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Sample records for buprenorphine substitution treatment

  1. Diversion of methadone and buprenorphine from opioid substitution treatment: a staff perspective.

    PubMed

    Johnson, Björn; Richert, Torkel

    2014-01-01

    Opioid substitution treatment (OST) is still controversial, despite positive results. The issue of diversion to the illicit drug market is a cornerstone in the criticism typically voiced against the treatment. Little research is available concerning how professionals who work in OST view the issue of diversion. In this article, we discuss existing ideas and attitudes toward diversion of methadone and buprenorphine among OST staff in Sweden. The article is based on semi-structured interviews with 25 professionals working in eight OST-programs in southern Sweden. Diversion was seen as a deleterious phenomenon by the interviewees. Three problematic aspects were highlighted: medical risks in the form of overdose fatalities and the recruitment of new opiate/opioid users; negative consequences for the legitimacy of OST; and moral objections, since diversion means that the patients remain in a criminal environment. However, positive aspects were also highlighted. Illicit methadone or buprenorphine is perceived as safer than heroin. In this way, diversion can fulfill a positive function; for instance, if there is a shortage of access to regular treatment. Patients who share their medication with opioid-dependent friends are seen as less culpable than those who sell to anyone for money. PMID:25364995

  2. Methadone vs. buprenorphine/naloxone during early opioid substitution treatment: a naturalistic comparison of cognitive performance relative to healthy controls

    PubMed Central

    Rapeli, Pekka; Fabritius, Carola; Alho, Hannu; Salaspuro, Mikko; Wahlbeck, Kristian; Kalska, Hely

    2007-01-01

    Background Both methadone- and buprenorphine-treated opioid-dependent patients frequently show cognitive deficits in attention, working memory, and verbal memory. However, no study has compared these patient groups with each other during early opioid substitution treatment (OST). Therefore, we investigated attention, working memory, and verbal memory of opioid-dependent patients within six weeks after the introduction of OST in a naturalistic setting and compared to those of healthy controls. Methods The sample included 16 methadone-, 17 buprenorphine/naloxone-treated patients, and 17 healthy controls matched for sex and age. In both groups buprenorphine was the main opioid of abuse during the recent month. Benzodiazepine codependence, recent use, and comedication were also common in both patient groups. Analysis of variance was used to study the overall group effect in each cognitive test. Pair-wise group comparisons were made, when appropriate Results Methadone-treated patients, as a group, had significantly slower simple reaction time (RT) compared to buprenorphine/naloxone-treated patients. In Go/NoGo RT methadone patients were significantly slower than controls. Both patient groups were significantly debilitated compared to controls in working memory and verbal list learning. Only methadone patients were inferior to controls in story recall. In simple RT and delayed story recall buprenorphine/naloxone patients with current benzodiazepine medication (n = 13) were superior to methadone patients with current benzodiazepine medication (n = 13). When methadone patients were divided into two groups according to their mean dose, the patient group with a low dose (mean 40 mg, n = 8) showed significantly faster simple RT than the high dose group (mean 67 mg, n = 8). Conclusion Deficits in attention may only be present in methadone-treated early phase OST patients and may be dose-dependent. Working memory deficit is common in both patient groups. Verbal memory deficit may be more pronounced in methadone-treated patients than in buprenorphine/naloxone-treated patients. In sum, to preserve cognitive function in early OST, the use of buprenorphine/naloxone may be more preferable to methadone use of, at least if buprenorphine has been recently abused and when benzodiazepine comedication is used. Longitudinal studies are needed to investigate if the better performance of buprenorphine/naloxone-treated patients is a relatively permanent effect or reflects "only" transient opioid switching effect. PMID:17565668

  3. Evaluation of buprenorphine CEDIA assay versus GC-MS and ELISA using urine samples from patients in substitution treatment.

    PubMed

    Böttcher, Michael; Beck, Olof

    2005-01-01

    As buprenorphine becomes more clinically used in heroin substitution treatment, there is an increasing need for methods suitable for high-volume screening. In this study, a new immunochemical test based on CEDIA technology was evaluated for the use in clinical urine drug testing. The method was compared with an existing ELISA method and a gas chromatography-mass spectrometry (GC-MS) method on urine specimens from patients in heroin substitution treatment. The precision of the CEDIA assay was < 9% both within- and between-day at levels at and above the cutoff limit of 5 microg/L. The concordance in qualitative results with an existing ELISA method was 96.8%. The CEDIA measuring range was extended by diluting urine samples 100-fold with saline, and the results agreed well (slope of regression line was 1.09, r(2) = 0.968) with GC-MS. The sensitivity of CEDIA in detecting authentic specimen containing buprenorphine at levels >or= 5 microg/L was 99.5%. Cross-reactivity causing false-positive response was discovered in patients receiving prescribed dihydrocodeine. The urine concentration of total buprenorphine in urine from patients prescribed daily doses between 0.2 and 24 mg ranged from 0.5 to 2900 microg/L. The concentration of the metabolite norbuprenorphine was usually higher, and the median ratio of buprenorphine to norbuprenorphine was 0.23 (95% were below 1). We conclude that the CEDIA assay is suitable for application in high-volume screening of buprenorphine for urine drug testing. PMID:16356333

  4. Naltrexone implant treatment for buprenorphine dependence--Mauritian case series.

    PubMed

    Jhugroo, Anil; Ellayah, Darmen; Norman, Amanda; Hulse, Gary

    2014-08-01

    Although substitution therapy with opiate agonist treatments such as methadone and buprenorphine has resulted in a reduction of illicit drug use related harm, such treatment has also resulted in severe problems in some countries where opioid-dependent individuals now inject illicitly sold buprenorphine or buprenorphine-naloxone instead of heroin. There is no approved treatment for buprenorphine dependence. Naltrexone is an opioid antagonist which has been used for the treatment of both alcohol and opioid dependencies. Although both buprenorphine and heroin resemble each other concerning their effects, buprenorphine has a higher affinity to opioid receptors than heroin. Therefore, it is not known if naltrexone can block the psychoactive effects of buprenorphine as it does for heroin. This paper presents observational case series data on the use of a sustained-release naltrexone implant for the treatment of buprenorphine dependence. To the authors' knowledge this is the first use of sustained-release naltrexone for this indication. PMID:24695742

  5. Buprenorphine substitution treatment in France: drug users' views of the doctor-user relationship

    PubMed Central

    Guichard, Anne; Lert, France; Brodeur, Jean-Marc; Richard, Lucie

    2007-01-01

    The French system for drug substitution, or maintenance treatment, established in 1996, differs from the often strict conditions attached to methadone clinics in other countries. Because of the predominant role of general practitioners and the flexible prescription rules for Subutex® in France, the relationship between the physician and the drug user becomes a central element in the treatment. This article deals with the expectations that these users have of the physician, and their perception of his or her attitude towards them. In order to identify possible reasons for the absence of treatment compliance and of Subutex® misuse, it focuses on the users’ assessment of the physician’s response to the problems they report. This study, based on a diversified sample of 28 persons in treatment, showed 4 patterns of relationships between physicians and users, which differed in their focus: a) dosage, b) compliance, c) the person and d) obtaining a prescription. In all four case types, users had difficulty reporting other drug use or intravenous Subutex® injection within this relationship in which the stigma attached to drug dependence seems to reappear. Moreover, the lack of clarity about the treatment objectives and time frame limits the users’ ability to integrate the treatment into their lives and to commit themselves to it. The heterogeneity and fragility of the users’ situations are elements related to dependence that, during contact with the physician, require regular assessment of the individual’s situation and of the treatment objectives. This constant reappraisal of the situation with the physician should help to optimize the treatment and avoid the hiatus that can generate or continue “misuse.” PMID:17442473

  6. Opioid substitution treatment with sublingual buprenorphine in Manipur and Nagaland in Northeast India: what has been established needs to be continued and expanded

    PubMed Central

    Kumar, M Suresh; Natale, Richard D; Langkham, B; Sharma, Charan; Kabi, Rachel; Mortimore, Gordon

    2009-01-01

    Manipur and Nagaland in northeast India report an antenatal HIV prevalence of > 1% and the current HIV prevalence among injecting drug users is 24% and 4.5% respectively. Through support from DFID's Challenge Fund, Emmanuel Hospital Association (EHA) established thirteen drop-in-centres across the two states to deliver opioid substitution treatment with sublingual buprenorphine for 1200 injecting drug users. Within a short span of time the treatment has been found to be attractive to the clients and currently 1248 injecting opioid users are receiving opioid substitution treatment. The project is acceptable to the drug users, the families, the communities, religious as well as the militant groups. The treatment centres operate all days of the week, have trained staff members, utilize standardized protocols and ensure a strict supervised delivery system to prevent illicit diversion of buprenorphine. The drug users receiving the substitution treatment are referred to HIV voluntary counselling and testing. As this treatment has the potential to change HIV related risk behaviours, what has been established in the two states needs to be continued and expanded with the support from the Government of India. PMID:19243636

  7. Buprenorphine in the treatment of opiate dependence.

    PubMed

    Wesson, Donald R; Smith, David E

    2010-06-01

    Compelling clinical evidence establishes that buprenorphine is similar to methadone in efficacy for opiate detoxification and maintenance but safer than methadone in an overdose situation. The Drug Abuse Treatment Act of 2000 (DATA 2000) enabled US physicians with additional training to prescribe buprenorphine to a limited number of opiate-dependent patients. The sublingual tablets Subutex (buprenorphine alone) and Suboxone (a combination of buprenorphine and naloxone) meet the specifications of DATA 2000. Suboxone is intended to discourage intravenously administration and has less abuse potential than buprenorphine alone. Suboxone is generally recommended for maintenance treatment except for women who are pregnant. Subutex is recommended in treatment of pregnant women. A buprenorphine opiate withdrawal syndrome can occur in newborns. Although intravenous buprenorphine abuse is a significant public health problem in some countries, buprenorphine alone or in combination with naloxone has less potential for abuse than heroin and some prescription opiates, such as oxycodone. Pharmacotherapy from physicians' offices makes buprenorphine treatment acceptable to some opiate-dependent patients who would not accept treatment in traditional opiate-maintenance clinics. For reasons not adequately understood, some patients find discontinuation of buprenorphine following long-term use difficult. This article reviews the pharmacology of buprenorphine, summarizes evidence supporting the safety and efficacy of buprenorphine and provides clinical guidelines for treatment. PMID:20648912

  8. Buprenorphine: clinical pharmacokinetics in the treatment of opioid dependence.

    PubMed

    Elkader, Alexander; Sproule, Beth

    2005-01-01

    Buprenorphine is a semi-synthetic opioid derived from thebaine, a naturally occurring alkaloid of the opium poppy, Papaver somniferum. The pharmacology of buprenorphine is unique in that it is a partial agonist at the opioid mu receptor. Buprenorphine undergoes extensive first-pass metabolism and therefore has very low oral bioavailability; however, its bioavailability sublingually is extensive enough to make this a feasible route of administration for the treatment of opioid dependence. The mean time to maximum plasma concentration following sublingual administration is variable, ranging from 40 minutes to 3.5 hours. Buprenorphine has a large volume of distribution and is highly protein bound (96%). It is extensively metabolised by N-dealkylation to norbuprenorphine primarily through cytochrome P450 (CYP) 3A4. The terminal elimination half-life of buprenorphine is long and there is considerable variation in reported values (mean values ranging from 3 to 44 hours). Most of a dose of buprenorphine is eliminated in the faeces, with approximately 10-30% excreted in urine. Naloxone has been added to a sublingual formulation of buprenorphine to reduce the abuse liability of the product. The presence of naloxone does not appear to influence the pharmacokinetics of buprenorphine. Buprenorphine crosses the placenta during pregnancy and also crosses into breast milk. Buprenorphine dosage does not need to be significantly adjusted in patients with renal impairment; however, since CYP3A activity may be decreased in patients with severe chronic liver disease, it is possible that the metabolism of buprenorphine will be altered in these patients. Although there is limited evidence in the literature to date, drugs that are known to inhibit or induce CYP3A4 have the potential to diminish or enhance buprenorphine N-dealkylation. It appears that the interaction between buprenorphine and benzodiazepines is more likely to be a pharmacodynamic (additive or synergistic) than a pharmacokinetic interaction. The relationship between buprenorphine plasma concentration and response in the treatment of opioid dependence has not been well studied. The pharmacokinetic and pharmacodynamic properties of buprenorphine allow it to be a feasible option for substitution therapy in the treatment of opioid dependence. PMID:15966752

  9. Factors affecting willingness to provide buprenorphine treatment

    PubMed Central

    Netherland, Julie; Botsko, Michael; Egan, James E.; Saxon, Andrew J.; Cunningham, Chinazo O.; Finkelstein, Ruth; Gourevitch, Mark N.; Renner, John A.; Sohler, Nancy; Sullivan, Lynn E.; Weiss, Linda; Fiellin, David A.

