives; Reproducibility of Results; Sweat

The treatment of heroin dependence with opioid maintenance has traditionally employed methadone and more recently buprenorphine administered in traditional drug treatment settings. In this pilot study we evaluated buprenorphine maintenance for the treatment of heroin dependence in a program administered by primary-care providers in a primary-care setting. Seven patients were admitted to this nonblinded open-label pilot study and were offered 6 months of primary-care-based buprenorphine maintenance. Buprenorphine was administered in doses of 16 mg on Monday and Wednesday and 32 mg on Friday. Patients were seen weekly by primary-care providers and attended self-help meetings. Of the seven patients admitted to the study, five (71%) completed the 6-month pilot study and two (29%) were removed from the study. Urine toxicology data showed that the majority of urines tested were clear of opioids in four out of five patients who remained in treatment. These results suggest that primary-care-based opioid maintenance using buprenorphine shows promise as a new approach to the treatment of heroin dependence.

Topics: Adult; Analgesics, Opioid; Analysis of Variance; Buprenorphine; Female; Heroin Dependence; Humans; Male; Narcotics; Patient Dropouts; Pilot Projects; Primary Health Care

Chronic cocaine and polydrug abuse have been associated with regional abnormalities in cerebral perfusion. The authors have previously demonstrated that these abnormalities are partially reversible after drug addiction treatment with buprenorphine. This study was designed to separate the effect on cerebral perfusion of abstinence from drug use from that of buprenorphine directly.. Fifteen cocaine- and heroin-dependent men were studied with 99mTc-hexamethylpropyleneamine oxime (HMPAO) brain SPECT. The men, all part of an inpatient drug abuse treatment research program, were randomly assigned after detoxification to receive placebo or either 6 or 12 mg daily buprenorphine treatment. SPECT studies were performed at baseline, after maximum dosage was reached and after tapering off the study drug. Studies were compared visually with regard to the number and location of perfusion defects by reviewers blinded to treatment assignment.. Subjects receiving buprenorphine had a significant reduction in the number of defects per study between baseline and maximum buprenorphine dose as compared with those receiving placebo (decrease of 4 +/- 5.4 versus increase of 4.8 +/- 4.7, p = 0.006). These differences were dose-related. Improvement with buprenorphine was temporary, with return to baseline after tapering off.. Buprenorphine treatment, and not abstinence from drug use alone, leads to improvement in regional cerebral perfusion abnormalities in chronic cocaine- and heroin-dependent men.

Topics: Adult; Brain; Buprenorphine; Cerebrovascular Circulation; Cocaine; Double-Blind Method; Heroin Dependence; Humans; Male; Middle Aged; Organotechnetium Compounds; Oximes; Substance-Related Disorders; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Large-scale placebo controlled clinical trials assessing the efficacy of medications for the treatment of drug dependence have generally been limited to alcohol, cocaine and nicotine dependent populations. The purpose of the present study was to assess the early (1-2 week) clinical effectiveness of buprenorphine versus placebo in an opioid dependent population. The study used a parallel-group design with a behavioral choice component to compare buprenorphine (a mu-opioid partial agonist) to placebo for the treatment of opioid dependence. Opioid dependent volunteer patients participated in a 14-day study to assess the effectiveness and patient acceptance of this new pharmacotherapy for the treatment of opioid dependence. Patients were randomly assigned to placebo (n = 60) or 2 mg (n = 60) or 8 mg (n = 30) daily sublingual buprenorphine. All doses were administered double-blind. On days 6-13 all patients could request a dose change, knowing that their new dose would be randomly chosen from the remaining 2 alternatives. Compared to placebo, patients given buprenorphine (independent of dose) showed greater time on initial dose, requested fewer dose changes, used less illicit opioids (assessed by urinalysis), and rated dose adequacy higher. These results demonstrate that a placebo controlled study with a behavioral choice component is an effective means of assessing the potential efficacy and acceptability of new pharmacotherapies for opioid dependence.

Topics: Administration, Sublingual; Adult; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Narcotic Antagonists; Patient Acceptance of Health Care; Substance Abuse Detection; Treatment Outcome

Buprenorphine, a mu-opioid partial agonist, has demonstrated efficacy for the treatment of opioid dependence comparable to that of methadone. The clinical utility of buprenorphine would be enhanced if it could be dosed on a less than daily basis. The current study is a parallel-group outpatient clinical trial of daily versus alternate-day dosing with 8 mg sublingual (s.l.) buprenorphine. Participants were randomly assigned to daily (n = 51) or alternate-day (n = 48) schedules of active medication administration for an 11-week double-blind trial. Patients assigned to alternate-day buprenorphine received placebo every other day. Primary outcome measures were retention in treatment and urine specimens positive for opiates. Clinic attendance, dose adequacy ratings, withdrawal symptomatology, and urine specimens positive for cocaine were secondary outcome measures. Neither endpoint analysis with the intent-to-treat sample nor time course analysis with treatment completers revealed any statistically significant differences between the dosing schedules on any outcome measure. Examination of 95% confidence intervals suggested a non-significant trend for the daily dosing schedule to have superior clinical efficacy at the dose tested. Nevertheless, these results are generally consistent with previous studies of less than daily dosing with buprenorphine and support the conclusion that an alternate-day dosing schedule can be effective in and acceptable to a substantial portion of patients.

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Narcotic Antagonists; Neurologic Examination; Substance Abuse Detection; Substance Withdrawal Syndrome

We compared the short-term efficacy of a high-dose, 3 day regimen of buprenorphine to a standard 5-day course of clonidine in attenuating the signs and symptoms of the acute opioid abstinence syndrome during rapid detoxification from heroin in 25 men and women admitted to a closed inpatient research ward for this randomized, double-blind, parallel-group trial. Among the 18 completers, there were no significant differences between the buprenorphine and clonidine groups on five subjective and six physiological measures. However, clonidine lowered blood pressure and buprenorphine provided more effective early relief of withdrawal symptoms.

Topics: Adult; Baltimore; Buprenorphine; Clonidine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Middle Aged; Opioid-Related Disorders; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome; Urban Population

Thirty-nine methadone maintenance patients were included in a 9-day, double blind, randomized, inpatient detoxification trial. Methadone was tapered to 10 mg/day and then patients were assigned to one of these 3 protocols: clonidine (0.3-0.9 mg/day), lefetamine (60-240 mg/day), buprenorphine (0.15-0.9 mg/day). Buprenorphine treatment was significantly superior to clonidine and to lefetamine (F = 3.96 df = 2, 29 P < 0.05) in controlling objective, subjective and psychological withdrawal symptomatology. Clonidine was more effective than lefetamine in suppressing withdrawal in the first 3 days of treatment (day 3: F = 4.10 df = 2, 30 P < 0.05), and this trend was apparent on the objective and psychological items. In addition to evaluations of the efficacy of the single drugs used, the study showed that tapering methadone to low doses before entering the pharmacologically assisted discontinuation phase was clinically acceptable in detoxification from long-term methadone treatment.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Clonidine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Methadone; Neurologic Examination; Opioid-Related Disorders; Patient Admission; Phenethylamines; Substance Withdrawal Syndrome

The effects of daily buprenorphine treatment (4 or 8 mg/day, sublingual) on reports of subjective effects after single intravenous doses of morphine (10 mg), cocaine (30 mg), and saline placebo were studied on an inpatient clinical research ward in 26 men concurrently dependent on opioids and cocaine (DSM-III-R). Latency to detection and certainty of a drug effect, as well as drug quality (intensity, euphoria, and dysphoria), were studied before and after 10 to 12 days of buprenorphine maintenance. Saline was accurately identified by all 26 patients during the drugfree baseline and by 25 patients during buprenorphine maintenance conditions. All patients accurately identified morphine during the drugfree period before treatment with buprenorphine, but 18 (69%) of 26 patients were unable to detect morphine during buprenorphine maintenance and 2 misidentified morphine as cocaine. Six men (23%) accurately identified morphine and reported that the intensity and quality of morphine's effects were equivalent to drugfree conditions. Cocaine levels in plasma 5 minutes after intravenous cocaine injection were equivalent before and during buprenorphine treatment and averaged 282.8 +/- 43.6 and 295.2 +/- 28.8 ng/ml during 4 and 8 mg/day of buprenorphine maintenance, respectively. All patients accurately identified cocaine before and during buprenorphine maintenance, and there were no significant changes in latency to detection and certainty of a drug effect or reports of cocaine-induced intensity or euphoria during buprenorphine treatment. The concordance between responses to morphine and cocaine during inpatient buprenorphine maintenance and drug use during the first 4 weeks of outpatient buprenorphine treatment was also examined in 16 men. The effects of buprenorphine on individual responses to an acute intravenous dose of morphine or cocaine during the inpatient study did not reliably predict the frequency of heroin or cocaine self-administration during the first 4 weeks of daily outpatient buprenorphine maintenance.

Topics: Administration, Sublingual; Adult; Ambulatory Care; Arousal; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Heroin Dependence; Humans; Male; Morphine; Morphine Dependence; Prognosis; Substance Abuse, Intravenous; Substance-Related Disorders; Treatment Outcome

Topics: Administration, Sublingual; Benzodiazepines; Buprenorphine; Heroin Dependence; Humans; Methadone; Naltrexone; Substance-Related Disorders

Five inpatients dependent on both intravenous cocaine and heroin were detoxified from opiates. They were then given 5 days of double-blind treatment with active or placebo buprenorphine 2 mg/d sublingually, followed by a crossover to the converse for 5 days (buprenorphine or placebo). Intranasal cocaine challenges (2 mg/kg) were performed on Days 3 and 5 of each treatment. Buprenorphine significantly enhanced patients' ratings of cocaine-induced pleasurable effects, and augmented cocaine-induced pulse increases. The buprenorphine enhancement of subjective cocaine effects appeared to be more prominent on Day 3 than on Day 5. This reduction from Day 3 to Day 5 suggests that cocaine may interact differently with buprenorphine as treatment is more prolonged.

Topics: Adult; Affect; Arousal; Buprenorphine; Cocaine; Comorbidity; Double-Blind Method; Drug Administration Schedule; Euphoria; Female; Heroin Dependence; Humans; Male; Pilot Projects; Substance Withdrawal Syndrome; Substance-Related Disorders

Recent preclinical and clinical studies suggest that buprenorphine, an opioid mixed agonist-antagonist, may be useful for the treatment of dual dependence on cocaine and opiates. This report describes an inpatient clinical evaluation of the safety of buprenorphine alone and in combination with single doses of cocaine and morphine. Twenty subjects with a DSM-III-R diagnosis of concurrent cocaine and opioid dependence were randomly assigned to maintenance treatment with single daily doses of 4 or 8 mg of sublingual buprenorphine for 21 days. Side effects and vital signs were evaluated every day once every 8 hours and for 2 hours after daily buprenorphine administration. The physiologic effects of a single-blind challenge dose of cocaine (30 mg intravenously), morphine (10 mg intravenously), and intravenous saline placebo were measured before and during buprenorphine maintenance. Before buprenorphine maintenance, subjects underwent methadone detoxification followed by a 9-day drug-free period. Three baseline single-blind challenge dose studies were conducted on study days 7, 8, and 9 during the drug-free period. Cardiovascular responses to cocaine and to morphine were equivalent under drug-free and buprenorphine maintenance conditions. Respiration and temperature changes in response to cocaine were also equivalent before and during buprenorphine maintenance. Respiratory rates were slightly lower after morphine administration during maintenance on 8 mg of buprenorphine, but this was not statistically significant. Mild opioid agonist-like side effects were reported during buprenorphine induction and maintenance. These included headache, sedation, nasal discharge, abdominal discomfort, and anxiety. Most opioid agonist side effects decreased within 12 to 14 days. An electrocardiogram and blood chemistry measures were normal before and during buprenorphine maintenance. These data suggest that daily maintenance on buprenorphine is not associated with adverse side effects or toxic interactions with a single acute dose of intravenous cocaine or morphine.

Topics: Administration, Sublingual; Adult; Arousal; Blood Pressure; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Drug Interactions; Heart Rate; Heroin Dependence; Humans; Liver Function Tests; Male; Morphine; Single-Blind Method; Substance-Related Disorders

Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients. As hypothesized, 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use, but higher dosage did not improve treatment retention. Self-reported illicit opioid use declined substantially in all groups, but by the third month, significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone. From an initial average of $1860/month, month 3 usage dropped to $41 (methadone 65 mg), $73 (methadone 35 mg), $118 (buprenorphine 6 mg), and $351/month (buprenorphine 2 mg). Days of use also dropped from 29 days to 1.7 (methadone 65 mg), 2.8 (methadone 35 mg), 4.0 (buprenorphine 6 mg), and 6.6 days/month (buprenorphine 2 mg). This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial, with 7.2 days/month and $235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $65/month for the other three groups. Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms. Our secondary hypothesis, that buprenorphine would be equivalent to methadone in efficacy, was not supported. Treatment retention was significantly better on methadone (20 vs. 16 weeks), and methadone patients had significantly more opioid-free urines (51% vs. 26%). Abstinence for at least 3 weeks was also more common on methadone than buprenorphine (65% vs. 27%).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Methadone; Opioid-Related Disorders; Substance Abuse Detection; Treatment Outcome

The spontaneous physical dependence of buprenorphine was assessed in opioid addicts who switched from heroin to sublingual or intravenous buprenorphine. Twenty-two patients were randomly assigned to double-blind administration of methadone (n = 11) or placebo (n = 11) for 13 days after abrupt withdrawal of buprenorphine. Methadone was administered according to four pre-established dosing schedules depending on the previous amount of daily consumed buprenorphine. No methadone-treated patient required modification of the therapeutic regimen, whereas eight of eleven placebo-treated patients needed treatment with methadone. Buprenorphine withdrawal syndrome was of opioid type, began somewhat more slowly, and showed a peak until day 5. The occurrence, time-course and characteristics of buprenorphine withdrawal syndrome make it necessary to reconsider the abuse potential of this analgesic.

Topics: Adult; Buprenorphine; Double-Blind Method; Female; Heroin Dependence; Humans; Male; Methadone; Neurologic Examination; Opioid-Related Disorders; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome

Data from these studies indicate that buprenorphine is efficacious in treating opioid dependence. It was possible to induct heroin addicts rapidly onto buprenorphine without precipitating an opioid withdrawal syndrome. A daily 8-mg SL dosage was sufficient to maintain individuals without producing reports of withdrawal symptoms. When buprenorphine was administered at the above dose every other day, however, mild withdrawal symptoms were reported, and responses to challenges with intravenously given hydromorphone appeared greater than when the challenges were given intramuscularly. From these results, the authors conclude that buprenorphine at this dose should be administered on a daily basis. These results are now being applied to a phase II outpatient clinical trial comparing buprenorphine with methadone.

Topics: Adult; Buprenorphine; Double-Blind Method; Female; Follow-Up Studies; Heroin Dependence; Humans; Hydromorphone; Male; Middle Aged; Naloxone; Substance Withdrawal Syndrome; Testosterone

To assess the efficacy of buprenorphine for short-term maintenance/detoxification.. A randomized, double-blind, parallel group study comparing buprenorphine, 8 mg/d, methadone, 60 mg/d, and methadone, 20 mg/d, in a 17-week maintenance phase followed by an 8-week detoxification phase.. Outpatient facilities at the Addiction Research Center, Baltimore, Md.. One hundred sixty-two volunteers seeking treatment for opioid dependence.. In addition to the medication, counseling using a relapse prevention model was offered but not required.. Retention time in treatment, urine samples negative for opioids, and failure to maintain abstinence.. Throughout the maintenance phase, retention rates were significantly greater for buprenorphine (42%) than for methadone, 20 mg/d (20%, P less than .04); the percentage of urine samples negative for opioids was significantly greater for buprenorphine (53%, P less than .001) and methadone, 60 mg/d (44%, P less than .04), than for methadone, 20 mg/d (29%). Failure to maintain abstinence during the maintenance phase was significantly greater for methadone, 20 mg/d, than for buprenorphine (P less than .03). During the detoxification phase, no differences were observed between groups with respect to urine samples negative for opioids. For the entire 25 weeks, retention rates for buprenorphine (30%, P less than .01) and methadone, 60 mg/d (20%, P less than .05), were significantly greater than for methadone, 20 mg/d (6%). All treatments were well tolerated, with similar profiles of self-reported adverse effects. The percentages of patients who received counseling did not differ between groups.. Buprenorphine was as effective as methadone, 60 mg/d, and both were superior to methadone, 20 mg/d, in reducing illicit opioid use and maintaining patients in treatment for 25 weeks.

Topics: Adult; Buprenorphine; Double-Blind Method; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotics; Opioid-Related Disorders; Proportional Hazards Models

Eighty-five heroin addicts who were unwilling to receive methadone maintenance or enter therapeutic communities were assessed, single-blind, for the lowest sublingual dose of buprenorphine that blocked heroin craving (8.0 mg max). All doses were administered daily under observation. After maintenance for 4 to 12 weeks, abstinent subjects (confirmed by urine drug screens) entered a double-blind discontinuation trial and were randomly assigned to receive dose reductions (10% twice weekly for 5 weeks to zero dose, then placebo for 2 weeks) or a stable dose for 7 weeks. Subjects were terminated from discontinuation if heroin was used or they had increased craving/symptoms. Subjects completed the trial if they did not use heroin and had no increase in craving/symptoms. A wide dose range (1.5-8.0 mg/day) was effective in reducing heroin craving and use. Of 73 subjects who received buprenorphine for 4 to 52 weeks, 40 had no prior treatment, despite high levels (mean $/day heroin = 70.5 +/- 94.7) and many years (mean years = 10.7 +/- 8.6) of dependence. Subjects who received dose reductions developed abstinence symptoms, low energy most commonly, associated with drug-seeking behavior. Discontinuation trial outcome (n = 51) shows a highly significant difference between 29 subjects who received dose reductions (28 terminated, 1 completed) and 22 subjects who received no dose reductions (3 terminated; 19 completed) (chi-square = 36.08; p less than .00001). The findings suggest that buprenorphine could be an important medication for reducing demand for heroin by many heroin addicts who remain outside the present health-care system.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Female; Heroin Dependence; Humans; Male; Middle Aged

1. A 26-32 month follow-up of 16 heroin-dependent subjects who entered a pilot trial of treatment with buprenorphine (a mixed agonist/antagonist) suggests that positive response to treatment may identify a subgroup of untreated addicts whose levels of psychosocial functioning are intermediate between those for whom methadone (a pure agonist) or naltrexone (a pure antagonist) would be indicated. 2. Buprenorphine's pharmacologic profile provides a missing link in available modalities for opiate dependence treatment, making it acceptable for many addicts who will not accept methadone maintenance treatment, join a residential therapeutic community, or be successful on naltrexone treatment. 3. Eight of the 16 ss were abstinent from heroin while receiving 0.6-3.9 mg/day buprenorphine and counseling. Responders (mean age 34 yrs) had been heroin dependent for a mean of 9.5 years (range 6-17 yrs), all were self-supporting, 4 lived with a non-addicted spouse, 5 had no prior treatment for addiction and 3 had prior naltrexone treatment, but had discontinued it and relapsed. Non-responders (mean age 30 yrs) had been heroin dependent for a mean of 7.4 yrs (range 2-19 yrs), 7 had no regular employment, all were single and 7 had no prior treatment for addiction. 4. Levels of psychosocial functioning (work, home, leisure) and global assessments of functioning were significantly higher for buprenorphine responders than non-responders (p less than .001 and p less than .01 respectively). 5. A new formulation of buprenorphine needs to be developed for addiction treatment, ideally consisting of 0.5 mg and 2.0 mg sublingual tablets.

Topics: Adult; Buprenorphine; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Pilot Projects; Social Behavior; Substance Withdrawal Syndrome

Thirty-nine opioid-dependent outpatients were treated with the partial agonist buprenorphine at 2 to 6 mg/day for 1 month. Treatment retention was good (72%), and illicit opioid use decreased from 50% overall to 17% for those who remained in treatment. Precipitated withdrawal symptoms were mild and related to dose of buprenorphine. At the end of this month, 28 subjects were abruptly discontinued from buprenorphine and given the antagonist naltrexone. Withdrawal symptoms from buprenorphine were quite mild, and naltrexone was initiated in 20 patients (51% of total or 71% of those 28 completing 30 days on buprenorphine), but only 4 patients (10% overall) were successfully maintained on naltrexone for at least 2 weeks.

Topics: Adult; Buprenorphine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Methadone; Naltrexone; Neurologic Examination; Substance Withdrawal Syndrome

Topics: Adult; Buprenorphine; Cocaine; Dose-Response Relationship, Drug; Drug Evaluation; Heroin Dependence; Humans; Male; Methadone; Substance Abuse, Intravenous

Sublingual buprenorphine (8 mg) was administered to heroin-dependent addicts daily for 18 days and continued from day 19-day 36 either daily or on alternate days. Final data are reported on 18 subjects. The number of self-reported symptoms reviewed as potential adverse drug reactions ranged from 1 to 88 per participant. None was considered to be related definitely to the study medication, and there were no reporting differences between the two dosing regimens. Forty-five reactions were considered probably related to buprenorphine: sedation/drowsiness (three reports) and constipation (42 reports). It was concluded that these were anticipated drug effects rather than adverse reactions. Although some participants showed increases in serum aminotransferase levels, those increases could not be directly attributed to buprenorphine. We conclude that buprenorphine was well tolerated, but further study is needed in this population to delineate the possible attributable risk of the drug to hepatic dysfunction in this population.

Topics: Administration, Sublingual; Adult; Arousal; Buprenorphine; Drug Administration Schedule; Heroin Dependence; Humans; Male

Following one month of sublingual buprenorphine treatment, 15 patients at either 2 mg (n = 7) or 3 mg (n = 8) were hospitalized and the buprenorphine was abruptly stopped by placebo substitution. On the morning following their last dose of buprenorphine, 10 patients were given 1 mg oral naltrexone and 5 were given 0.5 mg/kg intravenous naloxone in a double blind placebo controlled challenge. The naltrexone challenges produced no increase in opioid withdrawal symptoms, plasma MHPG levels, or blood pressure compared to placebo, while naloxone produced significant symptoms and blood pressure increases compared to placebo challenges.

Topics: Administration, Sublingual; Adult; Buprenorphine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Heroin Dependence; Humans; Infusions, Intravenous; Male; Methadone; Naloxone; Naltrexone; Substance Withdrawal Syndrome

Nineteen heroin-dependent male volunteers were administered buprenorphine sublingually, in ascending daily doses of 2, 4, and 8 mg. They were maintained on 8 mg daily through study day 18. On study days 19 through 36, subjects in group 1 continued to receive burprenorphine daily; subjects in group 2 received buprenorphine or placebo on alternate days. On days 37 through 52, all subjects received placebo. Subjects receiving buprenorphine on alternate days reported significantly greater urge for an opioid, increased dysphoria scores, and pupillary dilation on placebo days. After abrupt termination of buprenorphine, no withdrawal signs were detected with the Himmelsbach scale. However, subjects reported mild-to-moderate opioid withdrawal symptoms, peaking at 3 to 5 and lasting for 8 to 10 days. Daily administration of buprenorphine provided greater control of subtle opioid withdrawal symptoms, but subjects could tolerate a between-dose interval of 48 hours.

Topics: Adult; Behavior; Buprenorphine; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Middle Aged; Miosis; Sleep; Substance Withdrawal Syndrome

The efficacy of buprenorphine and methadone was compared in the outpatient detoxification of heroin addicts. Forty-five patients were randomized to receive either sublingual buprenorphine or oral methadone under double-dummy and double-blind conditions to study the pharmacology of buprenorphine in a 90-day detoxification protocol. The patients were administered either 2 mg buprenorphine or 30 mg methadone for 3 weeks followed by 4 weeks of dose reductions and 6 weeks of placebo medication. No significant between-group differences were seen on measures of treatment retention, drug use, or symptom report. During the hydromorphone challenge, methadone attenuated opioid effects to a greater extent than did buprenorphine on both physiologic (pupil constriction) and self-report measures. However, this did not result in greater abuse of illicit opioid drugs by subjects taking buprenorphine. The results of this clinical trial indicated that buprenorphine was acceptable to patients and as effective as methadone in the detoxification treatment of heroin addicts.

Topics: Adult; Buprenorphine; Clinical Trials as Topic; Double-Blind Method; Heroin Dependence; Humans; Male; Methadone; Random Allocation

Sixteen opioid dependent patients were assigned to treatment with buprenorphine for one month at three doses--2 mg (n = 10), 4 mg (n = 4), 8 mg (n = 2). Treatment retention was excellent--only one patient left due to withdrawal symptoms. Illicit opioid use was infrequent, with only 22% of the urines containing illicit opioids. Although buprenorphine dose was not associated with retention or illicit opioid use, patterns of withdrawal symptoms differed among dosage groups during the 30 day study. The 4 mg group had a substantial decline in symptoms, while the other two groups did not. Symptom levels were comparable to those during successful clonidine detoxification and much lower than those found in clonidine failures.

Topics: Adult; Buprenorphine; Clinical Trials as Topic; Female; Heroin Dependence; Humans; Male; Methadone; Substance Withdrawal Syndrome

Topics: Adult; Analysis of Variance; Buprenorphine; Clinical Trials as Topic; Heroin Dependence; Humans; Hydromorphone; Male; Methadone; Narcotic Antagonists; Substance Withdrawal Syndrome

Heroin-dependent out-patients who had been prescribed buprenorphine by general practitioners took part in a controlled study in which 2 mg or 4 mg of buprenorphine were administered by the sublingual route to assess its acceptability as a maintenance opiate and to determine the effects of its abrupt withdrawal and reintroduction a week later. Subjects who received 4 mg of buprenorphine reported being more intoxicated and having fewer symptoms of opiate withdrawal than did the subjects who received the 2-mg dose. Subjects who received the higher dose also abused opiate and benzodiazepine drugs less frequently. When buprenorphine was ceased abruptly, the subjects reported mild withdrawal discomfort for which many requested symptomatic treatment. The reintroduction of buprenorphine caused their condition to restabilize. The subjects' use of opiate drugs, as shown by urine assay, rose from a prevalence of around 15% of specimens at the beginning to about 50% of specimens at the end of the five-week study period. Sublingual buprenorphine was acceptable to opiate-addicted outpatients as a maintenance treatment. However, daily doses of greater than 4 mg will probably be required to suppress concurrent opiate abuse, and detoxification will need to be undertaken gradually.

Topics: Administration, Oral; Adult; Buprenorphine; Dose-Response Relationship, Drug; Female; Heroin Dependence; Humans; Male; Morphinans; Narcotics; Patient Dropouts; Random Allocation; Substance Withdrawal Syndrome; Surveys and Questionnaires

Cigarette smoking increased during administration of buprenorphine, an opioid mixed agonist-antagonist, in comparison to drug-free baseline in seven heroin addicts maintained on buprenorphine for 24 days (P less than 0.01-0.001). Ascending buprenorphine doses (0.5 - 8.0 mg/day) were associated with significant increases in cigarette smoking at doses of 2.0 mg/day sc and above. Cigarette smoking during 10 days of buprenorphine maintenance at 8 mg/day was significantly higher than during the buprenorphine induction phase (P less than 0.01). Six subjects given placebo buprenorphine over 14 days showed no change in cigarette smoking. The placebo group self-administered heroin for 10 days, and cigarette smoking increased significantly during heroin use (P less than 0.001). The rate of cigarette smoking defined by intercigarette intervals was highest during the 10 days of high-dose buprenorphine maintenance or placebo plus heroin self-administration. Both groups requested significantly more cigarettes at intervals of 0-10, 11-20, and 21-30 min than during the drug-free baseline. These data confirmed previous findings that opioid agonist administration is associated with increased cigarette smoking and suggest that buprenorphine has primarily agonist effects on cigarette smoking.

Topics: Adult; Buprenorphine; Dextroamphetamine; Dose-Response Relationship, Drug; Endorphins; Ethanol; Heroin; Heroin Dependence; Humans; Male; Methadone; Morphinans; Smoking; Time Factors

Cigarette smoking increased during heroin self-administration in comparison to drug-free and methadone detoxification conditions in eight heroin addicts given naltrexone placebo (P less than 0.01) and three heroin addicts given buprenorphine placebo. Cigarette smoking was stable across conditions for one subject who did not use heroin during naltrexone blockade of heroin effects. Five subjects smoked significantly more (P less than 0.01) during the hour following a heroin injection than during the preceding hour, and two subjects in the same group smoked significantly less following a heroin injection (P less than 0.05). Subjects smoked significantly more during the evening and night when self-administering heroin than during baseline conditions (P less than 0.05), but subjects did not sleep significantly less during heroin self-administration. The peak of the intercigarette interval distribution remained between 16-30 min during baseline and heroin conditions. However, the increased smoking during heroin use appeared to reflect a higher rate of smoking rather than a generalized increase across intercigarette intervals. These data extend previous findings, that alcohol consumption is associated with increased cigarette smoking, to IV heroin self-administration.

Topics: Adult; Buprenorphine; Heroin Dependence; Humans; Male; Naltrexone; Self Administration; Smoking; Time Factors

Orexins regulate the reward-seeking pathway and also play a role in drug addiction. The aim of this study was an investigation of the changes in serum level of orexin-A as well as changes in the functional brain network in heroin use disorder (HUD) patients undergoing harm reduction therapy (HRT). Twenty-five HUD patients undergoing HRT that included methadone and buprenorphine, and 31 healthy control (HC) subjects, were enrolled for this study. Serum orexin-A levels and brain-derived neurotrophic factor were measured with assay kits. The functional brain network in HUD patients and HC was investigated and assessed using seed-based analysis and functional brain MRI scans. t Tested orexin-A levels were found to be significantly higher in HUD patients undergoing HRT than in HCs (P < .05). Analysis showed the functional activity of the right ventral anterior insula (RVAI) in HUD patients to be significantly lower than in HCs (P < .05, Family-Wise Error) corrected). In addition, the internetwork functional connectivity was significantly lower in the left nucleus accumbens and left dorsal anterior insula in the HUD subjects than in HCs (P < .05, Family-Wise Error corrected). In this study, no significant correlation between orexin-A levels and functional brain networks was found. However, the results suggest that HRT might increase orexin-A levels and decrease functional activity in RVAI in HUD patients.

Topics: Brain; Buprenorphine; Harm Reduction; Heroin; Heroin Dependence; Humans; Methadone; Orexins

Methadone and buprenorphine are the two maintenance treatments in opiate addicts authorised in France since the end of the 1990's. More recently, some African countries such as Senegal have implemented a new health policy focused on reducing the risks by encouraging the use of methadone as maintenance treatment. The objectives of maintenance therapy are to reduce morbidity and mortality related to the consumption of heroin and other street opioids, to promote the integration of drug users into the healthcare system, and more generally, to improve their social integration. However, this strategy might have limitations in practice. Here, we report the experience of the Integrated Addiction Treatment Center in Dakar, Senegal, and discuss ethical considerations at both the individual and collective levels, which may improve care of opiate-dependent users in practice, especially in Africa.. Traitement de substitution des usagers dépendants des opiacés - L’expérience du Centre de prise en charge intégré des addictions de Dakar.. La méthadone et la buprénorphine sont les deux traitements de substitution des opiacés autorisés en France depuis la fin des années 1990. Plus récemment, certains pays africains, comme le Sénégal, ont mis en place une nouvelle politique de santé axée sur la réduction des risques, en encourageant le recours aux traitements de substitution des opiacés. Les objectifs de la substitution sont de réduire la morbi-mortalité liée à la consommation d’héroïne ou d’autres opioïdes de rue, de favoriser l’insertion des usagers de drogue dans le système de soins, et, plus généralement, de faciliter leur insertion sociale. Cette nouvelle stratégie trouve néanmoins des limites dans la pratique. Nous rapportons dans cette revue l’expérience du Centre de prise en charge intégré des addictions de Dakar, au Sénégal, et proposons une réflexion éthique, tant individuelle que collective, afin d’améliorer le traitement de substitution des opiacés, notamment en Afrique.

Topics: Analgesics, Opioid; Buprenorphine; Heroin; Heroin Dependence; Humans; Methadone; Opiate Alkaloids; Senegal

Chronic exposure to illicit opioid drugs can cause serious health and social problems. However, less is known about the differential effect of various opioid treatments, such as methadone and buprenorphine, on neurocognitive domains such as compulsivity and impulsivity, despite their relevance to the treatment of opioid dependence.. A total of 186 participants were recruited with a cross-sectional design: i) illicit heroin users (n = 27), ii) former heroin users stabilized on methadone MMT (n = 48), iii) a buprenorphine maintenance treatment (BMT) group (n = 18), iv) an abstinent (ABS) group with a history of opioid dependence who were previously stabilized on MMT or BMT (n = 29) and v) healthy controls (HC) (n = 64). We used the Intra-Extra Dimensional Shift (IED) and Cambridge Gambling Task (CGT) paradigms for measuring compulsivity and impulsivity constructs respectively.. Heightened compulsivity persisted in the heroin, buprenorphine and abstinent groups. Heroin, methadone and buprenorphine groups exhibited impaired behavioral responses to feedback, consisting of increased deliberation time and poorer risk adjustment. Higher compulsivity measures were negatively associated with opioid dose which may reflect sedation effects.. Our results suggest that compulsivity and impulsivity are core neurocognitive dimensions for opioid dependence which differ in their presentation according to the stage of treatment. Participants taking higher morphine equivalent doses performed better in compulsivity measures. These findings have implications for the treatment of opioid dependence and longitudinal studies are warranted.

Topics: Buprenorphine; Cross-Sectional Studies; Heroin Dependence; Humans; Impulsive Behavior; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders

Despite rising morbidity and mortality from the opioid epidemic and other addictions, people who inject drugs (PWID) remain understudied regarding pain outcomes. Data among PWID regarding chronic pain and drug use, including non-medical use of opioids, is largely unknown. We examined the prevalence of chronic pain and drug use for pain in this population.. Standardized surveys captured self-report of demographics, chronic pain, and non-prescription drug use in 203 PWID in an urban syringe services program between April and November 2016. Chronic pain was defined as self-report of chronic pain diagnosis or persistent pains over the past 6 months.. Overall, 47% (95% CI, 40%-54%) of PWID reported chronic pain, while 35% (95% CI, 29%-42%) reported non-prescription drug use of any type for pain. Among those with chronic pain, drug use to treat pain was commonly reported (76%; 95% CI, 66%-83%). Non-medical opioid use did not differ among PWID with or without chronic pain or drug use for pain. A multivariable logistic regression model showed chronic pain was more likely among non-Hispanic whites and those with arthritis, older age, and homelessness.. Chronic pain serves as an important factor in the persistence of drug use in more than one-third of PWID in this sample. The high prevalence of chronic pain with drug use for pain suggests that proper pain management is likely to be an essential component of preventing or regressing injection drug use in PWID, with data needed on effective interventions for this population.

Topics: Adolescent; Adult; Age Factors; Analgesics, Opioid; Arthritis; Baltimore; Black or African American; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chronic Pain; Cocaine-Related Disorders; Female; Heroin Dependence; Humans; Ill-Housed Persons; Male; Middle Aged; Needle-Exchange Programs; Odds Ratio; Opioid-Related Disorders; Prevalence; Risk Factors; Substance Abuse, Intravenous; White People; Young Adult

Extended-release (XR) naltrexone can prevent relapse to opioid use disorder following detoxification. However, one of the barriers to initiating XR-naltrexone is the recommendation for a 7-10-day period of abstinence from opioids prior to the first dose.. The current study evaluated the feasibility of an XR-naltrexone induction protocol that can be implemented over 1 week in the outpatient clinic.. Participants (N = 44) were seen in the clinic daily. On Day 1, after abstaining from opioids for at least 12 h, they received buprenorphine 6-8 mg. Adjunctive medications (clonidine, clonazepam, zolpidem, trazodone, and prochlorperazine) were dispensed on Days 2-5, while ascending oral doses of naltrexone were given on Days 3-5 starting with 1 mg dose. An injection of XR-naltrexone was given on Day 5, 1 h after receiving and tolerating naltrexone 24 mg.. Of the 44 participants (38 males), 35 (80%) were heroin users and 9 (20%) used prescription opioids. A total of 26 participants (59%) completed the induction and received their first injection of XR-naltrexone. XR-naltrexone was initiated in 54% (19/35) of heroin users and 78% (7/9) of prescription opioid users.. The results support the feasibility of a week-long outpatient induction onto XR-naltrexone with ascending doses of naltrexone and standing doses of adjunctive medications. By circumventing the need for a protracted period of abstinence and mitigating the severity of withdrawal symptoms experienced during naltrexone titration, this strategy has the potential to increase patient acceptability and access to relapse prevention treatment with XR-naltrexone.

Topics: Adult; Buprenorphine; Delayed-Action Preparations; Feasibility Studies; Female; Heroin Dependence; Humans; Injections, Intramuscular; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Outpatients; Recurrence; Substance Withdrawal Syndrome; Young Adult

Highly potent synthetic opioids (HPSO) are increasingly responsible for opioid overdose deaths in the United States.. In an open-label, uncontrolled trial to test the feasibility of extended-release buprenorphine (BXR) injection treatment of heroin-using individuals with opioid use disorder testing positive for HPSO, participants were enrolled and began an induction with sublingual BXR (n = 5). During the induction, ancillary medications (clonidine, clonazepam, zolpidem, and prochlorperazine) were provided for breakthrough opioid withdrawal symptoms.. Two participants received the BXR injection on the second day of the induction and three participants on the third day.. All five participants were retained at least 1-month postinduction.. It may be feasible to provide BXR treatment to HPSO-positive heroin users rapidly to achieve clinical stabilization. (Am J Addict 2020;00:00-00).

Topics: Adult; Buprenorphine; Delayed-Action Preparations; Female; Heroin Dependence; Humans; Induction Chemotherapy; Injections; Male; Middle Aged; Narcotic Antagonists; Psychotropic Drugs; Substance Withdrawal Syndrome; Treatment Outcome

Several epidemiological studies have evaluated the role of illicit drug use in suicide behaviour.. To assess patients with opioid use disorder and suicidal intent related to behavior, severity of acute poisoning and the most commonly used non-opioid substances.. This cross sectional study included 67 patients diagnosed with opioid use disorder. The study was conducted at the University Clinic of Toxicology in Skopje over a 5-year period (2013-2017). The following variables were examined: gender, age, duration and route of opioid administration, duration of hospitalization, and types of substances used in acute poisoning. Assessment of patients’ behavior and severity of poisoning was made by using the Suicide Behaviours Questionnaire-Revised and the Poison severity score.. The majority of patients were male (88.1%). The mean age of patients was 30±6.1 years. The average duration of opioid use disorder was 8.5±3.9. A single poisoning was found in 62.7%, double poisoning in 25.4%, and triple poisoning in 11.9% of participants. Benzodiazepines were most commonly used by the patients (55.2%). The largest number of patients (32.8%) had minor Poison severity score (PSS), and only 17.9% had severe PSS. None of the patients had a fatal suicide attempt. 86.6% of patients had a score of ≥7 indicating a high risk of repeat suicide attempts.. Benzodiazepines were most commonly used as a single or combined substance in patients with opioid use disorder. PSS indicated that most of the participants were with minor PSS and with high risk of a repeat suicide attempt.

Topics: Adolescent; Adult; Analgesics, Opioid; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Buprenorphine; Caustics; Cross-Sectional Studies; Drug Overdose; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Poisoning; Republic of North Macedonia; Substance Abuse, Intravenous; Suicide, Attempted; Tramadol; Young Adult

Puffy hand syndrome is a rare complication of intravenous drug addiction. Diagnosis is based on the patient's history and clinical examination.. A woman and two men, aged 42, 39 and 36 years old, are described. All had a history of intravenous drug use of heroin and oral buprenorphine misuse. Puffy hand syndrome appeared during drug addiction (n = 2) or after its withdrawal (n = 1). It was associated with acrocyanosis (n = 1) or injection scars (n = 1). Upper limb ultrasonography showed sequelae of venous (n = 3) or arterial (n = 1) thrombosis. An upper limb lymphoscintigraphy in one patient showed decreased radionuclide uptake of axillary lymph node and subdermal reflux tracer in the forearm. Treatment was based on low-stretch bandages to reduce the volume and then elastic compression sleeve for long-term stabilization.. Puffy hand syndrome seen in intravenous drug addicts is poorly understood. It is a chronic complication despite the cessation of drug use. This syndrome has to become more widely known because its management is mandatory, although symptomatic.

Topics: Adult; Buprenorphine; Diagnosis, Differential; Female; Hand; Heroin Dependence; Humans; Lymphedema; Male; Opiate Substitution Treatment; Substance Abuse, Intravenous; Syndrome

In the context of the current US opioid crisis and the compelling fact that a quarter to a third of all those addicted to heroin pass through its prisons and jails each year, the care of incarcerated opioid-using individuals (OUI) needs to be improved.. Little has been published on the effectiveness or outcomes of heroin-assisted treatment (HAT), a treatment option for severely dependent OUI delivered in a prison setting. The aim of this study was therefore to evaluate such treatment since its implementation. The primary objective was to investigate whether heroin-assisted treatment was associated with severe detrimental health outcomes. The secondary objective was to compare the heroin-assisted treatment group with the general prison population in terms of occupational functioning.. Retrospective cohort study SETTING: An open prison with 120 places SUBJECTS: Data on 1885 male prisoners with a total of 2239 imprisonment periods between 2000 and 2015 was available. Ninety-seven inmates in heroin-assisted treatment were compared with 1788 inmates from the general prison population (reference group).. Mortality, medical complications (including overdoses), and work performance (days worked, sick days, and monthly wages earned).. Inmates receiving HAT were on average 1 year younger (33.8 vs. 34.9 years), had longer prison stays (7.3 vs. 3.0 months), were more often of Swiss nationality (68.0% vs. 28.9%), and had committed more drug- and property-related offenses (49.5% vs. 23.2% and 63.9% vs. 38.3%, respectively) compared to the reference group. No serious heroin-related medical complication occurred during the 15-year window of observation among inmates with heroin-assisted treatment. Their work performance was comparable to that of the reference group.. This study shows that heroin-assisted treatment can be a valuable treatment option for severely dependent OUI during imprisonment, can be delivered safely by prison health staff over extended periods of time, and allows OUI in treatment to achieve work performance rates comparable to that of the general prison population.

Topics: Adult; Buprenorphine; Heroin; Heroin Dependence; Humans; Male; Prisoners; Prisons; Program Evaluation; Retrospective Studies; Switzerland; Treatment Outcome; Work Performance

We assessed the efficacy of buprenorphine replacement taper therapy in a psychiatric hospital in Japan.. Based on the medical records, a retrospective analysis was performed to evaluate the outcomes of buprenorphine replacement taper therapy in 106 subjects with heroin dependence.. We found that replacement and taper therapy with buprenorphine could significantly reduce withdrawal symptoms during detoxification. In addition, the completion rate of detoxification was significantly improved and the length of hospital stay was significantly reduced relative to those who received conventional treatment without buprenorphine. However, the readmission rate increased after the introduction of detoxication therapy with buprenorphine.. The present findings suggest not only the efficacy and safety of buprenorphine replacement and taper therapy, but also the requirement for maintenance therapy for individuals with heroin dependence.

Topics: Adult; Buprenorphine; Female; Heroin Dependence; Hospitals, Psychiatric; Humans; Injections, Intramuscular; Japan; Length of Stay; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Retrospective Studies; Substance Withdrawal Syndrome

Switching from methadone to buprenorphine/naloxone remains a challenge for heroin users receiving methadone maintenance treatment (MMT). The present study aimed to investigate the predictors for failed switching from methadone to buprenorphine/naloxone among patients receiving MMT.. This 5-year retrospective study included 168 individuals (138 males and 30 females) with opioid dependence who attempted to switch from methadone to buprenorphine/naloxone at our MMT clinics in Taiwan. We excluded patients with psychiatric comorbidity and other substance use disorders except nicotine. A univariate Cox proportional hazards regression model (Cox model) was used to estimate the potential factors of subsequent failed switching, followed by a multivariate Cox model to identify significant predictors after adjusting for other covariates.. Seventy of the 168 participants (41.7%) failed switching from methadone to buprenorphine/naloxone. After forward selection in the Cox hazard regression model, a greater average dose of methadone (HR = 1.02; P = 0.01), greater maximal maintenance dose of MMT (HR = 1.02; P < 0.001), greater average dose of buprenorphine (HR = 1.10; P = 0.021), and lower average attendance rate during the three months before switching (HR = 0.09; P = 0.002) were significantly associated with failed switching.. This study with limited participants showed that dose of methadone, dose of buprenorphine, and attendance rates were significantly associated with failed switching. Clinicians should discuss with their patients about tapering the dose of methadone and improving their attendance if they want to switch from methadone to buprenorphine. Further studies are necessary to verify whether our findings generalize to other populations.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Comorbidity; Female; Heroin Dependence; Humans; Male; Methadone; Opiate Substitution Treatment; Retrospective Studies; Taiwan

Conducted in the Dayton Metropolitan area of Southwestern Ohio, this qualitative study explores the self-treatment practices of people who use illicit opioids (PWUIO) amidst the new risk environment produced by illicit, non-pharmaceutical fentanyl (NPF). We explore local perceptions of the presence of NPF in the Dayton area, and how this has both positively and negatively impacted practices of non-prescribed buprenorphine use among PWUIO.. This study analyzes qualitative data from 63 interviews conducted between October 2018 and June 2019. Participants were selected from a larger longitudinal study on non-prescribed buprenorphine use among individuals with opioid use disorder. Qualitative interviews were transcribed in their entirety, and their transcriptions were analyzed using NVivo software, drawing on a mix of thematic and inductive coding.. Interview respondents ranged from 19 to 70 years old, with a mean age of 38.9 years. 54% of them were male, and 85.7% identified as non-Hispanic White. 98.4% of the sample had used heroin, and 93.7% of the sample reported use of NPF. Participants agreed NPF dominated the illicit opioids market in the area, and was perceived as both dangerous and desirable. The domination of NPF and associated overdose experiences prompted some to seek positive change and initiate self-treatment with non-prescribed buprenorphine. For others, NPF sabotaged established practices of harm reduction, as unanticipated experiences of precipitated withdrawals prompted some participants to give up non-prescribed buprenorphine use as a tactic of self-treatment.. The changing nature of heroin/NPF necessarily gives rise to new beliefs surrounding self-treatment attempts, treatment seeking behaviors, and harm reduction practices. While buprenorphine treatment continues to offer promising results for treating opioid use disorders, it is urgent to reconsider how the unpredictable biochemical mixture of NPFs circulating on the streets today may impact the initiation and success of treatment.

Topics: Adult; Aged; Analgesics, Opioid; Buprenorphine; Drug Overdose; Female; Fentanyl; Heroin Dependence; Humans; Interviews as Topic; Longitudinal Studies; Male; Middle Aged; Ohio; Opioid-Related Disorders; Young Adult

We present a case of elective naloxone-induced opioid withdrawal followed by buprenorphine rescue to initiate opioid use disorder treatment in the emergency department. This strategy may represent a safe alternative to prescribing buprenorphine for outpatient initiation, a method that puts the patient at risk for complications of unmonitored opioid withdrawal, including relapse. After confirmation that the naloxone-induced withdrawal was adequately treated with buprenorphine, the patient was discharged with prescribed buprenorphine to follow up in an addiction medicine clinic, where he was treated 2 days later.

Topics: Administration, Intravenous; Adult; Buprenorphine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Emergency Service, Hospital; Heroin Dependence; Humans; Male; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Substance Withdrawal Syndrome

Options for opioid agonist therapy (OAT) are expanding with the development of prolonged-release (also known as extended-release) 1-week, 1-month, and 6-month formulations of buprenorphine. There is an assumption that patients will welcome these new treatments and medication adherence will correspondingly increase. However, there has been little research exploring patients' views of prolonged-release buprenorphine. This paper aims to understand which durations patients prefer and why, and to consider the findings with reference to the development of future OAT products.. Data were generated as part of a qualitative interview study. Fieldwork was conducted in London, UK, during 2018 (before any prolonged-release OAT formulations were licensed in Europe). Participants (n = 36) were taking daily oral OAT (methadone or buprenorphine) or using heroin daily without OAT. They included 26 men and 10 women, aged 24-63 years. All were asked for their views on weekly, monthly, and six-monthly duration buprenorphine. Responses were audio-recorded, transcribed, and analyzed by Iterative Categorization.. Participants generally stated that having buprenorphine of different prolonged durations was positive. They tended to believe that 'longer' prolonged-release formulations would be beneficial for patients who wanted to avoid thinking about drugs and drug-using associates, wished to evade the stigma of substance use, and desired 'normality' and 'recovery.' In contrast, participants favored 'shorter' prolonged-release formulations for patients who are new to OAT, worried about the safety and reliability/effectiveness of OAT, want a 'break' from street opioids, and need contact with services to monitor/support them. Participants indicated that transitioning between OAT medications of different duration would be a very individual process. Some also linked prolonged-release OAT duration to political, philosophical, and ethical issues, such as patient coercion and mental capability.. Medication duration is an important but complex feature of prolonged-release buprenorphine, with patients' views and preferences likely to be influenced by a wide range of factors. We need further qualitative research to explore the experiences of people who have actually used prolonged-release OAT. Meanwhile, drug developers should continue to build flexibility and choice into OAT products to ensure that future treatment is acceptable to patients and able to accommodate their diverse individual needs.

Topics: Adult; Analgesics, Opioid; Attitude to Health; Buprenorphine; Delayed-Action Preparations; Drug Implants; Female; Heroin Dependence; Humans; London; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Qualitative Research; Young Adult

Opioid overdose is a leading cause of death in persons experiencing homelessness (PEH), despite effective medications for opioid use disorder (OUD). In 2016, the San Francisco Street Medicine Team piloted a low barrier buprenorphine program with the primary goal of engaging and retaining PEH with OUD in care as a first step toward reducing opioid use and improving overall health.. To characterize the patients; assess treatment retention, retention on buprenorphine, and opioid use; and to describe adverse events.. Retrospective chart review of patients receiving at least one buprenorphine prescription from Street Medicine (November 2016-October 2017). We abstracted demographic, medical, substance use, prescription, and health care utilization data from medical records. We assessed retention in care at 1, 3, 6, 9 and 12 months, defined as a provider visit 1 week prior to or any time after each time point. We considered patients to be retained on buprenorphine if they had active buprenorphine prescriptions for more than 2 weeks of the month. We estimated opioid use by the percentage of patients with any opioid-negative, buprenorphine-positive urine toxicology test. We reviewed emergency department and hospital records for adverse events, including deaths and nonfatal opioid overdoses.. Among the 95 persons eligible for analysis, mean age was 39.2, and 100% reported injecting heroin and homelessness. Medical and psychiatric comorbidities and co-occurring substance use were common. The percentages of patients retained in care at 1, 3, 6, 9 and 12 months were 63%, 53%, 44%, 38%, and 26%, respectively. The percentages of patients retained on buprenorphine at 1, 3, 6, 9 and 12 months were 37%, 27%, 27%, 26%, and 18%, respectively. Twenty-three percent of patients had at least one opioid-negative, buprenorphine-positive test result. One patient died from fentanyl overdose, and four patients presented on six occasions for non-fatal overdoses requiring naloxone.. This program engaged and retained a subset of PEH with OUD in care and on buprenorphine over 12 months. While uninterrupted treatment and abstinence are reasonable outcomes for conventional treatment programs, intermittent treatment with buprenorphine and decreased opioid use were more common in this pilot and may confer important reductions in opioid and injection-related harms.

Topics: Adult; Aged; Buprenorphine; Comorbidity; Drug Overdose; Female; Heroin Dependence; Humans; Ill-Housed Persons; Male; Mental Disorders; Middle Aged; Narcotic Antagonists; Opioid-Related Disorders; Patient Acceptance of Health Care; Retrospective Studies; San Francisco; Socioeconomic Factors; Young Adult

Improving access to treatment for opioid use disorder is a national priority, but little is known about the barriers encountered by patients seeking buprenorphine-naloxone ("buprenorphine") treatment.. To assess real-world access to buprenorphine treatment for uninsured or Medicaid-covered patients reporting current heroin use.. Audit survey ("secret shopper" study).. 6 U.S. jurisdictions with a high burden of opioid-related mortality (Massachusetts, Maryland, New Hampshire, West Virginia, Ohio, and the District of Columbia).. From July to November 2018, callers contacted 546 publicly listed buprenorphine prescribers twice, posing as uninsured or Medicaid-covered patients seeking buprenorphine treatment.. Rates of new appointments offered, whether buprenorphine prescription was possible at the first visit, and wait times.. Among 1092 contacts with 546 clinicians, schedulers were reached for 849 calls (78% response rate). Clinicians offered new appointments to 54% of Medicaid contacts and 62% of uninsured-self-pay contacts, whereas 27% of Medicaid and 41% of uninsured-self-pay contacts were offered an appointment with the possibility of buprenorphine prescription at the first visit. The median wait time to the first appointment was 6 days (interquartile range [IQR], 2 to 10 days) for Medicaid contacts and 5 days (IQR, 1 to 9 days) for uninsured-self-pay contacts. These wait times were similar regardless of clinician type or payer status. The median wait time from first contact to possible buprenorphine induction was 8 days (IQR, 4 to 15 days) for Medicaid and 7 days (IQR, 3 to 14 days) for uninsured-self-pay contacts.. The survey sample included only publicly listed buprenorphine prescribers.. Many buprenorphine prescribers did not offer new appointments or rapid buprenorphine access to callers reporting active heroin use, particularly those with Medicaid coverage. Nevertheless, wait times were not long, implying that opportunities may exist to increase access by using the existing prescriber workforce.. National Institute on Drug Abuse.

Topics: Ambulatory Care; Appointments and Schedules; Buprenorphine; Health Expenditures; Health Services Accessibility; Heroin Dependence; Humans; Medicaid; Medical Audit; Medically Uninsured; Narcotic Antagonists; Office Visits; Time-to-Treatment; United States

To analyse predictors of heroin abstinence in opiate substitution therapy (OST) based on frequency of crack use and its interactions with other predictors in a clinical non-experimental setting.. Retrospective study.. A community drug service in London, UK.. 325 clients starting OST between 2010 and 2014 (197 methadone and 128 buprenorphine).. Logistic regression models (a general model and separate models for methadone and buprenorphine) assessed demographic and clinical data as predictors of heroin abstinence at one year after treatment start (or at the date of transfer to another service).. For the general model participants choosing methadone were more likely to use heroin at follow up (OR=2.36, 95% CI: 1.40-3.17) as were daily crack users on methadone (OR=2.62, 95% CI: 0.96-7.16). For the methadone model only daily crack use predicted heroin use at follow up (OR=2.62, 95% CI: 0.96-7.16). For buprenorphine, higher amounts of baseline heroin use, lower buprenorphine dose and daily drinking predicted heroin use at follow up (OR=0.85, 95% CI: 0.75-0.95; OR=1.31, 95% CI: 1.06-1.60 and OR=6.04, 95% CI: 1.26-28.92). Both use of cannabis and depression increased likelihood of heroin abstinence for clients not using crack compared to occasional (OR=6.68, 95% CI: 0.37-119.59; OR=106.31, 95% CI: 3.41-3313.30) and daily (OR=57.49 (95% CI: 2.37-1396.46; OR=170.99 (95% CI: 4.61-6339.47) users.. Most of the predictors in the general model were found significant only in the buprenorphine but not in the methadone model, suggesting that a general model has little predictive value. Crack use was a significant predictor of heroin abstinence at follow up in all models, however for buprenorphine only when depression or cannabis use was present. Further research is needed to assess effective treatment approaches for the growing population of dual users.

Topics: Adult; Aged; Analgesics, Opioid; Buprenorphine; Cocaine-Related Disorders; Comorbidity; Female; Heroin Dependence; Humans; London; Male; Methadone; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Retrospective Studies; Treatment Outcome; Young Adult

Data at the individual-level provide evidence that opioid substitution treatment (OST) programs protect against mortality for opioid dependent populations. Prior research has not examined the merits of national implementation of opioid substitution programs for reducing mortality at the country-level. This study elucidates longitudinal associations between country-level implementation of opioid substitution treatment programs on mortality rates of drug related deaths (DRD) from 1995 to 2013 in 30 European nations. Cases of DRD were measured using National Definitions for each country from official sources of data. Preliminary analysis of dispersion of cases of DRD using means and variances justified use of the negative binomial regression model with a population offset. Year and country-level fixed effects negative binomial regression models investigated the association between years of implementation of methadone maintenance therapy (MMT), OST in prison, and high dose buprenorphine treatment (HDBT) implementation and mortality rates from drug related deaths after adjusting for unemployment rates, heroin seizures and per capita expenditures on health. Beta coefficients were converted to Incidence Rate Ratios (IRR) and standard errors bootstrapped using non-parametric methods to adjust for bias (SD

Topics: Analgesics, Opioid; Buprenorphine; Drug Overdose; Europe; Heroin Dependence; Humans; Methadone; Opiate Substitution Treatment

To explore potential study participants' views on willingness to join clinical trials of pharmacological interventions for illicit opioid use to inform and improve future recruitment strategies.. Qualitative focus group study [six groups: oral methadone (two groups); buprenorphine tablets (two groups); injectable opioid agonist treatment (one group); and former opioid agonist treatment (one group)].. Drug and alcohol services and a peer support recovery service (London, UK).. Forty people with experience of opioid agonist treatment for heroin dependence (26 males, 14 females; aged 33-66 years).. Data collection was facilitated by a topic guide that explored willingness to enrol in clinical pharmacological trials. Groups were audio-recorded and transcribed. Transcribed data were analysed inductively via Iterative Categorization.. Participants' willingness to join pharmacological trials of medications for opioid dependence was affected by factors relating to study burden, study drug, study design, study population and study relationships. Participants worried that the trial drug might be worse than, or interfere with, their current treatment. They also misunderstood aspects of trial design despite the researchers' explanations.. Recruitment of participants for clinical trials of pharmacological interventions for illicit opioid use could be improved if researchers became better at explaining clinical trials to potential participants, dispelling misconceptions about trials and increasing trust in the research process and research establishment. A checklist of issues to consider when designing pharmacological trials for illicit opioid use is proposed.

Topics: Adult; Aged; Attitude to Health; Buprenorphine; Clinical Trials as Topic; Female; Focus Groups; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Selection; Qualitative Research

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Heroin Dependence; Humans; Substance Withdrawal Syndrome; Takotsubo Cardiomyopathy; Treatment Outcome

Opioid dependence is a major health concern across the world and does also occur in adolescents. While opioid substitution treatment (OST) has been thoroughly evaluated in adult populations, very few studies have examined its use in adolescents. There are concerns that OST is underutilised in adolescents with heroin dependence. We sought to measure changes in drug use among adolescents receiving OST and also to examine treatment attrition during the first 12 months of this treatment.. We included all heroin dependent patients aged under 18.5 years commencing OST at one outpatient multidisciplinary adolescent addiction treatment service in Dublin, Ireland. Psycho-social needs were also addressed during treatment. Drug use was monitored by twice weekly urine drugs screens (UDS). Change in the proportion of UDS negative for heroin was examined using the Wilcoxon signed rank test. Attrition was explored via a Cox Regression multivariate analysis.. OST was commenced by 120 patients (51% female and mean age 17.3 years). Among the 39 patients who persisted with OST until month 12, heroin abstinence was 21% (95% confidence interval [CI] = 9-36%) at month three and it was 46% (95% CI = 30-63%) at month 12. Heroin use declined significantly from baseline to month three (p < 0.001) and from month three to month 12 (p = 0.01). Use of other drugs did not change significantly. People using cocaine during month 12 were more likely to be also using heroin (p = 0.02). Unplanned exit occurred in 25% patients by 120 days. The independent predictors of attrition were having children, single parent family of origin, not being in an intimate relationship with another heroin user and evidence of cocaine use just before treatment entry.. We found that heroin dependent adolescent patients achieved significant reductions in heroin use within three months of starting OST and this improved further after a year of treatment, about half being heroin abstinent at that stage. Patient drop out from treatment remains a challenge, as it is in adults. Cocaine use before and during treatment may be a negative prognostic factor.

Topics: Adolescent; Buprenorphine; Cocaine-Related Disorders; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Medication Adherence; Methadone; Opiate Substitution Treatment; Patient Dropouts

Tourette syndrome (TS) is a neurodevelopmental disorder with a high prevalence of psychiatric comorbidity. The most common comorbid disorder in patients with TS is attention-deficit/hyperactivity disorder (ADHD). To date, there have been few reports concerning the association of TS with addiction.. We report on 4 patients with TS, ADHD, and heroin addiction.. All 4 patients were male and initially presented with TS when they were between 5 and 12 years of age, although 2 of the patients were not diagnosed with TS until they were adults. The patients currently range in age from 21 to 52 years, all having experienced the onset of heroin addiction in adolescence. A reduction in tics during periods of heroin abuse was noted in all patients.. The lifetime prevalence of psychiatric comorbidity in patients with TS is 85.7%, with 57.7% of patients having ≥2 psychiatric conditions in addition to TS. All of the 4 patients in our case series demonstrated a pattern of severe tics, ADHD, impulsive behavior, and heroin addiction. Our observation that these 4 patients with TS showed reduced tics during periods of heroin dependence could be related to the previously described effects of opiates on dopaminergic transmission.. The observed reduction of tics during heroin dependence warrants further clinical research.

Topics: Adult; Age of Onset; Attention Deficit Disorder with Hyperactivity; Buprenorphine; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotics; Opiate Substitution Treatment; Serbia; Tourette Syndrome; Young Adult

Heroin-dependent adolescents demonstrate high rates of comorbid psychological problems. Among heroin-dependent adults, opiate substitution treatment (OST) programmes appear to reduce mental health problems. We sought to examine the impact of OST on psychological well-being in adolescents, as this is unknown.. We conducted a prospective study examining psychological well-being in heroin dependent adolescents, aged 18 years or younger, engaged in outpatient psychologically supported OST. Patients were treated with either methadone or buprenorphine. This was complimented with individual key working, counselling (motivational interviewing and cognitive behavioral therapy) and group work focusing on life skills. The Beck Youth Inventory was used to measure psychological well-being at treatment entry and repeated after 4 months of treatment.. Among 55 consecutive treatment episodes, we examined the 32 episodes where the patient persisted with the OST programme. Polysubstance use was the norm at treatment entry. At follow-up, the median doses of methadone and buprenorphine were 50 mgs and 8 mgs, respectively. Only three patients were treated with antidepressant medication. There was significant improvement in the mean depression (65.0 to 57.9, P = 0.001), anxiety (61.7 to 57.0, P = 0.006) and anger (57.8 to 54.6, P = 0.009) subscale scores. The self-concept and disruptive behaviour subscale scores did not improve significantly.. In this relatively short-term follow-up, psychosocially assisted OST appears to be associated with improved psychological well-being in heroin-dependent adolescents, especially in the area of depressive and anxiety symptoms.

Topics: Adolescent; Adolescent Behavior; Anger; Anxiety; Buprenorphine; Combined Modality Therapy; Depression; Female; Heroin Dependence; Humans; Male; Methadone; Opiate Substitution Treatment; Problem Behavior; Prospective Studies; Psychotherapy; Self Concept

In many countries, the opioid agonists, buprenorphine and methadone, are licensed for maintenance treatment of opioid dependence. Many short-term studies have been performed, but little is known about long-term effects. Therefore, this study described over 6 years (1) mortality, retention and abstinence rates and (2) changes in concomitant drug use and somatic and mental health.. A prevalence sample of n = 2,694 maintenance patients, recruited from a nationally representative sample of n = 223 substitution doctors, was evaluated in a 6-year prospective-longitudinal naturalistic study. At 72 months, n = 1,624 patients were assessed for outcome; 1,147 had full outcome data, 346 primary outcome data and 131 had died; 660 individuals were lost to follow-up.. The 6-year retention rate was 76.6%; the average mortality rate was 1.1%. During follow-up, 9.4% of patients became "abstinent" and 1.9% were referred for drug-free addiction treatment. Concomitant drug use decreased and somatic health status and social parameters improved.. The study provides further evidence for the efficacy and safety of maintenance treatment with opioid agonists. In the long term, the number of opioid-free patients is low and most patients are more or less continuously under opioid maintenance therapy. Further implications are discussed.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Heroin Dependence; Humans; Longitudinal Studies; Male; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Prevalence; Prospective Studies; Surveys and Questionnaires; Treatment Outcome

Attention Deficit Hyperactivity Disorder (ADHD) is a risk for substance use disorders. The aim of this study was to investigate the association between adult ADHD symptoms, opioid use disorder, life dysfunction and co-occurring psychiatric symptoms. 1057 heroin dependent patients on opioid substitution treatment participated in the survey. All patients were screened for adult ADHD symptoms using the Adult ADHD Self-Report Scale (ASRS-v1.1). 19.4% of the patients screened positive for concurrent adult ADHD symptoms status and heroin dependence. Education level was lower among patients with ADHD symptoms, but not significant with respect to non-ADHD patients. Patients with greater ADHD symptoms severity were less likely to be employed. A positive association was observed between ADHD symptoms status and psychiatric symptoms. Patients with ADHD symptoms status were more likely to be smokers. Patients on methadone had a higher rate of ADHD symptoms status compared to buprenorphine. Those individuals prescribed psychoactive drugs were more likely to have ADHD symptoms. In conclusion, high rate of ADHD symptoms was found among heroin dependent patients, particularly those affected by the most severe form of addiction. These individuals had higher rates of unemployment, other co-morbid mental health conditions, heavy tobacco smoking. Additional psychopharmacological interventions targeting ADHD symptoms, other than opioid substitution, is a public health need.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Behavior, Addictive; Buprenorphine; Comorbidity; Female; Heroin Dependence; Humans; Male; Mental Disorders; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Psychiatric Status Rating Scales; Quality of Life; Substance-Related Disorders; Surveys and Questionnaires; Young Adult

Topics: Alcoholism; Antisocial Personality Disorder; Buprenorphine; Heroin Dependence; Humans; Male; Medication Errors; Middle Aged; Naltrexone; Narcotic Antagonists; Substance Withdrawal Syndrome

Topics: Buprenorphine; Heroin Dependence; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders

Topics: Buprenorphine; Drug Overdose; Heroin Dependence; Humans; Methadone; Needle-Exchange Programs; Opiate Substitution Treatment; Substance Abuse, Intravenous; United States

Methadone has long been regarded as an effective treatment for opioid dependence. However, many patients discontinue maintenance therapy because of its side effects, with one of the most common being sexual dysfunction. Buprenorphine is a proven alternative to methadone. This study aimed to investigate sexual dysfunction in opioid-dependent men on buprenorphine maintenance treatment (BMT) and methadone maintenance treatment (MMT). The secondary aim was to investigate the correlation between sexual dysfunction and the quality of life in these patients.. Two hundred thirty-eight men participated in this cross-sectional study. Four questionnaires were used, the Mini International Neuropsychiatric Interview, Opiate Treatment Index, Malay version of the International Index of Erectile Function 15 (Mal-IIEF-15), and World Health Organization Quality of Life-BREF Scale. Multivariate analysis of covariance was used to examine the relationship between MMT and BMT and the Mal-IIEF 15 scores while controlling for all the possible confounders.. The study population consisted of 171 patients (71.8%) on MMT and 67 (28.2%) on BMT. Patients in the MMT group who had a sexual partner scored significantly lower in the sexual desire domain (p < 0.012) and overall satisfaction (p = 0.043) domain compared with their counterparts in the BMT group. Similarly, patients in the MMT group without a sexual partner scored significantly lower in the orgasmic function domain (p = 0.008) compared with those in the BMT group without a partner. Intercourse satisfaction (p = 0.026) and overall satisfaction (p = 0.039) were significantly associated with the social relationships domain after adjusting for significantly correlated sociodemographic variables.. Sexual functioning is critical for improving the quality of life in patients in an opioid rehabilitation program. Our study showed that buprenorphine causes less sexual dysfunction than methadone. Thus, clinicians may consider the former when treating heroin dependents who have concerns about sexual function.