    2010-01-01

    Buprenorphine is an effective long-term opioid agonist treatment. As the only pharmacological treatment for opioid dependence readily available in office-based settings, buprenorphine may facilitate a historic shift in addiction treatment from treatment facilities to general medical practices. Although many patients have benefited from the availability of buprenorphine in the United States, almost half of current prescribers are addiction specialists suggesting that buprenorphine treatment has not yet fully penetrated general practice settings. We examined factors affecting willingness to offer buprenorphine treatment among physicians with different levels of prescribing experience. Based on their prescribing practices, physicians were classified as experienced, novice, or as a nonprescriber and asked to assess the extent to which a list of factors impacted their prescription of buprenorphine. Several factors affected willingness to prescribe buprenorphine for all physicians: staff training; access to counseling and alternate treatment; visit time; buprenorphine availability; and pain medications concerns. Compared with other physicians, experienced prescribers were less concerned about induction logistics and access to expert consultation, clinical guidelines, and mental health services. They were more concerned with reimbursement. These data provide important insight into physician concerns about buprenorphine and have implications for practice, education, and policy change that may effectively support widespread adoption of buprenorphine. PMID:18715741

  10. Buprenorphine

    PubMed Central

    Valadez-Meltzer, Adela

    2005-01-01

    Opioid dependence is a significant and growing problem in the United States. For nearly a century, federal regulations have made it illegal for psychiatrists and other physicians to pharmacologically manage this condition in an office-based setting using opioids. The passage of the Drug Addiction Treatment Act of 2000 has made it possible for all physicians to prescribe buprenorphine to patients in such a setting. Buprenorphine, a partial mu-opoid receptor agonist, has unique pharmacologic properties that distinguish it from methadone and other medications used in the treatment of opioid dependence. It has been shown to be as effective as methadone and is generally safe and well-tolerated. It is available in two sublingual formulations: Subutex, which contains only buprenorphine, and Suboxone, which also contains naloxone. Physicians who wish to prescribe either must obtain a special waiver from the federal government and are currently limited to prescribing it for 30 patients at a time. PMID:21124750

  11. Diversion of methadone and buprenorphine from opioid substitution treatment: patients who regularly sell or share their medication.

    PubMed

    Johnson, Björn; Richert, Torkel

    2015-01-01

    Diversion-the practice of patients selling or sharing their medication-is a much debated problem of opioid substitution treatment. Regular diversion by patients was studied at 11 opioid substitution treatment programs in the south of Sweden. Using quantitative and qualitative data, it was investigated whether those patients differ from other patients, their motives for and means of diversion, and who the recipients are. Regular diverters are a small, yet heterogeneous group. Continued illicit drug use, however, stands out as a common risk factor. Pecuniary need and a desire to help friends are other important motives. The client base mainly consists of people from the regular diverters' own drug milieus. PMID:25496247

  12. Community Treatment Programs Take Up Buprenorphine

    PubMed Central

    Casadonte, Paul P.; Kolodner, George F.; Horton, Terry; McMurphy, Suzanne M.

    2004-01-01

    Clinicians have been working out ways to incorporate buprenorphine into their treatment models. Representatives of three addiction treatment programs—a Veterans Affairs methadone clinic, a group of outpatient mental health centers, and a nationwide organization of therapeutic communities—talk about their plans and experiences. PMID:18552729

  13. Illicit buprenorphine use, interest in and access to buprenorphine treatment among syringe exchange participants

    PubMed Central

    Fox, Aaron D.; Chamberlain, Adam; Sohler, Nancy L.; Frost, Taeko; Cunningham, Chinazo O.

    2014-01-01

    Poor access to buprenorphine maintenance treatment (BMT) may contribute to illicit buprenorphine use. This study investigated illicit buprenorphine use and barriers to BMT among syringe exchange participants. Computer-based interviews conducted at a New York City harm reduction agency determined: prior buprenorphine use; barriers to BMT; and interest in BMT. Of 102 opioid users, 57 had used illicit buprenorphine and 32 had used prescribed buprenorphine. When illicit buprenorphine users were compared to non-users: barriers to BMT (“did not know where to get treatment”) were more common (64% vs. 36%, p < 0.01); mean levels of interest in BMT were greater (3.37 ± 1.29 vs. 2.80 ± 1.34, p = 0.03); and more participants reported themselves likely to initiate treatment (82% vs. 50%, p < 0.01). Illicit buprenorphine users were interested in BMT but did not know where to go for treatment. Addressing barriers to BMT could reduce illicit buprenorphine use. PMID:25205666

  14. Buprenorphine-containing treatments: place in the management of opioid addiction.

    PubMed

    Robinson, Susan E

    2006-01-01

    Although the synthetic opioid buprenorphine has been available clinically for almost 30 years, its use has only recently become much more widespread for the treatment of opioid addiction. The pharmacodynamic and pharmacokinetic profiles of buprenorphine make it unique in the armamentarium of drugs for the treatment of opioid addiction. Buprenorphine has partial mu-opioid receptor agonist activity and is a kappa-opioid receptor antagonist; hence, it can substitute for other micro-opioid receptor agonists, yet is less apt to produce overdose reactions or dysphoria. On the other hand, buprenorphine can block the effects of opioids such as heroin (diamorphine) and morphine, and can even precipitate withdrawal in individuals physically dependent upon these drugs. Buprenorphine has significant sublingual bioavailability and a long half-life, making administration on a less than daily basis possible. Furthermore, its discontinuation is associated with only a mild withdrawal syndrome. Clinical trials have demonstrated that sublingual buprenorphine is effective in both maintenance therapy and detoxification of individuals addicted to opioids. The introduction of a sublingual formulation combining naloxone with buprenorphine further reduces the risk of diversion to illicit intravenous use. Because of its relative safety and lower risk of illegal diversion, buprenorphine has been made available in several countries for treating opioid addiction in the private office setting, greatly enhancing treatment options for this condition. PMID:16953647

  15. Buprenorphine treatment for narcotic addiction: not without risks.

    PubMed

    Sansone, Randy A; Sansone, Lori A

    2015-01-01

    While most clinicians will never prescribe buprenorphine or combined buprenorphine/naloxone, familiarity with the risks of these pharmacological approaches to the treatment of narcotic addiction remains relevant. Overall, medication-assisted treatment has clearly resulted in meaningful gains for a number of individuals who are addicted to narcotics (i.e., opiates and opioids). However, a certain level of risk is inherent with these approaches. For example, both buprenorphine and buprenorphine/naloxone may be diverted and misused (e.g., intravenously injected, intranasally administered), particularly buprenorphine. Likewise, when illicitly injected, both can cause infectious complications as well as result in death from overdose. The risk of death with buprenorphine overdose appears to be heightened with the coadministration of either benzodiazepines or sedative/hypnotics. To conclude, as with all interventions in medicine, buprenorphine treatment for narcotic addiction has a clinically fluctuating risk/benefit equation that must be continually monitored. PMID:25973324

  16. Buprenorphine Treatment for Narcotic Addiction: Not Without Risks

    PubMed Central

    Sansone, Lori A.

    2015-01-01

    While most clinicians will never prescribe buprenorphine or combined buprenorphine/naloxone, familiarity with the risks of these pharmacological approaches to the treatment of narcotic addiction remains relevant. Overall, medication-assisted treatment has clearly resulted in meaningful gains for a number of individuals who are addicted to narcotics (i.e., opiates and opioids). However, a certain level of risk is inherent with these approaches. For example, both buprenorphine and buprenorphine/naloxone may be diverted and misused (e.g., intravenously injected, intranasally administered), particularly buprenorphine. Likewise, when illicitly injected, both can cause infectious complications as well as result in death from overdose. The risk of death with buprenorphine overdose appears to be heightened with the coadministration of either benzodiazepines or sedative/hypnotics. To conclude, as with all interventions in medicine, buprenorphine treatment for narcotic addiction has a clinically fluctuating risk/benefit equation that must be continually monitored. PMID:25973324

  17. Smoking cessation treatment among office-based buprenorphine treatment patients.

    PubMed

    Nahvi, Shadi; Blackstock, Oni; Sohler, Nancy L; Thompson, Devin; Cunningham, Chinazo O

    2014-08-01

    Opioid-dependent patients smoke at high rates, and office-based buprenorphine treatment provides an opportunity to offer cessation treatment. We examined tobacco use and smoking cessation treatment patterns among office-based buprenorphine treatment patients. We reviewed records of 319 patients treated with buprenorphine from 2005 to 2010. We examined smoking status, cessation medication prescriptions, and factors associated with receipt of cessation prescriptions. Mean age was 43.9 years; most were men (74.2%) and Hispanic (70.9%). At buprenorphine initiation, 21.9% had no documentation of smoking status, while 67.4% were current, 10% former, and 0.9% never smokers. Of current smokers, 16.8% received smoking cessation prescriptions. Patients retained (vs. not retained) in buprenorphine treatment were more likely to receive smoking cessation medications (26.3% vs. 11.2%, p<0.005). We observed a high tobacco use prevalence among buprenorphine patients, and limited provision of cessation treatment. This is a missed opportunity to impact the high tobacco use burden in opioid-dependent persons. PMID:24912863

  18. Smoking cessation treatment among office-based buprenorphine treatment patients

    PubMed Central

    Nahvi, Shadi; Blackstock, Oni; Sohler, Nancy L.; Thompson, Devin; Cunningham, Chinazo O.

    2014-01-01

    Opioid-dependent patients smoke at high rates, and office-based buprenorphine treatment provides an opportunity to offer cessation treatment. We examined tobacco use and smoking cessation treatment patterns among office-based buprenorphine treatment patients. We reviewed records of 319 patients treated with buprenorphine from 2005–2010. We examined smoking status, cessation medication prescriptions, and factors associated with receipt of cessation prescriptions. Mean age was 43.9 years; most were men (74.2%) and Hispanic (70.9%). At buprenorphine initiation, 21.9% had no documentation of smoking status, while 67.4% were current, 10% former, and 0.9% never smokers. Of current smokers, 16.8% received smoking cessation prescriptions. Patients retained (vs. not retained) in buprenorphine treatment were more likely to receive smoking cessation medications (26.3% vs. 11.2%, p<0.005). We observed a high tobacco use prevalence among buprenorphine patients, and limited provision of cessation treatment. This is a missed opportunity to impact the high tobacco use burden in opioid-dependent persons. PMID:24912863

  19. Buprenorphine maintenance: a new treatment for opioid dependence.

    PubMed

    Collins, Gregory B; McAllister, Mark S

    2007-07-01

    Buprenorphine (Subutex) is a safe and effective treatment for opioid dependence, and has very low potential for abuse, especially when it is combined with naloxone (Narcan) in a single sublingual tablet (Suboxone). New regulations allow physicians who are certified in buprenorphine therapy to offer it in their offices, a development that can substantially increase patient access to treatment. PMID:17682629

  20. Medication-assisted treatment for opioid addiction: methadone and buprenorphine

    PubMed Central

    Saxon, Andrew J.; Hser, Yih-Ing; Woody, George; Ling, Walter

    2013-01-01

    Among agents for treatment of opioid addiction, methadone is a full mu-opioid receptor agonist, whereas buprenorphine is a partial agonist. Both are long-acting. Buprenorphine has a superior safety profile. Methadone is formulated for oral administration and buprenorphine for sublingual administration. A subdermal buprenorphine implant with a 6-month duration of action is being considered for approval by the U.S. Food and Drug Administration. Both medications reduce mortality rates and improve other outcomes. Data from a recent randomized controlled comparison of both medications (N = 1269) show better treatment retention with methadone but reduced illicit opioid use early in treatment with buprenorphine. Human immunodeficiency virus (HIV) risk behaviors were measured using the Risk Behavior Survey at baseline, 12 weeks, and 24 weeks for study completers. In the 30 days prior to treatment entry, 14.4% of the completers randomized to treatment with buprenorphine (n = 340) and 14.1% of the completers randomized to methadone treatment (n = 391) shared needles. The percent sharing needles decreased to 2.4% for buprenorphine and 4.8 for methadone in the 30 days prior to Week 24 (p < 0.0001). In the 30 days prior to treatment entry, 6.8% of the completers randomized to buprenorphine and 8.2% of the completers randomized to methadone had multiple sexual partners, with only 5.2% and 5.1%, respectively, reporting multiple partners at Week 24 (p < 0.04). PMID:24436573

  1. Emerging adult age status predicts poor buprenorphine treatment retention

    PubMed Central

    Schuman-Olivier, Zev; Weiss, Roger D.; Hoeppner, Bettina B.; Borodovsky, Jacob; Albanese, Mark J.

    2014-01-01

    Emerging adults (18–25 years old) are often poorly retained in substance use disorder treatment. Office-based buprenorphine often enhances treatment retention among people with opioid dependence. In this study, we examined the records of a collaborative care buprenorphine treatment program to compare the treatment retention rates of emerging adults versus older adults. Subjects were 294 adults, 71 (24%) aged 18–25, followed in treatment with buprenorphine, nurse care management, and an intensive outpatient program followed by weekly psychosocial treatment. Compared to older adults, emerging adults remained in treatment at a significantly lower rate at 3 months (56% versus 78%) and 12 months (17% versus 45%), and were significantly more likely to test positive for illicit opioids, relapse, or drop out of treatment. Further research into factors associated with buprenorphine treatment retention among emerging adults is needed to improve treatment and long-term outcomes in this group. PMID:24953168

  2. Association between gene variants and response to buprenorphine maintenance treatment.

    PubMed

    Gerra, Gilberto; Somaini, Lorenzo; Leonardi, Claudio; Cortese, Elena; Maremmani, Icro; Manfredini, Matteo; Donnini, Claudia

    2014-01-30

    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. PMID:24274990

  3. Buprenorphine Implants for Treatment of Opioid Dependence: Randomized Comparison to Placebo and Sublingual Buprenorphine/Naloxone

    PubMed Central

    Rosenthal, Richard N.; Ling, Walter; Casadonte, Paul; Vocci, Frank; Bailey, Genie L.; Kampman, Kyle; Patkar, Ashwin; Chavoustie, Steven; Blasey, Christine; Sigmon, Stacey; Beebe, Katherine L.