Topics: Adult; Buprenorphine; Cross-Sectional Studies; Erectile Dysfunction; Heroin Dependence; Humans; Maintenance Chemotherapy; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Quality of Life

To test if polysubstance use profiles and drug-related outcomes differ between those receiving and not receiving opioid substitution therapies (OST) among people who inject drugs (PWID).. An annual cross-sectional, sentinel sample of PWID across Australia.. Data came from 3 years (2011-13) of the Illicit Drug Reporting System (IDRS).. A total of 2673 participants who injected drugs from the combined national IDRS samples of 2011 (n = 868), 2012 (n = 922) and 2013 (n = 883).. Latent class analysis (LCA) was used to summarize participants' self-reported use of 18 types of substances, with the resulting polysubstance use profiles then associated with participant experience of a number of drug-related outcomes.. Polysubstance use profiles exhibiting a broad range of substance use were generally at increased risk of negative drug-related outcomes, whether or not participants were receiving OST, including thrombosis among OST receivers [odds ratio (OR) = 2.13, 95% confidence intervals (CI) = 1.09-4.17], injecting with used needles among OST receivers and non-receivers, respectively (OR = 2.78, 95% CI = 1.50-5.13; OR = 2.15, 95% CI = 1.34-3.45) and violent criminal offences among OST receivers and non-receivers, respectively (OR =2.30, 95% CI = 1.16-4.58; OR = 1.87, 95% CI = 1.14-3.07). An important exception was non-fatal overdose which was related specifically to a class of PWID who were not receiving OST and used morphine frequently (OR = 1.83, 95% CI = 1.06-3.17) CONCLUSION: Regardless of opioid substitution therapies usage, people who inject drugs who use a broad-range of substances experience greater levels of injecting-related injuries and poorer health outcomes and are more likely to engage in criminal activity than other groups of people who inject drugs.

Topics: Abscess; Adolescent; Adult; Alcoholism; Amphetamine-Related Disorders; Analgesics, Opioid; Australia; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Cocaine-Related Disorders; Cross-Sectional Studies; Drug Overdose; Female; Heroin Dependence; Humans; Male; Marijuana Abuse; Methadone; Middle Aged; Needle Sharing; Odds Ratio; Opiate Substitution Treatment; Opioid-Related Disorders; Substance Abuse, Intravenous; Substance-Related Disorders; Thrombosis; Violence; Young Adult

Preoperative narcotic use has been associated with poor outcomes after total joint arthroplasty (TJA). The purpose of this study is to compare clinical outcomes of patients undergoing elective TJA while concurrently being treated with methadone or buprenorphine/naloxone for prior heroin addiction to a matched control group.. From an electronic medical record, we collected age, gender, body mass index, the presence of back pain, smoking status, history of alcohol abuse, preoperative use of a pain clinic, and use of antipsychotics, antidepressants, or systemic corticosteroids. Validated outcome measures including the 12-Item Short Form Survey, Knee Society Score (KSS), and Harris Hip Score were used to assess functional outcomes preoperatively and postoperatively. Perioperative data were retrospectively obtained from patient charts. Postoperative functional outcomes were prospectively collected at follow-up visits. Subjects were matched to 2:1 control group on the basis of procedure, sex, diagnosis, age (±5 years), and body mass index (±5 kg/m(2)). Average follow-up was 27.2 months.. Significant preoperative differences between the groups included mean morphine-equivalent requirements (997.1 mg for study group vs 24.8 mg for controls), 12-Item Short Form Survey Mental Component Scores (MCS-12; 37.8 for study group vs 49.0 for controls), smoking history, and antipsychotic medication use. Perioperative referral to inpatient Acute Pain Service and mean in-hospital morphine-equivalent narcotic usage (793 mg/24 h for study group vs 109 mg/24 h for controls) also significantly differed between groups. Knee range of motion differed significantly between the cohorts at 1 year (77.5 for study group vs 109.4); however, no significant difference in KSS pain (87.6 vs 84.4), KSS function (61 vs 80.9), Harris Hip Score (89.2 vs 85.3), MCS-12 (47.1 vs 52.9), or complications was observed.. Equivalent pain control and successful clinical outcome at 1 year can be achieved in patients who use methadone or buprenorphine/naloxone preoperatively.

Topics: Aged; Arthroplasty, Replacement; Buprenorphine; Cohort Studies; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Pain Management; Pain, Postoperative; Prospective Studies; Registries; Retrospective Studies; Treatment Outcome

Psychiatric comorbidities complicate treatment of patients with chronic pain and opioid use disorder, but the prevalence of specific comorbid psychiatric disorders in this population has not been systematically investigated.. 170 consecutive participants entering a treatment research program for co-occurring chronic pain and opioid use disorder between March 2009 and July 2013 were evaluated with the Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID-I/P) and the Diagnostic Interview for DSM-IV Personality Disorders (DIPD-IV).. The prevalence of any lifetime (and current) comorbid Axis I disorder was 91% (75%); 52% met criteria for lifetime anxiety disorder (48% current), 57% for lifetime mood disorder (48% current), and 78% for lifetime nonopioid substance use disorder (34% current). Common current anxiety diagnoses were posttraumatic stress disorder (21%), generalized anxiety disorder (16%), and panic disorder without agoraphobia (16%). Common current mood diagnoses were major depressive disorder (40%) and dysthymia (11%). A majority of patients had a personality disorder (52%).. High rates and persistence of co-occurring psychiatric disorders, including anxiety or mood disorders, may explain in part the difficulty providers have treating patients with co-occurring opioid use disorder and chronic pain and suggest possible targets for improving treatment.. ClinicalTrials.gov identifiers: buprenorphine/naloxone treatment (NCT00634803), opioid treatment program-based methadone maintenance treatment (NCT00727675).

Topics: Adult; Buprenorphine; Chronic Pain; Comorbidity; Cross-Sectional Studies; Disability Evaluation; Female; Heroin Dependence; HIV Seropositivity; Humans; Illicit Drugs; Male; Mental Disorders; Methadone; Middle Aged; Naloxone; Opioid-Related Disorders; Pain Measurement; Prescription Drugs; Young Adult

Objectives To evaluate prevalence and severity of constipation and quality of life (QoL) in a cohort of opioid-addicted patients treated with opioid substitution treatments (OST).. A total of 1057 heroin-dependent patients treated with methadone or buprenorphine were enrolled in a multicenter observational study. Constipation was assessed by Wexner Constipation Scoring System (Wexner CSS), QoL by General Health Questionnaire (GHQ-12).. 38.5% patients reported mild constipation, 33.3% reported moderate constipation, 14.8% severe constipation and 5.1% very severe constipation. Mean Wexner CSS score was 6.6 ± 4.8. 44.9% patients showed a GHQ-12 score ≥14; of these 18.3% patients showed a GHQ-12 score ≥20. Mean GHQ score was 13.8 ± 6.5. Mean Wexner CSS score was significantly higher in methadone patients (p = 0.004), in those taking psychoactive drugs (p = 0.0001) and in female (p < 0.0001) with respect to counterparts. Similarly, GHQ-12 mean scores were higher methadone group (p = 0.003), in those taking psychoactive drugs (p < 0.0001), and in female (p = 0.039) with respect to counterparts. ANOVA and ANCOVA showed a significant influence of methadone and female gender on Wexner CSS score while psychoactive drugs significantly influenced both tests.. The present study shows that patients affected by opioid-dependence in OST with methadone and buprenorphine have a high prevalence of constipation and reduced QoL.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Constipation; Female; Heroin Dependence; Humans; Italy; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Prevalence; Quality of Life

The United Kingdom Drug Strategy emphasises recovery as a key focus in the treatment of drug dependence. A framework for recovery is defined in the Recovery-Orientated Drug Treatment report, written by an expert working group, and comprises four key phases: engagement and stabilisation, including the establishment of treatment goals; preparation for change, involving engagement in psychosocial and pharmacological interventions; active change, including detoxification and medical withdrawal; and completion, including interventions that strengthen community integration. A body of evidence supports the benefits of buprenorphine, a partial agonist at mu opioid receptors, in supporting individualised recovery based on this framework, specifically in relation to the potential for rapid stabilisation, flexibility to transition to other treatment options or achieve abstinence, effective blocking of on-top use of illicit drugs, the treatment of comorbidities through the minimisation of drug-drug interactions, and a good safety profile. In addition, the newer abuse-deterrent formulation of buprenorphine combined with the opioid antagonist naloxone is likely to strengthen recovery-orientated systems of care due to its potential to reduce misuse and diversion. Progress through the recovery journey and the ability to sustain recovery will depend on individual needs and goals and on the amount of recovery capital that individuals have developed.

Topics: Buprenorphine; Drug Therapy, Combination; Heroin Dependence; Humans; Narcotics; Opiate Substitution Treatment; United Kingdom

The United States has the highest rate of incarceration in the world (937 per 100,000 adults). Approximately one-third of heroin users pass through correctional facilities annually. Few receive medication assisted treatment (MAT; either methadone or buprenorphine) for opioid use disorder during incarceration, and nearly three-quarters relapse to heroin use within 3 months of release. This qualitative study investigated barriers to and facilitators of buprenorphine maintenance treatment (BMT) following release from incarceration ("re-entry").. We conducted 21 semistructured interviews of former inmates with opioid use disorder recruited from addiction treatment settings. Interviews were audio-recorded, transcribed, and analyzed using a grounded theory approach. Themes that emerged upon iterative readings of transcripts were discussed by the research team.. Participants reported adverse re-entry conditions, including persistent exposure to drug use and stressful life events, which were perceived to contribute to opioid relapse and affected addiction treatment decisions during re-entry. Themes that emerged relating to BMT included: 1) reliance on willpower; 2) fear of dependency on medications; 3) variable exposure to buprenorphine; and 4) acceptability of BMT following relapse. Willpower was perceived to be more important for recovery than medications. Many participants experienced painful withdrawal from methadone during incarceration and were fearful that using MAT would lead to opioid tolerance and painful withdrawal again in the future. Participants reported both positive and negative experiences taking illicit buprenorphine, which affected interest in BMT. Overall, BMT was perceived to be a good treatment option for opioid use disorder that could reduce the risk of re-incarceration.. BMT was perceived to be acceptable, but former inmates with opioid use disorder may be reluctant to utilize BMT upon re-entry. Factors limiting utilization of BMT could be mitigated though policy change or interventions. Policies of the criminal justice system (e.g., forced detoxification) may be dissuading former inmates from utilizing effective treatments for opioid use disorder. Interventions that improve education and access to BMT for former inmates with opioid use disorder could facilitate entrance into treatment. Both policy changes and interventions are urgently needed to reduce the negative consequences of opioid relapse following re-entry.

Topics: Buprenorphine; Female; Goals; Heroin Dependence; Humans; Interviews as Topic; Male; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Prisoners; Qualitative Research; Racial Groups; Recurrence; Self Efficacy; United States

The aim of this study was to develop and validate a method for the determination of buprenorphine (BUP), norbuprenorphine (NBUP) and naloxone (NAL) in fingernails and urine samples collected from former heroin users under suboxone substitution therapy. The analytes were extracted by solid-liquid or solid-phase extraction and were analyzed by liquid chromatography-mass spectrometry. The validation of the analytical methods developed included linearity, recovery, accuracy, precision, ion suppression, sensitivity of interfaces and limits of determination and quantification. The validated methods were applied to samples from 46 individuals. The majority of the urine samples were positive for all analytes (93.5% for BUP, 95.7% for NBUP and 84.8% for NAL). In nails, a higher detection rate was observed for NBUP and BUP (89.1%), compared with NAL (10.9%). The median values of the NBUP/BUP and the NAL/BUP ratio were 2.5 and 0.3 in urine and 0.8 and 0.3 in nails, respectively. A statistically significant correlation was found between the BUP, NBUP and total BUP (BUP and NBUP) concentrations in urine and those in nails. A weak correlation was observed between the daily dose (mg/day) and total BUP (P = 0.069), or NBUP (P = 0.072) concentrations in urine. In contrast, a strong correlation was found between the total amount of BUP administered during the last 12 months and total BUP (P = 0.038), or NBUP (P = 0.023) concentrations in urine. Moreover urine BUP, NBUP and total BUP concentrations correlated significantly. Our study demonstrated successfully the application of the developed method for the determination of the three analytes in urine and nails.

Topics: Adult; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chromatography, Liquid; Female; Heroin Dependence; Humans; Male; Mass Spectrometry; Nails; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Reproducibility of Results; Sensitivity and Specificity; Solid Phase Extraction

A seven-year follow-up of heroin dependent patients treated in a buprenorphine-maintenance program combining contracted work/education and low tolerance for non-prescribed drug use. Gender-specific differences in outcome were analysed.. A consecutively admitted cohort of 135 men and 35 women, with eight years of heroin abuse/dependence on average was admitted to enhanced buprenorphine maintenance treatment. Standardized interviews, diagnostic assessments of psychiatric disorders and psychosocial conditions were conducted at admission and at follow-ups. Outcome associated with gender was reported for abstinence, retention, psychiatric symptoms, employment and criminal convictions.. 148 patients started treatment. After seven years, 94/148 patients (64%) were retained in the program, employed and abstinent from drugs and alcohol. Women had more continuous abstinence, retention and employment than men (76% versus 60%). After one year patients with a high-risk consumption of alcohol were no longer heavy consumers of alcohol and remained so throughout the study (p < .001). All women regained custody of their children. At admission, more women than men had been admitted for psychiatric disorders (70%/44%) and to compulsory care for substance abuse (30%/18%). Initial gender differences of psychiatric co-morbidity decreased and were no longer significant after one year. More men than women had been imprisoned (62% versus 27%) or in non-institutional care (80% versus 49%). Criminal convictions were reduced from 1751 convictions at admission to 742 (58%) after seven years. Eight patients in the entire cohort died over the 7 years (0.7% per year). One patient died in the completers group while still in the program (0.1% per year).. After seven years, two thirds of the patients in the program were abstinent and employed. Convictions ceased in the completers group. One patient died in the completers group. Women had superior long-term outcome compared to men: more continuous abstinence, employment and fewer convictions. Women also lived with their children to a higher extent than men. The positive outcome highlights the importance of maintaining high structure in combining pharmacological treatment with a focus on employment and psychological treatment and low tolerance for non-prescribed drug use.

Topics: Adolescent; Adult; Buprenorphine; Cohort Studies; Comorbidity; Crime; Employment, Supported; Female; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Personality Disorders; Psychiatric Status Rating Scales; Sex Factors; Social Support; Sweden

This article reviews research conducted in Baltimore over the past 15 years, examining the following: (1) What factors differentiate heroin-addicted individuals who enter methadone treatment from those who do not? (2) How difficult is gaining access to methadone treatment? (3) What are effective ways to overcome barriers to treatment entry? (4) Why do so many methadone patients drop out of treatment prematurely? (5) What are the added benefits of counseling when coupled with methadone or buprenorphine treatment? (6) Does increasing access to treatment have an impact on overdose deaths? Specific recommendations are made for policymakers concerned with addressing heroin addiction.

Topics: Baltimore; Buprenorphine; Counseling; Criminal Behavior; Health Services Accessibility; Health Services Needs and Demand; Heroin Dependence; HIV Infections; Humans; Methadone; Narcotics; Opiate Substitution Treatment; Risk Factors; Substance Abuse Treatment Centers; United States

Topics: Buprenorphine; Heroin Dependence; Humans; Methadone; Opioid-Related Disorders; Safety

Topics: Administration, Oral; Buprenorphine; Dose-Response Relationship, Drug; Drug Users; France; Heroin Dependence; Humans; Practice Patterns, Physicians'; Public Health

Injection drug users (IDUs) are at increased risk of various medical conditions, including bacterial skin and soft tissue infections (SSTIs). SSTIs, which are painful and can lead to life-threatening complications, are common but scarcely studied.. To investigate life time, past 12 month and past 30-day prevalence for SSTI related to injection drug use, in IDUs at Malmö syringe exchange program (Malmö SEP). To investigate factors associated with having ever had an SSTI.. IDUs were recruited from Malmö SEP (N = 80). They participated in a survey with questions about demographics, drug use, and experience of SSTIs. Factors independently associated with self-reported SSTI ever were assessed using logistic regression analysis.. The lifetime reported prevalence of SSTI was 58%, past 12 months 30%, and past 30 days 14%. Factors independently associated with SSTI ever were age (adjusted odds ratio [AOR] = 1.09; 95% confidence interval [CI] = 1.01-1.18), female sex (AOR = 6.75; 95% CI = 1.40-32.47), having ever injected prescribed drugs (AOR = 52.15; 95% CI = 5.17-525.67), and having ever injected in the neck (AOR = 8.08; 95% CI = 1.16-56.08).. SSTI is common among IDUs in Malmö. Women and those injecting in the neck or injecting prescribed drugs (crushed tablets/liquids), are more likely to have had an SSTI.

Topics: Adult; Amphetamine-Related Disorders; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Users; Female; Heroin Dependence; Housing; Humans; Ill-Housed Persons; Logistic Models; Male; Methadone; Methylphenidate; Middle Aged; Neck; Needle-Exchange Programs; Odds Ratio; Opioid-Related Disorders; Prescription Drugs; Prevalence; Sex Factors; Skin Diseases, Bacterial; Soft Tissue Infections; Substance Abuse, Intravenous; Surveys and Questionnaires; Sweden; Young Adult

A variety of studies were addressed to differentiate responders and non-responders to substitution treatment among heroin dependent patients, without conclusive findings. In particular, preliminary pharmacogenetic findings have been reported to predict treatment effectiveness in mental health and substance use disorders. Aim of the present study was to investigate the possible association of buprenorphine (BUP) treatment outcome with gene variants that may affect kappa-opioid receptors and dopamine system function. One hundred and seven heroin addicts (West European, Caucasians) who underwent buprenorphine maintenance treatment were genotyped and classified into two groups (A and B) on the basis of treatment outcome. Non-responders to buprenorphine (group B) have been identified taking into account early drop out, continuous use of heroin, severe behavioral or psychiatric problems, misbehavior and diversion during the 6 months treatment period. No difference was evidenced between responders and non-responders to BUP in the frequency of kappa opioid receptor (OPRK1) 36G>T SNP. The frequency of dopamine transporter (DAT) gene polymorphism (SLC6A3/DAT1), allele 10, was evidently much higher in "non-responder" than in "responder" individuals (64.9% vs. 55.93%) whereas the frequency of the category of other alleles (6, 7 and 11) was higher in responder than in non-responder individuals (11.02% vs. 2.13% respectively). On one hand, the hypothesis that possible gene-related changes in kappa-opioid receptor could consistently affect buprenorphine pharmacological action and clinical effectiveness was not confirmed in our study, at least in relation to the single nucleotide polymorphism 36G>T. On the other hand, the possibility that gene-related dopamine changes could have reduced BUP effectiveness and impaired maintenance treatment outcome was cautiously supported by our findings. DAT1 gene variants such as allele 10, previously reported in association with personality and behavioral problems, would have influenced the effects of BUP-induced dopamine release, modulated through mu and kappa opioid receptors, and probably the related reinforcing capacity of the drug.

Topics: Adult; Alleles; Buprenorphine; Dopamine Plasma Membrane Transport Proteins; Female; Genotype; Heroin Dependence; Humans; Male; Middle Aged; Narcotics; Opiate Substitution Treatment; Polymorphism, Single Nucleotide; Receptors, Opioid, kappa; Treatment Outcome

To assess opioid-related mortality and correlation with filled prescriptions for buprenorphine and methadone.. A register study, including data from the Swedish Forensic Pathology and Forensic Toxicology databases 2003-2010, the Prescribed Drug Register and the National Patient Register.. A total of 1301 deaths, assessed as related to buprenorphine, methadone or heroin, or a combination of them, were studied. The largest number of fatalities was related to intake of heroin (n = 776), followed by methadone (n = 342) and buprenorphine (n = 168). The total annual number of fatal cases related to the studied drugs more than doubled (116 to 255) during the study period. There were increases in mortality related to both buprenorphine and methadone: from 1 to 49 cases for buprenorphine, and from 19 to 81 cases for methadone. Only one-fifth of the fatal cases had a filled prescription for the maintenance drug assessed as the cause of death.. This study showed that most fatalities were not related to filled prescriptions of maintenance drugs, and a substantial illicit use of buprenorphine and methadone resulting in deaths was revealed. To prevent opioid toxicity deaths it is important to make efforts not only to reduce drug diversion from maintenance programs, but also to improve the control of drug trafficking and other illegal sources.

Topics: Adolescent; Adult; Aged; Buprenorphine; Databases, Factual; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Registries; Sweden; Young Adult

In the current study, buprenorphine (BUP) and its major metabolite, nor-buprenorphine (NBUP), were determined in hair samples from former heroin users following Suboxone® treatment. Hair samples from 36 subjects were analyzed. The drugs of interest were isolated from hair by solid-liquid extraction with methanol and were determined by liquid chromatography-mass spectrometry, using an electrospray ionization interface. The analytical parameters of the method (such as linearity, limits of quantification, recovery, accuracy, and precision) were determined. The inter-quartile range of BUP levels was from 11.4 to 37.4 pg/mg (mean value 56.6 pg/mg) for the proximal hair segment, from 5.8 to 43.3 pg/mg for the middle hair segment (mean value 25.3 pg/mg), while a range from 4.3 to 33.9 pg/mg (mean value 105.2 pg/mg) for the distant to the root hair segment was determined. For NBUP the corresponding inter-quartile range was from 27.0 to 147.6 for the proximal segment (mean value 95.4 pg/mg), from 21.5 to 164.7 pg/mg for the middle segment (mean value 102.0 pg/mg) and from 20.4 to 103.6 pg/mg for the distant segment (mean value 156.8 pg/mg). The mean BUP/NBUP concentration ratio was 0.5. The daily dose of Suboxone® correlated significantly with BUP and NBUP levels in hair (p = 0.001 and p = 0.023) as well as with the BUP/NBUP ratio (p = 0.010). No significant correlation was found between the levels of BUP and NBUP and the duration of Suboxone® administration. The developed and validated method was successfully used for the determination of BUP and NBUP in hair samples collected from former heroin users under Suboxone® treatment.

Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chromatography, Liquid; Female; Hair; Heroin Dependence; Humans; Male; Mass Spectrometry; Naloxone; Narcotic Antagonists

Surveys of current trends indicate heroin abuse is associated with nonmedical use of pain relievers. Consequently, there is an interest in evaluating the presence of heroin-specific markers in chronic pain patients who are prescribed controlled substances. A total of 926,084 urine specimens from chronic pain patients were tested for heroin/diacetylmorphine (DAM), 6-acetylmorphine (6AM), 6-acetylcodeine (6AC), codeine (COD), and morphine (MOR). Heroin and markers were analyzed using liquid chromatography tandem mass spectrometry (LC-MS-MS). Opiates were analyzed following hydrolysis using LC-MS-MS. The prevalence of heroin use was 0.31%, as 2871 were positive for one or more heroin-specific markers including DAM, 6AM, or 6AC (a known contaminant of illicit heroin). Of these, 1884 were additionally tested for the following markers of illicit drug use: 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), methamphetamine (MAMP), 11-nor-9-carboxy-Δ(9)-tetracannabinol (THCCOOH), and benzoylecgonine (BZE); 654 (34.7%) had positive findings for one or more of these analytes. The overall prevalence of heroin markers were as follows: DAM 1203 (41.9%), 6AM 2570 (89.5%), 6AC 1082 (37.7%). MOR was present in 2194 (76.4%) and absent (

Topics: Analgesics, Opioid; Biomarkers; Buprenorphine; Chromatography, Liquid; Chronic Pain; Codeine; Heroin; Heroin Dependence; Humans; Illicit Drugs; Methadone; Morphine Derivatives; Pain Clinics; Tandem Mass Spectrometry

New Mexico has consistently high rates of drug-induced deaths, and opioid-related treatment admissions have been increasing over the last two decades. Youth in New Mexico are at particular risk: they report higher rates of nonmedical prescription opioid use than those over age 25, are more likely than their national counterparts to have tried heroin, and represent an increasing proportion of heroin overdoses.. Commissioned by the City of Albuquerque, semistructured interviews were conducted from April to June of 2011 with 24 substance use treatment agencies and eight key stakeholders in Albuquerque to identify recent changes in the treatment-seeking population and gaps in treatment availability. Themes were derived using template analysis and data were analyzed using NVivo 9 software.. Respondents reported a noticeable increase in youth seeking treatment for opioid use and a general increase in nonmedical prescription opioid use. Most noted difficulties with finding buprenorphine providers and a lack of youth services. Additionally, stigma, limited interagency communication and referral, barriers to prescribing buprenorphine, and a lack of funding were noted as preventing opioid users from quickly accessing effective treatment.. Recommendations for addressing these issues include developing youth-specific treatment programs, raising awareness about opioid use among youth, increasing the availability of buprenorphine through provider incentives and education, developing a resource guide for individuals seeking treatment in Albuquerque, and prioritizing interagency communication and referrals.

Topics: Adolescent; Age Factors; Analgesics, Opioid; Buprenorphine; Cause of Death; Cooperative Behavior; Cross-Sectional Studies; Health Planning Councils; Health Services Accessibility; Heroin; Heroin Dependence; Humans; Interdisciplinary Communication; Needs Assessment; New Mexico; Opioid-Related Disorders; Prescription Drugs; Referral and Consultation; Substance Withdrawal Syndrome; Young Adult

The prescribing of opioid pain medication has increased markedly in recent years, with strong opioid dispensing increasing 18-fold in Tayside, Scotland since 1995. Despite this, little data is available to quantify the problem of opioid pain medication dependence (OPD) and until recently there was little guidance on best-practice treatment. We report the case of a young mother prescribed dihydrocodeine for postoperative pain relief who became opioid dependent. When her prescription was stopped without support, she briefly used heroin to overcome her withdrawal. After re-exposure to dihydrocodeine following surgery 9 years later and treatment with methadone for dependency, she was transferred to buprenorphine/naloxone. In our clinical experience and in agreement with Department of Health and Royal College of General Practitioner guidance, buprenorphine/naloxone is the preferred opioid substitution treatment for OPD. Our patient remains within her treatment programme and has returned to work on buprenorphine 16 mg/naloxone 4 mg in conjunction with social and psychological support.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Codeine; Disease Management; Female; Heroin; Heroin Dependence; Humans; Methadone; Naloxone; Opiate Substitution Treatment; Opioid-Related Disorders; Pain, Postoperative; Substance Withdrawal Syndrome; Young Adult

Whilst there is a small literature on the cardiovascular toxicity of opiates, there is no detailed antemortem data on non-cardiovascular patient populations. A cross-sectional and longitudinal naturalistic observational study was performed comparing methadone (N = 71)-, buprenorphine (N = 593)-, naltrexone (N = 23)-treated patients with controls (N = 576) on indices of arterial stiffness and vascular age by Pulse Wave Analysis in primary care, 2006-2011. Controls were younger 29.96 ± 0.45 (mean ± SEM) vs. 34.00 ± 0.34-39.22 ± 1.11 years (all P < 0.005) and had fewer smokers (15.9 % vs. 86.9 %-92.96 %, all P < 0.0001). The sex ratio was similar (69.6 vs. 67.7 % male, P = 0.46). These baseline differences were controlled for by multiple regression. Linear regression of vascular age, central augmentation pressure, central augmentation index and other measures against chronologic age showed significant protective effects by treatment group against the treatment standard of methadone, in both sexes in additive and interactive models (all P < 0.02). Interactive terms in treatment type remained significant including all conventional risk factors accounting for differing opiate exposures. The principal findings from multiple regression were confirmed in the time series analysis up to 5 years by repeated measures nonlinear regression. These studies show that the deleterious impact of chronic opiate pharmacotherapy on vascular age and arterial stiffness varies significantly by treatment type.

Topics: Adult; Aging; Blood Vessels; Buprenorphine; Cross-Sectional Studies; Endothelium, Vascular; Female; Heroin Dependence; Humans; Longitudinal Studies; Male; Methadone; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Phenotype; Pulse Wave Analysis; Regression Analysis; Vascular Stiffness

This study explores strategies that Suboxone misusers utilize while in drug treatment. Ethnographic interviews were conducted with 14 patients who had cycled in and out of Suboxone treatment. The objective of the study is to identify strategies implemented by patients who intermittently use opiates/opioids while in Suboxone treatment. Findings indicate that some patients serially stop and start treatment in a Harm Reduction setting in New York City. Many patients suggest that they manage their opiate/opioid dependency through a sequential use of Suboxone and heroin to avoid withdrawal and to continue their misuse of opiates/opioids. Results are discussed in conjunction with the difficulties inherent to substance abuse treatment and suggestions for improvement are offered.

Topics: Adult; Behavior, Addictive; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Drug Combinations; Drug Users; Female; Harm Reduction; Heroin Dependence; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; New York City; Opiate Substitution Treatment; Patient Acceptance of Health Care; Prescription Drug Misuse; Qualitative Research; Recurrence; Social Environment; Substance Abuse Treatment Centers; Substance Withdrawal Syndrome

We examined the association between the expansion of methadone and buprenorphine treatment and the prevalence of heroin overdose deaths in Baltimore, Maryland from 1995 to 2009.. We conducted a longitudinal time series analysis of archival data using linear regression with the Newey-West method to correct SEs for heteroscedasticity and autocorrelation, adjusting for average heroin purity.. Overdose deaths attributed to heroin ranged from a high of 312 in 1999 to a low of 106 in 2008. While mean heroin purity rose sharply (1995-1999), the increasing number of patients treated with methadone was not associated with a change in the number of overdose deaths, but starting in 2000 expansion of opioid agonist treatment was associated with a decline in overdose deaths. Adjusting for heroin purity and the number of methadone patients, there was a statistically significant inverse relationship between heroin overdose deaths and patients treated with buprenorphine (P = .002).. Increased access to opioid agonist treatment was associated with a reduction in heroin overdose deaths. Implementing policies that support evidence-based medication treatment of opiate dependence may decrease heroin overdose deaths.

Topics: Baltimore; Buprenorphine; Drug Overdose; Heroin Dependence; Humans; Linear Models; Longitudinal Studies; Methadone; Mortality; Narcotic Antagonists; Opiate Substitution Treatment

Prescription opioid use has grown rapidly, but few studies examined whether users have similar treatment responses as heroin users. Participants were 1,648 opioid users in Florida Access to Recovery (2004-2007). Participants engaged in methadone or buprenorphine maintenance had better retention than those in nonmaintenance treatment. Heroin only users (HO) had better engagement in nonmaintenance treatments and had worse retention than prescription opioid only users (PO). In methadone maintenance, PO were more likely to report opioid abstinence during treatment than heroin and prescription opioid users (H&P). Future research should focus on understanding and improving the treatment experience of opioid use subgroups.

Topics: Adult; Buprenorphine; Female; Heroin Dependence; Humans; Male; Medication Adherence; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Acceptance of Health Care; Prescription Drugs; Qualitative Research; Treatment Outcome

Topics: Buprenorphine; Drug Overdose; Heroin Dependence; Humans; Methadone; Opiate Substitution Treatment

Topics: Buprenorphine; Drug Overdose; Heroin Dependence; Humans; Methadone; Opiate Substitution Treatment

Topics: Adrenal Cortex Hormones; Adult; Axilla; Biopsy, Needle; Buprenorphine; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique, Indirect; Follow-Up Studies; Heroin Dependence; Humans; Hydrotherapy; Immunoglobulin A; Immunohistochemistry; Linear IgA Bullous Dermatosis; Male; Risk Assessment; Treatment Outcome

The cost of opiate substitution is usually considered lower in cost when methadone is used, as compared to that of buprenorphine, however the overall cost effectiveness of substitution programmes comparing the two drugs remains largely unknown.. We evaluated the treatment cost and effectiveness of methadone and buprenorphine when used in an opiate substitution programme in Norfolk, UK. All programme costs, estimated from the perspective of the drug treatment clinic, were collected on 361 opiate-dependent participants over a six-month period. Total costs comprised medication (methadone or buprenorphine) costs, pharmacy supervision and dispensing costs, and drug service clinic costs. Effectiveness was measured in terms of (1) each programmes ability to retain participants in the programme for six months, and (2) the ability of the programme to accomplish complete abstinence from illicit opiate consumption.. Overall, mean medication-only costs of methadone were lower than that of buprenorphine, however, pharmacy and clinic costs were lower for the buprenorphine programme. The covariate-adjusted mean total cost of the two programmes was not significantly different. Mean six-month retention rates were higher on the methadone programme, therefore, the methadone programme "dominates" the buprenorphine programme as it was slightly more effective for the same cost. Conversely, when ability to stop taking illicit opiates concomitant with opiate substitution medication was considered, the buprenorphine programme was more effective with an additional cost of £903 per individual who stopped illicit opiate use.. The provision of buprenorphine should be considered an appropriate treatment if cessation of illicit opiate use, concomitant with programme retention is considered an important outcome.

Topics: Buprenorphine; Cost-Benefit Analysis; Costs and Cost Analysis; Drug Costs; Health Care Costs; Health Personnel; Heroin Dependence; Humans; Methadone; Narcotics; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Compliance; Pharmacies; Substance Abuse Detection; Treatment Outcome

'Non-compliant' individuals in opioid maintenance treatment, OMT, are often met with tight control regimes to reduce the risk of 'diversion', which may lead to harm or death among persons outside of OMT. This article explores reported practices of, and motivations for, diversion of methadone and buprenorphine, in a group of imprisoned individuals in OMT.. 28 in-depths interviews were conducted among 12 OMT-enrolled, imprisoned individuals, most of whom were remand prisoners. All had experienced tight control regimes prior to imprisonment due to varying degrees of 'non-compliance' and illicit drug use during treatment. Their acquired norm of sharing with others in a drug using community was maintained when entering OMT. Giving one's prescription opioids to an individual in withdrawal was indeed seen as an act of helping, something that takes on particular significance for couples in which only one partner is included in OMT and the other is using illicit heroin. Individuals enrolled in OMT might thus be trapped between practicing norms of helping and sharing and adhering to treatment regulations. 'Diversion', as this term is conventionally used, is not typically understood as practices of giving and helping, but may nevertheless be perceived as such by those who undertake them.. As we see it, the need to sustain oneself as a decent person in one's own eyes and those of others through practices such as sharing and helping should be recognized. Treatment providers should consider including couples in which both individuals are motivated for starting OMT.

Topics: Adult; Buprenorphine; Crime; Female; Heroin Dependence; Humans; Illicit Drugs; Male; Methadone; Middle Aged; Narcotics; Norway; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Compliance; Prescription Drug Diversion; Prisoners; Substance-Related Disorders; Young Adult

The link between nasal inhalation of cocaine and nasal and palatal necrosis is well documented. In contrast, few data are available concerning nasal mucosa necrosis related to heroin snorting. The authors report here the retrospective analysis of 24 cases of orofacial lesions in patients with nasal heroin usage, collected between 2006 and 2012.. The cases concern 17 males and 7 females (median age 29.5 (range: 24-42)) with chronic consumption of intranasal heroin (from 2 months to more than 10 years). Six patients had a history of cocaine abuse. The median daily amount of heroin consumption was 5 g (range: 0.5-10). The complications were nasal perforation (11 cases), nasal ulceration or erythema (5 cases), nasal septum necrosis (5 cases), pharyngeal ulceration (3 cases), and palate damages (5 cases). The most common clinical signs and symptoms were nasal pain, purulent sputum, dysphagia, and rhinitis. Maintenance therapy with methadone (19 cases) or buprenorphine (3 cases) was initiated. In 8 cases, the injury improved.. The potential of heroin to induce destructive orofacial lesions should be considered when nasal damages are observed in patients with drug abuse. A multidisciplinary approach seems to be the most effective means of managing such patients.

Topics: Administration, Intranasal; Adult; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Male; Methadone; Necrosis; Nose; Opiate Substitution Treatment; Palate, Soft; Pharynx

Absence of successful transition to post-detoxification treatment leads to high rates of relapse among detoxified heroin users. The present study evaluated a pilot buprenorphine treatment program (BTP). Heroin dependent individuals were inducted onto buprenorphine/naloxone in detox, maintained while transitioning through an intensive inpatient program (IIP), and gradually tapered off medication over 5 months of outpatient (OP) treatment. Compared to programmatic indicators of treatment engagement in the year prior to BTP implementation, referrals from detox to IIP, entry into and completion of IIP and subsequent OP, and days in OP treatment increased substantially. BTP completers, compared to non-completers, viewed abstinence as more difficult and as requiring more assistance to achieve, were less likely to be current cocaine and alcohol users or to have relapsed during the course of treatment. Although preliminary and in need of replication, initial adjunctive use of buprenorphine in an abstinence-based continuum of care may improve post-detoxification treatment entry, engagement, and completion.

Topics: Adolescent; Adult; Alcoholism; Ambulatory Care; Buprenorphine; Cocaine-Related Disorders; Data Interpretation, Statistical; Diagnostic and Statistical Manual of Mental Disorders; Female; Health Personnel; Heroin Dependence; Humans; Income; Length of Stay; Male; Narcotic Antagonists; Patient Compliance; Patient Selection; Pilot Projects; Recurrence; Socioeconomic Factors; Young Adult

Topics: Animals; Brain; Buprenorphine; Ethics, Medical; Female; Fetal Development; Heroin Dependence; Humans; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Research Design

conduct needs assessments and treatment compliance evaluations in MMT and Suboxone Substitution State Programs in Georgia (Republic of). 506 patients (2 females) were surveyed (92% on Methadone, 8% on Suboxone) from 6 Tbilisi and 4 regional State Programs in 2011 November. Mean age - 40±8,56 (22-65) year; 254 (51.4%) were in treatment for 1-3 year. Evaluation was carried out on the base of structured self-questionnaire that covers demographics, drug use history, general drug use trends, psychotherapeutic sessions' acceptance and open label question regarding treatment challenges and satisfaction. 305 (60.3%) attended individual and 57 (11.3%) group psychotherapy sessions with 50.79% attending once/month or rare. The main reason given for therapy non-attendance - no needs for it (29.48%); the main drugs before admission - heroin (80.04%), buprenorphine (53.49%); Main drugs used in Georgia nowadays - desomorphine ("crocodile"), alcohol and marihuana. Commonly used drugs by program patients (136 positive answers) - alcohol-13.62%, marihuana-10.39%, pregabalin - 8.17%, opioids- 6.62% (mostly-"crocodile"), home-made stimulants-6.23%, sedatives -5.45%. 55.4% are extremely satisfied with treatment, 82.4% - with program staff. Patients' main wishes- free of charge programs (46.4%) and provide take-home doses (22.07%). Methadone and Suboxone ST are being well accepted in Georgia and appear to be reducing illegal opioid use. However, the psychotherapeutic sessions' attendance is very low.

Topics: Adult; Aged; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Female; Georgia (Republic); Government Programs; Heroin Dependence; Humans; Hypnotics and Sedatives; Male; Marijuana Abuse; Methadone; Middle Aged; Naloxone; Needs Assessment; Opiate Substitution Treatment; Patient Compliance; Patient Satisfaction; Psychotherapy; Substance-Related Disorders; Surveys and Questionnaires; Young Adult

Social networks have been hypothesized to protect people from the harmful effects of stress, but may also provide dysfunctional role models and provide cues associated with drug use. This study describes the range, type and level of social support available to patients engaged in UK opiate substitution treatment (OST) programmes, and explores the association between network factors and continued use of illicit heroin.. A cross-sectional survey of a randomly selected sample of OST patients (n = 118) utilised measures of current substance use and social network structure and support.. More than half of the participants had used heroin in the previous month, and most described networks that were both supportive and positive about treatment. Multivariate analysis showed that the substance use involvement of network members was higher in those patients still using heroin, even when other treatment factors were controlled for.. There was a strong association between ongoing contact with other drug users and continued use of illicit heroin in this treatment sample. Whilst there is potential for the involvement of social networks in treatment, future research needs to ascertain the exact nature of the relationship between social support and drug use.

Topics: Adult; Buprenorphine; Cross-Sectional Studies; England; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Social Support; Substance-Related Disorders; Treatment Outcome

Topics: Adult; Amphotericin B; Antifungal Agents; Buprenorphine; Candidiasis; Endocarditis; Endophthalmitis; Eye Infections, Fungal; Fatal Outcome; Flucytosine; Hepatitis C, Chronic; Heroin Dependence; Humans; Male; Mycoses; Pneumonia, Staphylococcal; Recurrence; Shock, Cardiogenic; Substance Abuse, Intravenous; Tricuspid Valve; Ultrasonography

The Substitution Treatment National Registry provided from mid 2006 till mid 2009 an exhaustive documentation on all patients being prescribed methadone or buprenorphine in Belgium. This endeavour was possible through cooperation of all community pharmacies and their representative organizations was supported at the time by the former Health federal minister. The Liberal belgian opiate medical substitution process authorizes untill now de facto any doctor to prescribe methadone and pharmacists are supported to dispense it. Results show the regional, provincial and county numbers of professionals and patients prevalence in the population. Nationwide, n = 16974 patients (prevalence for population aged 20-64: 26/10000) have been offered substitution from mid 2008 till mid 2009, n = 3390 pharmacies 164,4% of all pharmacies) and n = 2937 MDs (16,75% of all MDs) have been involved. Subutex or Suboxone have been dispensed to 11,1% of substitution patients with 7,4% receiving only buprenorphine on a yearly basis. Number of substitution patients by MD and prevalence by gender, age group and region are presented. Important variations are observed locally, possibly mirroring heroin addiction due to widespread access to substitution treatment. Younger patients are more prevalent in semi rural or border areas. The exhaustivity of available data enables also to observe patients quitting substitution altogether and a strong difference of maintenance rate is observed favoring methadone over buprenorphine.

Topics: Adult; Age Factors; Analgesics, Opioid; Belgium; Buprenorphine; Female; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Pain; Pharmacies; Physicians; Prevalence; Sex Factors; Young Adult

Pre-clinical research indicates that opioids reduce extracellular glutamate in acute opioid treatment, whereas during withdrawal, glutamatergic neurotransmission is increased and withdrawal symptoms can be blocked by glutamate receptor antagonists. The glutamate hypothesis of addiction suggests that withdrawal-associated hyperglutamatergic states destabilize the glutamatergic system chronically and contribute to relapse. magnetic resonance spectroscopy at three tesla optimized for glutamate assessment (TE 80 ms) was performed in the anterior cingulate gyrus (ACC) and frontal white matter (fWM) of 17 opiate-dependent patients during opiate maintenance therapy and 20 healthy controls. Controlling for age and gray matter content, glutamate in the ACC was positively associated with the number of previous withdrawals. For glutamate + glutamine (Glx), a significant group-age interaction was found. Whereas Glx declines with age in healthy controls, Glx increases with age in opiate-dependent patients. The number of previous withdrawals did not correlate with age. In fWM spectra, increased Cho concentrations were observed in opiate-dependent patients. Both new findings, the positive correlation of glutamate and previous withdrawals and increasing Glx with age in contrast to an age-dependent Glx decrease in controls indicate a destabilization of the glutamate system in opiate-dependent patients and support the glutamate hypothesis of addiction. Increased Cho concentrations in fWM corroborate findings of WM abnormalities in opioid-dependent subjects.

Topics: Adult; Analysis of Variance; Buprenorphine; Case-Control Studies; Female; Glutamic Acid; Gyrus Cinguli; Heroin Dependence; Humans; Magnetic Resonance Spectroscopy; Male; Methadone; Middle Aged; Narcotics; Substance Withdrawal Syndrome

Case-management is a client-centred intervention to improve the coordination and continuity of delivery of services for people with complex needs. This service has been incorporated into opioid treatment programs in various ways. This study was undertaken to compare two case-management models, termed individual case-management (ICM) and team-based case-management (TBCM). This study aims to describe the new TBCM and client attitudes to, and acceptance of, this model compared with ICM.. Clients from two opioid treatment programs, one implementing ICM and one implementing the TBCM, were recruited to undertake a self-complete survey examining satisfaction with case-management during dosing hours over 7 months. Surveys took approximately 10 min to complete.. One hundred and sixty-three clients were surveyed (62 ICM, 101 TBCM). Clients were demographically similar, but differed in terms of treatment and drug use characteristics. Significantly higher ratings of case-management were reported from TBCM compared with ICM clients for help with opiate use (P < 0.001), other drug use (P < 0.001), mental health (P < 0.001), accommodation (P = 0.023), relationships/parenting (P = 0.003) and physical health (P = 0.002) and clinic services in terms of fairness and consistency, safety, respect, staff quality and confidentiality (P < 0.001). Compared with ICM clients, TBCM clients were more likely to report ease of access to case-management (P < 0.001), wait significantly less time to see a case-manager (38% vs. 7% seen same day) and 93% and 47% of clients, respectively, reported satisfaction with treatment (P < 0.001).. These initial data indicate client acceptance and satisfaction with the TBCM model. Further evaluation of the model, including cost-effectiveness, is warranted.

Topics: Adult; Buprenorphine; Case Management; Female; Health Care Surveys; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Patient Preference; Patient Satisfaction

Because the outcome of methadone and buprenorphine substitution treatment in adolescents is unclear, we completed a retrospective cohort study of 100 consecutive heroin-dependent adolescents who sought these treatments over an 8-year recruitment period. The participants' average age was 16.6 years, and 54 were female. Half of the patient group remained in treatment for over 1 year. Among those still in treatment at 12 months, 39% demonstrated abstinence from heroin. The final route of departure from the treatment program was via planned detox for 22%, dropout for 32%, and imprisonment for 8%. The remaining 39% were transferred elsewhere for ongoing opiate substitution treatment after a median period of 23 months of treatment. Males were more likely to exit via imprisonment (p < .05), but other outcomes were not predicted by gender. There were no deaths during treatment among these 100 patients who had a cumulative period of 129 person years at risk. Our findings suggest that this treatment delivers reductions in heroin use and that one fifth of patients will exit treatment following detox completion within a 1- to 2-year time frame.

Topics: Adolescent; Buprenorphine; Cohort Studies; Female; Heroin Dependence; Humans; Male; Methadone; Narcotics; Opiate Substitution Treatment; Prisoners; Retrospective Studies; Sex Factors; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome

To expand its public-sector treatment capacity, Baltimore City made buprenorphine treatment accessible to low-income, largely African American residents. This study compares the characteristics of patients entering methadone treatment vs. buprenorphine treatment to determine whether BT was attracting different types of patients.. Participants consisted of two samples of adult heroin-dependent African Americans. The first sample was newly admitted to a health center or a mental health center providing buprenorphine (N=200), and the second sample was newly admitted to one of two hospital-based methadone programs (N=178). The Addiction Severity Index (ASI) and the Friends Supplemental Questionnaire were administered at treatment entry and data were analyzed with logistic regression.. BT participants were more likely to be female (p=.017) and less likely to inject (p=.001). Participants with only prior buprenorphine treatment experience were nearly five time more likely to enter buprenorphine than methadone treatment (p<.001). Those with experience with both treatments were more than twice as likely to enter BT (OR=2.7, 95% CI=1.11-6.62; p=.028). In the 30 days prior to treatment entry, BT participants reported more days of medical problems (p=.002) and depression (p=.044), and were more likely to endorse a lifetime history of depression (p<.001).. Methadone and buprenorphine treatment provided in the public sector may attract different patient subpopulations. Providing buprenorphine treatment through drug treatment programs co-located with a health and mental health center may have accounted for their higher rates of medical and psychiatric problems and appears to be useful in attracting a diverse group of patients into public-sector funded treatment.

Topics: Adult; Baltimore; Black or African American; Buprenorphine; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotics; Opiate Substitution Treatment; Patient Admission; Public Sector; Sex Factors; Substance Abuse Treatment Centers; Treatment Outcome

Develop and apply new costing methodologies to estimate costs of opioid dependence treatment in countries worldwide.. Micro-costing methodology developed and data collected during randomized controlled trial (RCT) involving 126 patients (July 2003-May 2005) in Malaysia. Gross-costing methodology developed to estimate costs of treatment replication in 32 countries with data collected from publicly available sources.. Fixed, variable, and societal cost components of Malaysian RCT micro-costed and analytical framework created and employed for gross-costing in 32 countries selected by three criteria relative to Malaysia: major heroin problem, geographic proximity, and comparable gross domestic product (GDP) per capita.. Medication, and urine and blood testing accounted for the greatest percentage of total costs for both naltrexone (29-53 percent) and buprenorphine (33-72 percent) interventions. In 13 countries, buprenorphine treatment could be provided for under $2,000 per patient. For all countries except United Kingdom and Singapore, incremental costs per person were below $1,000 when comparing buprenorphine to naltrexone. An estimated 100 percent of opiate users in Cambodia and Lao People's Democratic Republic could be treated for $8 and $30 million, respectively.. Buprenorphine treatment can be provided at low cost in countries across the world. This study's new costing methodologies provide tools for health systems worldwide to determine the feasibility and cost of similar interventions.

Topics: Buprenorphine; Cambodia; Cost of Illness; Drug Costs; Gross Domestic Product; Health Care Costs; Heroin Dependence; Humans; Laos; Malaysia; Naltrexone; Narcotic Antagonists

Heroin abuse remains an important public health problem, particularly in economically disadvantaged areas. Insight into this problem is gained from interviewing addicted individuals. However, we lack systematic data on factors that motivate heroin users to participate in non-treatment research that offers both financial incentives (compensation) and non-financial incentives (e.g., short-term medication).. To better understand the relative importance of several types of personal motivations to participate in non-treatment buprenorphine research, and to relate self-motivations to social, economic, demographic and drug use factors.. Heroin dependent volunteers (N=235 total; 57 female and 178 male; 136 African American, 86 Caucasian, and 13 Other) applied for non-therapeutic buprenorphine research in an urban outpatient setting from 2004 to 2008. We conducted a semi-structured behavioral economic interview, after which participants ranked 11 possible motivations for research participation.. Although the study was repeatedly described as non-treatment research involving buprenorphine, participants often ranked some treatment-related motivations as important (wanting to reduce/stop heroin use, needing a medication to get stabilized/detoxify). Some motivations correlated with income, heroin use, and years since marketing of buprenorphine. Two dimensions emerged from principal component analysis of motivation rankings: (1) treatment motivation vs. greater immediate needs and (2) commitment to trying alternatives vs. a more accepting attitude toward traditional interventions. In summary, heroin addicts' self-motivations to engage in non-therapeutic research are complex--they value economic gain but not exclusively or primarily--and relate to variables such as socioeconomic factors and drug use.

Topics: Adolescent; Adult; Black or African American; Buprenorphine; Data Interpretation, Statistical; Female; Heroin Dependence; Humans; Income; Intelligence Tests; Male; Marketing of Health Services; Middle Aged; Motivation; Narcotic Antagonists; Patient Acceptance of Health Care; Recurrence; Research Subjects; Socioeconomic Factors; Time Perception; Young Adult

Individuals with a history of heroin dependence are overrepresented in American correctional facilities and 75% of inmates with a drug use disorder do not receive treatment during incarceration or after release. Medication-assisted treatment (MAT) with opiate agonists, such as methadone or buprenorphine, constitutes standard of care; to guide planning for an expansion of drug treatment services in correctional facilities, a needs assessment was conducted at the Department of Correction and Rehabilitation (DCR) of Puerto Rico (PR). The authors report on the research process, the findings that informed their recommendations for the DCR to expand MAT for eligible inmates, and lessons learned.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cross-Sectional Studies; Female; Health Services Needs and Demand; Heroin Dependence; Humans; Male; Methadone; Needs Assessment; Opiate Substitution Treatment; Prisoners; Puerto Rico; Young Adult

The Rikers Island Key Extended Entry Program (KEEP) has offered methadone treatment for opioid dependent inmates incarcerated in New York City's jails since 1986. In response to a trend toward low-dose methadone maintenance prescribing, a quality improvement (QI) protocol trained KEEP counselors, physicians, and pharmacists in the evidence base supporting moderate-to-high methadone maintenance doses in order to maximize therapeutic effects and rates of successful reporting to community methadone treatment programs (MTPs) post release. Discharge dose level and length of incarceration data were analyzed for 2 groups of KEEP patients discharged pre/post-QI. Among patients incarcerated for 21 or more days, the proportion of those on moderate-to-high doses of methadone increased significantly. Patients who reached a moderate-to-high methadone dose demonstrated higher rates of reporting to community MTP versus lower doses, both pre- and post-QI. Overall, a higher proportion of all patients reported to community MTP post-QI.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Heroin Dependence; Humans; Male; Methadone; New York City; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Compliance; Prisoners; Quality Improvement

Topics: Buprenorphine; Heroin Dependence; Humans; Narcotic Antagonists; Opiate Substitution Treatment

The dosing of opioid receptor agonist medications adequately and on an individual basis is crucial in the pharmacotherapy of opioid dependence. Clinical tools that are able to measure dose appropriateness are sorely needed. The recently developed and validated Opiate Dosage Adequacy Scale (ODAS) comprehensively evaluates the main outcomes relevant for methadone dose optimization, namely relapse, cross-tolerance, objective and subjective withdrawal symptoms, craving and overdose. Based on the ODAS, we developed a new assessment tool (BUprenorphine-naloxone Dosage Adequacy eVAluation [BUDAVA]) for evaluating dosage adequacy in patients in treatment with buprenorphine-naloxone.. The main goal of this observational study was to explore whether the BUDAVA questionnaire could be used to assess buprenorphine-based, long-term substitution therapy for heroin addiction.. The study included heroin-dependent patients who had been in treatment with buprenorphine-naloxone for at least 3 months. Patients (n = 196) were recruited from 11 drug abuse treatment centres in Italy. Dosage adequacy was assessed with the BUDAVA questionnaire. Patients classified as inadequately treated had their dosage modified. After 1 week, they were again administered the questionnaire to assess the adequacy of the new dosage.. The buprenorphine-naloxone dosage was found to be inadequate in 61 of the 196 patients. In 13 patients, the treatment scored as inadequate only in the subjective withdrawal symptoms item of the questionnaire and therefore no dosage adjustment was made in the 2 weeks that have characterized this work. The remaining 48 inadequately treated patients had their dosage modified (42 dose increases and six dose decreases). After 1 week on the modified dosage, in 24 of these patients the new regimen was found by the assessment with the questionnaire to be adequate.. These preliminary results suggest that the BUDAVA questionnaire may be useful for guiding buprenorphine-naloxone maintenance dose adjustments in heroin-dependent patients.

Topics: Analgesics, Opioid; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Chi-Square Distribution; Drug Dosage Calculations; Drug Monitoring; Heroin Dependence; Humans; Italy; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Predictive Value of Tests; Receptors, Opioid; Secondary Prevention; Substance Withdrawal Syndrome; Surveys and Questionnaires; Time Factors; Treatment Outcome

Topics: Adult; Buprenorphine; Female; Heroin Dependence; Humans; Methadone; Narcotic Antagonists; Opiate Substitution Treatment

There is an increasing body of evidence that heroin addiction is associated with severe alterations in immune function, which might contribute to an increased risk to contract infectious diseases like hepatitis B and C or HIV. However, the impact of heroin consumption on the CD4(+) T cell compartment is not well understood. Therefore, we analyzed the frequency and functional phenotype of CD4(+) T cells as well as immune-suppressive CD4(+)CD25(high) regulatory T cells (Tregs) isolated from the peripheral blood of opiate addicts currently abusing heroin (n=27) in comparison to healthy controls (n=25) and opiate addicts currently in opioid maintenance treatment (OMT; n=27). Interestingly, we detected a significant increase in the percentage of CD4(+)CD25(high) Tregs in the peripheral blood of heroin addicted patients in contrast to patients in OMT. The proliferative response of CD4(+) T cells upon stimulation with anti-CD3 and anti-CD28 antibodies was significantly decreased in heroin users, but could be restored by depletion of CD25(high) regulatory T cells from CD4(+) T cells to similar values as observed from healthy controls and patients in OMT. These results suggest that impaired immune responses observed in heroin users are related to the expansion of CD4(+)CD25(high) Tregs and more importantly, can be restored by OMT.

Topics: Adult; Buprenorphine; CD4-Positive T-Lymphocytes; Cell Proliferation; Cell Separation; Cytokines; Female; Flow Cytometry; Heroin Dependence; Humans; Interleukin-2 Receptor alpha Subunit; Male; Naloxone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; T-Lymphocytes, Regulatory

Aims of the present investigation were: (i) to assess the prevalence of current smokers and relative smoking status among a large number of heroin addicts attending opioid-substitution therapy prevalence; (ii) to evaluate the relationship between the type (methadone, buprenorphine) and dosage of opioid substitution therapy and nicotine dependence. Three hundred and five (305) heroin addicts under opioid-substitution therapy were recruited at five Addiction Units. All participants completed a questionnaire assessing sociodemographic information, type and dose of opioid-substitution therapy, smoking history and status, Fagerström Test for Nicotine Dependence (FTND), and the Zung Self-Rating Depression scale (SDS). 298 subjects, out of 305 (97.2%) were smokers, with an average of 20.5 cigarette/day and a median FTND of 6. Our data confirmed the high prevalence of smokers among heroin addicts, the highest described in the literature to date among heroin addicts under substitution therapies, without any significant difference between methadone vs. buprenorphine therapy groups. There was no correlation between dose of methadone or buprenorphine and average number of cigarettes/day. Patients in substance abuse treatment very frequently smoke cigarettes and often die of tobacco-related diseases. Substance abuse treatment programs too often ignore tobacco use. We hope that these findings will help to incorporate smoking cessation in substance abuse treatments.

Topics: Adult; Buprenorphine; Female; Heroin Dependence; Humans; Italy; Male; Methadone; Narcotic Antagonists; Narcotics; Opiate Substitution Treatment; Smoking; Tobacco Use Disorder

Topics: Buprenorphine; Female; Heroin Dependence; Humans; Methadone; Narcotic Antagonists; Opiate Substitution Treatment

The aim of this pilot study was to assess the effectiveness of buprenorphine/naloxone (BUP/NX) among marginalized, opioid-dependent individuals in terms of retention in and cycling into and out of a harm-reduction program. This pilot study enrolled 100 participants and followed them from November 2005 to July 2008. The overall proportion of patients retained in the program at the end of 3, 6, 9, and 12 months was 68%, 63%, 56%, and 42%, respectively. This pilot study demonstrated that BUP/NX could be successfully used to treat marginalized heroin users.

Topics: Adult; Buprenorphine; Drug Combinations; Ethnicity; Female; Harm Reduction; Health Services Accessibility; Heroin Dependence; Humans; Ill-Housed Persons; Male; Naloxone; Narcotic Antagonists; Needle-Exchange Programs; New York City; Opiate Substitution Treatment; Patient Acceptance of Health Care; Pilot Projects; Social Marginalization; Young Adult

In humans, exposure to cues previously associated with heroin use often provokes relapse after prolonged withdrawal periods. In rats, cue-induced heroin seeking progressively increases after withdrawal (incubation of heroin craving). Here, we examined the role of orbitofrontal cortex (OFC) neuronal ensembles in the enhanced response to heroin cues after prolonged withdrawal or the expression of incubation of heroin craving. We trained rats to self-administer heroin (6 h/d for 10 d) and assessed cue-induced heroin seeking in extinction tests after 1 or 14 withdrawal days. Cue-induced heroin seeking increased from 1 to 14 d and was accompanied by increased Fos expression in ∼12% of OFC neurons. Nonselective inactivation of OFC neurons with the GABA agonists baclofen + muscimol decreased cue-induced heroin seeking on withdrawal day 14 but not day 1. We then used the Daun02 inactivation procedure to assess a causal role of the minority of selectively activated Fos-expressing OFC neurons (that presumably form cue-encoding neuronal ensembles) in cue-induced heroin seeking after 14 withdrawal days. We trained c-fos-lacZ transgenic rats to self-administer heroin and 11 d later reexposed them to heroin-associated cues or novel cues for 15 min (induction day), followed by OFC Daun02 or vehicle injections 90 min later; we then tested the rats in extinction tests 3 d later. Daun02 selectively decreased cue-induced heroin seeking in rats previously reexposed to the heroin-associated cues on induction day but not in rats exposed previously to novel cues. Results suggest that heroin-cue-activated OFC neuronal ensembles contribute to the expression of incubation of heroin craving.

Topics: Animals; Baclofen; Behavior, Animal; Buprenorphine; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Conditioning, Operant; Cues; Daunorubicin; Extinction, Psychological; GABA-B Receptor Agonists; Gene Expression Regulation; Glutamate Decarboxylase; Heroin; Heroin Dependence; In Vitro Techniques; Male; Muscimol; Narcotic Antagonists; Neurons; Oncogene Proteins v-fos; Phosphopyruvate Hydratase; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Self Administration

The use of psychoactive drugs by militaries is not compatible with the analytical skills and self-control required by their jobs. Military physicians take this problem into consideration by organising systematic drugs screening in the French forces. However, for technical reasons, opiates are not concerned by this screening with the agreement of the people concerned. The estimated number of militaries who use an opiate substitute may be an approach of heroin consumption in the French forces. This study describes buprenorphine and methadone reimbursements made during 2007 by the national military healthcare centre to French militaries.. Each French soldier is affiliated to a special health insurance. The national military healthcare centre has in its information system, all the data concerning drug reimbursement made to French military personnel. This is a retrospective study of buprenorphine and methadone reimbursements made during 2007 by the military healthcare centre, to militaries from the three sectors of the French forces, and from the gendarmerie and joint forces. Only one reimbursement of one of these two drugs during this period allowed the patient to be included in our study. Daily drug dose and treatment steadiness profile have been calculated according to the criteria of the French monitoring centre for drugs and drug addiction. The criteria of the National guidelines against frauds have been used to identify misuse of these drugs. Doctors' shopping behaviour has also been studied. Finally, the nature of the prescriber and the consumption of other drugs in combination with opiate substitute have been analysed.. One hundred and eighty-one military consumers of opiate substitute drugs (167 men and 14 women) participated. This sample included people from the three sectors of the French forces as well as from the gendarmerie and from the joint forces. The average age of the consumers was 26.6 years (20-42 years). The average length of service was 6.1 years (maximum 22 years service). One hundred and fifty-nine militaries had been delivered buprenorphine, 15 had been delivered methadone and seven had been delivered both. The prevalence of opiate substitute drug consumption by the militaries (52 per 100,000) is lower than in general population. According to the criteria of the National Healthcare Insurance, this population is not affected by abuse or fraud behaviour. Doctors' shopping behaviour is unusual. Opiate substitutes are prescribed by general physicians in 88% of issues. Only one prescriber was a military physician. An analysis of reimbursement of some drugs associated with opiate substitute has been made. The sampled military consume more psychoactive drugs (anxiolytics, antidepressants, hypnotics) than the French population under opiate substitution.. In our observation, the military physician is almost always excluded the process of substitution. His/her different responsibilities of care, but also in determining the working aptitude, lead to dissimulation behaviour by the militaries. The difficulty for military physicians is to identify such consumption. They have to evaluate the capacity to work through a physical and psychological examination.

Topics: Buprenorphine; Cross-Sectional Studies; Drug Utilization; Female; France; Heroin Dependence; Humans; Insurance, Health, Reimbursement; Male; Methadone; Military Personnel; Narcotics; National Health Programs; Opiate Substitution Treatment; Retrospective Studies; Substance Abuse Detection; Young Adult

Carbohydrate metabolism disorder in heroin dependence is an issue with long history and contradicting results. The aim of the study was to evaluate basal insulin sensitivity in hepatitis C virus seronegative heroin dependents with normal body mass index, taking into consideration the duration of heroin dependence.. 78 heroin dependents and 32 healthy controls were enrolled in the cross-sectional, prospective study. The dependents were observed in 2 groups: group 1 with dependence duration less than or equal to 3 years and group 2 with more than 3 years. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) and β-cell function (HOMA-B%) were used to define basal glucose-insulin homeostasis.. The group with longer dependence duration had HOMA-IR (2.23 ± 3.15) significantly higher compared with the control group (1.23 ± 0.53, P = 0.016) but lower compared with the group with the shorter dependence duration (2.65 ± 2.66, P = 0.024), after adjustment for HOMA-B%, waist circumference, and aspartate aminotransferase. The decrease in HOMA-IR during prolonged heroin addiction was significantly associated with the reduced β-cell function (P < 0.001) and waist circumference (P = 0.004).. Heroin dependence is associated with increased insulin resistance in hepatitis C virus seronegative heroin dependents. Prolonged heroin use is associated with reduction of basal β-cell pancreatic function with decreased insulin resistance controlled for waist circumference, but still inducing significantly decreased basal insulin sensitivity.

Topics: Adult; Body Mass Index; Buprenorphine; Cross-Sectional Studies; Female; Hepatitis C; Heroin; Heroin Dependence; Homeostasis; Humans; Insulin Resistance; Insulin-Secreting Cells; Male; Metabolic Syndrome; Models, Theoretical; Narcotics; Opiate Substitution Treatment; Prospective Studies; Republic of North Macedonia; Statistics as Topic; Waist Circumference; Young Adult

Opioid substitution therapy (OST) is the most commonly provided treatment for heroin dependence in Australia and has been shown to be effective. Access to OST outside of specialised public clinics and prisons relies on the participation of general practitioners. In Australia there is a shortage of GPs available to prescribe OST, which results in an unmet need for OST services. Studies have reported barriers to GP involvement in drug and alcohol work and there is little research looking at the perceptions and experiences of GPs involved in prescribing OST.. Semistructured qualitative interviews were conducted with eight experienced prescribers of OST in general practice settings in South Australia.. All participants described similar positive and negative aspects associated with prescribing OST. Some participants commenced prescribing in such a manner as to limit the scope of their involvement. Ceasing OST prescribing was not necessarily linked to negative experiences. Exprescribers indicated that they were unlikely to recommence prescribing.. This study has limited generalisability due to the small sample size but it does highlight some insights that can be gained from talking to experienced OST prescribers.

Topics: Adult; Aged; Aged, 80 and over; Buprenorphine; Female; Heroin Dependence; Humans; Interviews as Topic; Male; Methadone; Middle Aged; Narcotic Antagonists; Practice Patterns, Physicians'; South Australia

The sublingual combination of buprenorphine and naloxone (Suboxone(®)) and Methadone Maintenance Therapy have been found effective in treating heroin addiction. A new analytical method suitable for the simultaneous determination of buprenorphine, norbuprenorphine, methadone and naloxone in human plasma by means of liquid chromatography with coulometric detection has been developed. The chromatographic separation was achieved with a phosphate buffer-acetonitrile mixture as the mobile phase on a cyano column. The monitoring cell of the coulometric detector was set at an oxidation potential of +0.600 V. A rapid clean-up procedure of the biological samples using a microextraction by packed sorbent technique has been implemented, employing a C8 sorbent inserted into a syringe needle. The extraction yield values were satisfactory for all analytes (>85%). The calibration curves were linear over a range of 0.25-20.0 ng mL(-1) for buprenorphine and norbuprenorphine, 3.0-1000.0 ng mL(-1) for methadone and 0.13-10.0 ng mL(-1) for naloxone. The sensitivity was also high with limits of detection of 0.08 ng mL(-1) for both buprenorphine and norbuprenorphine, 0.9 ng mL(-1) for methadone and 0.04 ng mL(-1) for naloxone. The intraday and interday precision data were always satisfactory. The method was successfully applied to plasma samples obtained from former heroin addicts treated with opioid replacement therapy.

Topics: Acetonitriles; Analgesics, Opioid; Buffers; Buprenorphine; Calibration; Chromatography, High Pressure Liquid; Electrochemical Techniques; Heroin Dependence; Humans; Limit of Detection; Methadone; Naloxone; Phosphates; Solid Phase Microextraction; Solvents

Necrosis of the penis glans is commonly described after circumcision or strangulation. We report the case of a patient, opioid abuser, who presented an isolated glans necrosis after an injection of buprenorphin. The buprenorphin (Subutex) is a sublingual partial mu-opioid agonist used for the treatment of heroin dependance. Its intravenous or subcutaneous abuse is associated with local infection. The patient require a surgical intervention. After the failure of a mucosal graft, a soft skin graft was done.

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Follow-Up Studies; Heroin Dependence; Humans; Injections, Subcutaneous; Male; Narcotic Antagonists; Necrosis; Penis; Reoperation; Skin Transplantation; Surgical Wound Infection; Wound Healing

Maintenance treatment with buprenorphine tablets (Subutex) has been associated with reductions in heroin use; however, concerns for intravenous misuse exist. A buprenorphine/naloxone formulation (Suboxone) was designed to reduce this misuse risk while retaining buprenorphine's efficacy and safety. This prospective, open-label, multicenter trial compared preferences for buprenorphine and buprenorphine/naloxone in 53 opioid-dependent patients stabilized on buprenorphine. Buprenorphine was first administered at the patient's current dose (Days 1-2), followed by a direct switch to buprenorphine/naloxone (Days 3-5). Global satisfaction rates were high and similar between buprenorphine and buprenorphine/naloxone; however, patients preferred the tablet taste, size, and sublingual dissolution time of buprenorphine/naloxone. At the end of the study, 54% of patients preferred buprenorphine/naloxone, 31% preferred buprenorphine, and 15% had no preference; most patients (71%) wished to continue treatment with buprenorphine/naloxone. This study did not identify any impediments to a direct buprenorphine-to-buprenorphine/naloxone switch and revealed some characteristics that may facilitate treatment with buprenorphine/naloxone.