    2015-01-01

    Aims To evaluate safety and efficacy of buprenorphine implants (BI) versus placebo implants (PI) for the treatment of opioid dependence. A secondary aim compared BI to open-label sublingual buprenorphine/naloxone tablets (BNX). Design Randomized, double-blind, placebo-controlled trial. Subjects received either 4 buprenorphine implants (80 mg/implant) (n=114), 4 placebo implants (n=54), or open-label BNX (12–16 mg/d) (n=119). Setting 20 addiction treatment centers. Participants Adult outpatients (ages 18 to 65) with DSM-IV-TR opioid dependence. Measurements The primary efficacy endpoint was the percent of urine samples negative for opioids collected from weeks 1 to 24, examined as a cumulative distribution function (CDF). Findings The BI CDF was significantly different from placebo (P<.0001). Mean (95% CI) proportions of urines negative for opioids were: BI: 31.2% (25.3, 37.1) and PI: 13.4% (8.3, 18.6). BI subjects had a higher study completion rate relative to placebo (64% vs. 26%, P<.0001), lower clinician-rated (P<.0001) and patient-rated (P<.0001) withdrawal, lower patient-ratings of craving (P<.0001), and better subjects’ (P=.031) and clinicians’ (P=.022) global ratings of improvement. BI also resulted in significantly lower cocaine use (P=.0016). Minor implant-site reactions were comparable in the buprenorphine (27.2% [31/114]) and placebo groups (25.9% [14/54]). BI were non-inferior to BNX on percent urines negative for opioids [mean (95% CI): 33.5 (27.3, 39.6); CI for the difference of proportions, (?10.7, 6.2)]. Conclusions Compared with placebo, buprenorphine implants result in significantly less frequent opioid use, and are non-inferior to sublingual buprenorphine/naloxone tablets. PMID:23919595

  4. I Heard About It From a Friend: Assessing Interest in Buprenorphine Treatment

    PubMed Central

    Fox, Aaron D.; Shah, Pooja A.; Sohler, Nancy L.; Lopez, Carolina M.; Starrels, Joanna L.; Cunningham, Chinazo O.

    2013-01-01

    Background In the United States, opioid abuse and dependence continue to be a growing problem, while treatment for opioid abuse and dependence remains fairly static. Buprenorphine treatment for opioid dependence is safe and effective but underutilized. Prior research has demonstrated low awareness and use of buprenorphine among marginalized groups. This study investigates syringe exchange participants’ awareness of, exposure to, and interest in buprenorphine treatment. Methods Syringe exchange participants were recruited from a mobile unit performing outreach to nine street-side sites in New York City. Computer-based interviews were conducted to determine: (1) opioid users’ awareness of, exposure to, and interest in buprenorphine treatment; and (2) the association between awareness or exposure and interest in buprenorphine treatment. Logistic regression models were used to examine the associations between awareness, direct exposure (i.e. having taken buprenorphine), or indirect exposure (i.e. knowing someone who had taken buprenorphine) and interest in buprenorphine treatment. Results Of 158 opioid users, 70% were aware of, 32% had direct exposure to, and 31% had indirect exposure to buprenorphine; 12% had been prescribed buprenorphine. Of 138 opioid users who had never been prescribed buprenorphine, 57% were interested in buprenorphine treatment. In multivariate models, indirect exposure was associated with interest in buprenorphine treatment (AOR = 2.65, 95% CI: 1.22 – 5.77), but awareness and direct exposure were not. Conclusions Syringe exchange participants were mostly aware of buprenorphine and interested in treatment, but few had actually been prescribed buprenorphine. Because indirect exposure to buprenorphine was associated with interest in treatment, future interventions could capitalize on indirect exposure, such as through peer mentorship, to address underutilization of buprenorphine treatment. PMID:24588297

  5. Safety and tolerability of the switch from buprenorphine to buprenorphine/naloxone in an Italian addiction treatment centre.

    PubMed

    Stimolo, Clementina; Favero, Valentina Del; Zecchinato, Giancarlo; Buson, Roberto; Cusin, Davide; Pellachin, Patrizia; Simonetto, Pamela

    2010-01-01

    Abuse and misuse of pharmacological therapies represent major challenges in the healthcare system, particularly in patients receiving long-acting opioid drugs for the treatment of heroin or opioid addiction. The partial mu-opioid receptor agonist buprenorphine is used to treat opioid dependence, but diversion and misuse may occur. The sublingual combination formulation of buprenorphine and the opioid receptor antagonist naloxone (buprenorphine/naxolone) is associated with a reduced abuse potential, and has been shown to have promising efficacy for the treatment of opioid dependence. This observational study assessed the safety and efficacy of sublingual buprenorphine/naloxone combination therapy in patients with opioid dependence after therapeutic switch from buprenorphine monotherapy. A total of 94 patients being treated with buprenorphine monotherapy (average dose 8 mg/day; mean duration of therapy 840 days) were switched to buprenorphine/naloxone combination therapy. Patients were asked to rate their level of satisfaction with buprenorphine/naloxone combination treatment with respect to the management of withdrawal symptoms, and urinary toxicology tests were carried out before and 14 days after switching to combination therapy. Within 3 months, 75/94 patients (80%) previously treated with buprenorphine monotherapy had switched to sublingual buprenorphine/naloxone combination treatment (average dose buprenorphine 8 mg). Among patients receiving combination treatment for >3 months, 83% were receiving medication either weekly or fortnightly, based on the results of toxicological testing. A reduction in positive urinary toxicology tests was observed in patients within two weeks after being switched to combination treatment (before switch: 28, 9 and 2 positive tests for heroin, cocaine and heroin + cocaine, respectively vs 11, 3 and 1 after switch) and a total of 64 patients of the 75 who switched to combination therapy (85%) were satisfied with the management of withdrawal symptoms during buprenorphine/naloxone treatment. Few adverse events were reported and no patients dropped out of treatment. This study shows that switching from buprenorphine monotherapy to sublingual buprenorphine/naloxone combination therapy is effective and well tolerated, and associated with good control of withdrawal symptoms in the majority of patients. In addition, combination therapy reduced illicit drug use (based on negative urinary toxicology texts) and allowed the time between clinic visits to be increased. PMID:20450243

  6. Buprenorphine Treatment for Hospitalized, Opioid-Dependent Patients

    PubMed Central

    Liebschutz, Jane M.; Crooks, Denise; Herman, Debra; Anderson, Bradley; Tsui, Judith; Meshesha, Lidia Z.; Dossabhoy, Shernaz; Stein, Michael

    2016-01-01

    IMPORTANCE Buprenorphine opioid agonist treatment (OAT) has established efficacy for treating opioid dependency among persons seeking addiction treatment. However, effectiveness for out-of-treatment, hospitalized patients is not known. OBJECTIVE To determine whether buprenorphine administration during medical hospitalization and linkage to office-based buprenorphine OAT after discharge increase entry into office-based OAT, increase sustained engagement in OAT, and decrease illicit opioid use at 6 months after hospitalization. DESIGN, SETTING, AND PARTICIPANTS From August 1, 2009, through October 31, 2012, a total of 663 hospitalized, opioid-dependent patients in a general medical hospital were identified. Of these, 369 did not meet eligibility criteria. A total of 145 eligible patients consented to participation in the randomized clinical trial. Of these, 139 completed the baseline interview and were assigned to the detoxification (n = 67) or linkage (n = 72) group. INTERVENTIONS Five-day buprenorphine detoxification protocol or buprenorphine induction, intrahospital dose stabilization, and postdischarge transition to maintenance buprenorphine OAT affiliated with the hospital’s primary care clinic (linkage). MAIN OUTCOMES AND MEASURES Entry and sustained engagement with buprenorphine OAT at 1, 3, and 6 months (medical record verified) and prior 30-day use of illicit opioids (self-report). RESULTS During follow-up, linkage participants were more likely to enter buprenorphine OAT than those in the detoxification group (52 [72.2%] vs 8 [11.9%], P < .001). At 6 months, 12 linkage participants (16.7%) and 2 detoxification participants (3.0%) were receiving buprenorphine OAT (P = .007). Compared with those in the detoxification group, participants randomized to the linkage group reported less illicit opioid use in the 30 days before the 6-month interview (incidence rate ratio, 0.60; 95% CI, 0.46-0.73; P < .01) in an intent-to-treat analysis. CONCLUSIONS AND RELEVANCE Compared with an inpatient detoxification protocol, initiation of and linkage to buprenorphine treatment is an effective means for engaging medically hospitalized patients who are not seeking addiction treatment and reduces illicit opioid use 6 months after hospitalization. However, maintaining engagement in treatment remains a challenge. PMID:25090173

  7. A Retrospective Evaluation of Inpatient Transfer from High-Dose Methadone to Buprenorphine Substitution Therapy.

    PubMed

    Oretti, Rossana

    2015-10-01

    The product license of buprenorphine/naloxone for opioid substitution therapy indicates reducing methadone concentrations to 30 mg or less per day for a minimum of 1 week before transferring patients to buprenorphine and no sooner than 24 hours after the last methadone dose, because of the risk of precipitated withdrawal and a corresponding high risk of relapse to opioid use. There are few studies describing high-dose methadone transfers. This retrospective case review assessed the feasibility of transferring patients on methadone doses above 30 mg/day to buprenorphine or buprenorphine/naloxone in the inpatient setting. Six of seven patients on 60-120 mg/day of methadone successfully completed the transfer, and four cases tested negative for opiates at long-term follow-up (6-15 months). This suggests that methadone transfer to buprenorphine can be performed rapidly without the need to taper methadone doses in patients indicated for a therapeutic switch. This small study is hypothesis-generating; larger, well-designed trials are needed to define a protocol that can be used routinely to improve and widen transfers to buprenorphine when indicated. PMID:26048187

  8. Buprenorphine and methadone in the treatment of opioid dependence: methods and design of the COBRA study.

    PubMed

    Wittchen, Hans-Ulrich; Apelt, Sabine M; Bühringer, Gerhard; Gastpar, Markus; Backmund, Markus; Gölz, Jörg; Kraus, Michael R; Tretter, Felix; Klotsche, Jens; Siegert, Jens; Pittrow, David; Soyka, Michael

    2005-01-01

    Buprenorphine and methadone are the two established substitution drugs licensed in many countries for the treatment of opioid dependence. Little is known, however, about how these two drugs are applied and how they work in clinical practice. In this paper we present the aims, methods, design and sampling issues of a collaborative multi-stage epidemiological study (COBRA) to address these issues. Based on a nationally representative sample of substitution physicians, the study is designed as an observational, naturalistic study, consisting of three major parts. The first part was a national survey of substitution doctors (prestudy, n = 379 doctors). The second part was a cross-sectional study (n = 223 doctors), which consisted of a target-week assessment of 2,694 consecutive patients to determine (a) the severity and problem profiles and treatment targets; (b) the choice and dosage scheme of the substitution drug; (c) past and current interventions, including treatment of comorbid hepatitis C; and (d) cross-sectional differences between the two drugs with regard to comorbidity, clinical course, acceptance/compliance and social integration. The third part consists of a prospective-longitudinal cohort study of 48 methadone-treated and 48 buprenorphine-treated patients. The cohort is followed up over a period of 12 months to investigate whether course and outcome of the patients differ by type or treatment received in terms of clinical, psychosocial, pharmaco-economic and other related measures. The response rate among substitution doctors was 57.1%; that among eligible patients was 71.7%. Comparisons with the federal registers reveal that the final samples of doctors and patients may be considered nationally representative with regard to regional distribution, training, type of setting as well as the frequency of patients treated with buprenorphine or methadone. The COBRA study provides a unique comprehensive database, informing about the natural allocation and intervention processes in routine care and about the course and outcome of patients treated with buprenorphine or methadone. PMID:16097397

  9. Buprenorphine.

    PubMed

    Mazurek, Jaroslaw; Hoffmann, Marcel; Fernandez Casares, Anna; Cox, Phillip D; Minardi, Mathew D

    2014-06-01

    In the crystal structure of a semi-synthetic opioid drug buprenorphine, C29H41NO4 {systematic name: (2S)-2-[(5R,6R,7R,14S)-9?-cyclo-propyl-methyl-3-hy-droxy-6-meth-oxy-4,5-ep-oxy-6,14-ethano-morphinan-7-yl]-3,3-di-methyl-butan-2-ol}, the cyclo-propyl-methyl group is disordered over two sites with an occupancy factor of 0.611?(3) for the major component. One of the hy-droxy groups is involved in intra-molecular O-H?O hydrogen bond. The other hy-droxy group acts as a proton donor in an inter-molecular O-H?O inter-action that connects mol-ecules into a zigzag chain along the b axis. PMID:24940223

  10. Buprenorphine

    PubMed Central

    Mazurek, Jaroslaw; Hoffmann, Marcel; Fernandez Casares, Anna; Cox, Phillip D.; Minardi, Mathew D.