Topics: Adolescent; Adult; Buprenorphine; Drug Administration Schedule; Drug Combinations; Female; France; Heroin Dependence; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Patient Preference; Patient Satisfaction; Prospective Studies; Surveys and Questionnaires; Treatment Outcome

A prospective longitudinal design was employed to examine the effects of buprenorphine maintenance on quality of life (QOL), clinical, and psychosocial characteristics of heroin-dependent patients.. Between 2003 and 2005 data were collected on 259 patients attending the outpatient centers for treatment of drug addictions across Israel, of which 157 were reevaluated 16 weeks later and 105 reevaluated 32 weeks later using the Clinical Global Impression, Distress Scale for Adverse Symptoms, Quality of Life Enjoyment and Satisfaction Questionnaire, General Health Questionnaire, General Self-Efficacy Scale, and the Multidimensional Scale of Perceived Social Support. Univariate and multivariate analyses were conducted to examine the association between the parameters and the cross-sectional and longitudinal predictions of the QOL outcomes.. The groups did not differ in baseline values and their post-treatment ratings revealed significant improvement on virtually all the scales. Perceived self-efficacy and social support from friends and significant others at baseline as well as their changes over time were the best predictors of the QOL in the short and long terms. The study's limitations are noted.. The beneficial effects on the QOL were associated with improvement in the psychosocial parameters and a reduction in buprenorphine-related side effects and psychological distress. This study could stimulate research to compare the QOL related to buprenorphine and methadone treatment and serve as a basis on which a controlled study should be performed.

Topics: Adolescent; Adult; Ambulatory Care; Buprenorphine; Female; Heroin Dependence; Humans; Male; Narcotic Antagonists; Patient Compliance; Prospective Studies; Quality of Life; Self Efficacy; Social Support; Stress, Psychological; Treatment Outcome

Misuse of high-dose buprenorphine (HDB), mainly by injection, is responsible of frequent infectious adverse events.. This is a retrospective study of infectious complications occurring in patients using HDB by injection. Forty-two cases were identified (29 men and ten women) and the data were collected between March 1999 and December 2008.. The infectious complications included cutaneous infections (27 cases), endocarditis (nine cases), osteoarticular infections (four spondylodiscitis and one sacroiliitis), and a vascular embolism with decrease in visual acuity.. The results of HDB maintenance treatment must be improved, both from the point of view of substitution and to limit its misuse by intravenous route injection. Health professionals have to play an important role in drug addict patients' education and supervision, to prevent buprenorphine injection and related infectious complications.

Topics: Abscess; Adult; Bacterial Infections; Buprenorphine; Discitis; Dose-Response Relationship, Drug; Endocarditis, Bacterial; Female; Heroin Dependence; Humans; Injections, Intravenous; Injections, Subcutaneous; Male; Narcotic Antagonists; Retrospective Studies

Topics: Buprenorphine; Drug Overdose; European Union; Family Practice; France; Heroin Dependence; Humans; Narcotics; Norway; Physician's Role

Buprenorphine is a partial opioid agonist with a "ceiling effect" for respiratory depression. Despite this, it has been associated with severe overdoses. Conflicting data exist regarding its response in overdose to naloxone. We compared clinical overdose characteristics of buprenorphine with heroin and methadone and assessed responses to naloxone and flumazenil. Patients admitted to two intensive care units with severe opioid overdoses were enrolled into this 4-year prospective study. Urine and blood toxicological screening were performed to identify overdoses involving predominantly buprenorphine, heroin, or methadone. Eighty-four patients with heroin (n = 26), buprenorphine (n = 39), or methadone (n = 19) overdoses were analyzed. In the buprenorphine group, sedative drug coingestions were frequent (95%), whereas in the methadone group, suicide attempts were significantly more often reported (p = .0007). Buprenorphine overdose induced an opioid syndrome not differing significantly from heroin and methadone in mental status (as measured by Glasgow Coma Score) or arterial blood gases. Mental status depression was not reversed in buprenorphine overdoses with naloxone (0.4-0.8 mg) but did improve with flumazenil (0.2-1 mg) if benzodiazepines were coingested. In conclusion, buprenorphine overdose causes an opioid syndrome clinically indistinguishable from heroin and methadone. Although mental status and respiratory depression are often unresponsive to low-dose naloxone, flumazenil may be effective in buprenorphine overdoses involving benzodiazepines.

Topics: Adult; Antidotes; Buprenorphine; Drug Overdose; Female; Flumazenil; Heroin; Heroin Dependence; Humans; Intensive Care Units; Male; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Prospective Studies; Suicide, Attempted

While long-term heroin addiction is associated with hypothalamus-pituitary-adrenal (HPA) axis dysregulation, few studies have used in vivo brain imaging to examine the impact on pituitary gland volume (PGV) or its relationship with substitution pharmacotherapy. We examined 28 heroin users stable on methadone or buprenorphine and 28 healthy controls. Heroin users exhibited larger PGVs than healthy controls, and this was particularly evident among the buprenorphine-treated group. These findings indicate that substitution pharmacotherapy may have differential effects on normalising HPA axis activity.

Topics: Adult; Buprenorphine; Female; Heroin Dependence; Humans; Male; Methadone; Narcotic Antagonists; Narcotics; Neuropsychological Tests; Pituitary Gland; Psychiatric Status Rating Scales; Socioeconomic Factors

Abuse of addictive substances is a serious problem that has a significant impact on areas such as health, the economy, and public safety. Heroin use among young women of reproductive age has drawn much attention around the world. However, there is a lack of information on effects of prenatal exposure to opioids on their offspring. In this study, an animal model was established to study effects of prenatal exposure to opioids on offspring.. Female pregnant Sprague-Dawley rats were sub-grouped to receive (1) vehicle, (2) 2-4 mg/kg morphine (1 mg/kg increment per week), (3) 7 mg/kg methadone, and (4) 3 mg/kg buprenorphine, subcutaneously, once or twice a day from E3 to E20. The experiments were conducted on animals 8-12 weeks old and with body weight between 250 and 350 g.. Results showed that prenatal exposure to buprenorphine caused higher mortality than other tested substance groups. Although we observed a significantly lower increase in body weight in all of the opioid-administered dams, the birth weight of the offspring was not altered in all treated groups. Moreover, no obvious behavioral abnormality or body-weight difference was noted during the growing period (8-12 weeks) in all offspring. When the male offspring received morphine injection twice a day for 4 days, the prenatally opioid-exposed rats more quickly developed a tolerance to morphine (as shown by the tail-flick tests), most notably the prenatally buprenorphine-exposed offspring. However, the tolerance development to methadone or buprenorphine was not different in offspring exposed prenatally to methadone or buprenorphine, respectively, when compared with that of the vehicle controlled group. Similar results were also obtained in the female animals.. Animals prenatally exposed to morphine, methadone, or buprenorphine developed tolerance to morphine faster than their controlled mates. In our animal model, prenatal exposure to buprenorphine also resulted in higher mortality and much less sensitivity to morphine-induced antinociception than prenatal exposure to morphine or methadone. This indicates that buprenorphine in higher doses may not be an ideal maintenance drug for treating pregnant women. This study provides a reference in selecting doses for clinical usage in treating pregnant heroin addicts.

Topics: Analgesics; Animals; Buprenorphine; Disease Models, Animal; Drug Tolerance; Female; Heroin Dependence; Humans; Male; Methadone; Morphine; Morphine Dependence; Pain Measurement; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley

Methadone and buprenorphine are both efficacious treatments for opioid dependency, but they also have different pharmacological properties and clinical delivery methods that can affect their acceptability to patients. This study was intended to increase our knowledge of heroin-dependent individuals' perceptions of methadone vs. buprenorphine maintenance based on actual experiences with each. The study sample consists of heroin-dependent men at the Rikers Island jail in New York City who were voluntarily randomly assigned to methadone or buprenorphine maintenance in jail. Methadone patients were more likely to report feeling uncomfortable the first few days, having side/withdrawal effects during treatment, and being concerned about continued dependency on medication after release. In contrast, buprenorphine patients' main issue was the bitter taste. All of the buprenorphine patients stated that they would recommend the medication to others, with almost all preferring it to methadone. Ninety-three percent of buprenorphine vs. 44% of methadone patients intended to enroll in those respective treatments after release, with an added one-quarter of the methadone patients intending to enroll in buprenorphine instead. These results reinforce the importance of increasing access to buprenorphine treatment in the community for indigent heroin-dependent offenders.

Topics: Adult; Buprenorphine; Heroin Dependence; Humans; Male; Methadone; Narcotics; New York City; Opiate Substitution Treatment; Patient Preference; Prisoners; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Taste

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Hand; Heroin Dependence; Humans; Lymph Nodes; Lymphatic Vessels; Lymphedema; Male; Opioid-Related Disorders; Radionuclide Imaging; Substance Abuse, Intravenous

Topics: Adult; Analgesics, Opioid; Aorta; Blood Pressure; Buprenorphine; Female; Hemodynamics; Heroin; Heroin Dependence; Humans; Substance Withdrawal Syndrome

The study aimed to determine patterns of major depression (MD) across 36 months, and the relationship to outcomes for the treatment of heroin dependence. As part of a longitudinal cohort study, 429 heroin users were interviewed at 36 month follow-up. MD declined from 23.8% at baseline to 8.2% at 36 months. Females were more likely to have MD at both baseline (31.1 vs. 19.8) and 36 months (11.9 vs. 6.1%). Those with MD at baseline were significantly more likely to be diagnosed with MD at a follow-up interview (40.2 vs. 15.9%) and at 36 months (14.7 vs. 6.1%). Antidepressant use did not decrease across 36 months amongst either gender. Baseline MD was not related to treatment exposure across 36 months. There were large and significant declines in drug use and drug-related problems, and improvements in physical health with no group differences evident at 36 months. Despite improvements in global mental health, at both baseline and 36 months those with MD at baseline had significantly lower SF12 mental health scores. It was concluded that, with the exception of depression, the prognosis of depressed heroin users is not worse than that of non-depressed users.

Topics: Adolescent; Adult; Buprenorphine; Cohort Studies; Comorbidity; Crime; Depressive Disorder, Major; Drug Overdose; Female; Health Status; Health Status Indicators; Heroin; Heroin Dependence; Humans; Longitudinal Studies; Male; Methadone; Middle Aged; Narcotics; Needle Sharing; New South Wales; Prognosis; Substance Abuse, Intravenous; Suicide, Attempted; Treatment Outcome; Young Adult

Subutex (buprenophine) was approved by the Health Science Authority of Singapore for heroin detoxification in 2002. The number of heroin addicts has decreased in Singapore since the introduction of Subutex. However, Subutex abuse and its associated complications became arising medical problems. We report the management of a series of infective endocarditis cases secondary to Subutex abuse.. We identified 12 cases of infective endocarditis in former heroin addicts treated with Subutex from August 2005 to April 2006. All patients were interviewed by the research coordinator and prospectively followed-up for two years.. The treatment period of Subutex endocarditis was often prolonged with a mean hospitalisation stay of 48 days, with 3.8 days in the intensive care unit. Multiple medical complications were noted. Staphylococcus aureus septicaemia accounted for 92 percent of cases. Mortality rate was 42 percent. Failure rate of medical therapy alone was common. 25 percent underwent open heart valve surgery. All patients were subsidised. Mean hospitalisation expenses was S$31,218.. Subutex endocarditis causes significant morbidity and mortality. It imposes a heavy medical and financial burden to the patient and society. Multidisciplinary treatment involving cardiologists, infectious disease physicians, psychiatrists, surgeons, medical counsellors and social workers is required to manage these patients.

Topics: Adult; Buprenorphine; Endocarditis, Bacterial; Female; Heroin Dependence; Humans; Injections, Intravenous; Length of Stay; Male; Middle Aged; Narcotic Antagonists; Prospective Studies; Singapore

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

Topics: Buprenorphine; Health Services Research; Heroin Dependence; Humans; Narcotic Antagonists; Pharmacists; Physicians; Practice Patterns, Physicians'; Prescriptions; Program Evaluation; Randomized Controlled Trials as Topic; Research Design; Time Factors; Victoria

Opioid abuse is common in Iran. In 2005, a new version of locally produced illicit opioid vials, so called Norgesic, appeared in the illicit market, which gained popularity rapidly and led to an improvement of stigmatizing the general appearance of dependent cases. Later, some cases suffered Cushing's-like problems. A prospective case series was designed to evaluate 18 Norgesic-dependent subjects who volunteered for abstinence therapy in a rehabilitation clinic from November 1, 2005, to December 30, 2005. In this study, we aimed to describe the clinical and paraclinical findings in detail and define the potential determinants of this Cushing's syndrome outbreak. History, physical examination, plasma cortisol level, and urine screen tests were used to describe the patients. All subjects were male with a mean (SEM) age of 29.8 +/- 1.6 years. The opioid-dependence period was 8.4 +/-0.9 years. In an average of 4.7 +/- 0.3 months, subjects increased their usage to 5.5 +/- 0.5 vials a day. Patients claimed to gain weight. Striae were seen in 38.9%, previously documented psychological problems in 33.3%, weakness in 27.8%, high systolic blood pressure in 22.2%, moon face in 16.7%, hirsutism in 11.1%, extensive dermal infection in 11.1%, gynecomastia in 5.6%, back pain in 5.6%, insomnia in 5.6%, and lack of potency in 5.6%. Their cortisol level, on average, was 4.8 +/- 1.1 microg/dL. Hepatitis C virus was positive in 22.2%. Urine-screening tests were positive for morphine and negative for buprenorphine. In conclusion, these new vials contain steroids as well as opioids. This combination could be more dangerous than opioids themselves.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cushing Syndrome; Disease Outbreaks; Heroin Dependence; Humans; Iran; Male; Morphine; Opioid-Related Disorders; Risk Factors; Steroids; Substance-Related Disorders

The purposes of this study were to assess outcomes of patients prescribed buprenorphine at a primary care practice and to identify factors associated with favorable outcomes. All 255 patients given at least one prescription for buprenorphine between August 2003 and September 1, 2007, at a primary care practice in Baltimore were included. Data regarding demographics and comorbidities were collected retrospectively. Patients were classified as "opioid-positive" or "opioid-negative" each month based on patient report, urine toxicology, and provider assessment. After 12 months, 145 (56.9%) patients remained in treatment, and 64.7% of their months were opioid-negative. Patients using heroin were less likely to be opioid-negative, whereas those using prescription opioids were more likely to be opioid-negative. Polysubstance use was associated with increased treatment retention. The prescription of buprenorphine for opioid dependence treatment can be incorporated into primary care practice, and many patients, including polysubstance users, benefit from this treatment.

Topics: Administration, Sublingual; Adult; Aged; Baltimore; Buprenorphine; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Middle Aged; Narcotics; Opioid-Related Disorders; Primary Health Care; Retrospective Studies; Treatment Outcome; Young Adult

Forty-four heroin dependence patients took detoxification treatment in Fukko-kai Tarumi Hospital from October 1998 to April 2008 (total of 80 admissions). Injectable formulation of buprenorphine (0.2 mg) was used intramuscularly to relieve withdrawal symptoms from October 2002. In the initial phase, small dosage of buprenorphine (0.4 mg per day) was dispensed but obvious effects were not confirmed. Therefore, the dosage was increased to 0.6 mg (3 ampoules), possibly more for 27 patients (total of 53 admissions) from October 2005. While treatment was interrupted by various reasons in 6 patients (total of 10 admissions), the rest completed detoxification. Dosage of buprenorphine given to the patients varied from 0.6 mg (3 ampoules) to 1.6 mg (8 ampoules) per day, and only 4 patients required over 1.0 mg. While duration of administration ranged from 5 days to 15 days, it was between 7 days and 10 days in over the half cases. When sufficient amount of buprenorphine was administered, severity and duration of heroin withdrawal symptoms was distinctly reduced. Since the introduction of heroin detoxification with buprenorphine, number of patients who request the treatment voluntarily increased including those who relapsed, but the length of hospital stay was shortened. One patient rejected buprenorphine injection for unknown reason and one patient left the hospital because of insufficient effect due to insufficient amount of buprenorphine dose, serious adverse effect was not observed. Detoxification treatment with buprenorphine cannot ensure sustained abstinence but can motivate heroin-using patients to receive treatment and strive for abstinence.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Heroin Dependence; Humans; Inactivation, Metabolic; Injections; Male; Middle Aged; Refugees

More than 50% of incarcerated individuals have a history of substance use, and over 200,000 individuals with heroin addiction pass through American correctional facilities annually. Opiate replacement therapy (ORT) with methadone or buprenorphine is an effective treatment for opiate dependence and can reduce drug-related disease and recidivism for inmates. Provision of ORT is nevertheless a frequently neglected intervention in the correctional setting.. We surveyed the 50 state; Washington, District of Columbia (DC); and Federal Department of Corrections' medical directors or their equivalents about their facilities' ORT prescribing policies and referral programs for inmates leaving prison.. We received responses from 51 of 52 prison systems nationwide. Twenty-eight prison systems (55%) offer methadone to inmates in some situations. Methadone use varies widely across states: over 50% of correctional facilities that offer methadone do so exclusively for pregnant women or for chronic pain management. Seven states' prison systems (14%) offer buprenorphine to some inmates. The most common reason cited for not offering ORT was that facilities "prefer drug-free detoxification over providing methadone or buprenorphine." Twenty-three states' prison systems (45%) provide referrals for some inmates to methadone maintenance programs after release, which increased from 8% in 2003; 15 states' prison systems (29%) provide some referrals to community buprenorphine providers.. Despite demonstrated social, medical, and economic benefits of providing ORT to inmates during incarceration and linkage to ORT upon release, many prison systems nationwide still do not offer pharmacological treatment for opiate addiction or referrals for ORT upon release.

Topics: Buprenorphine; Drug Utilization; Female; Health Care Surveys; Heroin Dependence; Humans; Male; Methadone; Narcotic Antagonists; Narcotics; Pregnancy; Prisoners; Prisons; Referral and Consultation; United States

Addiction to heroin and crack cocaine is debilitating and persistent, but such disorders are treatable. We present the first effectiveness study of the main community interventions for addiction to heroin and crack cocaine in England, using data from the National Drug Treatment Monitoring System (NDTMS).. The study cohort consisted of all adults with a heroin or crack cocaine addiction, or both, who started pharmacological treatment (n=18 428 patients) or psychosocial treatment (n=2647) between Jan 1 and Nov 30, 2008, received at least 6 months' treatment or were discharged by the study endpoint (May 31, 2009), and had outcome data submitted to the NDTMS. Effectiveness was assessed from change in days of heroin or crack cocaine use, or both in the 28 days before the start of treatment and in the 28 days before review.. 14 656 clients-74% of the cohort eligible for analysis at review with available data-were analysed at the study endpoint. During the 28 days before review, 37% (5016/13 542) of heroin users abstained from heroin and 52% (3941/7636) of crack cocaine users abstained from crack cocaine. A higher proportion of users of heroin only abstained than did users of both heroin and crack cocaine (42% [2465/5863] vs 33% [2551/7679]; OR 1.46, 95% CI 1.36-1.56), and more users of crack cocaine only abstained than did users of both drugs (57% [295/522] vs 51% [3646/7114]; 1.24, 1.03-1.48). Overall heroin use reduced by 14.5 days (95% CI 14.3-14.7) and crack cocaine use by 7.7 days (7.5-7.9). For clients given pharmacological treatment, reduction in days of heroin use was smaller for users of both heroin and crack cocaine than for users of heroin alone (p<0.0001), but this differential effectiveness was not recorded for psychosocial treatment in heroin or crack cocaine users compared with users of both drugs.. The first 6 months of pharmacological or psychosocial treatment is associated with reduced heroin and crack cocaine use, but the effectiveness of pharmacological treatment is less pronounced for users of both drugs. New strategies are needed to treat individuals with combined heroin and crack cocaine addiction.. National Treatment Agency for Substance Misuse.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cocaine-Related Disorders; Community Mental Health Services; England; Female; Heroin Dependence; Humans; Linear Models; Male; Methadone; Multivariate Analysis; Narcotic Antagonists; Program Evaluation; Prospective Studies; Psychotherapy; Treatment Outcome

Buprenorphine is a semi-synthetic opioid derivative commonly used in the treatment of heroin addiction. Life-threatening complications have been described following overdoses while few cases of hepatotoxicity due to drug use at therapeutic doses have been recently described in hepatitis C virus carriers. In these cases, however, histological assessment was not exhaustive and no extra-hepatic organ failure was observed. We describe herein a case of acute liver and kidney failure in a patient with previously latent hepatitis C virus chronic infection following recommended doses of buprenorphine. Histology did not demonstrate any feature compatible with hepatitis C virus reactivation or liver cirrhosis and suspension of the treatment led to the resolution of both liver and kidney failure. Causality criteria fulfillment indicates a high probability of buprenorphine-induced liver toxicity. No signs of pre-existant kidney impairment or of pre- or post-renal causes were observed. Since buprenorphine is metabolized through cytochrome P450 3A4, we genotyped six genetic polymorphisms previously described in poor metabolizers but could not confirm these pharmacogenetic bases in this case. In conclusion, we surmise that buprenorphine at suggested doses can induce liver and kidney failure in susceptible individuals, possibly through direct mitochondrial toxicity.

Topics: Acute Kidney Injury; Adult; Buprenorphine; Heroin Dependence; Humans; Liver Failure, Acute; Male; Narcotic Antagonists

Heroin addiction is a complicated medical and psychiatric issue, with well-established as well as newer modes of treatment. The case of Ms W, a 50-year-old woman with a long history of opiate addiction who has been treated successfully with methadone for 9 years and who now would like to consider newer alternatives, illustrates the complex issues of heroin addiction. The treatment of heroin addiction as a chronic disease is reviewed, including social, medical, and cultural issues and pharmacologic treatment with methadone and the more experimental medication options of buprenorphine and naltrexone.

Topics: Buprenorphine; Drug Therapy, Combination; Female; Heroin Dependence; History, 19th Century; History, 20th Century; Humans; Methadone; Middle Aged; Naltrexone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Recurrence; Self-Help Groups; United States

Topics: Buprenorphine; Drug Utilization; Heroin Dependence; Humans; Malaysia; Methadone; Naltrexone; Patient Compliance; Pilot Projects; Policy Making

Topics: Buprenorphine; Heroin Dependence; Humans; Naltrexone; Narcotic Antagonists; Randomized Controlled Trials as Topic; Time Factors

Maternal drug addiction can cause problems for the fetus and the newborn, and hamper long-term development. The prevalence of drug addiction during pregnancy varies from 1 % to more than 10 % depending on the country and the maternity unit. Management of these mothers can be further complicated by medical, social and psychological problems. Compared to methadone, heroin replacement therapy with buprenorphine provides better stabilization of the mother and causes fewer withdrawal symptoms in the newborn. Despite numerous publications on the effects of this partly preventive medication, data on buprenorphine pharmacology at birth are scarce. In this study, 20 newborns of mothers using oral buprenorphine were observed until the end of the withdrawal syndrome, when present. Buprenorphine plasma levels were determined with HPLC and mass spectrometry in the mother at delivery and in the newborn at birth (cord blood), 24 and 48 hours. Fifteen newborns were born at term (mean +/- SD birth weight 3029 +/- 273 g), and the other five between 32 and 36 weeks. All Apgar scores were > or =7. Withdrawal symptoms were observed in 8 of the 15 infants born to mothers taking buprenorphine alone, and lasted between 5 and 35 days. The newborns were classified in three groups. Groups I (N8) and II (N7) comprised newborns with and without withdrawal symptoms, respectively. In group III (N5), the mothers were polyintoxicated (as shown by urinary drug or neurotropic substance screening) and the newborns were symptomatic for 1 to 69 days. Buprenorphine plasma levels in the mothers ranged from 0 to 2.9 microg/L, suggesting large differences in adherence. At birth there was no significant difference in the mean plasma buprenorphine level between newborns with and without withdrawal symptoms; the respective values were 0.7 (0.4-1.3) and 0.5 (0-0.6) microg/L. In asymptomatic newborns (group II), buprenorphine was no longer detectable at 48 h, whereas in symptomatic newborns (group I), the mean level rose from 0.7 microg/l at birth to 1.5 microg/L at 48 h (+114 %). In the absence of breastfeeding, this increase appears to be related to tissue release of this strongly lipophilic compound. The difference in plasma buprenorphine kinetics between groups I and II might be explained by genetic polymorphism of drug-metabolizing enzymes. The paradoxically high plasma buprenorphine levels at 48 hours in infants with withdrawal symptoms are intriguing. One possibility is that the mothers missed

Topics: Buprenorphine; Female; Heroin Dependence; Humans; Infant, Newborn; Male; Narcotics; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome; Young Adult

The use of heroin, cocaine, and other drugs is well researched in New York City, but prescription opioids (POs) have been overlooked. This study documents patterns of PO use, misuse, and diversion among street drug users, and begins to indicate how drug culture practices interact with the legitimate therapeutic goals of PO prescriptions (e.g. pain management).. Staff completed interviews inquiring about the reasons for use of POs and illicit drugs with 586 street drug users. Ethnographers wrote extensive field notes about subjects' complex patterns of PO use.. Methadone was used (71.9%) and sold (64.7%) at a higher level than OxyContin, Vicodin, and Percocet, used by between 34% and 38% of the users and sold by between 28% and 41% of the sellers. Recent PO use is associated with the recency of using heroin and cocaine (p<.001). Half of the heroin/cocaine sellers sold POs, and one quarter of the PO sellers only sold POs. Subjects were classified into four groups by whether they diverted POs or used POs to relieve pain or withdrawal rather than for euphoria. This classification was associated with frequency of PO use, whether POs were obtained from doctors/pharmacies or from drug dealers and family members, and those mostly likely to use POs for pain and withdrawal.. POs are an important component of street drug users' drug-taking regimes, especially those who are Physically Ill Chemical Abusers (PICA). Future research is needed to model PO use, misuse, and diversion among this population.

Topics: Administration, Intranasal; Adult; Aged; Analgesics, Opioid; Buprenorphine; Cocaine-Related Disorders; Drug Prescriptions; Ethnicity; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; Narcotics; New York City; Pain; Patient Selection; Socioeconomic Factors; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Substance-Related Disorders

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

Topics: Adolescent; Adult; Buprenorphine; Depression; Erectile Dysfunction; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotics; Prevalence; Psychology; Sexual Partners; Statistics, Nonparametric; Surveys and Questionnaires

Topics: Adult; Analgesics, Opioid; Buprenorphine; Cerebral Angiography; Cerebrovascular Circulation; Chronic Disease; Dose-Response Relationship, Drug; Female; Heroin Dependence; Humans; Intracranial Hemorrhages; Marijuana Abuse; Tomography, X-Ray Computed; Vasospasm, Intracranial

In many countries, buprenorphine and methadone are licensed for the maintenance treatment (MT) of opioid dependence. Despite many short-term studies, little is known about the long-term (12-month) effects of these treatments in different settings, i.e. primary care-based (PMC) and specialized substitution centers (SSCs).. To describe over a period of 12 months: (1) mortality, retention and abstinence rates; (2) changes in concomitant drug use, somatic and mental health; and (3) to explore differences between different types of provider settings.. 12-Month prospective-longitudinal naturalistic study with four waves of assessment in a prevalence sample of N=2694 maintenance patients, recruited from a nationally representative sample of N=223 substitution physicians.. The 12-month retention rate was 75%; the mortality rate 1.1%. 4.1% of patients became "abstinent" during follow-up. 7% were referred to drug-free addiction treatment. Concomitant drug use decreased and somatic health status improved. No significant improvements were observed for mental health and quality of life. When controlling for initial severity, small PMC settings revealed better retention, abstinence and concomitant drug use rates.. The study underlines the overall 12-month effectiveness of various forms of agonist MT. Findings reveal relatively high retention rates, low mortality rates, and improvements in most 12-month outcome domains, except for mental health and quality of life. PMC settings appear to be a good additional option to improve access to MTs.

Topics: Adult; Ambulatory Care Facilities; Buprenorphine; Catchment Area, Health; Feasibility Studies; Female; Germany; Heroin Dependence; Humans; Male; Mental Health Services; Methadone; Narcotics; Prevalence; Primary Health Care; Prospective Studies; Retention, Psychology

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

Topics: Birth Weight; Buprenorphine; Female; Fetal Growth Retardation; Heroin Dependence; Humans; Infant Mortality; Infant, Newborn; Methadone; Narcotic Antagonists; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Sweden

To identify causes of death among Norwegian drug abusers and to investigate the risk factors for fatal overdose and other causes of death, with specific attention to ageing and duration of abuse.. In a cohort of 501 drug abusers admitted to treatment in the period 1981-1991, mortality has been calculated as incidence rates. The analyses of time to death were conducted as proportional hazard regression models using a competing risk approach.. Crude incidence rates for all deaths and overdose deaths did not vary with age. For non-overdose deaths, however, the incidence was significantly higher after the age of 40. Explanatory factors associated with age at fatal overdoses are also associated with age at death by other causes. At every age the risk of death was higher with a long-term abuse of drugs, and more so for fatal overdose than for death by other causes.. With respect to fatal overdose duration of abuse, but not ageing, is found to be a risk factor. With respect to death by other causes both ageing and duration of abuse are factors associated with such death.

Topics: Adult; Age Factors; Amphetamine-Related Disorders; Buprenorphine; Cause of Death; Cohort Studies; Comorbidity; Drug Overdose; Female; Follow-Up Studies; Heroin Dependence; Humans; Illicit Drugs; Male; Methadone; Middle Aged; Narcotics; Norway; Patient Admission; Poisoning; Proportional Hazards Models; Psychotropic Drugs; Risk; Substance-Related Disorders

Buprenorphine is a partial mu receptor agonist used in opiate detoxification. It has been shown to cause delayed gastric emptying in healthy volunteers.. 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.. 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.

Topics: Adult; Buprenorphine; Female; Gastroparesis; Heroin Dependence; Humans; Narcotic Antagonists

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-week 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.

Topics: Adult; Alcoholism; Buprenorphine; Clinical Trials as Topic; Cocaine-Related Disorders; Female; Heroin Dependence; Humans; Long-Term Care; Male; Middle Aged; Naloxone; Narcotic Antagonists; Narcotics; Neurologic Examination; New York City; Opioid-Related Disorders; Patient Dropouts; Residential Treatment; Retrospective Studies; Substance Withdrawal Syndrome; Therapeutic Community

Buprenorphine 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.

Topics: Acute Disease; Adult; Buprenorphine; Clonidine; Diffusion of Innovation; Female; Heroin; Heroin Dependence; Humans; Length of Stay; Male; Middle Aged; Narcotics; Oregon; Patient Acceptance of Health Care; Retrospective Studies; Substance Withdrawal Syndrome; Treatment Outcome

Topics: Buprenorphine; Heroin Dependence; Humans; Injections; Long-Term Care; Methadone; Naltrexone; Narcotic Antagonists; Narcotics; Pain; Prisoners; Treatment Outcome

Attitudes, perceived social norms, 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, buprenorphine, 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 ibogaine 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.

Topics: Adult; Ambulatory Care; Attitude of Health Personnel; Buprenorphine; Clonidine; Counseling; Culture; Female; Focus Groups; Heroin Dependence; Humans; Ibogaine; Male; Methadone; Middle Aged; Narcotics; Opioid-Related Disorders; Patient Admission; Patient Satisfaction; Peer Group; Psychotropic Drugs; Substance Withdrawal Syndrome; Treatment Outcome

Methadone is prescribed to heroin addicts to decrease illicit opioid use. Prolongation of the QT interval in the ECG of patients with torsade de pointes (TdP) has been reported in methadone users. As heroin addicts sometimes faint while using illicit drugs, doctors might attribute too many episodes of syncope to illicit drug use and thereby underestimate the incidence of TdP in this special population, and the high mortality in this population may, in part, be caused by the proarrhythmic effect of methadone.. In this cross-sectional study interview, ECGs and blood samples were collected in a population of adult heroin addicts treated with methadone or buprenorphine on a daily basis. Of the patients at the Drug Addiction Service in the municipal of Copenhagen, 450 (approximately 52%) were included. The QT interval was estimated from 12 lead ECGs. All participants were interviewed about any experience of syncope. The association between opioid dose and QT, and methadone dose and reporting of syncope was assessed using multivariate linear regression and logistic regression, respectively.. Methadone dose was associated with longer QT interval of 0.140 ms/mg (p = 0.002). No association between buprenorphine and QTc was found. Among the subjects treated with methadone, 28% men and 32% women had prolonged QTc interval. None of the subjects treated with buprenorphine had QTc interval >0.440 s((1/2)). A 50 mg higher methadone dose was associated with a 1.2 (95% CI 1.1 to 1.4) times higher odds for syncope.. Methadone is associated with QT prolongation and higher reporting of syncope in a population of heroin addicts.

Topics: Adult; Buprenorphine; Cross-Sectional Studies; Dose-Response Relationship, Drug; Electrocardiography; Female; Heroin Dependence; Humans; Long QT Syndrome; Male; Methadone; Middle Aged; Narcotics; Syncope

The mechanisms through which buprenorphine (BUP), a mixed opioid agonist-antagonist, reduces both heroin and cocaine taking remain unclear. Evidence suggests that chronic exposure to BUP blunts drug seeking by attenuating the salience of drug-associated cues. Here, we examined the effect of chronic BUP treatment (osmotic minipumps, 3.0 mg/kg/day) in rats on responding for sucrose pellets and associated cues on FR1, FR5, and PR schedules and on extinction and reinstatement of sucrose seeking by sucrose priming. The effect of chronic BUP treatment on the dopamine (DA) response in the nucleus accumbens (NAc) to sucrose pellets and to lab chow was also measured using in vivo microdialysis. Whereas chronic BUP treatment had only a modest effect on pellet intake on the FR1 schedule, it significantly reduced responding at the outset of sessions and reduced lever pressing during sucrose-associated cue presentations. No effect was observed in the FR5 or PR schedules. BUP slightly reduced responding during extinction and significantly reduced reinstatement. Chronic BUP did not alter the NAc DA response to either sucrose pellets or lab chow, although it did significantly increase basal DA. Consistent with previous studies with heroin and cocaine, chronic BUP reduced responding in the presence of reward-related cues.

Topics: Animals; Buprenorphine; Cocaine-Related Disorders; Cues; Eating; Extinction, Psychological; Heroin Dependence; Male; Narcotic Antagonists; Rats; Rats, Long-Evans; Reinforcement Schedule; Reward; Self Administration; Sucrose

Opioids make the single largest contribution to illicit drug-related mortality and morbidity worldwide In this paper we reflect upon what has been learnt regarding treatment outcome and the natural history of heroin use from the Australian Treatment Outcome Study (ATOS). We focus on what we knew prior to ATOS, what ATOS revealed that is novel, and the implications for research, practice and policy. ATOS provided strong evidence for sustained improvement attributable to treatment across the three years of the study. It is argued that treatment for heroin dependence is money well spent, and leads to clear and sustained benefits to both heroin users and society.

Topics: Australia; Buprenorphine; Cohort Studies; Comorbidity; Cost-Benefit Analysis; Follow-Up Studies; Heroin Dependence; Humans; Methadone; Narcotics; Social Problems; Treatment Outcome

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.

Topics: Adult; Buprenorphine; Catchment Area, Health; Counseling; Employment; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Narcotic Antagonists; Norway; Program Development; Psychology; Retention, Psychology; Treatment Outcome

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

Topics: Attitude of Health Personnel; Australia; Buprenorphine; Catchment Area, Health; Community Pharmacy Services; Cross-Sectional Studies; Demography; Drug Administration Routes; Health Care Surveys; Health Services Misuse; Heroin Dependence; Humans; Methadone; Narcotic Antagonists; Pharmacists; Prevalence

Prescription opioid dependence is increasing, but treatment outcomes with office-based buprenorphine/naloxone among these patients have not been described.. 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).. 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.. 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.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Male; Office Visits; Opioid-Related Disorders; Primary Health Care

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

Topics: Adult; Buprenorphine; Cohort Studies; Comorbidity; Diagnosis, Dual (Psychiatry); Female; Follow-Up Studies; Heroin Dependence; Humans; Illicit Drugs; Italy; Male; Mental Disorders; Methadone; Narcotics; Patient Dropouts; Program Evaluation; Prospective Studies; Quality of Life; Substance Abuse Detection; Substance-Related Disorders

Buprenorphine is now increasingly prescribed as an alternative to methadone for the treatment of heroin addiction. Because of its potency (dosage usages from 0.2 mg to 8 mg), the drug concentrations in body fluids are normally very low. Here, we report the first recombinant glucose-6-phosphate dehydrogenase (G6PDH)-based homogeneous immunoassay (EMIT-type assay) for free buprenorphine and free norbuprenorphine in urine. The antibody used in this assay cross-reacts nearly identically with buprenorphine and norbuprenorphine and, at the same time, has less than 1% cross-reactivity with a wide range of commonly prescribed opiates, particularly those structurally related compounds such as morphine, codeine, and dihydrocodeine. More importantly, this assay has a low detection limit of 1 ng/mL for buprenorphine or norbuprenorphine. Further evaluation of this technique using gas chromatography-mass spectrometry (GC-MS) of authentic urine samples demonstrated that the accuracy of the assay is greater than 95%. Because this assay is designed to measure the free drugs in urine, it resulted in simplification for GC-MS or liquid chromatography-MS confirmation methods that did not require urine hydrolysis before solid-phase or liquid-liquid extraction.

Topics: Analgesics, Opioid; Buprenorphine; Cross Reactions; Enzyme Multiplied Immunoassay Technique; Gas Chromatography-Mass Spectrometry; Glucosephosphate Dehydrogenase; Heroin Dependence; Humans; Recombinant Proteins; Reproducibility of Results; Substance Abuse Detection

The opioid systems play an important role in mediating both physical pain and negative affects (eg, the pain of social isolation). From an evolutionary perspective, it is not surprising that the neurocircuitry and neurochemistry of physical pain would overlap with that involved in complex social emotions. Exposure to trauma as well as a range of gene variants in the opioid system may be associated with alterations in opioid systems function, with changes in reward processing, and with vulnerability to substance abuse. A role for interventions with opioid agents in depression and anxiety disorders has been suggested.

Topics: Adult; Brain; Buprenorphine; Cerebrovascular Circulation; Combined Modality Therapy; Endorphins; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Narcotic Antagonists; Nociceptors; Pain; Pain Management; Psychotherapy; Receptors, Opioid, mu; Rejection, Psychology; Social Isolation

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

Topics: Administration, Inhalation; Administration, Sublingual; Adult; Amphetamine-Related Disorders; Buprenorphine; Comorbidity; Cross-Sectional Studies; Euphoria; Female; Health Surveys; Heroin Dependence; Humans; Illicit Drugs; Male; Motivation; Needle-Exchange Programs; Opioid-Related Disorders; Substance Abuse, Intravenous; Substance Withdrawal Syndrome; Sweden

Topics: Ambulatory Care; Buprenorphine; Cognitive Behavioral Therapy; Delayed-Action Preparations; Family Practice; Heroin Dependence; Hospitalization; Humans; Methadone; Naltrexone; Office Visits; Opioid-Related Disorders; Secondary Prevention; Substance-Related Disorders

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

Topics: Administration, Oral; Administration, Sublingual; Adult; Buprenorphine; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Methadone; Narcotic Antagonists; Narcotics; Personal Satisfaction; Quality of Life; Substance Abuse Treatment Centers; Surveys and Questionnaires; Treatment Outcome

Evaluation of the effect of substitution therapy on the birth weight of the newborn, its postpartum adaptation and course of the neonatal abstinence syndrome.. A three-year prospective study.. The Department of Gynecology and Obstetrics of the Teaching Hospital and the 2nd Medical Faculty of the Charles University, Prague.. This prospective study was carried out in the period of 2005-2007. Included in the study were heroin-addicted pregnant women and pregnant women who undergoing methadone and buprenorphine substitution therapy. During the 3 years we followed-up 47 heroin-addicted women and 60 women under substitution therapy for prenatal screening. Of this number, 36 pregnant women were methadone-substituted and 24 buprenorphine-substituted. Individual groups were compared using the Kruskal-Wallis ANOVA test. Correlation of dichotomic variables was evaluated by means of longlinear models. Calculations were done by means of NCSS 2002 statistical software (Number Cruncher Statistical Systems, Kaysville, UT, USA).. Statistically birth weight of newborns was significantly lowest in the group of heroin-addicted women as compared to the group receiving substitution with buprenorphine p<0.01 and as compared to the group of methadone-substituted patients p<0.05. Having monitores changes in the placenta the statistically highest number of changes was exhibited by heroin users, both when compared to methadone users (p<0.01) and buprenorphine users (p<0.001). The highest statistically significant number of newborns with IUGR symptoms were born to heroin-addicted women. The lowest Apgar score was recorded in all three evaluations in the group of buprenorphine users and the highest in methadone-substituted women.. Substitution therapy provides pregnant women with the possibility of social stabilization, adaptation, and adequate prenatal care. With regard to the fact that methadone substitution protracts the newborn's abstinence syndrome, attention has been recently focused on substitution with buprenorphine that seems to be a more considerate option, from this point of view.

Topics: Apgar Score; Birth Weight; Buprenorphine; Female; Fetal Growth Retardation; Heroin Dependence; Humans; Infant, Newborn; Methadone; Narcotic Antagonists; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications

Topics: Buprenorphine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Heroin Dependence; Humans; Methadone; Naloxone; Narcotic Antagonists; Randomized Controlled Trials as Topic; Treatment Outcome

(1) Two drugs with similar efficacy are available in France for heroin replacement therapy: methadone and buprenorphine. (2) Buprenorphine is sold in the form of sublingual tablets, but some patients dissolve and inject them. Methadone is the main alternative for these patients. Other intravenous opiate derivatives can also be tried, although they have not been approved for this indication. (3) In order to help prevent patients from injecting themselves with buprenorphine, a sublingual combination of buprenorphine + naloxone is to be marketed in France. (4) From a pharmacological point of view, this combination makes sense. Naloxone, an opiate antagonist, is very poorly absorbed with sublingual administration, but if it is injected intravenously, it will antagonise the effects of buprenorphine. However, clinical studies are needed to determine whether or not this prevents injection. (5) A double-blind trial in 326 patients compared replacement therapy with buprenorphine 16 mg + naloxone 4 mg/day versus buprenorphine 16 mg + placebo. The addition of naloxone did not reduce the efficacy of sublingual buprenorphine, but the frequency with which patients injected the drugs was not studied in this trial. (6) This combination of buprenorphine + naloxone has not been directly compared with methadone. (7) In addition to the classical adverse effects of opiates, buprenorphine can cause hepatic adverse effects. (8) Little evidence is available on the effects of intravenous injection of buprenorphine + naloxone. According to an epidemiological survey conducted in Finland, where the combination is also marketed, about 8% of patients regularly inject it intravenously. (9) Patients who are likely to inject buprenorphine should be switched to methadone.

Topics: Administration, Sublingual; Analgesics, Opioid; Buprenorphine; Drug Therapy, Combination; Finland; France; Heroin Dependence; Humans; Methadone; Morphine; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Patient Compliance; Patient Dropouts; Randomized Controlled Trials as Topic; Self Administration; Treatment Outcome

Topics: Alleles; Buprenorphine; Genetic Variation; Heroin Dependence; Humans; Methadone; Naltrexone; Narcotic Antagonists; Receptors, Opioid, mu; Substance-Related Disorders

This economic evaluation was part of the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD) project. Data from four trials of heroin detoxification methods, involving 365 participants, were pooled to enable a comprehensive comparison of the cost-effectiveness of five inpatient and outpatient detoxification methods. This study took the perspective of the treatment provider in assessing resource use and costs. Two short-term outcome measures were used-achievement of an initial 7-day period of abstinence, and entry into ongoing post-detoxification treatment. The mean costs of the various detoxification methods ranged widely, from AUD 491 dollars(buprenorphine-based outpatient); to AUD 605 dollars for conventional outpatient; AUD 1404 dollars for conventional inpatient; AUD 1990 dollars for rapid detoxification under sedation; and to AUD 2689 dollars for anaesthesia per episode. An incremental cost-effectiveness analysis was carried out using conventional outpatient detoxification as the base comparator. The buprenorphine-based outpatient detoxification method was found to be the most cost-effective method overall, and rapid opioid detoxification under sedation was the most cost-effective inpatient method.

Topics: Adult; Analgesics, Opioid; Analysis of Variance; Buprenorphine; Chi-Square Distribution; Cost-Benefit Analysis; Female; Heroin Dependence; Humans; Hypnotics and Sedatives; Male; Methadone; Naltrexone; Narcotic Antagonists

To determine 1 year outcomes for drug use, criminality, psychopathology and injection-related health problems in those entering treatment for heroin dependence in Australia.. Longitudinal prospective cohort study.. Seven hundred and forty five individuals entering treatment (methadone/buprenorphine maintenance therapy; detoxification; residential rehabilitation) and 80 heroin users not seeking treatment.. Sydney, Melbourne and Adelaide, Australia.. A total of 657 individuals were re-interviewed at 1 year, 80% of the original sample. There were substantial reductions in heroin and other drug use across all three treatment modalities. The majority of those who had entered treatment were heroin abstinent at 1 year (maintenance therapy 65%, detoxification 52%, residential rehabilitation 63%) compared to 25% of the non-treatment sample. The reduction in heroin use among the treatment samples was paralleled by reductions in poly drug use. There were also substantial reductions in risk-taking, crime and injection-related health problems across all treatment groups, and less marked reductions among the non-treatment group. Psychopathology was dramatically reduced among the treatment modalities, while remaining stable among the non-treatment group. Positive outcomes at 1 year were associated with a greater number of cumulative treatment days experienced over the 1 year follow-up period ('treatment dose') and fewer treatment episodes undertaken in that time ('treatment stability').. At 1 year, there were impressive reductions in drug use, criminality, psychopathology and injection-related health problems following treatment exposure. The positive findings were associated with a greater "dose" of treatment, and with more treatment stability over the follow-up period.

Topics: Adolescent; Adult; Australia; Buprenorphine; Crime; Female; Heroin Dependence; Humans; Inactivation, Metabolic; Interviews as Topic; Male; Mental Disorders; Middle Aged; Narcotics; Prevalence; Prospective Studies; Risk-Taking; Time Factors; Treatment Outcome

Naltrexone treatment has demonstrated some advantages for special populations of heroin addicted individuals, but patients' compliance seems to be very poor, with a low adherence and low retention rate. Kappa-opioid system overdrive seems to contribute to opioid protracted abstinence syndrome, with dysphoria and psychosomatic symptoms during naltrexone treatment. The objective of this observational study was to determine the effectiveness of a functional k antagonist in improving naltrexone treatment outcome. A partial mu agonist/kappa antagonist (buprenorphine) and a mu antagonist (naltrexone) were combined during a 12 weeks protocol, theoretically leaving k antagonism as the major medication effect. Sixty patients were submitted to outpatient rapid detoxification utilizing buprenorphine and opioid antagonists. Starting on the fifth day, 30 patients (group A) received naltrexone alone. Alternatively, 30 patients (group B) received naltrexone (50mg oral dose) plus buprenorphine (4 mg sublingual) for the 12 weeks of the observational study. The endpoints of the study were: retention in treatment, negative urinalyses, changes in psychological symptoms (Symptom Checklist-90 Revised: SCL-90) and craving scores (visual analysis scale (VAS)). Thirty-four subjects (56.67%) completed the 12 weeks study. Twenty-one patients (35.0%) had all urine samples negative for opiates and cocaine. nine subjects (15.0%) had urine samples negative for cocaine and opiates for the last 4 weeks of the study. five subjects (8.3%) continued to use cocaine during the 12 weeks of the study. No significant change in pupillary diameter after buprenorphine administration was evidenced during clinical observations from baseline across the weekly measurements. Retention rates in group A (naltrexone) and group B (naltrexone + buprenorphine) at week 12 were respectively 40% (12 patients) and 73.33% (22 patients), with a significant difference in favour of group B (p= 0.018). Patients treated with naltrexone in combination with buprenorphine (B patients) showed a significantly lower rate of positive urines for morphine (4.45%) and cocaine metabolites (9.09%) than those treated with naltrexone alone (A) (25%, morphine; 33.33% cocaine) (p< 0.05; p< 0.05). Irritability, depression, tiredness, psychosomatic symptoms and craving scores decreased significantly less in Group A patients than in group B patients. The dysfunction of opioid system with kappa receptors hyper-activation provoked by heroi

Topics: Adult; Affect; Buprenorphine; Cocaine; Cocaine-Related Disorders; Female; Heroin Dependence; Humans; Liver; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Psychiatric Status Rating Scales; Substance Abuse Detection; Survival Analysis

Methadone and buprenorphine 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.

Topics: Attitude of Health Personnel; Buprenorphine; Drug Prescriptions; Female; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Narcotic Antagonists; New York City; Physicians; Surveys and Questionnaires

Several medications are approved for treatment of opiate abuse, but determinants of their clinical effectiveness are not completely understood. States of opiate dependence or withdrawal may constitute one important set of determinants. To test this hypothesis, the effects of naloxone, buprenorphine, and methadone were assessed on choice between heroin and food in nondependent rhesus monkeys and in heroin-dependent monkeys undergoing withdrawal. A choice procedure was used to permit dissociation of medication effects on the relative reinforcing properties of heroin from nonselective effects on response rates. In nondependent monkeys, increasing unit doses of heroin (0-0.1 mg/kg/injection) maintained dose-dependent increases in heroin choice. Chronic 5-day treatment with naloxone (0.01-0.32 mg/kg/h) or buprenorphine (0.01-0.1 mg/kg/day) produced dose-dependent rightward shifts in heroin choice dose-effect curves, whereas chronic methadone (0.1-0.56 mg/kg/h) had little effect on heroin choice up to doses that suppressed responding. In heroin-dependent monkeys, opiate withdrawal produced overt abstinence signs as well as increases in heroin choice, manifested as leftward shifts in heroin choice dose-effect curves. The withdrawal-associated increases in heroin choice suggest that opiate withdrawal increased the relative reinforcing efficacy of heroin in comparison with food, an effect that may be related to relapse in humans. Methadone prevented withdrawal-associated increases in heroin choice, whereas buprenorphine was less effective. These findings suggest that agonist medications such as methadone may derive their clinical utility from their ability to attenuate withdrawal-associated increases in opiate reinforcement. Moreover, this procedure may be useful for exploring mechanisms underlying withdrawal-associated increases in opiate reinforcement and for testing candidate medications.

Topics: Animals; Buprenorphine; Disease Models, Animal; Feeding Behavior; Heroin; Heroin Dependence; Macaca mulatta; Male; Methadone; Naloxone; Self Administration; Substance Withdrawal Syndrome

Longitudinal studies have indicated that most opioid agonist-using patients are not able to successfully complete tapering attempts. Little is known, however, about tapering within a treatment environment that is supportive of indefinite agonist treatment and medication tapering. In this study, all records of patients beginning a slow methadone taper were reviewed (N = 30). No patient successfully completed methadone tapering. Four patients (13.3%) successfully switched to buprenorphine/naloxone, one of whom tapered off buprenorphine/naloxone. Three patients (10%) were continuing their taper at the study's end. One patient transferred to another program, one was administratively discharged, and one had his taper stopped for mishandling doses. The remaining patients (n = 20, 66.7%) stopped their tapers for the following reasons: feeling unstable/withdrawal symptoms (n = 4, 13.3%), drug use/positive urinalysis results (n = 12, 40%), psychiatric instability (n = 3, 10%), and pain management (n = 1, 3.3%). Only one patient prematurely left treatment secondary to a failed taper attempt. Patients attempting tapers should be informed about the difficulty involved and be monitored closely for signs of instability. For a few patients, a taper to a lower methadone dose and a switch to buprenorphine/naloxone are obtainable. Program policies that support both tapering attempts and indefinite maintenance are described in this article.

Topics: Adult; Buprenorphine; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Mental Health Services; Methadone; Middle Aged; Naloxone; Narcotic Antagonists; Program Development; Substance Withdrawal Syndrome

Topics: Anesthesia, General; Buprenorphine; Clonidine; Drug Therapy, Combination; Heroin Dependence; Humans; Naltrexone; Narcotic Antagonists; Substance Withdrawal Syndrome

Topics: Anesthesia, General; Buprenorphine; Clonidine; Drug Therapy, Combination; Heroin Dependence; Humans; Naltrexone; Narcotic Antagonists; Substance Withdrawal Syndrome

This study of a cohort of drug addicts receiving buprenorphine maintenance treatment in a district in western France focused on changes in their drug use and their social and work lives. It also looked at the health consequences of their drug use before and after maintenance treatment (mean: four years).. From the files of an agency providing services to drug addicts, we randomly selected 180 of the 236 patients receiving buprenorphine maintenance treatment (BMT). Usable questionnaires were returned by 118 subjects (66% response rate). This self-administered questionnaire included 32 items.. The respondents accounted for half the population receiving drug maintenance treatment and were representative of the population for age and sex. The mean age was 30 +/- 5 years, mean BMT dose 6,5 mg/day, and mean duration of drug maintenance treatment 47 +/- 27 months. Other drug use diminished during the four years of maintenance treatment: three of every four heroin users had stopped, opiate users dropped from 31% to 5% of the population, and cocaine use followed a similar trend. Benzodiazepine use also fell, but remained relatively frequent (27%, compared with 68% four years earlier). Drinking patterns changed from strongly alcoholic beverages to lower-proof drinks. Arrest rates dropped from 70% to 25%. The percentage of persons seropositive for HIV (4%) and HCV (33%) remained low, but too many subjects had not been screened (35%). Roughly 10% of these subjects had returned to work, mainly those who had cut their drug use most.. While our survey reveals some positive points, especially a reduction in illegal drug use, several negative observations appeared, including combined use of cannabis and benzodiazepines, inadequate screening, and misuse of BMD. These results underline how important it is for care providers to focus simultaneously on medical treatment and identification of co-morbidities and to provide social work when necessary. The employment rate remains too low.

Topics: Adult; Behavior, Addictive; Benzodiazepines; Buprenorphine; Cocaine-Related Disorders; Cohort Studies; Employment; Female; France; Heroin Dependence; HIV Seropositivity; Humans; Male; Marijuana Abuse; Narcotic Antagonists; Opioid-Related Disorders; Socioeconomic Factors; Substance-Related Disorders; Surveys and Questionnaires; Time Factors

The TaqI A polymorphism (A(1)) of the dopamine D(2) receptor gene (DRD2), although not a specific predictor of opioid dependence, has been strongly associated with high levels of prior heroin use and poor treatment outcomes among methadone maintenance patients. The aims of this study were to confirm these findings via a retrospective analysis of A(1) allele frequency in methadone (n = 46) and buprenorphine (n = 25) patients, and non-opioid-dependent controls (n = 95). Subjects were genotyped at the DRD2 TaqI A locus using PCR amplification followed by TaqI restriction enzyme digestion and gel electrophoresis. For methadone and buprenorphine subjects, heroin use (prior to treatment), treatment outcomes, and withdrawal occurrence were determined from comprehensive case notes. No significant differences in A(1) allele frequency (%) were observed between: methadone (19.6%), buprenorphine (18.0%), and control (17.9%) groups (P > 0.7); successful and poor treatment outcome groups, methadone: 20.0% and 19.2%, respectively (P = 1.0); buprenorphine: 18.4% and 20.0%, respectively (P = 1.0). Also, there were no significant relationships between TaqI A genotype and prior heroin use (P = 0.47). However, among the successful methadone subjects, significantly fewer A(1) allele carriers experienced withdrawal than non-A(1) carriers (P = 0.04). In conclusion, the DRD2 genotype effects did not affect opioid maintenance treatment outcomes. This suggests the need for a further prospective investigation into the role of the DRD2 A(1) allele in heroin use and response to maintenance pharmacotherapies for opioid dependence.

Topics: Adult; Alleles; Analgesics, Opioid; Buprenorphine; Deoxyribonucleases, Type II Site-Specific; Female; Gene Frequency; Genotype; Heroin Dependence; Humans; Male; Methadone; Receptors, Dopamine D2; Retrospective Studies; Substance Withdrawal Syndrome; Time Factors; Treatment Outcome

(1) The aim of replacement therapy for heroin addiction is to suppress craving for other opiates and to prevent opiate withdrawal symptoms. (2) In France, methadone was the first drug to be licensed for this use, in 1995, with very strict prescribing and dispensing conditions. Buprenorphine was approved in 1996, and was subject to less restrictive conditions. (3) In 2003 in France, an estimated 80 000 people were receiving replacement therapy with buprenorphine and 14 000 with methadone. (4) A meta-analysis of 13 comparative trials involving a total of 2544 patients showed that buprenorphine 6 to 12 mg initially reduced both opiate and benzodiazepine use, whereas doses of 2 to 4 mg had no marked impact on heroin use. This meta-analysis concluded that buprenorphine and methadone had similar efficacy in clinical trials in which the dose was adjusted to outcome. There were more dropouts with buprenorphine than with methadone. A daily dose of 16 mg appeared to be roughly equivalent to 60 mg/day methadone. (5) France appears to be the only country to have relied primarily on buprenorphine as replacement therapy for heroin addiction. This has been the case in France since 1996. The frequency of heroin overdose has fallen markedly in France since 1996, possibly due in part to the availability of replacement therapies. Overall mortality among drug users has also declined, but this is largely due to more effective treatment of HIV infection. (6) In France, a two-year cohort study of patients treated with buprenorphine and a survey conducted during the first year of buprenorphine replacement were funded by the manufacturer, Schering-Plough. The results showed that more than two-thirds of patients remained on treatment, and that, overall, the patients' general condition improved. (7) Opioid-like adverse effects are infrequent under normal conditions of use. There are reports of cases of hepatitis in patients taking buprenorphine, with or without a benzodiazepine. Attribution to buprenorphine is unclear, however, due to the lack of appropriate analyses. (8) Some of the key adverse effects occur during misuse: buprenorphine tablets are often injected, especially during the first few months of treatment (sometimes for more than two years). Injection carries a risk of infections; other potential long-term effects are poorly understood. Compared with methadone users, and regardless of the substances involved, buprenorphine users appear more likely to self-inject. (9) The

Topics: Benzodiazepines; Buprenorphine; Cohort Studies; Drug Therapy, Combination; Female; France; Heroin Dependence; HIV Seroprevalence; Humans; Male; Meta-Analysis as Topic; Methadone; Pregnancy; Self Medication; Treatment Outcome

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.

Topics: Adolescent; Adult; Buprenorphine; Documentation; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Medical Records; Middle Aged; Narcotic Antagonists; New South Wales; Patient Compliance; Patient Dropouts; Recurrence; Retreatment; Retrospective Studies; Treatment Outcome

Some recent studies have suggested a lower risk of fatal intoxications in drug-dependent patients under buprenorphine compared to methadone treatment.. Epidemiological reference data for the Munich region suggest that in 2003 approximately 10 % of all substitution patients were treated with buprenorphine, and 87 % with methadone. We studied the proportion of patients under methadone and buprenorphine substitution among drug-related deaths. Data from forensic post-mortem and toxicological analysis were analyzed.. Data indicate that in 96 (35 %) of all 272 so-called drug deaths, methadone was involved compared to a single case of buprenorphine, possibly indicating a relatively better risk profile of buprenorphine.. More prospective studies are necessary to assess the risk of fatal intoxications under different substitution regimens.

Topics: Adult; Buprenorphine; Cause of Death; Drug Evaluation, Preclinical; Drug Interactions; Drug Overdose; Ethanol; Female; Germany; Heroin Dependence; Humans; Male; Methadone; Narcotics; Retrospective Studies; Risk; Substance Abuse, Intravenous

In the late 1990s there was major concern regarding heroin use among the Nunga community in Adelaide. [Nunga is a generic term used for Aboriginal people from South Australia, similar to Koori's from Victoria and Nyungars from south-western Australia.] Heroin use was so common that community members reported that most families were affected by it in some way. There were few Nunga specific services provided, and those mainstream services available were not seen as culturally appropriate or for other reasons were difficult to access. In response to this, the Parks Community Health Centre, together with the Drug and Alcohol Services Council (DASC) [in 2005 the Drug and Alcohol Services Council (DASC) changed its name to Drug and Alcohol Services South Australia (DASSA)], and with the assistance of Nunkuwarrin Yunti Aboriginal Health Service [Adelaide's Aboriginal Community Controlled Health Service, based in the City Centre], commenced a programme offering treatment interventions for Nunga heroin users. The 'Way Out' Program commenced in March 1999. It is multi-faceted and includes an opioid substitution programme which is attracting and maintaining Nunga clients in greater numbers than ever before in South Australia. The programme locates the drug problem within a holistic view of the individual's health. It utilises networks throughout the Nunga community and in recent years has formed a strong working partnership with the Aboriginal Kinship Program [the Aboriginal Kinship Program (Department of Human Services, Metropolitan Health Division) works with Aboriginal families and individuals seeking support for family members in relation to illicit drug issues by providing support, referral, follow-up and advocacy services]. The 'Way Out' Program is succeeding in making essential treatment services available to Aboriginal people using heroin within Adelaide. This article provides an overview of the programme.

Topics: Buprenorphine; Community Mental Health Services; Community Participation; Female; Health Services, Indigenous; Heroin Dependence; Humans; Male; Methadone; Narcotics; Native Hawaiian or Other Pacific Islander; Patient Acceptance of Health Care; Program Development; Referral and Consultation; Retreatment; South Australia; Treatment Outcome

Malaysia is experiencing severe problems with heroin dependence and HIV infection. This, study evaluated drug use and other HIV risk behaviors and their association with HIV and other infectious diseases in heroin-dependent subjects enrolled in a clinical trial of drug abuse treatment in Muar, Malaysia.. Baseline assessment of treatment-seeking subjects (n=177) included the Addiction Severity Index; AIDS Risk Inventory; serological tests for HIV, hepatitis B, and hepatitis C; and chest X-ray.. All of the subjects were male; 67.8% were Malays, 28.8% Chinese, and 2.3%. Indian. Subjects had a mean (SD) age of 37.2 (9.1) years and 14.4 (8.5) years of using heroin; 76.3% reported lifetime injection drug use (IDU), and 41.5% reported current IDU; 30 of 156 (19.2%) tested HIV positive, 143 of 159 (89.9%) tested hepatitis C positive, and 25 of 159 (15.7%) had radiological evidence of pulmonary tuberbulosis. Malay subjects had a significantly higher prevalence of current IDU, needle sharing (p<0.01), and HIV infection (p<0.05) compared with Chinese subjects. Lifetime IDU, needle sharing, lack of consistent condom use, and Malay ethnicity were significantly associated with HIV infection.. The high prevalence of HIV infection among heroin-dependent individuals, in Malaysia supports the important of interventions to reduce the major risk factors for HIV, including IDU, needle sharing, and unprotected sex.

Topics: Adult; Buprenorphine; Demography; Female; Heroin Dependence; HIV Infections; Humans; Malaysia; Male; Naltrexone; Narcotic Antagonists; Prevalence; Risk-Taking

The purpose of this study was the evaluation of clinical heroin symptoms and buprenorphine drug addiction in the withdrawal period with the purpose of their comparison, study of parameters of bone metabolism in the both groups. In the study group were included 40 patients with heroin and 27 with buprenorphine addiction in the period of abstinence. Our investigations have shown, that in the both groups, among clinical symptoms ossalgias, arthralgias and mialgias attributes to the expressed dysfunction of vegetative system, were most prominent. Decrease of sexual functions was found in half of inspected patients. Biochemical investigations have shown intensive clearance of calcium with the urine that indicates intensifying resorbtion processes in the bone tissue. Symptoms of hypogonadism were accompanied by the decrease of the level of testosterone in the blood. Parameters of mineral consistency of the bone tissue was decreased both in patients with heroin and buprenorphine addiction.

Topics: Behavioral Symptoms; Biomarkers; Bone and Bones; Bone Density; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Male; Morphine Dependence; Pain; Radiography; Substance Withdrawal Syndrome

Buprenorphine is an opioid analgesic drug that is used as an alternative to methadone to treat heroin addiction. Established methods for the analysis of buprenorphine and its metabolites in urine such as gas chromatography-mass spectrometry (GC-MS) involve complicated sample extraction procedures. The aim of the present study was to develop a sensitive yet straightforward method for the simultaneous analysis of buprenorphine and norbuprenorphine in urine using liquid chromatography-MS-MS. The method comprised an enzymatic hydrolysis using Patella vulgata b-glucuronidase, followed by centrifugation and direct analysis of the supernatant. The limits of detection and quantitation were < 1 microg/L for buprenorphine and < 1 and 4 microg/L, respectively, for norbuprenorphine. Assay coefficients of variation (CVs) were < 15%, with the exception of concentrations close to the limit of quantitation, where CVs were below 20%. In direct comparison with an established GC-MS protocol, the method showed minimal negative bias (8.7% for buprenorphine and 1.8% for norbuprenorphine) and was less susceptible to sample carryover. The extent of conjugation in unhydrolyzed urine was investigated and found to be highly variable, with proportions of unconjugated buprenorphine and norbuprenorphine of 6.4% [range 0% to 67%; standard deviation (SD) 9.7%] and 34% (range 0% to 100%; SD 23.8%), respectively.

Topics: Analgesics, Opioid; Buprenorphine; Chromatography, Liquid; Heroin Dependence; Humans; Mass Spectrometry

In the present study, we examined the composition of electroencephalographic (EEG) brain oscillations in broad frequency band (0.5-30 Hz) in 22 opioid-dependent patients and 14 healthy subjects during resting condition (closed eyes). The exact compositions of brain oscillations and their temporal behavior were assessed by the probability-classification analysis of short-term EEG spectral patterns. It was demonstrated that EEG of patients with opioid dependence was characterized by (a) significant reorganization of brain oscillations with increase in the percentage of beta- and mostly fast-alpha-rhythmic segments, (b) longer periods of temporal stabilization for alpha and beta brain oscillations and by shorter periods of temporal stabilization for theta and polyrhythmic activity when compared with control subjects, and (c) right-sided dominance (significantly larger relative presence of particular spectral patterns in EEG channels of the right hemisphere). These effects were widely distributed across the cortex with the maximum magnitude in the occipital, right parietal, temporal, and frontal areas. Taken together the present study suggested (a) an allostatic state with neuronal activation, and (b) high sensitivity of the right hemisphere to adverse opioid effects.

Topics: Adult; Analgesics, Opioid; Artifacts; Brain; Buprenorphine; Electroencephalography; Heroin Dependence; Humans; Opioid-Related Disorders; Oscillometry; Patient Selection; Reference Values; Reproducibility of Results; Rest

An increase in illicit drug use in Northern Ireland may well have links to the resolution of political conflict, which started in the mid 1990s. Social issues, heretofore hidden, have emerged into the limelight and may be worsened by paramilitary involvement. Registered addicts in the four Health Board areas have shown an increase from 1997 with the greatest number resident within the Northern Board Area. As the prevalence of heroin use in Northern Ireland increased, the Department of Health and Social Services and Public Safety (DHSSPS) commissioned a report, to recommend the development of substitute prescribing services. A case series of pregnancies was reviewed, within the Northern Board Area, where the mother was taking opioid substitution therapy. This resulted in baseline data of outcome for both mother and baby specific to a Northern Ireland population. The different medications for opioid substitution are also assessed. This information will guide a co-ordinated approach that involves obstetrician, anaesthetist, psychiatrist, midwife and social worker to the care of these high-risk pregnancies. Eighteen pregnancies were identified in the study period. Sixteen of these had viable outcomes. One was a twin pregnancy. Outcome data was therefore available for 17 infants. Information was obtained regarding patients' social and demographic background, drug taking behaviour and substitution regimen. Antenatal and intrapartum care was assessed and infants were followed up to the time of hospital discharge.

Topics: Adult; Buprenorphine; Codeine; Female; Heroin Dependence; Humans; Infant, Newborn; Maternal-Fetal Exchange; Methadone; Neonatal Abstinence Syndrome; Northern Ireland; Obstetrics and Gynecology Department, Hospital; Perinatal Care; Pregnancy; Pregnancy Complications; Risk Assessment; Substance Abuse Detection

Topics: Buprenorphine; Combined Modality Therapy; Double-Blind Method; Heroin Dependence; Humans; Methadone; Narcotics; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Substance Abuse Detection; Treatment Outcome

Topics: Buprenorphine; Drug and Narcotic Control; Heroin Dependence; Humans; Narcotic Antagonists; Singapore; Substance-Related Disorders

A 37-year-old man with a 19-years history of injection drug use (IDU) who had acquired a chronic hepatitis C virus (HCV-) infection 9 years ago, entered the German clinical study on heroine assisted treatment ("Modellprojekt zur heroingestützten Behandlung Opiatabhängiger"). Before study onset he received buprenorphine maintainance treatment, while at the same time engaging in illicit IDU (heroine, cocaine). He lived in a caravan and was on social welfare.. PCR revealed a genotype 2 and an HCV-viral load of 310,000 IU/ml. Liver biopsy showed a moderate chronic active hepatitis and a mild portal fibrosis without signs of liver cirrhosis.. Within the heroine-assisted treatment program the patient injected heroine under medical supervision several times a day and attended the standardized psychosocial program that comprised an intensive education on HCV-infection. Within a period of ten months of physical and social stabilization he managed to stop illicit drug use, found stable housing and started to work. We then initiated treatment of HCV-infection. Subcutaneous pegylated interferon alpha-2a, peroral ribavirin and intravenous heroine were administered as directly observed therapy. Based on the close mashed care of the heroine assisted treatment setting, side effects were well controllable and reversible after the end of antiviral therapy. A sustained response was obtained.. After careful indication, heroine-assisted treatment with particularly intensive medical and psychological care can offer appropriate conditions for a save and successful treatment of hepatitis C as well as for a sustained result.