    2014-01-01

    In the crystal structure of a semi-synthetic opioid drug buprenorphine, C29H41NO4 {systematic name: (2S)-2-[(5R,6R,7R,14S)-9?-cyclo­propyl­methyl-3-hy­droxy-6-meth­oxy-4,5-ep­oxy-6,14-ethano­morphinan-7-yl]-3,3-di­methyl­butan-2-ol}, the cyclo­propyl­methyl group is disordered over two sites with an occupancy factor of 0.611?(3) for the major component. One of the hy­droxy groups is involved in intra­molecular O—H?O hydrogen bond. The other hy­droxy group acts as a proton donor in an inter­molecular O—H?O inter­action that connects mol­ecules into a zigzag chain along the b axis. PMID:24940223

  11. Buprenorphine-based regimens and methadone for the medical management of opioid dependence: selecting the appropriate drug for treatment.

    PubMed

    Maremmani, Icro; Gerra, Gilberto

    2010-01-01

    Maintenance therapy with methadone or buprenorphine-based regimens reduces opioid dependence and associated harms. The perception that methadone is more effective than buprenorphine for maintenance treatment has been based on low buprenorphine doses and excessively slow induction regimens used in early buprenorphine trials. Subsequent studies show that the efficacy of buprenorphine sublingual tablet (Subutex®) or buprenorphine/naloxone sublingual tablet (Suboxone®) is equivalent to that of methadone when sufficient buprenorphine doses, rapid induction, and flexible dosing are used. Although methadone remains an essential maintenance therapy option, buprenorphine-based regimens increase access to care and provide safer, more appropriate treatment than methadone for some patients. PMID:20958853

  12. Buprenorphine: a (relatively) new treatment for opioid dependence.

    PubMed

    Welsh, Christopher; Valadez-Meltzer, Adela

    2005-12-01

    Opioid dependence is a significant and growing problem in the United States. For nearly a century, federal regulations have made it illegal for psychiatrists and other physicians to pharmacologically manage this condition in an office-based setting using opioids. The passage of the Drug Addiction Treatment Act of 2000 has made it possible for all physicians to prescribe buprenorphine to patients in such a setting. Buprenorphine, a partial mu-opoid receptor agonist, has unique pharmacologic properties that distinguish it from methadone and other medications used in the treatment of opioid dependence. It has been shown to be as effective as methadone and is generally safe and well-tolerated. It is available in two sublingual formulations: Subutex, which contains only buprenorphine, and Suboxone, which also contains naloxone. Physicians who wish to prescribe either must obtain a special waiver from the federal government and are currently limited to prescribing it for 30 patients at a time. PMID:21124750

  13. A Comparison of Buprenorphine + Naloxone to Buprenorphine and Methadone in the Treatment of Opioid Dependence during Pregnancy: Maternal and Neonatal Outcomes

    PubMed Central

    Lund, Ingunn O.; Fischer, Gabriele; Welle-Strand, Gabrielle K.; O’Grady, Kevin E.; Debelak, Kimber; Morrone, William R.; Jones, Hendrée E.

    2013-01-01

    Given that buprenorphine + naloxone is prescribed for opioid-dependent pregnant women, it is important to examine the extent to which it differs from buprenorphine alone, methadone, or methadone-assisted withdrawal on neonatal and maternal outcomes. Summary statistics on maternal and neonatal outcomes were collected from 7 previously published studies examining treatment for opioid-dependent pregnant women that represented a range of research methodologies. Outcomes from these studies were compared to the same outcomes for 10 women treated with the combined buprenorphine + naloxone product. There were no significant differences in maternal outcomes for buprenorphine + naloxone compared to buprenorphine, methadone, or methadone-assisted withdrawal. Preliminary findings suggest no significant adverse maternal or neonatal outcomes related to the use of buprenorphine + naloxone for the treatment of opioid dependence during pregnancy. However, further research should examine possible differences between buprenorphine + naloxone and buprenorphine alone or methadone in fetal physical development. PMID:23531704

  14. Naltrexone and buprenorphine combination in the treatment of opioid dependence.

    PubMed

    Gerra, G; Fantoma, A; Zaimovic, A

    2006-11-01

    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 heroin exposure, probably underlying dysphoric and psychosomatic symptoms during naltrexone treatment, seems to be counteracted, at least in part, by buprenorphine. The combination of buprenorphine and naltrexone may significantly improve the outcome of opioid antagonists treatment in terms of retention, negative urinalyses, and reduced dysphoria, mood symptoms and craving. PMID:16401652

  15. Buprenorphine Prescribing Availability in a Sample of Ohio Specialty Treatment Organizations

    PubMed Central

    Molfenter, Todd; Sherbeck, Carol; Zehner, Mark; Starr, Sandy

    2015-01-01

    Objective Buprenorphine, a medication for treating opioid dependence, is underutilized in specialty addiction treatment organizations. Only physicians who have obtained a buprenorphine prescribing license or “waiver” may administer this medication. A limited number of physicians are pursuing this waiver, and a concern in the substance use disorder treatment field is that the shortage of prescribers could be contributing to the low use of buprenorphine at specialty addiction treatment centers. The objective of this study is to assess Ohio specialty treatment organizations’ access to buprenorphine prescribers and the barriers they encounter when seeking new physician prescribing capacity. Methods Forty-one Ohio specialty addiction treatment organizations were invited to complete a survey of their buprenorphine practices and availability of buprenorphine prescribers during August–October 2014. Data was collected on pharmacotherapies used in the treatment of opioid dependence, arrangements treatment organizations have with prescribing physicians, buprenorphine prescribing capacity, and barriers encountered in recruiting new physician prescribers. Results Thirty-seven treatment organizations responded, for a response rate of 90.2%. Seventy-eight percent (n=29) of the sample provided buprenorphine therapy. Of those treatment organizations, 48.3% (n=14) reported insufficient prescribing capacity. Of those, 50% (n=7) indicated they had to turn patients away from buprenorphine therapy due to limited physician prescribing capacity. Conclusion The study suggests that buprenorphine use is constrained by limited physician prescribing capacity, to the degree that 24.1% of the organizations surveyed using buprenorphine therapy had to turn patients away. Potential remedies include encouraging more specialty treatment organizations to have physicians on staff, removing the Drug Addiction Treatment Act (DATA 2000) cap that limits physician buprenorphine caseloads at 100 patients (after year 1), and developing strategies to recruit physicians into addiction treatment practice. Additional research is needed to increase the knowledge of physician prescribing capacity as a barrier to buprenorphine use, how to overcome these barriers, and to understand the extent physician capacity shortages are affecting buprenorphine use. PMID:26380328

  16. Comparison of Behavioral Treatment Conditions in Buprenorphine Maintenance

    PubMed Central

    Ling, Walter; Hillhouse, Maureen; Ang, Alfonso; Jenkins, Jessica; Fahey, Jacqueline

    2013-01-01

    Background and aims The Controlled Substances Act requires physicians in the United States to provide or refer to behavioral treatment when treating opioid-dependent individuals with buprenorphine; however no research has examined the combination of buprenorphine with different types of behavioral treatments. This randomized controlled trial compared the effectiveness of 4 behavioral treatment conditions provided with buprenorphine and medical management (MM) for the treatment of opioid dependence. Design After a 2-week buprenorphine induction/stabilization phase, participants were randomized to 1 of 4 behavioral treatment conditions provided for 16 weeks: Cognitive Behavioral Therapy (CBT=53); Contingency Management (CM=49); both CBT and CM (CBT+CM=49); and no additional behavioral treatment (NT=51). Setting Study activities occurred at an outpatient clinical research center in Los Angeles, California, USA. Participants Included were 202 male and female opioid-dependent participants. Measurements Primary outcome was opioid use, measured as a proportion of opioid-negative urine results over the number of tests possible. Secondary outcomes include retention, withdrawal symptoms, craving, other drug use, and adverse events. Findings No group differences in opioid use were found for the behavioral treatment phase (Chi-square=1.25, p=0.75), for a second medication-only treatment phase, or at weeks 40 and 52 follow-ups. Analyses revealed no differences across groups for any secondary outcome. Conclusion There remains no clear evidence that cognitive behavioural therapy and contingency management reduce opiate use when added to buprenorphine and medical management in opiates users seeking treatment. PMID:23734858

  17. Patterns of non-compliant buprenorphine, levomethadone, and methadone use among opioid dependent persons in treatment

    PubMed Central

    2014-01-01

    Background The non-compliant use of opioid substitution treatment (OST) medicines is widespread and well-documented. However, less is known about characteristics of non-compliant OST medicine use and the factors that predict it. The two main goals of this study are to compare characteristics of non-compliant levomethadone, methadone, and buprenorphine use and to explore factors that may differentially predict it among opioid dependent persons in treatment. Methods Data from 595 opioid dependent patients with non-compliant OST medicine use were analyzed. Characteristics of use between substances were compared using chi-squared tests and predictive factors were explored through multinomial logistic regressions. Results Non-compliant levomethadone and methadone use was characterized by more frequent parallel consumption of other psychoactive substances and intravenous use, whereas buprenorphine was more often procured without a prescription. Regarding predictive factors, methadone was perceived to relieve withdrawal symptoms better than buprenorphine and levomethadone was perceived as being better at modulating the effects of other substances and worst at enhancing mood. Conclusions Patterns of non-compliant use differ according to OST medicine. These patterns are considered with the reduction of non-compliant use and the improvement of treatment in mind. PMID:24885218

  18. Spotlight on buprenorphine/naloxone in the treatment of opioid dependence.

    PubMed

    Orman, Jennifer S; Keating, Gillian M

    2009-10-01

    Buprenorphine/naloxone (Suboxone) comprises the partial micro-opioid receptor agonist buprenorphine in combination with the opioid antagonist naloxone in a 4 : 1 ratio. When buprenorphine/naloxone is taken sublingually as prescribed, the naloxone exerts no clinically significant effect, leaving the opioid agonist effects of buprenorphine to predominate. However, when buprenorphine/naloxone is parenterally administered in patients physically dependent on full agonist opioids, the opioid antagonism of naloxone causes withdrawal effects, thus reducing the abuse potential of the drug combination. Buprenorphine/naloxone is an effective maintenance therapy for opioid dependence and has generally similar efficacy to methadone, although more data are needed. Less frequent dispensing of buprenorphine/naloxone (e.g. thrice weekly) does not appear to compromise efficacy and can improve patient satisfaction. Buprenorphine/naloxone is more effective than clonidine as a medically supervised withdrawal therapy. Moreover, buprenorphine/naloxone is a generally well tolerated medically supervised withdrawal and maintenance treatment. Thus, sublingual buprenorphine/naloxone is a valuable pharmacotherapy for the treatment of opioid dependence. PMID:19739698

  19. Buprenorphine/naloxone: a review of its use in the treatment of opioid dependence.

    PubMed

    Orman, Jennifer S; Keating, Gillian M

    2009-01-01

    Buprenorphine/naloxone (Suboxone) comprises the partial mu-opioid receptor agonist buprenorphine in combination with the opioid antagonist naloxone in a 4 : 1 ratio. When buprenorphine/naloxone is taken sublingually as prescribed, the naloxone exerts no clinically significant effect, leaving the opioid agonist effects of buprenorphine to predominate. However, when buprenorphine/naloxone is parenterally administered in patients physically dependent on full agonist opioids, the opioid antagonism of naloxone causes withdrawal effects, thus reducing the abuse potential of the drug combination. Buprenorphine/naloxone is an effective maintenance therapy for opioid dependence and has generally similar efficacy to methadone, although more data are needed. Less frequent dispensing of buprenorphine/naloxone (e.g. thrice weekly) does not appear to compromise efficacy and can improve patient satisfaction. Buprenorphine/naloxone is more effective than clonidine as a medically-supervised withdrawal therapy. Moreover, buprenorphine/naloxone is a generally well tolerated medically-supervised withdrawal and maintenance treatment. Thus, sublingual buprenorphine/naloxone is a valuable pharmacotherapy for the treatment of opioid dependence. PMID:19368419

  20. Bridging waitlist delays with interim buprenorphine treatment: initial feasibility.

    PubMed

    Sigmon, Stacey C; C Meyer, Andrew; Hruska, Bryce; Ochalek, Taylor; Rose, Gail; Badger, Gary J; Brooklyn, John R; Heil, Sarah H; Higgins, Stephen T; Moore, Brent A; Schwartz, Robert P

    2015-12-01

    Despite the effectiveness of agonist maintenance for opioid dependence, individuals can remain on waitlists for months, during which they are at significant risk for morbidity and mortality. Interim dosing, consisting of daily medication without counseling, can reduce these risks. In this pilot study, we examined the initial feasibility of a novel technology-assisted interim buprenorphine treatment for waitlisted opioid-dependent adults. Following buprenorphine induction during Week 1, participants (n=10) visited the clinic at Weeks 2, 4, 6, 8, 10 and 12 to ingest their medication under staff observation, provide a urine specimen and receive their remaining doses via a computerized Med-O-Wheel Secure device. They also received daily monitoring via an Interactive Voice Response (IVR) platform, as well as random call-backs for urinalysis and medication adherence checks. The primary outcome was percent of participants negative for illicit opioids at each 2-week visit, with secondary outcomes of past-month drug use, adherence and acceptability. Participants achieved high levels of illicit opioid abstinence, with 90% abstinent at the Week 2 and 4 visits and 60% at Week 12. Significant reductions were observed in self-reported past-month illicit opioid use (p<.001), opioid withdrawal (p<.001), opioid craving (p<.001) and ASI Drug composite score (p=.008). Finally, adherence with buprenorphine administration (99%), daily IVR calls (97%) and random call-backs (82%) was high. Interim buprenorphine treatment shows promise for reducing patient and societal risks during delays to conventional treatment. A larger-scale, randomized clinical trial is underway to more rigorously examine the efficacy of this treatment approach. PMID:26256469