Topics: Administration, Oral; Adult; Antiviral Agents; Buprenorphine; Cocaine-Related Disorders; Combined Modality Therapy; Comorbidity; Drug Therapy, Combination; Hepatitis C, Chronic; Heroin; Heroin Dependence; Humans; Injections, Intravenous; Injections, Subcutaneous; Interferon alpha-2; Interferon-alpha; Male; Polyethylene Glycols; Recombinant Proteins; Rehabilitation, Vocational; Ribavirin; Social Adjustment; Social Welfare; Substance Abuse, Intravenous

Previous studies indicate that buprenorphine has efficacy in medically supervised opioid withdrawal, but the optimal dosing for maximum tolerability and ease of administration remains undetermined. Five heroin-dependent individuals entered this open-label study of inpatient detoxification with a single 24 mg dose of buprenorphine. The mean Clinical Opiate Withdrawal Scale (COWS) score prior to buprenorphine administration was 17.6 (SD = 3.36). COWS scores declined significantly thereafter. There was one episode of precipitated withdrawal that resolved within four hours. Use of ancillary medications was minimal. This study suggests that a single high dose of buprenorphine can be used safely and effectively for inpatient detoxification.

Topics: Adult; Buprenorphine; Female; Heroin Dependence; Humans; Male; Pilot Projects; Substance Withdrawal Syndrome

This study included 380 participants in five heroin detoxification trials whose data were pooled to enable direct comparison of five detoxification methods in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD). Rapid detoxification achieved similar initial abstinence rates with either anaesthesia or sedation (average 59%), which were higher than was achieved by inpatient detoxification using clonidine plus other symptomatic medications (24%), which in turn was higher than outpatient detoxification using either buprenorphine (12%) or clonidine plus other symptomatic medications (4%). Older participants and those using more illicit drugs were more likely to achieve abstinence. Entry rates into ongoing postdetoxification treatment were as follows: buprenorphine outpatient (65%), sedation (63%), anaesthesia (42%), symptomatic outpatient (27%), and symptomatic inpatient (12%). Postdetoxification treatment with buprenorphine or methadone was preferred over naltrexone. Participants with more previous detoxification attempts were more likely to enter postdetoxification treatment. Given that outpatient detoxification was more effective with buprenorphine than with symptomatic medications and that rapid detoxification was more effective than the symptomatic inpatient method, the roles of the symptomatic methods should be reconsidered.

Topics: Adolescent; Adult; Ambulatory Care; Analgesics, Opioid; Anesthesia; Buprenorphine; Female; Heroin Dependence; Hospitalization; Humans; Hypnotics and Sedatives; Inactivation, Metabolic; Male; Methadone; Middle Aged; Naltrexone; Narcotic Antagonists; Treatment Outcome

Topics: Buprenorphine; Family Practice; Heroin Dependence; Humans; Methadone; Narcotic Antagonists; Narcotics

General practitioners (GPs) in their surgeries and substitution treatment centres are the major providers of opioid maintenance treatment in a number of European countries. Although in the Czech Republic any GP has been allowed to prescribe buprenorphine (Subutex) since 2001, the opioid substitution treatment provided by primary care professionals has not been the subject of research to date.. To collect and analyze data on GPs' experience gained with opioid maintenance treatment in the Czech Reupblic, their attitudes and needs.. A structured questionnaire was distributed via the Bulletin of the Association of General Practitioners and district Association representatives. The validity of study results may be affected by a low respondence rate (10%) with 398 questionnaires only returned by mail.. Twenty-eight (7%) GPs reported to have gained experience with buprenorphine which was most frequently prescribed in the regions with the highest prevalence of heroin users, i.e. in Prague and the Ustí nad Labem region (27% and 12%, respectively). Other regions, including wes- tern and southern Bohemia with relatively high prevalence of heroin users, showed lower buprenorphine prescription rates (0-6%). Most buprenorphine prescribers (78%) rated their experience as positive or highly positive. Availability and effectiveness were seen as the main pros of the substitution treatment. One third of the GPs who have not prescribed opioid maintenance treatment yet are considering doing so in the future. Greater awareness of drug abuse issues and availability of methodical guidance and consulting in opioid substitution treatment are going to become the most relevant factors in the future. Possible reportability of data on opioid maintenance treatment to a central registry does not seem to be a major obstacle to implementing the substitution treatment in the GPs' surgeries. Decision makers should take advantage of the GPs' potential to promote the opioid maintenance treatment in the Czech Republic.

Topics: Adult; Aged; Attitude of Health Personnel; Buprenorphine; Czech Republic; Drug Utilization; Family Practice; Female; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Surveys and Questionnaires

Torsade de pointes is a rare but potentially fatal ventricular arrhythmia that is often triggered by drugs that prolong the rate-corrected QT (QTc) interval. This arrhythmia has been attributed to levacetylmethadol and methadone, synthetic opioids used to treat heroin addiction. Levacetylmethadol, a derivative of methadone, is being withdrawn from the United States market because its use waned after a black box warning was issued to require electrocardiographic monitoring. Therefore, methadone and buprenorphine are the only opioids available for the treatment of heroin addiction. To our knowledge, the cardiac safety of buprenorphine in patients with methadone-related QTc prolongation has not been described. We report a patient who developed torsade de pointes while receiving high-dose methadone and was successfully inducted onto buprenorphine under close medical supervision. No clinically important QTc prolongation was observed in the acute setting or during follow-up. This observation suggests that buprenorphine may be a safe alternative to oral methadone in patients with opioid addiction who develop torsade de pointes.

Topics: Analgesics, Opioid; Buprenorphine; Dose-Response Relationship, Drug; Heroin Dependence; Humans; Male; Methadone; Middle Aged; Torsades de Pointes

High-dose buprenorphine (HDB) treatment began in France in 1996 according to relatively unrestricted prescription rules. Continued heroin injection by patients on HDB maintenance treatment and even HDB injection remain underestimated and may lead to a variety of infectious diseases.. Description of infectious complications occurring in patients receiving HDB maintenance treatment.. Retrospective study of drug addicts receiving HDB maintenance treatment, injecting (or highly suspected of injecting) it, and hospitalized for infections (other than HIV or viral hepatitis) in the department of infectious and tropical diseases in Nancy University Hospital. Data collection covered 1998 through 2003.. We identified 21 case reports, 9 concerning infectious endocarditis, 8 cutaneous abscesses, 2 osteoarticular infections, 1 meningitis and 1 Candida retinitis. The sex-ratio was of 1 woman for 2 men, and the patients' mean age was 29.8 years. Globally 13 patients had systemic infections. Nine patients admitted having injected HDB (and no other drugs) (including the case of Candida retinitis), while in the other 12 cases, the patients continued injecting heroin as well. The role of misused HDB was strongly suspected in those 12 infections, but was not clearly confirmed. All patients recovered from the infections. The long-term psychosocial outcome remains unknown.. The cases analyzed illustrate the dual reality that HDB is often ineffective as a maintenance treatment, since some patients continue to inject heroin, and that its misuse can have infectious consequences. The results of HDB maintenance treatment substitution are mixed. The individual benefit/risk ratio must be improved. Networking is crucial, notably between physician and pharmacist, and the monitoring system must be reinforced.

Topics: Abscess; Adult; Analgesics, Opioid; Buprenorphine; Dose-Response Relationship, Drug; Endocarditis, Bacterial; Female; Heroin Dependence; Humans; Male; Meningitis; Osteomyelitis; Retinitis; Retrospective Studies; Skin Diseases; Substance Abuse, Intravenous

We report a case of Enterobacter cloacae spondylodiscitis related to risk practices in intravenous drug addicts (IVDA).. The patient, a former heroin addict, was receiving long-term, high-dose buprenorphine maintenance treatment. He had been misusing the treatment, injecting it daily for several months. The clinical course included several uncommon features that are usually found in IVDA patients: subacute infection, apyrexia, and minimal inflammatory syndrome. This infection also led to the discovery of his HIV infection.. Any dorsolumbar pain in IVDA patients, including those receiving regular drug maintenance treatment and especially those with HIV infection, should suggest spondylodiscitis, because of these patients' enhanced sensitivity to infection and the frequent bacteremia caused by persistent or transitory relapse involving injection (exchange of material, reuse of needles, syringes, cotton swabs, and risk of contamination through the hands or saliva).

Topics: Adult; Analgesics, Opioid; Buprenorphine; Discitis; Enterobacter cloacae; Enterobacteriaceae Infections; Heroin Dependence; Humans; Male; Substance Abuse, Intravenous

Topics: Anesthesia, General; Buprenorphine; Clonidine; Female; Heroin Dependence; Humans; Male; Naltrexone; Narcotic Antagonists; Opioid-Related Disorders; Substance Withdrawal Syndrome; Treatment Failure

Although buprenorphine is used worldwide as a safe and effective maintenance medication for opioid dependence, some countries have reported a growing incidence of abuse of this medication. Buprenorphine is considered to have lower abuse potential because of its partial agonist profile, but no studies have directly compared the reinforcing effects of buprenorphine with those of full mu opioid agonists in humans. The present double-blind, placebo-controlled inpatient study compared the reinforcing and subjective effects of intravenously administered buprenorphine (0.5, 2, and 8 mg) and methadone (5, 10, and 20 mg). Participants (n = 6) were detoxified from heroin during the first 1 to 2 weeks after admission. During subsequent weeks, participants received a sample drug dose and $20 on Monday, and they could self-administer either the sampled dose or $20 during one choice session per day on Thursday and Friday. Participants responded under a modified progressive ratio schedule during each choice session. All active doses maintained higher progressive ratio break points (largest completed ratio) than placebo. There were no significant differences in break point values between buprenorphine and methadone or among the different doses of drug. However, several subjective ratings, including "good drug effect", "high", and "liking" dose-dependently increased after administration of buprenorphine and methadone. The peak ratings for these effects did not significantly differ for the two drugs. These results demonstrate that under these experimental conditions, buprenorphine and methadone were equally effective in producing reinforcing and subjective effects.

Topics: Adult; Black People; Blood Pressure; Buprenorphine; Controlled Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Female; Heroin Dependence; Hispanic or Latino; Humans; Injections, Intravenous; Male; Methadone; Narcotics; Oximetry; Pupil; Reinforcement, Psychology; Self Administration; Surveys and Questionnaires; White People

Topics: Buprenorphine; Heroin Dependence; Humans; Methadone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Treatment Outcome

Topics: Ambulatory Care; Buprenorphine; Combined Modality Therapy; Comprehensive Health Care; Continuity of Patient Care; Drug Approval; Education, Medical, Continuing; Heroin Dependence; Humans; Methadone; Narcotics; Opioid-Related Disorders; Patient Care Team; Primary Health Care; Psychotherapy; Public Policy; Substance Abuse Detection; Substance Abuse Treatment Centers; United States

The current study aimed to describe the characteristics (demographics, drug use, mental and physical health) of entrants to treatment for heroin dependence in three treatment modalities; and to compare these characteristics with heroin users not in or seeking treatment. Participants were 825 current heroin users recruited from Sydney, Adelaide and Melbourne: 277 entering methadone/buprenorphine maintenance treatment (MT), 288 entering detoxification (DTX), 180 entering drug-free residential rehabilitation (RR) and 80 not in treatment (NT). Treatment entrants were generally long-term heroin users with previous treatment experience. The majority of the sample (55%) were criminally active in the month preceding interview. Injection-related health problems (74%) and a history of heroin overdose (58%) were commonly reported. There were high degrees of psychiatric co-morbidity, with 49% reporting severe psychological distress, 28% having current major depression, 37% having attempted suicide and 42% having a lifetime history of post-traumatic stress disorder. Personality disorders were also prevalent, with 72% meeting criteria for antisocial personality disorder and 47% screening positive for borderline personality disorder. Striking similarities were noted between the non-treatment and treatment groups in length of heroin use career, drug use and treatment histories.

Topics: Adult; Australia; Buprenorphine; Comorbidity; Crime; Demography; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Female; Health Status; Heroin Dependence; Humans; Inactivation, Metabolic; Male; Methadone; Narcotics; Patient Acceptance of Health Care; Residential Treatment; Severity of Illness Index; Stress Disorders, Post-Traumatic; Suicide; Treatment Outcome

Buprenorphine is a narcotic analgesic used in the treatment of moderate-to-severe pain. In Italy, buprenorphine is now being used as an alternative in the therapeutic treatment of heroin abusers. Even if confirmation methods are needed for identification and quantitation, a rapid and sensitive test, such as an immunoassay, is essential for screening. We evaluated the Buprenorphine One-step ELISA test (designed for serum specimens) for the qualitative determination of buprenorphine in other matrices, such as urine, saliva and hair.

Topics: Buprenorphine; Enzyme-Linked Immunosorbent Assay; Hair; Heroin; Heroin Dependence; Humans; Italy; Narcotic Antagonists; Reference Standards; Saliva; Sensitivity and Specificity; Serum; Substance Abuse Detection; Urine

Topics: Buprenorphine; Health Services Accessibility; Heroin Dependence; HIV Infections; Humans; Narcotic Antagonists

To determine the lifetime and recent histories of attempted suicide among entrants to treatment for heroin dependence in three treatment modalities and a non-treatment comparison group; and to ascertain factors associated with a recent history of attempted suicide.. Cross-sectional structured interview.. Sydney, Australia.. Six hundred and fifteen current heroin users: 201 entering methadone/buprenorphine maintenance (MT), 201 entering detoxification (DTX), 133 entering drug free residential rehabilitation (RR) and 80 not in treatment (NT).. A lifetime history of attempted suicide was reported by 34% of subjects, 13% had attempted suicide in the preceding year and 5% had done so in the preceding month. Females were more likely to have lifetime (44% versus 28%) and 12 month (21% versus 9%) suicide attempt histories. The 12 month prevalence of attempted suicide among treatment groups ranged between 11% (MT, NT) and 17% (RR). Factors associated with recent suicide attempts were: being an RR entrant, female gender, younger age, less education, more extensive polydrug use, benzodiazepine use, recent heroin overdose, Major Depression, current suicidal ideation, Borderline Personality Disorder (BPD)and Post-Traumatic Stress Disorder.. Recent suicidal behaviour is a major clinical problem for heroin users, and for females and RR entrants in particular. An essential adjunct to treatment for heroin dependence is routine screening for depression and suicidal ideation, with the provision of appropriate treatment where needed.

Topics: Adolescent; Adult; Age Factors; Ambulatory Care; Antisocial Personality Disorder; Borderline Personality Disorder; Buprenorphine; Cross-Sectional Studies; Depressive Disorder, Major; Drug Overdose; Drug Therapy, Combination; Female; Heroin; Heroin Dependence; Humans; Male; Mass Screening; Methadone; Middle Aged; Narcotics; Needle-Exchange Programs; New South Wales; Outcome and Process Assessment, Health Care; Patient Admission; Rehabilitation Centers; Risk Factors; Sex Factors; Stress Disorders, Post-Traumatic; Substance Abuse, Intravenous; Suicide, Attempted

Topics: Adult; Apgar Score; Buprenorphine; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Gestational Age; Heroin Dependence; Humans; Infant, Newborn; Labor, Induced; Narcotic Antagonists; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Outcome; Pregnancy, High-Risk; Victoria

In most European countries, methadone treatment is provided to only 20-30% of opiate abusers who need treatment due to regulations and concerns about safety. To address this need in France, all registered medical doctors since 1995 have been allowed to prescribe buprenorphine (BUP) without any special education or licensing. This led to treating approximately 65,000 patients per year with BUP, about ten times more than with more restrictive methadone policies. French physician compensation mechanisms, pharmacy services, and medical insurance funding all minimized barriers to BUP treatment. About 20% of all physicians in France are using BUP to treat about half of the estimated 150,000 problem heroin users. Daily supervised dosing by a pharmacist for the first six months resulted in significantly better treatment retention (80% vs 46%) and lower heroin use. Intravenous diversion of BUP may occur in up to 20% of BUP patients and has led to various infections and relatively rare overdoses in combination with sedatives. Opiate overdose deaths have declined substantially (by 79%) since BUP was introduced in 1995. Newborn opiate withdrawal in mothers treated with buprenorphine compared to methadone was reported to be less frequent, less severe, and of shorter duration. Although some of the public health benefits seen during the time of buprenorphine expansion in France might be contingent upon characteristics of the French health and social services system, the French model raises questions about the value of tight regulations on prescribing BUP imposed by many countries throughout the world.

Topics: Adult; Buprenorphine; Cause of Death; Cross-Cultural Comparison; Drug Approval; Drug Overdose; Drug Utilization; Female; Forecasting; France; Health Services Accessibility; Heroin Dependence; Humans; Infant, Newborn; Male; Methadone; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy

Buprenorphine was registered in Australia as a maintenance and detoxification agent for the management of opioid dependence in November, 2000, and became widely available in August, 2001. This paper provides an overview of key developments in the introduction of buprenorphine treatment in Australia, with an emphasis upon the delivery of services in community-based (primary care) settings. A central study in this work was the Buprenorphine Implementation Trial (BIT), a randomized, controlled trial comparing buprenorphine and methadone maintenance treatment delivered under naturalistic conditions by specialist and community-based service providers (general practitioners and community pharmacists) in 139 subjects across nineteen treatment sites. In addition to conventional patient outcome measures (treatment retention, drug use, psychosocial functioning, and cost effectiveness), the BIT study also involved the development and evaluation of clinical guidelines, training programs for clinicians, and client literature, which are described here. Integration of treatment systems (methadone with buprenorphine, specialist and primary-care programs) and factors thought to be important in the uptake of buprenorphine treatment in Australia since registration are discussed.

Topics: Adolescent; Adult; Australia; Buprenorphine; Community Health Services; Cost-Benefit Analysis; Female; Health Plan Implementation; Heroin Dependence; Humans; Inservice Training; Long-Term Care; Male; Methadone; Narcotic Antagonists; Narcotics; Outcome Assessment, Health Care; Practice Guidelines as Topic; Randomized Controlled Trials as Topic

Topics: Adolescent; Buprenorphine; Child; Health Promotion; Heroin Dependence; Humans; Insurance, Health; Narcotic Antagonists; Office Visits; Stereotyping

Topics: Acute Disease; Adult; Analgesics, Opioid; Buprenorphine; Female; Heroin Dependence; Humans; Pancreatic Function Tests; Pancreatitis; Substance-Related Disorders

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Buprenorphine; Female; Heroin Dependence; Humans

The availability of buprenorphine promises to return the treatment of heroin addiction to mainstream medicine in the United States for the first time in nearly a century. This new treatment also provides an opportunity to reflect on the introduction of methadone and LAAM and their subsequent successes and failures in clinical implementation. The three articles that follow in this issue highlight the potential pharmacological, clinical, and logistic advantages of buprenorphine and provide clinicians with guidelines for its use in an integrated treatment setting. The clinical success of buprenorphine, however, depends in large part on factors beyond its pharmacological advantages. Clinician attitude and the extent to which they embrace buprenorphine will play an important role in determining the future success of this medication.

Topics: Buprenorphine; Heroin Dependence; Humans; Methadone; Methadyl Acetate; Narcotic Antagonists; Narcotics; Substance-Related Disorders

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

Topics: Adult; Buprenorphine; Chi-Square Distribution; Female; Heroin Dependence; Humans; Male; Middle Aged; Substance Withdrawal Syndrome

A sample of 535 entrants to opioid dependence treatments across three treatment modalities were administered a structured interview to ascertain the prevalence of non-injecting heroin use. Ten per cent of participants had used heroin primarily by smoking/inhaling in the month preceding interview, and 9% had used heroin and other drugs exclusively by non-injecting routes. Non-injectors were younger (25.3 vs. 29.5 years), had higher levels of education (10.6 vs. 10.0 years), were more likely to be employed (33 vs. 18%) and had lower levels of recent crime (31 vs. 56%). They also had shorter heroin using careers (5.1 vs. 9.9 years), fewer symptoms of dependence (5.1 vs. 5.6), had been enrolled in fewer previous treatment episodes (3.3 vs. 11.5) and had less extensive lifetime (8.0 vs. 9.1 drug classes) and recent (3.6 vs. 4.9) polydrug use. Non-injectors were substantially less likely to report lifetime (13% vs. 58%) or recent (2% vs. 29%) heroin overdoses. There were no differences between the general physical and psychological health of the two groups. While non-injectors had a lower level of post-traumatic stress disorder (29% vs. 34%), there were no differences in levels of major depression, attempted suicide, antisocial personality disorder, or borderline personality disorder. A substantial minority of Australian treatment entrants are now using heroin exclusively by non-injecting routes. While this group is younger, and has substantially reduced risk of overdose and blood borne virus transmission, the physical and psychological health of non-injectors mirrors that of injectors.

Topics: Administration, Inhalation; Adolescent; Adult; Antisocial Personality Disorder; Borderline Personality Disorder; Buprenorphine; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Drug Overdose; Female; Follow-Up Studies; Heroin; Heroin Dependence; Humans; Inactivation, Metabolic; Male; Methadone; Middle Aged; Narcotic Antagonists; Residential Treatment; Suicide, Attempted

New methods of ultra-rapid opiate detoxification (URD) under intravenous sedation have been criticized because of limited data on safety and long-term follow-up. Premedication with buprenorphine has been advocated to improve safety by decreasing vomiting. Prior research has not explored URD in socially impaired patients.. Sixteen patients were detoxified with URD and prospectively evaluated over at least 30 months. Data of this procedure were compared with those of our previous study without buprenorphine preparation (Drug Alcohol Depend. 52(3) (1998) 243). The 16 patients were followed up by a general practitioner (GP) before and after URD. The GPs also supervised the 7-day course of buprenorphine treatment prescribed for the 16 patients prior to URD.. During the procedure, only one episode of vomiting occurred instead of 13 out of 20 in our previous study. Post-procedure, only two patients experienced moderate withdrawal symptoms, such as persistent nausea, abdominal cramps and vomiting lasting from 24 to 48 h, in comparison with most patients in the previous study without buprenorphine. After a period of at least 30 months (36.0+/-6.38), the 16 patients were still alive and were regularly monitored by their GP. Only two of the 16 never relapsed after URD and reported total opiate abstinence. Fourteen patients relapsed; 12 of these were prescribed a licensed methadone substitution program and two were still using heroin.. In this small sample, the data indicated that URD with buprenorphine preparation was safe and that it markedly decreased post-procedure morbidity. No patient died over a minimum 30-month follow-up period. Furthermore, the procedure was employed with socially impaired patients. In the long term, a few patients were still free of opiates, while the majority opted for a methadone maintenance program, showing that URD can serve as one possible step in a long-term treatment program.

Topics: Adult; Buprenorphine; Conscious Sedation; Family Practice; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Naltrexone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Outcome and Process Assessment, Health Care; Premedication; Recurrence; Substance Withdrawal Syndrome; Time Factors; Vomiting

Topics: Buprenorphine; Ethics, Clinical; Heroin Dependence; Humans; Narcotic Antagonists; Reproducibility of Results; Research Design

Topics: Buprenorphine; Ethics, Clinical; Heroin Dependence; Humans; Narcotic Antagonists; Reproducibility of Results; Research Design

The clinical effectiveness of opioid maintenance for heroin dependence is believed to result from a medication's ability to decrease mu-opioid receptor (muOR) availability thereby replacing agonist effects, alleviating withdrawal symptoms and attenuating heroin effects. We empirically tested this hypothesis in five heroin-dependent volunteers who were successively maintained on 32, 16, 2, and 0 mg daily buprenorphine (BUP) tablet doses. We predicted and confirmed that higher BUP doses would decrease in vivo muOR availability (measured with PET and [(11)C]carfentanil), increase plasma levels of BUP and its metabolite nor-BUP, and decrease withdrawal symptoms and hydromorphone (HYD) responses. Relative to placebo, BUP significantly decreased mean (+/-SEM) whole-brain muOR availability 41+/-8, 80+/-2, and 84+/-2% at 2, 16, and 32 mg, respectively. Regions of interest (ROIs) (prefrontal cortex, anterior cingulate, thalamus, amygdala, nucleus accumbens, caudate) showed similar dose-dependent effects. Changes in muOR availability varied across ROIs (prefrontal cortex, 47% vs amygdala, 27%) at BUP 2 mg, but were more homogeneous across ROIs at BUP 32 mg (94-98%; except thalamus, 88%). Relative to placebo (0 ng/ml), peak plasma levels of BUP and nor-BUP were comparable and dose-dependent (0.5-1, 5-6, and 13-14 ng/ml at 2, 16, and 32 mg, respectively). muOR availability decreases were negatively correlated with BUP plasma level and positively correlated with questionnaire-based opioid withdrawal symptoms and attenuation of HYD symptoms. These findings suggest that high-dose BUP maintenance produces near-maximal muOR occupation, muOR availability correlates well with plasma levels, and BUP-related opioid symptoms and antagonist blockade exhibit concentration-effect relationships.

Topics: Adult; Analysis of Variance; Buprenorphine; Dose-Response Relationship, Drug; Female; Heroin Dependence; Humans; Male; Middle Aged; Narcotic Antagonists; Receptors, Opioid, mu; Tomography, Emission-Computed

This article presents the cost-effectiveness results of a randomised controlled trial conducted in two Australian cities. The trial was designed to assess the safety, efficacy and cost-effectiveness of buprenorphine versus methadone in the management of opioid dependence. The trial utilised a flexible dosing regime that was tailored to the clinical need of the patients, with high maximum doses, using the marketed formulation, under double-blind conditions. A total of 405 subjects were randomised to a treatment at one of three specialist outpatient drug treatment centres in Adelaide and Sydney, Australia. The perspective of the cost-effectiveness analysis was that of the service provider and included costs relevant to the provision of treatment. The primary outcome measure used in the economic analysis was change in heroin-free days from baseline to the sixth month of treatment. Treatment with methadone was found to be both less expensive and more effective than treatment with buprenorphine, which suggests methadone dominates buprenorphine. However, statistical testing found that the observed difference between the cost-effectiveness of methadone and buprenorphine treatments was not statistically significant. The results of this study provide useful policy information on the costs and outcomes associated with the use of methadone and buprenorphine and indicate that buprenorphine provides a viable alternative to methadone in the treatment of opioid dependence.

Topics: Adult; Buprenorphine; Cost-Benefit Analysis; Female; Heroin Dependence; Humans; Male; Methadone; Statistics, Nonparametric

Topics: Buprenorphine; Drug Therapy, Combination; Heroin Dependence; Humans; Methadone; Narcotic Antagonists; Narcotics; Socioeconomic Factors; Sweden

Topics: Adult; Buprenorphine; Child Development; Female; Heroin Dependence; Humans; Infant, Newborn; Male; Narcotic Antagonists; Narcotics; Neonatal Abstinence Syndrome; Opioid-Related Disorders; Pregnancy; Pregnancy Complications

Buprenorphine was approved in France for treating opiate dependence in July 1995 and can be prescribed by general practitioners (GPs). Most studies assessing buprenorphine maintenance treatment (BMT) outcomes have taken place in GP settings. An evaluation of BMT outcomes in patients already followed for their HIV-infection could supply additional information about the changes in addictive practices in a non-GP setting.. We assessed BMT discontinuations and the course of self-reported addictive behaviours and characteristics associated with buprenorphine-injection misuse in 114 HIV-infected patients on BMT who were followed in a hospital-based outpatient department.. The continuous series of follow-up visits at which these 114 patients reported regular buprenorphine prescriptions accounted for 237.5 person-years of observation, i.e. 475 follow-up visits. Of the 114 patients on BMT, 43% continued BMT throughout the follow-up, 40% stopped it, and results for 17% were not available either because they did not answer the self-administered questionnaire (5%) or because they were lost to follow-up (12%). Addictive behaviours declined but buprenorphine injection misuse remained stable. Depression measured by the CESD score (RR=1.04 95%CI [1.01-1.06]), cocaine use (RR=2.48 95%CI [1.31-4.68]) and alcohol consumption exceeding 4 alcohol units (AU) per day (RR=2.29, 95%CI [1.17-4.46]) were independently associated with buprenorphine injection misuse among stabilised BMT patients.. Despite the reduction in drug injection after starting BMT, buprenorphine injection misuse mainly involves patients with characteristics of severe addiction. Better monitoring of the illicit drug use patterns of patients on BMT may suggest new medical strategies for GPs to improve BMT outcomes.

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Cohort Studies; Depression; Female; Follow-Up Studies; Heroin Dependence; HIV Seropositivity; Humans; Injections, Intravenous; Male; Narcotic Antagonists; Severity of Illness Index; Substance Abuse, Intravenous; Surveys and Questionnaires; Treatment Refusal

Topics: Buprenorphine; Clinical Trials as Topic; Heroin Dependence; Humans; Methadone; Narcotic Antagonists; Narcotics; Placebos

Topics: Analgesics, Opioid; Buprenorphine; Clinical Trials as Topic; Clonidine; Heroin Dependence; Humans; Methadone; Narcotic Antagonists; Opioid-Related Disorders; Retrospective Studies; Substance Withdrawal Syndrome; Tramadol

Topics: Adult; Buprenorphine; Candidiasis; Drug Contamination; Endophthalmitis; Food Contamination; Heroin Dependence; Humans; Injections, Intravenous; Male; Narcotics

This study aimed to establish a buprenorphine regime suitable for the short-term management of out-patient heroin withdrawal using an open-label, single-group case series. Eighteen dependent injecting heroin users underwent an 8-day withdrawal episode with supervised dosing of sublingual Subutex tablets. Buprenorphine doses were titrated daily over a 5-day period. Fifteen subjects (83%) completed the 5-day regime, and 14 (78%) completed the 8-day withdrawal episode. The mean doses ((SD) were 6.1 (1.2) mg on day 1; 9.6 (1.7) mg on day 2; 10.1 (1.9) mg on day 3; 8.9 (2.0) mg on day 4; 4.1 (1.5) mg on day 5; and a total regime dose of 38.9 (5.8) mg. Withdrawal severity was mild, with minimal rebound upon the cessation of dosing. Five subjects reported no heroin use, and five subjects reported using on only one occasion during the 8 days. An out-patient buprenorphine regime is recommended.

Topics: Adult; Ambulatory Care; Buprenorphine; Drug Administration Schedule; Female; Heroin Dependence; Humans; Male; Patient Satisfaction; Severity of Illness Index; Substance Withdrawal Syndrome

A retrospective study was carried out using 3 606 medical files of nine detention centers in France, over a three-month period (May to July 1997). The files were analyzed to determine, age, type of addiction and subsequent type of therapy proposed: methadone, high-dose buprenorphine or abstinence. A comparison was then made to determine whether or not there exists a statistical relationship between the type of therapy given in prison for drug abuse and subsequent recurrent use during the following three and a half years, until December 2000.

Topics: Adult; Buprenorphine; Female; France; Heroin Dependence; Humans; Male; Methadone; Narcotic Antagonists; Prisoners; Recurrence; Retrospective Studies

Twenty street-heroin dependent subjects were given 32 mg of sublingual buprenorphine, following heroin abstinence of 24 hours. Withdrawal symptoms were monitored during the first few hours, and followed for six days after buprenorphine administration, after which naltrexone 50 mg was introduced to prevent future heroin use. All 20 subjects completed the seven-day trial with negligible withdrawal symptoms, and smooth transition to naltrexone. These results strongly demonstrate that symptom-free detoxification from heroin can be obtained by a single high dose of buprenorphine.

Topics: Adult; Buprenorphine; Drug Administration Schedule; Heroin Dependence; Humans; Inactivation, Metabolic; Male; Narcotic Antagonists

Topics: Buprenorphine; Heroin Dependence; Humans; Narcotic Antagonists; Opioid-Related Disorders

By diverting his dispensed medication, our patient collected 11 buprenorphine tablets (8 mg each), which he took in one day. The result was not respiratory depression, but instead severe opiate withdrawal lasting four days--this scenario has not previously been reported. This case highlights features of the unique pharmacology of buprenorphine and some key issues for its use in the management of heroin dependence.

Topics: Adult; Buprenorphine; Drug Overdose; Heroin Dependence; Humans; Male; Narcotic Antagonists; Patient Compliance; Receptors, Opioid; Self Medication; Substance Withdrawal Syndrome

Buprenorphine is an effective treatment for heroin dependence. The feasibility and potential efficacy of buprenorphine with brief counseling in primary care is unknown. We enrolled 14 heroin dependent patients in a 13-week clinical trial using thrice weekly buprenorphine along with brief counseling in the primary care center of an urban medical center. Primary outcomes included urine toxicology and treatment retention. Opioid-positive urine toxicology tests reduced over the 13-week period from 95 to 25% (p < 0.05). Eleven patients (79%) had greater than or equal to one week of opioid-free urine toxicologies. Nine patients (64%) had greater than or equal to three weeks of opioid-free urine toxicologies. Eleven patients (79%) were retained through the maintenance phase. We conclude that buprenorphine maintenance is feasible in a primary care setting.

Topics: Administration, Sublingual; Adult; Ambulatory Care; Buprenorphine; Combined Modality Therapy; Connecticut; Counseling; Dose-Response Relationship, Drug; Drug Administration Schedule; Feasibility Studies; Female; Heroin Dependence; Humans; Male; Middle Aged; Primary Health Care; Social Support; Treatment Outcome; Urban Population

Topics: Buprenorphine; Drug Overdose; France; Heroin Dependence; Humans; Methadone; Narcotics

This study examined the relationship between novelty seeking between treatment retention and among heroin dependent cocaine users. Participants were treated with buprenorphine maintenance and contingency management. The Tridimensional Personality Questionnaire's (TPQ) Novelty Seeking scale was administered to 68 participants prior to buprenorphine induction. Demographics, mood and anxiety disorders, antisocial personality disorder, and substance use were also assessed. Variables with significant relationships with overall retention were entered into a logistic regression analysis. In addition, using a survival analysis, all variables with significant relationships with time to drop-out were entered into a multivariate proportional hazards regression with time dependent covariates. Results demonstrated that although high novelty seekers, in comparison to low novelty seekers, were more likely to drop-out by the end of treatment, they had higher retention rates during the early phases of treatment. It is suggested that buprenorphine and contingency management were viewed by participants as novel treatment components and thus facilitated high novelty seekers' success early in treatment. If replicated, results suggest that inclusion of novel treatment components might facilitate retention among this at-risk group.