  1. Parenting and Concerns of Pregnant Women in Buprenorphine Treatment

    PubMed Central

    Rizzo, Rachel A; Neumann, Anne M; King, Stella OC; Hoey, Robert F; Finnell, Deborah S; Blondell, Richard D

    2014-01-01

    Purpose Opioid-dependent pregnant women are characterized by drug use during pregnancy and deficits in knowledge of newborn care and feeding, and of child development. We assessed parenting skills and concerns among pregnant women in buprenorphine treatment for prescription opioid-dependence. Study Design and Methods We interviewed 32 pregnant women who received buprenorphine treatment for prescription opioid dependence in a primary care setting and administered questionnaires, including the Adult-Adolescent Parenting Inventory version 2 (AAPI-2) and Childhood Experience of Care and Abuse Questionnaire. Results AAPI-2 scores revealed medium risk of abuse for all five scales: inappropriate expectations of the child, low level of empathy, strong belief in corporal punishment, reversal of parent-child roles, and oppression of children’s power and independence. Primary concerns of participants were neonatal abstinence syndrome (NAS) and their child’s health. Pregnant women who received buprenorphine for treatment of prescription opioid dependence showed a lack of appropriate parenting skills, but did not express concern about their ability to parent. Clinical Implications Our findings suggest need for nurses to assist prescription opioid-dependent pregnant women in acquiring additional parenting skills, to refer for educational parenting intervention, and to educate patients about NAS. PMID:25137081

  2. Sublingual Buprenorphine for Treatment of the Neonatal Abstinence Syndrome: A Randomized Trial

    PubMed Central

    Kraft, Walter K.; Gibson, Eric; Dysart, Kevin; Damle, Vidula S.; LaRusso, Jennifer L.; Greenspan, Jay S.; Moody, David E.; Kaltenbach, Karol; Ehrlich, Michelle E.

    2008-01-01

    Objective In utero exposure to drugs of abuse can lead to the Neonatal Abstinence Syndrome (NAS), a condition that is associated with prolonged hospitalization. Buprenorphine is a partial mu opioid agonist used for treatment of adult detoxification and maintenance, but has never been administered to neonates with opioid abstinence. The primary objective of this study was to demonstrate the feasibility and to the extent possible in this sized study, the safety of sublingual buprenorphine in the treatment of NAS. Secondary goals were to evaluate efficacy relative to standard therapy and to characterize buprenorphine pharmacokinetics when sublingually administered. Methods We conducted a randomized, open-label, active control study of sublingual buprenorphine for the treatment of opiate withdrawal. Thirteen term infants were allocated to sublingual buprenorphine 13.2–39 mcg/kg/day administered in three divided doses and thirteen to standard of care oral neonatal opium solution (NOS). Dose decisions were made using a modified Finnegan scoring system. Results Sublingual buprenorphine was largely effective in controlling NAS. Greater than 98% of plasma concentrations ranged from undetectable to approximately 0.60 ng/ml, which is less than needed to control abstinence symptoms in adults. The ratio of buprenorphine to norbuprenorphine was larger than that seen in adults, suggesting a relative impairment of N-dealkylation. Three infants receiving buprenorphine and one infant receiving standard of care reached protocol-specified maximum doses and required adjuvant therapy with phenobarbital. The mean length of treatment for the NOS group was 32 compared to 22 days for the buprenorphine group. The mean length of stay for the NOS group was 38 days compared to 27 days for the buprenorphine group. Treatment with buprenorphine was well tolerated. Conclusions Buprenorphine administered via the sublingual route is feasible and apparently safe, and may represent a novel treatment for NAS. PMID:18694901

  3. Optimizing psychosocial support during office-based buprenorphine treatment in primary care: patients’ experiences and preferences

    PubMed Central

    Fox, Aaron D.; Masyukova, Mariya; Cunningham, Chinazo O.

    2015-01-01

    Background Buprenorphine maintenance treatment is effective and has been successfully integrated into HIV and primary care settings. However, one key barrier to providers prescribing buprenorphine is their perception that they are unable to provide adequate counseling or psychosocial support to patients with opioid addiction. This qualitative study investigated supportive elements of office-based buprenorphine treatment that patients perceived to be most valuable. Methods We conducted five focus groups with 33 buprenorphine treatment-experienced participants. Focus groups were audio-recorded and transcribed. Iterative readings of transcripts and grounded theory analysis revealed common themes. Results Overall, participants perceived that buprenorphine treatment helped them to achieve their treatment goals and valued the flexibility, accessibility, and privacy of treatment. Participants identified interpersonal and structural elements of buprenorphine treatment that provided psychosocial support. Participants desired good physician-patient relationships, but also valued care delivery models that were patient-centered, created a safe place for self-disclosure, and utilized coordinated team-based care. Conclusions Participants derived psychosocial support from their prescribing physician, but were also open to collaborative or team-based models of care, as long as they were voluntary and confidential. Buprenorphine prescribing physicians without access to referral options for psychosocial counseling could focus on maintaining non-judgmental attitudes and shared decision making during patient encounters. Adding structure and psychosocial support to buprenorphine treatment through coordinated team-based care also seems to have great promise. PMID:26566712

  4. Bringing Buprenorphine-Naloxone Detoxification to Community Treatment Providers: The NIDA Clinical Trials Network Field Experience

    PubMed Central

    Amass, Leslie; Ling, Walter; Freese, Thomas E.; Reiber, Chris; Annon, Jeffrey J.; Cohen, Allan J.; M.F.T.; McCarty, Dennis; Reid, Malcolm S.; Brown, Lawrence S.; Clark, Cynthia; Ziedonis, Douglas M.; Krejci, Jonathan; Stine, Susan; Winhusen, Theresa; Brigham, Greg; Babcock, Dean; L.C.S.W.; Muir, Joan A.; Buchan, Betty J.; Horton, Terry

    2005-01-01

    In October 2002, the U.S. Food and Drug Administration approved buprenorphine-naloxone (Suboxone®) sublingual tablets as an opioid dependence treatment available for use outside traditionally licensed opioid treatment programs. The NIDA Center for Clinical Trials Network (CTN) sponsored two clinical trials assessing buprenorphine-naloxone for short-term opioid detoxification. These trials provided an unprecedented field test of its use in twelve diverse community-based treatment programs. Opioid-dependent men and women were randomized to a thirteen-day buprenorphine-naloxone taper regimen for short-term opioid detoxification. The 234 buprenorphine-naloxone patients averaged 37 years old and used mostly intravenous heroin. Direct and rapid induction onto buprenorphine-naloxone was safe and well tolerated. Most patients (83%) received 8 mg buprenorphine-2 mg naloxone on the first day and 90% successfully completed induction and reached a target dose of 16mg buprenorphine-4 mg naloxone in three days. Medication compliance and treatment engagement was high. An average of 81% of available doses was ingested, and 68% of patients completed the detoxification. Most (80.3%) patients received some ancillary medications with an average of 2.3 withdrawal symptoms treated. The safety profile of buprenorphine-naloxone was excellent. Of eighteen serious adverse events reported, only one was possibly related to buprenorphine-naloxone. All providers successfully integrated buprenorphine-naloxone into their existing treatment milieus. Overall, data from the CTN field experience suggest that buprenorphine-naloxone is practical and safe for use in diverse community treatment settings, including those with minimal experience providing opioid-based pharmacotherapy and/or medical detoxification for opioid dependence. PMID:15204675

  5. Adherence to Buprenorphine Maintenance Treatment in Opioid Dependence Syndrome: A Case Control Study

    PubMed Central

    Bandawar, Mrunal; Kandasamy, Arun; Chand, Prabhat; Murthy, Pratima; Benegal, Vivek

    2015-01-01

    Background: Opioid Use disorders are emerging as a serious public health concern in India. Opioid substitution treatment is one of the emerging forms of treatment in this population which needs more evidence to increase its availability and address prejudices towards the same. Materials and Methods: This is a case control study with retrospective design reviewing the charts of patients with opioid dependence syndrome registered between January 2005 to December 2012. Adherence to treatment was the outcome variable assessed in this study. Results: The odds of the Buprenorphine Maintenance Treatment (BMT) group remaining in treatment is 4.5 (P < 0.005) times more than Naltrexone Maintenance Treatment (NMT) group and 7 times (P < 0.001) more than Psychosocial intervention (PST) alone group. Discussion: We believe that these study findings will help in reducing the prejudice towards BMT and encourage further research in this field. Conclusion: BMT has a better adherence rate than other treatments in opioid use disorders. PMID:26664083

  6. Prior Experience with Non-Prescribed Buprenorphine: Role in Treatment Entry and Retention.

    PubMed

    Monico, Laura B; Mitchell, Shannon Gwin; Gryczynski, Jan; Schwartz, Robert P; O'Grady, Kevin E; Olsen, Yngvild K; Jaffe, Jerome H

    2015-10-01

    Buprenorphine availability continues to expand as an effective treatment for opioid dependence, but increases in availability have also been accompanied by increases in non-prescribed use of the medication. Utilizing data from a randomized clinical trial, this mixed-method study examines associations between use of non-prescribed buprenorphine and subsequent treatment entry and retention. Quantitative analyses (N = 300 African American buprenorphine patients) found that patients with prior use of non-prescribed buprenorphine had significantly higher odds of remaining in treatment through 6 months than patients who were naïve to the medication upon treatment entry. Qualitative data, collected from a subsample of participants (n = 20), identified three thematic explanations for this phenomenon: 1) perceived effectiveness of the medication; 2) cost of obtaining prescription buprenorphine compared to purchasing non-prescribed medication; and 3) convenience of obtaining the medication via daily-dosing or by prescription compared to non-prescribed buprenorphine. These findings suggest a dynamic relationship between non-prescribed buprenorphine use and treatment that indicates potential directions for future research into positive and negative consequences of buprenorphine diversion. PMID:25980599

  7. Impact of research network participation on the adoption of buprenorphine for substance abuse treatment.

    PubMed

    Rieckmann, Traci R; Abraham, Amanda J; Kovas, Anne E; McFarland, Bentson H; Roman, Paul M

    2014-05-01

    There is a growing body of research supporting the use of buprenorphine and other medication assisted treatments (MATs) for the rapidly accelerating opioid epidemic in the United States. Despite numerous advantages of buprenorphine (accessible in primary care, no daily dosing required, minimal stigma), implementation has been slow. As the field progresses, there is a need to understand the impact of participation in practitioner-scientist research networks on acceptance and uptake of buprenorphine. This paper examines the impact of research network participation on counselor attitudes toward buprenorphine addressing both counselor-level characteristics and program-level variables using hierarchical linear modeling (HLM) to account for nesting of counselors within treatment programs. Using data from the National Treatment Center Study, this project compares privately funded treatment programs (N=345) versus programs affiliated with the National Institute on Drug Abuse Clinical Trials Network (CTN) (N=198). Models included 922 counselors in 172 CTN programs and 1203 counselors in 251 private programs. Results of two-level HLM logistic (Bernoulli) models revealed that counselors with higher levels of education, larger caseloads, more buprenorphine-specific training, and less preference for 12-step treatment models were more likely to perceive buprenorphine as acceptable and effective. Furthermore, buprenorphine was 50% more likely to be perceived as effective among counselors working in CTN-affiliated programs as compared to private programs. This study suggests that research network affiliation positively impacts counselors' acceptance and perceptions of buprenorphine. Thus, research network participation can be utilized as a means to promote positive attitudes toward the implementation of innovations including medication assisted treatment. PMID:24594902

  8. Harm reduction agencies as a potential site for buprenorphine treatment

    PubMed Central

    Fox, Aaron D.; Chamberlain, Adam; Frost, Taeko; Cunningham, Chinazo O.

    2015-01-01

    Introduction Harm reduction agencies complement addiction treatment by providing diverse services that improve the health of people who use drugs. Buprenorphine maintenance treatment (BMT) is an effective opioid addiction treatment that may be provided from flexible settings, potentially including harm reduction agencies. This study investigated attitudes toward different potential sites for BMT (harm reduction agencies, general medical clinics, and drug treatment programs) among harm reduction clients. Methods Using computer-based interviews, participants indicated preferred potential site for BMT (harm reduction agency, drug treatment program, or general medical clinic), interest in BMT by potential site, motivation for treatment, and barriers to BMT. We used multivariable logistic regression to determine factors associated with harm reduction agency preference. Results Of 102 opioid users, the most preferred potential site for BMT was a harm reduction agency (51%), while fewer preferred general medical clinics (13%), drug treatment programs (12%) or were not interested in BMT (25%). In multivariable analysis, experiencing ? 1 barrier to BMT was strongly associated with preferring harm reduction agencies (aOR = 3.39, 95% CI: 1.00 – 11.43). Conclusion The potential to initiate BMT at harm reduction agencies is highly favorable among harm reduction clients, especially among those experiencing barriers to BMT. Offering BMT at harm reduction agencies could improve access to treatment, but studies are needed to determine safety and efficacy of this approach. PMID:25837290

  9. Adoption of Evidence-Based Clinical Innovations: The Case of Buprenorphine Use by Opioid Treatment Programs

    PubMed Central

    Andrews, Christina M.; D’Aunno, Thomas A.; Pollack, Harold A.; Friedmann, Peter D.