Topics: Adult; Age Factors; Buprenorphine; Chi-Square Distribution; Cocaine-Related Disorders; Confidence Intervals; Exploratory Behavior; Female; Heroin Dependence; Humans; Logistic Models; Male; Middle Aged; Narcotics; Patient Dropouts; Survival Analysis; Treatment Outcome

Sublingual buprenorphine is used as a substitution drug in heroin addicts. Although buprenorphine inhibits mitochondrial function at high concentrations in experimental animals, these effects should not occur after therapeutic sublingual doses, which give very low plasma concentrations.. We report four cases of former heroin addicts infected with hepatitis C virus and placed on substitution therapy with buprenorphine. These patients exhibited a marked increase in serum alanine amino transferase (30-, 37-, 13- and 50-times the upper limit of normal, respectively) after injecting buprenorphine intravenously and three of them also became jaundiced. Interruption of buprenorphine injections was associated with prompt recovery, even though two of these patients continued buprenorphine by the sublingual route. A fifth patient carrying the hepatitis C and human immunodeficiency viruses, developed jaundice and asterixis with panlobular liver necrosis and microvesicular steatosis after using sublingual buprenorphine and small doses of paracetamol and aspirin.. Although buprenorphine hepatitis is most uncommon even after intravenous misuse, addicts placed on buprenorphine substitution should be repeatedly warned not to use it intravenously. Higher drug concentrations could trigger hepatitis in a few intravenous users, possibly those whose mitochondrial function is already impaired by viral infections and other factors.

Topics: Administration, Sublingual; Adult; Animals; Buprenorphine; Chemical and Drug Induced Liver Injury; Hepatitis C; Heroin Dependence; HIV Infections; Humans; Injections, Intravenous; Male; Narcotics

At the conclusion of a 3-year demonstration project in a medical setting in which refusal to accept methadone was an inclusion criterion, 12 subjects were unable to detoxify from buprenorphine and remained adamant in their refusal to enroll in a MMTP. In order to study the feasibility of expanding opportunities for treatment previously unavailable to this under-served population of heroin addicts, these 12 subjects plus an additional 11 subjects (N = 23) were recruited for a 12 months trial of buprenorphine treatment conducted in an office-based setting on a fee-for-service basis. An additional cohort of 40 heroin dependent subjects were entered in a protocol for detoxification only. The findings demonstrate both feasibility and patient acceptance of office based fee-for-service buprenorphine treatment, supporting the need for (1) additional studies of this population and (2) changes in government regulations to reintroduce addiction treatment under physician auspices in private practice settings.

Topics: Adult; Buprenorphine; Drug Monitoring; Female; Follow-Up Studies; Heroin Dependence; Humans; Inactivation, Metabolic; Male; Middle Aged; Narcotics; Private Practice

The simultaneous intravenous (i.v.) administration of heroin and cocaine, called a "speedball," is often reported clinically, and identification of effective pharmacotherapies is a continuing challenge. We hypothesized that treatment with combinations of a dopamine reuptake inhibitor, indatraline, and a mu partial agonist, buprenorphine, might reduce speedball self-administration by rhesus monkeys more effectively than either drug alone. Speedballs (0.01 mg/kg/inj cocaine + 0.0032 mg/kg/inj heroin) and food (1 g banana pellets) were available in four daily sessions on a second-order schedule of reinforcement [fixed ratio (FR)4; variable ratio (VR)16:S]. Monkeys were treated for 10 days with saline or ascending dose combinations of indatraline (0.001-0.032 mg/kg/day) and buprenorphine (0.00032-0.01 mg/kg/day). Two combinations of indatraline (0.32 and 0.56 mg/kg/day) + buprenorphine (0.10 and 0.18 mg/kg/day) significantly reduced speedball self-administration in comparison to the saline treatment baseline (p <.01-.001), whereas the same doses of each compound alone had no significant effect on speedball-maintained responding. Daily treatment with 0.56 mg/kg/day indatraline + 0.18 mg/kg/day buprenorphine produced a significant downward shift in the speedball dose-effect curve (p <.01) and transient changes in food-maintained responding. These findings suggest that medication mixtures designed to target both the stimulant and opioid component of the speedball combination may be an effective approach to polydrug abuse treatment.

Topics: Animals; Buprenorphine; Cocaine; Cocaine-Related Disorders; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Interactions; Female; Heroin; Heroin Dependence; Indans; Macaca mulatta; Male; Methylamines; Narcotics; Neurotransmitter Uptake Inhibitors; Self Administration

Topics: Acute Disease; Adult; Buprenorphine; Chemical and Drug Induced Liver Injury; Female; Heroin Dependence; Humans; Injections, Intravenous

Since 1994-1995, rapid development of widely available substitution treatments has appeared to be a major healthcare step in heroin addiction. Currently approximately 60000 patients are taking daily maintenance doses of oral methadone and about 7200 are taking sublingual buprenorphine. In parallel with the expansion of these treatments, the number of lethal overdoses has fallen off regularly: 564 in 1994, 393 in 1996 and 143 in 1998 (-74.6% in 4 years).. We searched for a correlation between the rise in the number of patients taking maintenance treatments and the decreased in recorded deaths due to heroin overdose. Other factors which may influence this decrease were also considered.. A linear correlation was found between the increasing number of patients on maintenance treatment (high-dose buprenorphine or methadone) and the decrease in fatal heroin overdoses in France between 1994 and 1998. The importance of this correlation must be modulated by the presence of other events such as political, social, healthcare and behavioral events concerning drug users.

Topics: Acquired Immunodeficiency Syndrome; Attitude to Health; Buprenorphine; Drug Overdose; Drug Prescriptions; Drug Utilization; Female; France; Health Knowledge, Attitudes, Practice; Heroin; Heroin Dependence; Humans; Linear Models; Male; Methadone; Mortality; Narcotics; Population Surveillance; Risk Factors

Topics: Adult; Buprenorphine; Cocaine-Related Disorders; Heroin Dependence; Humans; Male; Office Visits; Private Practice; Psychiatry

A pilot study was carried out in Bangladesh during August and September, 1995, using a "snowball" technique with 30 male multiple drug users in order to investigate buprenorphine use, characteristics of the users, their reasons for its use and the drug's effects.

Topics: Adult; Bangladesh; Buprenorphine; Female; Heroin Dependence; Humans; Illicit Drugs; Male; Narcotic Antagonists; Substance Withdrawal Syndrome; Substance-Related Disorders

Topics: Buprenorphine; Drug and Narcotic Control; Drug Prescriptions; Heroin Dependence; Humans; Methadone; Narcotics; Politics; Regional Medical Programs; Sweden

Topics: Buprenorphine; Cost-Benefit Analysis; Crime; Heroin Dependence; Humans; Narcotics

Topics: Buprenorphine; Cost-Benefit Analysis; Heroin Dependence; Humans; Methadone; Narcotics; Quality-Adjusted Life Years

Topics: Buprenorphine; Evidence-Based Medicine; Heroin Dependence; Humans; Methadone; Narcotics; Psychotherapy; Social Support

France was the first country to promote the extensive use of buprenorphine for the treatment of drug-addicted subjects through the primary care system. To assess both professional commitment and patients' characteristics, all the physicians and pharmacists of a French area having prescribed/dispensed buprenorphine from 2/12/96 (the official release date) to 1/31/98 were identified from data files of the Health Insurance and then interviewed. During the first 61 weeks of buprenorphine maintenance treatment (BMT), 27.5% of physicians and 51.2% of pharmacists of that area were involved; 142 patient records were documented. Features of the clinical routines spontaneously implemented for practice-based BMT were: a high level of on-site supervised dispensation by the pharmacist (71% at treatment induction and 23% thereafter); the absence of objective measurement of illicit drug use; and a low buprenorphine dosage. These features are consistent with the lack of physicians' experience and training, and also the relatively good status of the population treated (no HIV-positives, heroin use duration averaging 4.2 +/- 3.1 years, and 81.7% with stable accommodations). Despite liberal regulations guiding BMT, a negligible proportion of cases had a "nomadic" attitude (multiple buprenorphine prescribers/deliverers). The treatment outcomes (no deaths, three drug overdoses, improvement in occupational status) are encouraging.. Practice-based BMT appears to be a safe and acceptable response to moderate heroin addiction, but further training of the professionals involved and longitudinal investigations of individual outcomes are needed.

Topics: Adult; Buprenorphine; Drug Utilization Review; Family Practice; Female; France; Heroin Dependence; Humans; Male; Narcotic Antagonists; National Health Programs; Outcome Assessment, Health Care; Pharmacies; Retrospective Studies; Surveys and Questionnaires

Topics: Buprenorphine; Electrocardiography; Heroin Dependence; Humans; Methadone; Methadyl Acetate; Naltrexone; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Time Factors

Buprenorphine might be an alternative drug to be used in opiate detoxification. Its main advantage is that it carries a low risk for respiratory depression, it gives less euphoria and limited withdrawal effects. In a pilot detoxification project ten heroin addicts were given buprenorphine; seven completed the course. Before detoxification seven patients showed five or more signs on the Himmelsbach scale [6]. After the second day four patients showed no signs, four patients displayed one sign, two patients two signs. Buprenorphine may be a valuable alternative to clonidine, dextropropoxiphene and methadone in the detoxification of opiate addicts.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Female; Heroin Dependence; Humans; Inactivation, Metabolic; Male; Narcotic Antagonists; Pilot Projects; Substance Abuse, Intravenous; Substance Withdrawal Syndrome

Topics: Analgesics, Opioid; Buprenorphine; Female; Heroin Dependence; Humans; Infant, Newborn; Methadone; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications; Risk Factors; Treatment Outcome

The development of maintenance treatment for subjects with addictive behavior is an important public health issue. As such, the social effectiveness of maintenance products must be examined from an economical and social point of view. This paper aims at presenting the financial costs involved in the use of Subutex, a product commercialized since 1996.. A complete typology of costs related to drug addiction and its consequences was set up. Some of these costs were estimated on the basis of data drawn from the literature. The cost of Subutex use for maintenance treatment was assessed and compared with the financial stakes including the potential reduction of the economic and social cost of drug addiction.. Monthly treatment cost of Subutex was 1252 FrF per drug abuser on maintenance treatment. By extrapolation, for a population of 40,000 drug abusers, the direct medical cost of Subutex during a course of maintenance treatment with general practitioner follow-up was estimated at 600 millions FrF. US data sources were applied to France to assess the cost of illnesses attributable to drug addiction. The cost reached 4.8 billions FrF. The cost of delinquency associated with drug addiction, which mostly concerns money laundered to purchase substances was an estimated 6.4 billions FrF. Finally, the cost of public anti-drug abuse programs was nearly 4.7 billions FrF. Thus, the direct cost of drug addiction consequences reached 15.6 billions FrF. This cost should be compared with the annual cost of Subutex for public organizations which was an estimated 600 millions FrF.. The "profit" threshold of maintenance treatment with Subutex in terms of direct costs is very low. A decrease of only 4% of the costs associated with drug addiction would make it possible to balance the financial budget for the community. Our analysis does not take into acount absolutely all the public health and safety aspects involved in the use of Subutex. It does however provide a useful assessment of the financial aspects of the question and justification for this therapeutic strategy from a budgetary point of view.

Topics: Buprenorphine; Cost of Illness; Drug Prescriptions; France; Heroin Dependence; Humans; Narcotic Antagonists

This is a case report and literature review concerning the use of buprenorphine for detoxification in a pregnant addict. It presents the clinical management of the complexities of opiate addiction and pregnancy. I suggest a more vigorous study of buprenorphine for opiate withdrawal in motivated pregnant addicts.

Topics: Adult; Buprenorphine; Female; Heroin; Heroin Dependence; Humans; Inactivation, Metabolic; Narcotic Antagonists; Narcotics; Pregnancy; Pregnancy Complications

Since February 1996, French GPs are allowed to prescribe high dosage buprenorphine for maintenance treatment of major opioid drug addiction. A prospective cohort of major opioid addicts was initiated in order to assess patient outcomes: follow-up, retention rate in treatment, drug use, intravenous injection and social situation evolution.. Each GP, known to be involved in drug user management, had to include the first 10 opioid drug addict patients to whom he prescribed high dosage buprenorphine, with a maximum inclusion period of 3 months. Patients were followed up for two years and a regular standardized information was collected (usual data on drug users and prescription modalities).. Between May and July 1996, 919 patients (664 men and 255 women, mean age: 30 years) were included by 101 GPs. They had a long and serious history of drug addiction, important parallel consumption of cocaine, codeine and other illicit drugs and psychiatric problems (28% of definite problems and 45% of probable) and frequent hepatic conditions (hepatitis B: 23%, hepatitis C: 21%). Two years later, 55% of patients were still followed-up by the same GP and an additional 12% were followed by another GP or in a health care service (hospitalized or receiving methadone in a specialized centre). 13% were not followed, but GPs were able to describe their situation. 8% had been included by GPs who had dropped the study. Finally, 12% of patients were lost to follow-up. Among the 508 patients still followed-up by the same GP after 2 years, the substitution treatment rate was 84%. The dosage bracket had widened (inclusion: mean dosage=7.8 mg +/-4.5, minimum=0.8, maximum=28, median=8; after 2 years: mean=7.6 mg +/-5.4, minimum=0.4, maximum=28, median=8) and the duration of the prescription and dispensing had increased. Declaration of heroin intake in the previous month had fell from 40% to 11% and declaration of drug intake from 53% to 20%. Social situation had improved on average (housing conditions and work). There were 12 seroconversions for hepatitis B, 21 for hepatitis C and 4 for HIV. 14% of patients had declared intravenous injection of high dosage buprenorphine in the previous month.. After two years of follow-up, 55% of patients were still followed-up by the same GP and an additional 12% was followed by another GP or in a health care service. Among patients still followed up by the same GP, a reduction of drug related harm (seroconversions for hepatitis B, hepatitis C and HIV) was observed.

Topics: Adult; Buprenorphine; Employment; Family Practice; Female; Follow-Up Studies; France; Health Services Research; Heroin Dependence; Housing; Humans; Male; Narcotics; National Health Programs; Patient Compliance; Pharmacoepidemiology; Program Evaluation; Treatment Outcome

The aim of this study was to compare the various clinical practices in four health care networks and to access how the variations in treatment effected the outcome in opiate-dependent patients.. A retrospective study was carried out with 71 participating general practitioners. These were chosen from a group of 354 practitioners from four health care networks. Each practitioner could enroll up to 5 patients who were currently undergoing treatment with high-dose buprenorphine(HDB). The patients treatment had to have been initiated between the 1(st) of February 1996 and the 31(st) of October 1996, and excluded any patients who had lapsed on their treatment during the first month. Patients were selected until a total of 75 cases were enrolled from each network. Data were then collected retrospectively between June and December 1997. Information collected concerned the initial stage of treatment, the stabilizing stage or level of treatment and followed up data on the most recent prescriptions.. The final patient maintenance totals were high for all four care networks (82.7 to 96% of patients were still being followed by their doctor at the final evaluation). A positive outcome as indicated by reduction of risk and decreased social vulnerability was also observed in all networks. Additionally, in each network there was a clear correlation between prescription practices and patient behavior. For example, the prescription of HDB at a daily dose of less than 6.2mg was associated with a higher rate of benzodiazepine use; and prescription of several daily doses of HDB was associated with a higher percentage of injecting patients.. This retrospective study provides evidence that general practitioner care of drug-dependent patients as outpatients, within a health care network helps to stabilize patient visits, allows treatment of associated comorbidities and favors social rehabilitation. The prescription of HDB as a single daily dose, individually adapted for each patient, optimizes the outcome and reduces misuse.

Topics: Adult; Buprenorphine; Codeine; Data Interpretation, Statistical; Female; Follow-Up Studies; France; Health Services; Heroin Dependence; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Retrospective Studies; Risk-Taking; Time Factors; Treatment Outcome

Topics: Buprenorphine; Drug Approval; Female; Heroin Dependence; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications; United States; United States Food and Drug Administration

Topics: Abortion, Legal; Adult; Buprenorphine; Cohort Studies; Female; France; Heroin Dependence; Humans; Methadone; Obstetric Labor Complications; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prospective Studies

(1) Three years after high-dose buprenorphine preparations were first marketed in France, we examine their use as replacement therapy for heroin addiction. (2) Various surveys of community pharmacists have shown that the prescribing and dispensing conditions are feasible in the routine ambulatory setting. However, teamwork between physicians and pharmacists is rarely optimal, and fractionated dispensing is under-used. This could lead to abuse by a minority of patients. (3) During ambulatory management, at a mean dose of 8 mg/day sublingually, long-term buprenorphine therapy seems to yield a reduction in drug consumption by most patients, and can help with social reintegration. (4) The risks of buprenorphine treatment are mainly linked to abuse (massive doses, intravenous injection). Fatalities have occurred after high doses of buprenorphine combined with benzodiazepines, especially when taken intravenously. (5) The limited data on buprenorphine intake during pregnancy are reassuring.

Topics: Ambulatory Care; Benzodiazepines; Buprenorphine; Female; Heroin Dependence; Humans; Infant, Newborn; Narcotics; Practice Patterns, Physicians'; Pregnancy; Treatment Outcome

A rapid, sensitive, precise and accurate HPLC assay with UV detection was developed for the determination of buprenorphine (BN) in human plasma. This method involved a two-step extraction in the presence of clothiapine as internal standard. The compounds were chromatographied on a reversed-phase Spherisorb C8 column with a mobile phase consisting of 0.06 M KH2PO4/Na2HPO4 pH 6.4-acetonitrile-triethylamine-Pic B5 (520:480:0.5:15, v/v) and detected at 214 nm. The recovery of BN was greater than 94% with an intra-day relative standard deviation < or = 4.8% and an inter-day relative standard deviation < or = 14.6% at any studied level. Studies of drug stability during sample storage at -20 degrees C and at +4 degrees C did not show any significative degradation of BN. This method was successfully applied to explore the overdose state of heroin-dependent subjects treated by high-dose BN.

Topics: Buprenorphine; Chromatography, High Pressure Liquid; Drug Stability; Equipment Design; Heroin Dependence; Humans; Narcotic Antagonists

A pregnant woman who was addicted to heroin rapidly withdrew from illicit drugs after the onset of a 4 mg/day buprenorphine treatment. In the newborn's blood, urine, and meconium 20 hours after birth, high concentrations of buprenorphine and its metabolite norbuprenorphine were detected, with a higher buprenorphine/norbuprenorphine ratio than in adults, possibly as a consequence of immature hepatic function; no illicit drugs were found. The child had a weak withdrawal syndrome on the second day of life and recovered rapidly. The measured buprenorphine daily dose ingested by the newborn through mother's milk was very low (3.28 micrograms) and probably had little pharmacologic effect because no withdrawal signs could be noted when maternal feeding was later abruptly interrupted. Further investigations are required to determine whether buprenorphine can be considered to be a good alternative to methadone in the treatment of pregnant heroin addicts to prevent marked withdrawal syndromes in newborns.

Topics: Adult; Breast Feeding; Buprenorphine; Female; Heroin Dependence; Humans; Infant, Newborn; Narcotics; Neonatal Abstinence Syndrome; Pregnancy; Pregnancy Complications

To evaluate the clinical efficacy of buprenorphine (Bup) in treatment of acute heroin withdrawal.. Bup was given sublingually daily to 60 cases of heroin addicts in 3 groups: low, medium, and high doses. Withdrawal signs and symptoms of heroin were rated by Clinical Institute Narcotic Assessment. Craving for heroin during detoxification was assessed by Visual Analogue Scale. The side effects of Bup was assessed by Treatment Emergent Symptom Scale.. The mean daily consumption of Bup in low, medium, and high group was 2.0, 2.9, and 3.6 mg, respectively. Bup not only suppressed objective signs and withdrawal symptoms for heroin withdrawal, but also reduced the duration for heroin detoxification over 7-8 d.. Bup is an effective and rapid detoxification agent with fewer side effects for treatment of acute heroin withdrawal.

Topics: Adult; Buprenorphine; Female; Heroin Dependence; Humans; Male; Narcotic Antagonists; Substance Withdrawal Syndrome

Topics: Administration, Sublingual; Adult; AIDS Serodiagnosis; Buprenorphine; Dose-Response Relationship, Drug; Drug Administration Schedule; Heroin Dependence; HIV Seropositivity; Humans; Male; Opioid-Related Disorders; Substance Abuse, Intravenous; Treatment Outcome

Topics: Buprenorphine; Clonidine; Heroin Dependence; Humans; Methadone; Methadyl Acetate

Withdrawal of opiates drug addicts in Internal Medicine is unusual in France. Four main preliminary conditions are requested: 1--Drug addict preparation and self motivation, 2--Inter and intra institution team collaboration, 3--Opening the hospital towards community agencies, 4--Hospital staff recruited on volunteer basis. Within two years (1992-1993), 210 opiates drug addicts were hospitalized for withdrawal. Two third were males, median age was 27, median years of addiction was 7. Thirty percent were seropositive for HIV, 70% for HCV. Hospitalisation lasted 7 days for heroin addicts and 10 days for morphin, codein or buprenorphin addicts. Successful withdrawn was observed for 70% patients but six months after withdrawal, only 15% remained abstinent.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Codeine; Female; France; Heroin Dependence; Hospital Departments; Hospitalization; Humans; Internal Medicine; Male; Morphine Dependence; Opioid-Related Disorders; Recurrence; Time Factors

Topics: Administration, Oral; Adolescent; Adult; Buprenorphine; Heroin Dependence; Humans; Injections, Intramuscular; Methadone; Patient Compliance; Therapeutic Equivalency; Time Factors

Topics: Administration, Sublingual; Buprenorphine; Drug Evaluation; France; Heroin Dependence; Humans; Methadone; Opioid-Related Disorders; Time Factors

Topics: Belgium; Buprenorphine; Drug Prescriptions; France; Heroin Dependence; Humans; Methadone; Physicians, Family; Recurrence; Time Factors; Urban Population

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Buprenorphine; Emergencies; Heroin Dependence; HIV Infections; Hospitalization; Humans; Methadone; Morphine; Outpatients; Patient Care Team; Substance-Related Disorders

Topics: Buprenorphine; Codeine; Family Practice; Flunitrazepam; Heroin Dependence; Humans; Morphine; Pharmacists; Self Medication; Substance-Related Disorders

Topics: Buprenorphine; Clinical Trials as Topic; Heroin; Heroin Dependence; Humans; Methadone; Narcotics; Quality of Life; Social Support; Substance Withdrawal Syndrome; Substance-Related Disorders; Time Factors

Topics: Buprenorphine; Heroin Dependence; Humans; Inpatients; Methadone; Narcotics; Outpatients; Patient Compliance; Recurrence; Time Factors

Topics: Buprenorphine; Developing Countries; Heroin Dependence; HIV Seropositivity; Humans; India; Injections, Intravenous; Needle Sharing; Physician Impairment; Quackery

Topics: Buprenorphine; Heroin Dependence; Humans; Methadone; Methadyl Acetate; Practice Guidelines as Topic; Psychiatry; Societies, Medical; United States

In recent years much attention has been drawn to the use of buprenorphine (Temgesic) by heroin injectors in Glasgow and elsewhere. Glasgow has also witnessed a parallel increase in use of the benzodiazapine temazepam, often used as a 'cocktail' with buprenorphine. This paper presents new evidence that, although buprenorphine use among Glasgow drug injectors may now be declining, the use of temazepam-opioid cocktails has continued.

Topics: Adult; Buprenorphine; Comorbidity; Cross-Cultural Comparison; Cross-Sectional Studies; Heroin Dependence; Humans; Incidence; Male; Opioid-Related Disorders; Prisoners; Scotland; Substance Abuse, Intravenous; Substance-Related Disorders; Temazepam; Urban Population

Two surveys of 12 months duration were undertaken on opioid users presenting to the Wellington Alcohol and Drug Centre before and after the introduction of a combination buprenorphine 0.2 mg-naloxone 0.17 mg tablet (Bu-Nx), which was launched in 1991 in the hope of reducing intravenous misuse. There was considerable intravenous (i.v.) misuse of buprenorphine 0.2 mg tablets (Bu) in 1990 with self-reports of misuse in 81% of the patients over the 4 weeks prior to presentation, and 65% of the patients had buprenorphine in their urine. In the repeat survey 57% reported misuse of the Bu-Nx combination over the previous 4 weeks, and 43% had buprenorphine +/- naloxone detected in their urine. There was a reduction in the street price of Bu-Nx. One-third of the patients who used Bu-Nx i.v. reported instances of withdrawal symptoms, and subjectively the drug was less attractive to misusers. The combination product may have less misuse potential than buprenorphine alone, but it remains a preparation, in the dosages employed, that is intravenously misused.

Topics: Adult; Buprenorphine; Cross-Sectional Studies; Drug Combinations; Female; Heroin Dependence; Humans; Incidence; Male; Morphine Dependence; Naloxone; New Zealand; Substance Abuse Detection; Substance-Related Disorders

Sociodemographic, toxicologic, and psychopathologic characteristics of 22 buprenorphine addicts and 45 heroin addicts admitted for inpatient detoxification were compared. Although the buprenorphine addicts were older, clinically significant differences were not apparent. The availability of buprenorphine may be the main reason for its abuse.

Topics: Adult; Age Factors; Anxiety Disorders; Buprenorphine; Depressive Disorder; Female; Heroin Dependence; Hospitalization; Humans; Male; Personality Inventory; Psychiatric Status Rating Scales; Substance Abuse, Intravenous; Substance-Related Disorders

Topics: Adult; Buprenorphine; Conditioning, Operant; Heroin Dependence; Humans; Male; Models, Biological; Naltrexone; Self Administration

There has been concern over the growing misuse of buprenorphine and temazepam in Scotland. In interviews with 78 clients of Glasgow drug agencies during 1989-1990, it was found that buprenorphine and temazepam are now more widely and frequently misused than heroin or other opiates. Fifty-eight percent of buprenorphine users used six to seven days weekly. Fewer users of other drugs used as frequently. Heroin, other opiates and temazepam were associated with criminality. Buprenorphine, perhaps because it is relatively inexpensive, was not associated with criminality. Implications for drug policy and treatment are discussed.

Topics: Adolescent; Adult; Buprenorphine; Cross-Sectional Studies; Female; Heroin Dependence; Humans; Incidence; Male; Psychotropic Drugs; Risk Factors; Scotland; Substance Abuse, Intravenous; Substance-Related Disorders; Temazepam

The pupillary effects of the partial opiate agonist buprenorphine were studied in 16 male subjects who were heroin dependent at the time of admission to the study. Sublingual buprenorphine (8 mg) was administered daily for 18 days and continued either daily or on alternate days from study days 19 through 36. On days 37 through 56, all subjects received buprenorphine placebo. Compared to placebo, buprenorphine decreased pupil size and diminished the constriction and dilation velocities of the light reflex. These effects occurred within 5 hours of buprenorphine administration. Following placebo administration during alternate-day dosing of buprenorphine, pupil size increased and constriction and dilation velocities of the light reflex were significantly greater than after buprenorphine administration in the same subjects. This pattern of effects was observed after buprenorphine was discontinued (day 37). The results indicated that buprenorphine has pupillary effects like those of full opiate agonists. The time course of these effects was similar to previously-reported effects of buprenorphine on the electroencephalogram but not to the time course of subjective effects.

Topics: Adult; Buprenorphine; Heroin Dependence; Humans; Light; Male; Middle Aged; Pupil

After buprenorphine was introduced as an analgesic, several clinical observations have stimulated the investigation of its potential abuse by heroin addicts. To evaluate the prevalence of buprenorphine use by a group of heroin abusers being treated on an outpatient basis, a cross-sectional study was carried out where the information given by the 188 subjects was verified by urine drug analyses. The patients had three different therapeutic modalities: methadone maintenance program (MMP), antagonist maintenance program (AMP), and drug-free program (DFP). The urine samples were analyzed with an enzyme immunoassay technique for the detection of heroin, methadone, dextropropoxyphene, cannabis and benzodiazepines. Buprenorphine was investigated with a radioimmunoassay technique. Overall 66% of the patients admitted having used buprenorphine throughout their toxicologic history (period prevalence) and 6.7% had positive urine controls for this drug (5% in the MMP group, 0% in the AMP group and 12% in the DFP group) (point prevalence). In 72% of the cases the drug was administered intravenously. In addition, a clinically statistically significant association was found between positivity for heroin and buprenorphine. The possible tolerance to the latter is suggested by the fact that the mean current dose was higher than the mean initial dose. In the study population, the use of cannabis and benzodiazepines was also very high. The results suggest that most patients had a previous history of buprenorphine use. This drug could have a higher potential for abuse than that found in previous experimental studies.

Topics: Adult; Buprenorphine; Female; Heroin Dependence; Humans; Male; Methadone; Substance-Related Disorders

A new, rapid dose-induction procedure was used in the evaluation of buprenorphine hydrochloride (buprenorphine) as a treatment for opiate dependence. Nineteen heroin-dependent men were given buprenorphine sublingually in ascending daily doses of 2, 4, and 8 mg and then maintained on 8 mg daily. The observations of the transition from heroin to buprenorphine for the first 4 days are described. During this period, subjects reported significantly elevated ratings of "good effects" and feelings of "overall well-being" and decreased ratings of "overall sickness." Data from subscales of the Addiction Research Center Inventory indicated increasing euphoria and decreasing dysphoria and sedation after buprenorphine administration. Subjects and observers consistently identified buprenorphine as an opiate and not as an opiate antagonist. These findings indicate that a rapid dose induction with buprenorphine is acceptable to heroin-dependent persons and that it causes minimal withdrawal symptoms.

Topics: Administration, Sublingual; Adult; Blood Pressure; Buprenorphine; Heroin Dependence; Humans; Male; Middle Aged; Pulse; Pupil; Surveys and Questionnaires; Time Factors

Topics: Administration, Oral; Administration, Sublingual; Adult; Buprenorphine; Cocaine; Combined Modality Therapy; Female; Follow-Up Studies; Heroin Dependence; Humans; Male; Methadone; Substance-Related Disorders

Twelve heroin addicts on the 8th day after withdrawal, and 8 healthy volunteers were given a single i.m. injection of buprenorphine 0.6 mg and their subjective response rated on 10 psychological variables. Pre-injection rating differed significantly between addicts and controls on 7 variables out of 10. Following buprenorphine more subjective changes were noted in the control group which became more calm, depressed, more aware of the environment, sleepy, tired, intoxicated, dizzy and nauseated. The drug addicts reported changes only in 2 variables (less tense and dysphoric) but otherwise showed no significant changes. These findings support the notion that buprenorphine induces low or normalizing effects in heroin addicts. This drug might thus be suitable for maintenance therapy in opiate addiction.

Topics: Adult; Buprenorphine; Female; Heroin Dependence; Humans; Male; Psychological Tests

Dr. Jasinski suggested years ago that on the basis of some preliminary findings buprenorphine could hold promise for the treatment of heroin dependence (D. Jasinski, J.S. Pevnick and J.D. Griffith, Arch. Gen. Psychiatry, 35 (1978) 501)). No significant report has been published to confirm that assumption, and no treatment program seems to have started on that ground. Buprenorphine is now available in several countries including Belgium. We tried to devise a treatment program for heroin addicts combining chemotherapy with sublingual buprenorphine and psychotherapy. The interim results of this treatment program--initiated in 65 heroin addicts and undertaken by 34 of them for periods varying from 2 to 17 months--seem sufficiently promising to pursue our research.

Topics: Adult; Buprenorphine; Female; Heroin Dependence; Humans; Male; Morphinans; Patient Dropouts; Physician-Patient Relations; Time Factors

Topics: Anti-Anxiety Agents; Buprenorphine; Double-Blind Method; Dronabinol; Drug Synergism; Heroin Dependence; Humans; Marijuana Abuse; Methadone; Opioid-Related Disorders; Pentazocine; Smoking Prevention; Substance Withdrawal Syndrome; Substance-Related Disorders; Tripelennamine

Topics: Buprenorphine; Heroin Dependence; Humans; Injections; Injections, Intramuscular; Morphinans; Tongue

Topics: Adult; Buprenorphine; Drug Tolerance; Heroin Dependence; Humans; Male; Morphinans; Social Facilitation; Substance-Related Disorders

Topics: Animals; Buprenorphine; Dose-Response Relationship, Drug; Eating; Heroin Dependence; Humans; Hydromorphone; Macaca mulatta; Macaca nemestrina; Male; Methadone; Morphinans; Opioid-Related Disorders; Self Administration

Buprenorphine, a mixed opiate agonist-antagonist, suppressed plasma luteinizing hormone (LH) and increased prolactin levels after 12 consecutive days of ascending dose administration (0.5-8 mg/day s.c.) in comparison to drug-free control conditions. During a subsequent 10-day period of buprenorphine maintenance at a dose of a 8 mg s.c., LH levels remained suppressed and prolactin levels continued to be elevated. Tolerance to buprenorphine effects on LH and prolactin levels did not occur during chronic drug administration. Buprenorphine-induced changes in plasma LH and prolactin after chronic administration to human males were smaller than those observed with less potent opiate agonist drugs. Effects of buprenorphine on LH and prolactin levels are more consistent with the actions of opiate agonists rather than opiate antagonists.

Topics: Adult; Buprenorphine; Double-Blind Method; Heroin Dependence; Humans; Luteinizing Hormone; Male; Morphinans; Narcotic Antagonists; Narcotics; Prolactin; Radioimmunoassay

Topics: Adult; Buprenorphine; Conditioning, Operant; Double-Blind Method; Heroin Dependence; Humans; Male; Morphinans; Reinforcement, Psychology; Self Administration; Work

Heroin-dependent men were given buprenorphine (a partial opiate agonist-antagonist) or a placebo under duoble-blind conditions on a clinical research ward where they could acquire heroin (21 to 40.5 milligrams per day, intravenously). Buprenorphine significantly (P less than .001) suppressed the self-administration of heroin over 10 days. Control subjects took between 93 and 100 percent of the available heroin. The effects of buprenorphine were dose-dependent; a dose of 8 milligrams per day reduced heroin use by 69 to 98 percent; a dose of 4 milligrams per day reduced heroin use by 45 percent. Termination of buprenorphie maintenance did not result in opiate withdrawal signs or symptoms. The subjects liked buprenorphine and indicated that it was preferable to methadone or naltrexone. Buprenorphine should be a safe and effective new pharmacotherapy for heroin dependence.

Topics: Adult; Buprenorphine; Double-Blind Method; Heroin Dependence; Humans; Informed Consent; Morphinans; Substance Withdrawal Syndrome; Substance-Related Disorders