    2015-01-01

    This article examines changes from 2005 to 2011 in the use of an evidence-based clinical innovation, buprenorphine use, among a nationally representative sample of opioid treatment programs and identifies characteristics associated with its adoption. We apply a model of the adoption of clinical innovations that focuses on the work needs and characteristics of staff; organizations’ technical and social support for the innovation; local market dynamics and competition; and state policies governing the innovation. Results indicate that buprenorphine use increased 24% for detoxification and 47% for maintenance therapy between 2005 and 2011. Buprenorphine use was positively related to reliance on private insurance and availability of state subsidies to cover its cost and inversely related to the percentage of clients who injected opiates, county size, and local availability of methadone. The results indicate that financial incentives and market factors play important roles in opioid treatment programs’ decisions to adopt evidence-based clinical innovations such as buprenorphine use. PMID:24051897

  10. Adoption of evidence-based clinical innovations: the case of buprenorphine use by opioid treatment programs.

    PubMed

    Andrews, Christina M; D'Aunno, Thomas A; Pollack, Harold A; Friedmann, Peter D

    2014-02-01

    This article examines changes from 2005 to 2011 in the use of an evidence-based clinical innovation, buprenorphine use, among a nationally representative sample of opioid treatment programs and identifies characteristics associated with its adoption. We apply a model of the adoption of clinical innovations that focuses on the work needs and characteristics of staff; organizations' technical and social support for the innovation; local market dynamics and competition; and state policies governing the innovation. Results indicate that buprenorphine use increased 24% for detoxification and 47% for maintenance therapy between 2005 and 2011. Buprenorphine use was positively related to reliance on private insurance and availability of state subsidies to cover its cost and inversely related to the percentage of clients who injected opiates, county size, and local availability of methadone. The results indicate that financial incentives and market factors play important roles in opioid treatment programs' decisions to adopt evidence-based clinical innovations such as buprenorphine use. PMID:24051897

  11. Methadone versus buprenorphine for the treatment of opioid abuse in pregnancy: science and stigma.

    PubMed

    Holbrook, Amber M

    2015-01-01

    The past decade has seen an increase in rates of opioid abuse during pregnancy. This clinical challenge has been met with debate regarding whether or not illicit and prescription opioid-dependent individuals require different treatment approaches; whether detoxification is preferable to maintenance; and the efficacy of methadone versus buprenorphine as treatment options during pregnancy. The clinical recommendations resulting from these discussions are frequently influenced by the comparative stigma attached to heroin abuse and methadone maintenance versus prescription opioid abuse and maintenance treatment with buprenorphine. While some studies have suggested that a subset of individuals who abuse prescription opioids may have different characteristics than heroin users, there is currently no evidence to suggest that buprenorphine is better suited to treatment of prescription opioid abuse than methadone. Similarly, despite its perennial popularity, there is no evidence to recommend detoxification as an efficacious approach to treatment of opioid dependence during pregnancy. While increased access to treatment is important, particularly in rural areas, there are multiple medical and psychosocial reasons to recommend comprehensive substance abuse treatment for pregnant women suffering from substance use disorders rather than office-based provision of maintenance medication. Both methadone and buprenorphine are important treatment options for opioid abuse during pregnancy. Methadone may still remain the preferred treatment choice for some women who require higher doses for stabilization, have a higher risk of treatment discontinuation, or who have had unsuccessful treatment attempts with buprenorphine. As treatment providers, we should advocate to expand available treatment options for pregnant women in all States. PMID:26154531

  12. Buprenorphine - an attractive opioid with underutilized potential in treatment of chronic pain.

    PubMed

    Khanna, Ish K; Pillarisetti, Sivaram

    2015-01-01

    Despite proven clinical utility, buprenorphine has not been used widely for the treatment of chronic pain. Questions about "ceiling effect" or bell-shaped curve observed for analgesia in preclinical studies and potential withdrawal issues on combining with marketed ?-agonists continue to hinder progress in expanding full potential of buprenorphine in the treatment of cancer and noncancer pain. Mounting evidence from clinical studies and conclusions drawn by a panel of experts strongly support superior safety and efficacy profile of buprenorphine vs marketed opioids. No ceiling on analgesic effect has been reported in clinical studies. The receptor pharmacology and pharmacokinetics profile of buprenorphine is complex but unique and contributes to its distinct safety and efficacy. The buprenorphine pharmacology also allows it to be combined with other ?-receptor opioids for additivity in efficacy. Transdermal delivery products of buprenorphine have been preferred choices for the management of pain but new delivery options are under investigation for the treatment of both opioid dependence and chronic pain. PMID:26672499

  13. Buprenorphine – an attractive opioid with underutilized potential in treatment of chronic pain

    PubMed Central

    Khanna, Ish K; Pillarisetti, Sivaram

    2015-01-01

    Despite proven clinical utility, buprenorphine has not been used widely for the treatment of chronic pain. Questions about “ceiling effect” or bell-shaped curve observed for analgesia in preclinical studies and potential withdrawal issues on combining with marketed μ-agonists continue to hinder progress in expanding full potential of buprenorphine in the treatment of cancer and noncancer pain. Mounting evidence from clinical studies and conclusions drawn by a panel of experts strongly support superior safety and efficacy profile of buprenorphine vs marketed opioids. No ceiling on analgesic effect has been reported in clinical studies. The receptor pharmacology and pharmacokinetics profile of buprenorphine is complex but unique and contributes to its distinct safety and efficacy. The buprenorphine pharmacology also allows it to be combined with other μ-receptor opioids for additivity in efficacy. Transdermal delivery products of buprenorphine have been preferred choices for the management of pain but new delivery options are under investigation for the treatment of both opioid dependence and chronic pain. PMID:26672499

  14. Buprenorphine in the treatment of opiate dependence: its pharmacology and social context of use in the U.S.

    PubMed

    Wesson, Donald R

    2004-05-01

    Buprenorphine's physiological effects are produced when it attaches to specific opiate receptors that are designated mu, kappa, or delta. Buprenorphine, a partial agonist at the mu receptor and an antagonist at the kappa receptor, produces typical morphine-like effects at low doses. At higher doses, it produces opiate effects that are less than those of full opiate agonists. Knowledge of the physiological effects of opiate receptors and the way they interact with opiate agonists, partial opiate agonists, and opiate antagonists is fundamental to understanding the safety and efficacy of buprenorphine in treatment of pain and opiate addiction. Knowledge of the historical and social context of opiate agonist treatment of opiate dependence is fundamental to understanding how nonpharmacological factors may limit the clinical adoption and utility of a safe and effective medication in treatment of opiate dependence. This article reviews the pharmacology of sublingual buprenorphine and the historical context of opiate agonist therapy; delineates classes of opiate receptors and their interaction with opiate agonists, partial agonists, and antagonists; and describes the commercially available pharmaceutical formulations of buprenorphine. It focuses on sublingual buprenorphine tablets, Subutex and Suboxone, the FDA-approved formulations of buprenorphine for treatment of opiate dependence. Sublingual buprenorphine, and the combination of sublingual buprenorphine/naloxone, have unique pharmacological properties that make them a logical first-line intervention in the treatment of opioid dependence. PMID:15279124

  15. A Randomized Controlled Trial of Prison-Initiated Buprenorphine: Prison Outcomes and Community Treatment Entry

    PubMed Central

    Gordon, Michael S.; Kinlock, Timothy W.; Schwartz, Robert P.; Fitzgerald, Terrence; O’Grady, Kevin E.; Vocci, Frank J.

    2014-01-01

    Background 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. Methods 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. Results 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%). Conclusions 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. PMID:24962326

  16. Changes in Quality of Life following Buprenorphine Treatment: Relationship with Treatment Retention and Illicit Opioid Use

    PubMed Central

    Mitchell, Shannon Gwin; Gryczynski, Jan; Schwartz, Robert P.; Myers, C. Patrick; O’Grady, Kevin E.; Olsen, Yngvild K.; Jaffe, Jerome H.

    2015-01-01

    Studies of substance abuse treatment outcomes that give priority to cessation of all drug use may obscure other tangible benefits of treatment that are important to patients. The aim of this study was to examine the association between changes in quality of life (QoL) and: (a) retention in treatment and (b) opioid use as measured by self-report and urine testing. Participants were 300 African American men and women starting outpatient buprenorphine treatment. Participants completed assessments at baseline, 3- and 6-months consisting of the World Health Organization’s Quality of Life brief scale, Addiction Severity Index, and urine testing for opioids. There were statistically significant increases over time across all four QoL domains: physical, psychological, environmental, and social. Self-reported frequency of opioid use was negatively associated with psychological QoL, but opioid urine test results were not significantly associated with any QoL domains. Continued treatment enrollment was significantly associated with higher psychological QoL and environmental QoL. Patients entering buprenorphine treatment experience improvements in QoL, which are amplified for patients who remain in treatment. Point-prevalence opiate urine test results obtained at each assessment were not associated with any of the QoL domains and may not accurately reflect improvements perceived by patients receiving buprenorphine treatment. PMID:25950595

  17. Changes in Quality of Life following Buprenorphine Treatment: Relationship with Treatment Retention and Illicit Opioid Use.

    PubMed

    Mitchell, Shannon Gwin; Gryczynski, Jan; Schwartz, Robert P; Myers, C Patrick; O'Grady, Kevin E; Olsen, Yngvild K; Jaffe, Jerome H

    2015-01-01

    Studies of substance abuse treatment outcomes that give priority to cessation of all drug use may obscure other tangible benefits of treatment that are important to patients. The aim of this study was to examine the association between changes in quality of life (QoL) and: (1) retention in treatment; and (2) opioid use as measured by self-report and urine testing. Participants were 300 African American men and women starting outpatient buprenorphine treatment. Participants completed assessments at baseline, three and six months consisting of the World Health Organization's Quality of Life brief scale, Addiction Severity Index, and urine testing for opioids. There were statistically significant increases over time across all four QoL domains: physical, psychological, environmental, and social. Self-reported frequency of opioid use was negatively associated with psychological QoL, but opioid urine test results were not significantly associated with any QoL domains. Continued treatment enrollment was significantly associated with higher psychological QoL and environmental QoL. Patients entering buprenorphine treatment experience improvements in QoL, which are amplified for patients who remain in treatment. Point-prevalence opiate urine test results obtained at each assessment were not associated with any of the QoL domains and may not accurately reflect improvements perceived by patients receiving buprenorphine treatment. PMID:25950595

  18. Developing and Implementing a New Prison-Based Buprenorphine Treatment Program

    PubMed Central

    Kinlock, Timothy W.; Gordon, Michael S.; Schwartz, Robert P.; Fitzgerald, Terrence T.

    2010-01-01

    Research suggests that buprenorphine treatment may be a promising intervention for incarcerated individuals with heroin addiction histories. However, its implementation varies from corrections-based methadone because of unique challenges regarding dosing, administration, and regulation. Describing the first randomized clinical trial of prison-initiated buprenorphine treatment in the United States, this manuscript focuses on how these obstacles were overcome through collaboration among correctional, treatment, and research personnel. Building on the present authors' work in developing prison-based methadone treatment, and considering the lack of experience in implementing corrections-based buprenorphine programs in the United States, this manuscript may serve as a guide for interested corrections officials, treatment providers, and researchers. PMID:20473351

  19. A Preliminary Randomized Controlled Trial of a Distress Tolerance Treatment for Opioid Dependent Persons Initiating Buprenorphine

    PubMed Central

    Stein, Michael D.; Herman, Debra S.; Moitra, Ethan; Hecht, Jacki; Lopez, Rosalie; Anderson, Bradley J; Brown, Richard A.

    2014-01-01

    Background Buprenorphine opioid agonist treatment (OAT) has established efficacy for treating opioid dependency but early relapse rates are high and are often associated with withdrawal-related or emotional distress. Methods To determine whether a novel distress tolerance (DT) intervention during buprenorphine initiation decreases opioid relapse, we conducted a preliminary randomized controlled trial with opioid-dependent outpatients. Participants received buprenorphine-naloxone induction and 3-months of maintenance buprenorphine plus seven, 50-minute manualized, individual sessions (DT vs. Health Education (HE) control) over a 28-day period, linked to clinician medication dosing visits, and beginning 2 days prior to buprenorphine induction. Primary outcomes included use of illicit opioids (positive defined as any self-reported use in the prior 28 days or detected by urine toxicology) and treatment drop out. Results Among 49 participants, the mean age was 41 years, 65.3% were male. Persons randomized to DT had lower rates of opioid use at all three monthly assessments, and at 3-months, 72% of HE participants were opioid positive compared with 62.5% of DT participants. Rates of dropout were 24% and 25% in the HE and DT arms, respectively. Conclusions This distress tolerance treatment produced a small, but not statistically significant reduction in opioid use during the first three months of treatment although no differences were found in drop-out rates between conditions. If replicated in a larger study, DT could offer clinicians a useful behavioral treatment to complement the effects of buprenorphine. Trial registered at clinicaltrials.org. Trial number NCT01556087. PMID:25510307

  20. Comment on "a comparison of buprenorphine + naloxone to buprenorphine and methadone in the treatment of opioid dependence during pregnancy: maternal and neonatal outcomes".

    PubMed

    Newman, Robert G; Gevertz, Susan G

    2013-01-01

    In a recent article, Lund et al sought to compare maternal and neonatal outcomes of various treatment regimens for opioid dependence during pregnancy.1 In their background, discussion the authors state that "In the United States buprenorphine plus naloxone [Suboxone(®)] … has been the preferred form of prescribed buprenorphine due to its reduced abuse liability relative to buprenorphine alone [Subutex(®)]." This claim is certainly consistent with the view of the firm that has manufactured and sold both products, Reckitt Benckiser. In September of 2011, the company announced that it was "… discontinuing distribution and sale of Subutex(®) tablets as we believe that mono product (product containing buprenorphine alone with no naloxone) creates a greater risk of misuse, abuse and diversion …".2 Supporting evidence for the alleged "reduced abuse liability" appears to be lacking, however, and evidence cannot be located in the two references cited by Dr. Lund and his co-authors, which in fact are silent on the subject of abuse potential.3,4 In contrast, it has been reported that the transition to buprenorphine/naloxone from the mono formulation has been associated with "… no reduction in injection risk behaviors among IDUs."5. PMID:23772177

  1. The evidence doesn't justify steps by state Medicaid programs to restrict opioid addiction treatment with buprenorphine.

    PubMed

    Clark, Robin E; Samnaliev, Mihail; Baxter, Jeffrey D; Leung, Gary Y

    2011-08-01

    Many state Medicaid programs restrict access to buprenorphine, a prescription medication that relieves withdrawal symptoms for people addicted to heroin or other opiates. The reason is that officials fear that the drug is costlier or less safe than other therapies such as methadone. To find out if this is true, we compared spending, the use of services related to drug-use relapses, and mortality for 33,923 Massachusetts Medicaid beneficiaries receiving either buprenorphine, methadone, drug-free treatment, or no treatment during the period 2003-07. Buprenorphine appears to have significantly expanded access to treatment because the drug can be prescribed by a physician and taken at home compared with methadone, which by law must be administered at an approved clinic. Buprenorphine was associated with more relapse-related services but $1,330 lower mean annual spending than methadone when used for maintenance treatment. Mortality rates were similar for buprenorphine and methadone. By contrast, mortality rates were 75 percent higher among those receiving drug-free treatment, and more than twice as high among those receiving no treatment, compared to those receiving buprenorphine. The evidence does not support rationing buprenorphine to save money or ensure safety. PMID:21821560

  2. Developing and Implementing a New Prison-Based Buprenorphine Treatment Program

    ERIC Educational Resources Information Center

    Kinlock, Timothy W.; Gordon, Michael S.; Schwartz, Robert P.; Fitzgerald, Terrence T.

    2010-01-01

    Research suggests that buprenorphine treatment may be a promising intervention for incarcerated individuals with heroin addiction histories. However, its implementation varies from corrections-based methadone because of unique challenges regarding dosing, administration, and regulation. Describing the first randomized clinical trial of…

  3. Developing and Implementing a New Prison-Based Buprenorphine Treatment Program

    ERIC Educational Resources Information Center

    Kinlock, Timothy W.; Gordon, Michael S.; Schwartz, Robert P.; Fitzgerald, Terrence T.

    2010-01-01

    Research suggests that buprenorphine treatment may be a promising intervention for incarcerated individuals with heroin addiction histories. However, its implementation varies from corrections-based methadone because of unique challenges regarding dosing, administration, and regulation. Describing the first randomized clinical trial of…

  4. French Experience with Buprenorphine : Do Physicians Follow the Guidelines?

    PubMed Central

    Guillou Landreat, Morgane; Rozaire, Charles; Guillet, Jean yves; Victorri Vigneau, Caroline; Le Reste, Jean Yves; Grall Bronnec, Marie

    2015-01-01

    Opiate dependence affects about 15,479,000 people worldwide. The effectiveness of opiate substitution treatments (OST) has been widely demonstrated. Buprenorphine plays a particular role in opiate dependence care provision in France. It is widely prescribed by physicians and national opiate substitution treatment guidelines have been available since 2004. In order to study the prescribing of buprenorphine, we used a questionnaire sent by email, to a large sample of physicians. These physicians were either in practice, or belonged to an addiction treatment network or a hospital. The main objective of this work was to measure the extent to which the theoretical, clinical attitude of physicians towards prescribing buprenorphine (BHD) complied with the statutory guidelines. We showed that the physicians we interviewed rarely took into account the guidelines regarding buprenorphine prescription. The actual prescribing of Buprenorphine differed from the guidelines. Only 42% of independent Family Physicians (FPs), working outside the national health care system, had prescribed buprenorphine as a first-time prescription and 40% of FPs do not follow up patients on buprenorphine. In terms of compliance with the guidelines, 55% of FPs gave theoretical answers that only partially complied with the guidelines. The variations in compliance with the guidelines was noted according to different variables and took into particular account whether the physician were affiliated to a network or in training. PMID:26479400

  5. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40

    ERIC Educational Resources Information Center

    Boone, Margaret; Brown, Nancy J.; Moon, Mary A.; Schuman, Deborah J.; Thomas, Josephine; Wright, Denise L.

    2004-01-01

    This Treatment Improvement Protocol (TIP) addresses the clinical use of buprenorphine in the treatment of opioid addiction. TIPs are best-practice guidelines for the treatment of substance use disorders that make the latest research in substance abuse treatment available to counselors and educators. The content was generated by a panel of experts…

  6. Cost-Effectiveness of Buprenorphine and Naltrexone Treatments for Heroin Dependence in Malaysia

    PubMed Central

    Ruger, Jennifer Prah; Chawarski, Marek; Mazlan, Mahmud; Ng, Nora; Schottenfeld, Richard

    2012-01-01

    Aims To aid public health policymaking, we studied the cost-effectiveness of buprenorphine, naltrexone, and placebo interventions for heroin dependence in Malaysia. Design 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. Setting Muar, Malaysia. Participants 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. Measurements 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. Findings 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. Conclusions Buprenorphine appears to be a cost-effective alternative to naltrexone that might enhance economic productivity and reduce drug use over a longer term. PMID:23226534

  7. Practice Guidance for Buprenorphine for the Treatment of Opioid Use Disorders: Results of an Expert Panel Process

    PubMed Central

    Farmer, Carrie M.; Lindsay, Dawn; Williams, Jessica; Ayers, Amanda; Schuster, James; Cilia, Alyssa; Flaherty, Michael T.; Mandell, Todd; Gordon, Adam J.; Stein, Bradley D.

    2015-01-01

    Background Although numbers of physicians credentialed to prescribe buprenorphine has increased over time, many credentialed physicians may be reluctant to treat individuals with opioid use disorders due to discomfort with prescribing buprenorphine. Though prescribing physicians are required to complete a training course, many have questions about buprenorphine and treatment guidelines have not been updated to reflect clinical experience in recent years. We report on an expert panel process to update and expand buprenorphine guidelines. Methods We identified candidate guidelines through expert opinion and a review of the literature and used a modified RAND/UCLA Appropriateness Method to assess the validity of the candidate guidelines. An expert panel completed two rounds of rating, with a meeting to discuss the guidelines between the first and second rating. Results Through the rating process, expert panel members rated 90 candidate guideline statements across eight domains, including candidacy for buprenorphine treatment, dosing of buprenorphine, psychosocial counseling, and treatment of co-occurring depression and anxiety. A total of 65 guideline statements (72%) were rated as valid. Expert panel members had agreement in some areas, such as the treatment of co-occurring mental health problems, but disagreement in others, including the appropriate dosing of buprenorphine given patient complexities. Conclusions Through an expert panel process, we developed an updated and expanded set of buprenorphine treatment guidelines; this additional guidance may increase credentialed physicians’ comfort with prescribing buprenorphine to patients with opioid use disorders. Future efforts should focus on appropriate dosing guidance and ensuring that guidelines can be adapted to a variety of practice settings. PMID:25844527

  8. Preference for buprenorphine/naloxone and buprenorphine among patients receiving buprenorphine maintenance therapy in France: a prospective, multicenter study.

    PubMed

    Daulouède, Jean-Pierre; Caer, Yves; Galland, Pascal; Villeger, Pierre; Brunelle, Emmanuel; Bachellier, Jérôme; Piquet, Jean-Michel; Harbonnier, Jean; Leglise, Yves; Courty, Pascal

    2010-01-01

    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. PMID:19800758

  9. Sublingual buprenorphine is effective in the treatment of chronic pain syndrome.

    PubMed

    Malinoff, Herbert L; Barkin, Robert L; Wilson, Geoffrey

    2005-01-01

    Many patients with chronic pain have less than optimal therapeutic outcomes after prolonged treatment with opiate analgesics. Worsening of pain perception, functional capacity, and mood often result. Medical detoxification is often undertaken in this situation. Ninety-five consecutive patients (49 men and 46 women; age range, 26-84) with chronic noncancer pain (maldynia) were referred by local pain clinics for detoxification from long-term opiate analgesic (LTOA) therapy. All patients had failed treatment as manifest by increasing pain levels, worsening functional capacity, and, in 8%, the emergence of opiate addiction. Length of prior LTOA therapy ranged from 1.5 to 27 years (mean, 8.8 years). After a minimum of 12 hours of abstinence from all opiate analgesics, patients were given low doses of sublingual (SL) buprenorphine or buprenorphine/naloxone (Reckitt Benckiser). Maintenance dosing was individualized to treat chronic pain. Daily SL dose of buprenorphine ranged from 4 to 16 mg (mean, 8 mg) in divided doses. Mean duration of treatment is 8.8 months (range, 2.4-16.6 months). At clinic appointments, patients were assessed for pain reports, functional capacity, and mood inventory. Eighty-six percent of patients experienced moderate to substantial relief of pain accompanied by both improved mood and functioning. Patient and family satisfaction was robust. Only 6 patients discontinued therapy secondary to side effects and/or exacerbation of pain. In this open-label study, SL buprenorphine and buprenorphine/naloxone were well tolerated and safe and appeared to be effective in the treatment of chronic pain patients refractory to LTOA. PMID:16148422

  10. A pilot study of buprenorphine-naloxone combination tablet (Suboxone) in treatment of opioid dependence.

    PubMed

    Bell, James; Byron, Gaye; Gibson, Amy; Morris, Amanda

    2004-09-01

    In Australia, maintenance treatment for opioid dependence involves supervised daily administration of a dose of methadone or buprenorphine. A sublingual tablet combining buprenorphine and naloxone in a 4:1 ratio (Suboxone) has been developed, designed to deter diversion and intravenous misuse, and may be suitable for unsupervised administration. The aim of this study was to investigate the tolerability of Suboxone, and investigate whether unsupervised administration can be effective in stabilized patients. Employed patients on buprenorphine maintenance, who had ceased heroin use, were switched to Suboxone and provided with weekly supplies of medication to take without supervised administration. Subjects were monitored closely with weekly clinical reviews, and research interviews at baseline, 3 and 6 months. Only 11% of people receiving buprenorphine met eligibility criteria. Seventeen subjects were recruited. Fifteen were retained for the full 6 months. No subject appeared destabilized by unsupervised dosing. Suboxone was well tolerated. The current trial demonstrated that unsupervised administration with regular clinical monitoring can be effective in selected patients. However, using access to unsupervised dosing to promote abstinence from heroin probably limits the potential benefits of unsupervised administration to a very small proportion of patients. PMID:15370011

  11. Failure to identify or effectively manage prescription opioid dependence acted as a gateway to heroin use-buprenorphine/naloxone treatment and recovery in a surgical patient.

    PubMed

    Conroy, Stephen; Hill, Duncan

    2014-01-01

    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. PMID:25519865

  12. Treatment Outcomes of African American Buprenorphine Patients by Parole and Probation Status.

    PubMed

    Mitchell, Shannon Gwin; Gryczynski, Jan; Kelly, Sharon M; O'Grady, Kevin E; Jaffe, Jerome H; Olsen, Yngvild K; Schwartz, Robert P

    2014-01-01

    This secondary analysis compared outcomes of African-American adults newly-admitted to buprenorphine treatment who were on parole and probation to patients who were not under criminal justice supervision. Buprenorphine patients (N=300) were randomly assigned to receive either Intensive Outpatient Treatment (IOP) or Standard Outpatient Treatment (OP) treatment and were assessed at baseline, 3- and 6-months. There were no differences between groups in treatment retention. Among probationers/parolees, IOP was associated with lower 3-month treatment retention compared to OP, but among participants not on probation/parole the relationship was reversed (p=.004). Both conditions showed significant declines in heroin and cocaine use, illegal activity, and in meeting DSM-IV criteria for opioid and cocaine dependence. Probationers/parolees reported lower frequency of illegal activities at 3-months compared to non-probationers/parolees (p=.007). Buprenorphine treatment should be made more widely available to individuals on parole/probation as they respond as well to treatment as patients not supervised by the criminal justice system. PMID:25364037

  13. Association between hepatitis C virus and opioid use while in buprenorphine treatment: preliminary findings

    PubMed Central

    Murphy, Sean M.; Dweik, Dana; McPherson, Sterling; Roll, John R.

    2015-01-01

    Background The prevalence of hepatitis-C-virus (HCV) infections is high among opioid-dependent individuals. Prior research on the simultaneous treatment of both conditions has primarily assessed success as it pertains to HCV; although, it has been noted that favorable substance-use-therapy outcomes may improve the likelihood of HCV-treatment initiation and success. Therefore, current guidelines for the treatment of HCV among illicit drug users suggest that treatment for addiction be given the highest priority. Objectives To determine whether opioid-dependent participants in a clinical trial of buprenorphine-treatment tapering regimens, who tested positive for the HCV antibody, experienced significantly different levels of opioid abstinence than those not infected. Methods Data came from the National Drug Abuse Treatment Clinical Trial Network study 0003, in which 516 eligible opioid-dependent participants were randomized to either a 7-day or 28-day buprenorphine tapering schedule following a 4-week buprenorphine stabilization period. Generalized estimating equations were used to test the research question. Results Participants with the HCV antibody were significantly less likely to submit opioid-negative urine analyses during and/or immediately following active treatment [OR = 0.69; CI = 0.51–0.93], which indicates a higher rate of opioid use among this group. Conclusion Individualized opioid-dependence treatment strategies may be required for opioid-dependent individuals who test positive for the HCV antibody in order to ensure resources for both opioid-dependence and HCV therapies are used efficiently. PMID:25490610

  14. Direct Injection LC-MS-MS Analysis of Opiates, Methamphetamine, Buprenorphine, Methadone and Their Metabolites in Oral Fluid from Substitution Therapy Patients.

    PubMed

    Liu, Hsiu-Chuan; Lee, Hsi-Tzu; Hsu, Ya-Ching; Huang, Mei-Han; Liu, Ray H; Chen, Tai-Jui; Lin, Dong-Liang

    2015-01-01

    A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed, validated and applied to simultaneous analysis of oral fluid samples for the following 10 analytes: methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, norbuprenorphine, morphine, codeine, 6-acetylmorphine, 6-acetylcodeine, amphetamine, and methamphetamine. The oral fluid sample was briefly centrifuged and the supernatant was directly injected into the LC-MS-MS system operated under reverse-phase chromatography and electrospray ionization (ESI). Deuterated analogs of the analytes were adopted as the internal standards and found to be effective (except for buprenorphine) to compensate for potential matrix effects. Each analytical run took <10 min. Linearity range (r(2) > 0.99) established for buprenorphine and the other nine analytes were 5-100 and 1-100 ng/mL. Intra- and interday precision (% CV) ranges for the 10 analytes were 0.87-12.2% and 1.27-12.8%, while the corresponding accuracy (%) ranges were 91.8-113% and 91.9-111%. Limits of detection and quantitation established for these 10 analytes were in the ranges of 0.1-1.0 and 0.25-1.0 ng/mL (5 ng/mL for buprenorphine). The method was successfully applied to the analysis of 62 oral fluid specimens collected from patients participating in methadone and buprenorphine substitution therapy programs. Analytical results of methadone and buprenorphine were compared with data derived from GC-MS analysis and found to be compatible. Overall, the direct injection LC-MS-MS method performed well, permitting rapid analysis of oral fluid samples for simultaneous quantification of methadone, buprenorphine, opiate and amphetamine drug categories without extensive sample preparation steps. PMID:25935159

  15. Buprenorphine for office-based treatment of patients with opioid addiction.

    PubMed

    Manlandro, James J

    2005-06-01

    The Drug Addiction Treatment Act of 2000 (DATA 2000) was established to create a new paradigm for medication-assisted treatment of opiate addiction in the United States. Before enactment of DATA 2000, the use of opioid medications to treat opioid addiction was permissible only in federally approved treatment programs, ie, methadone clinics. The only medications permitted were Schedule II drugs (eg, methadone and l-a-acetylmethadol [LAAM]), which could only be dispensed, not prescribed. Under provisions of DATA 2000, qualified physicians in a medical office and other appropriate settings outside the opioid treatment program system may prescribe or dispense (or both), Schedule III, IV, and V opioid medications for treatment of opioid addiction if such medications have been specifically approved by the the US Food and Drug Administration for that indication. Opioid addiction treatment programs were commonly known as methadone clinics. They now may also dispense buprenorphine hydrochloride and the buprenorphine hydrochloride-naloxone combination. The information in this article is extracted (with revision) from: Center for Substance Abuse Treatment. Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. Treatment Improvement Protocol (TIP) Series 40. DHS Publication No. (SMA) 04-3939. Rockville, Md: Substance Abuse and Mental Health Services Administration; 2004. The Clinical Guidelines document is in the public domain except for material indicated as reprinted from a copyrighted source. The author served on both the Expert Panel and the Consensus Panel that produced the guidelines, available in portable document format at http://buprenorphine.samhsa.gov/Bup%20Guidelines.pdf. PMID:16118361

  16. Addiction to Prescription Opioids: Characteristics of the Emerging Epidemic and Treatment with Buprenorphine

    PubMed Central

    Mendelson, John; Flower, Keith; Pletcher, Mark; Galloway, Gantt P.

    2015-01-01

    Dependence on and abuse of prescription opioid drugs is now a major health problem, with initiation of prescription opioid abuse exceeding cocaine in young people. Coincident with the emergence of abuse and dependence on prescription opioids, there has been an increased emphasis on the treatment of pain. Pain is now the “5th vital sign” and physicians face disciplinary action for failure to adequately relieve pain. Thus, physicians are whipsawed between the imperative to treat pain with opioids and the fear of producing addiction in some patients. In this article we characterize the emerging epidemic of prescription opioid abuse, discuss the utility of buprenorphine in the treatment of addiction to prescription opioids, and present illustrative case histories of successful treatment with buprenorphine. PMID:18837640

  17. Emergency Department–Initiated Buprenorphine/Naloxone Treatment for Opioid Dependence

    PubMed Central

    D’Onofrio, Gail; O’Connor, Patrick G.; Pantalon, Michael V.; Chawarski, Marek C.; Busch, Susan H.; Owens, Patricia H.; Bernstein, Steven L.; Fiellin, David A.

    2015-01-01

    IMPORTANCE Opioid-dependent patients often use the emergency department (ED) for medical care. OBJECTIVE To test the efficacy of 3 interventions for opioid dependence: (1) screening and referral to treatment (referral); (2) screening, brief intervention, and facilitated referral to community-based treatment services (brief intervention); and (3) screening, brief intervention, ED-initiated treatment with buprenorphine/naloxone, and referral to primary care for 10-week follow-up (buprenorphine). DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial involving 329 opioid-dependent patients who were treated at an urban teaching hospital ED from April 7, 2009, through June 25, 2013. INTERVENTIONS After screening, 104 patients were randomized to the referral group, 111 to the brief intervention group, and 114 to the buprenorphine treatment group. MAIN OUTCOMES AND MEASURES Enrollment in and receiving addiction treatment 30 days after randomization was the primary outcome. Self-reported days of illicit opioid use, urine testing for illicit opioids, human immunodeficiency virus (HIV) risk, and use of addiction treatment services were the secondary outcomes. RESULTS Seventy-eight percent of patients in the buprenorphine group (89 of 114 [95% CI, 70%-85%]) vs 37% in the referral group (38 of 102 [95% CI, 28%-47%]) and 45% in the brief intervention group (50 of 111 [95% CI, 36%-54%]) were engaged in addiction treatment on the 30th day after randomization (P < .001). The buprenorphine group reduced the number of days of illicit opioid use per week from 5.4 days (95% CI, 5.1-5.7) to 0.9 days (95% CI, 0.5-1.3) vs a reduction from 5.4 days (95% CI, 5.1-5.7) to 2.3 days (95% CI, 1.7-3.0) in the referral group and from 5.6 days (95% CI, 5.3-5.9) to 2.4 days (95% CI, 1.8-3.0) in the brief intervention group (P < .001 for both time and intervention effects; P = .02 for the interaction effect). The rates of urine samples that tested negative for opioids did not differ statistically across groups, with 53.8% (95% CI, 42%-65%) in the referral group, 42.9% (95% CI, 31%-55%) in the brief intervention group, and 57.6% (95% CI, 47%-68%) in the buprenorphine group (P = .17). There were no statistically significant differences in HIV risk across groups (P = .66). Eleven percent of patients in the buprenorphine group (95% CI, 6%-19%) used inpatient addiction treatment services, whereas 37% in the referral group (95% CI, 27%-48%) and 35% in the brief intervention group (95% CI, 25%-37%) used inpatient addiction treatment services (P < .001). CONCLUSIONS AND RELEVANCE Among opioid-dependent patients, ED-initiated buprenorphine treatment vs brief intervention and referral significantly increased engagement in addiction treatment, reduced self-reported illicit opioid use, and decreased use of inpatient addiction treatment services but did not significantly decrease the rates of urine samples that tested positive for opioids or of HIV risk. These findings require replication in other centers before widespread adoption. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00913770 PMID:25919527

  18. Buprenorphine Pharmacotherapy and Behavioral Treatment: Comparison of Outcomes among Prescription Opioid Users, Heroin Users and Combination users

    PubMed Central

    Nielsen, Suzanne; Hillhouse, Maureen; Mooney, Larissa; Ang, Alfonso; Ling, Walter

    2014-01-01

    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 16 weeks 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. PMID:25065489

  19. Randomized trial of buprenorphine for treatment of concurrent opiate and cocaine dependence

    PubMed Central

    Montoya, Ivan D.; Gorelick, David A.; Preston, Kenzie L.; Schroeder, Jennifer R.; Umbricht, Annie; Cheskin, Lawrence J.; Lange, W. Robert; Contoreggi, Carlo; Johnson, Rolley E.; Fudala, Paul J.

    2008-01-01

    Background Buprenorphine is a partial ?-opiate agonist and ?-opiate antagonist with established efficacy in the treatment of opiate dependence. Its efficacy for cocaine dependence is uncertain. This study evaluated buprenorphine for the treatment of concomitant cocaine and opiate dependence. Methods Two hundred outpatients currently dependent on both cocaine and opiates were randomly assigned to double-blind groups receiving a sublingual solution of buprenorphine (2, 8, or 16 mg daily, or 16 mg on alternate days, or placebo), plus weekly individual drug abuse counseling, for 13 weeks. The chief outcome measures were urine concentrations of opiate and cocaine metabolites (quantitative) and proportion of urine samples positive for opiates or cocaine (qualitative). Group differences were assessed by use of mixed regression modeling. Results The target dose of buprenorphine was achieved in 179 subjects. Subjects receiving 8 or 16 mg buprenorphine daily showed statistically significant decreases in urine morphine levels (P = .0135 for 8 mg and P < .001 for 16 mg) or benzoylecgonine concentrations (P = .0277 for 8 mg and P = .006 for 16 mg) during the maintenance phase of the study. For the 16-mg group, mean benzoylecgonine concentrations fell from 3715 ng/mL during baseline to 186 ng/mL during the withdrawal phase; mean morphine concentrations fell from 3311 ng/mL during baseline to 263 ng/mL during withdrawal. For the 8-mg group, mean benzoylecgonine concentrations fell from 6761 ng/mL during baseline to 676 ng/mL during withdrawal; mean morphine concentrations fell from 3890 ng/mL during baseline to 661 ng/mL during withdrawal. Qualitative urinalysis showed a similar pattern of results. Subjects receiving the highest dose showed concomitant decreases in both urine morphine and benzoylecgonine concentrations. There were no significant group differences in treatment retention or adverse events. Conclusions A sublingual buprenorphine solution at 16 mg daily is well tolerated and effective in reducing concomitant opiate and cocaine use. The therapeutic effect on cocaine use appears independent of that on opiate use. PMID:14749690

  20. Substitution treatment for opioid addicts in Germany

    PubMed Central

    Michels, Ingo Ilja; Stöver, Heino; Gerlach, Ralf

    2007-01-01

    Background After a long and controversial debate methadone maintenance treatment (MMT) was first introduced in Germany in 1987. The number of patients in MMT – first low because of strict admission criteria – increased considerably since the 1990s up to some 65,000 at the end of 2006. In Germany each general practitioner (GP), who has completed an additional training in addiction medicine, is allowed to prescribe substitution drugs to opioid dependent patients. Currently 2,700 GPs prescribe substitution drugs. Psychosocial care should be made available to all MMT patients. Results The results of research studies and practical experiences clearly indicate that patients benefit substantially from MMT with improvements in physical and psychological health. MMT proves successful in attaining high retention rates (65 % to 85 % in the first years, up to 50 % after more than seven years) and plays a major role in accessing and maintaining ongoing medical treatment for HIV and hepatitis. MMT is also seen as a vital factor in the process of social re-integration and it contributes to the reduction of drug related harms such as mortality and morbidity and to the prevention of infectious diseases. Some 10 % of MMT patients become drug-free in the long run. Methadone is the most commonly prescribed substitution medication in Germany, although buprenorphine is attaining rising importance. Access to MMT in rural areas is very patchy and still constitutes a problem. There are only few employment opportunities for patients participating in MMT, although regular employment is considered unanimously as a positive factor of treatment success. Substitution treatment in German prisons is heterogeneous in access and treatment modalities. Access is very patchy and the number of inmates in treatment is limited. Nevertheless, substitution treatment plays a substantial part in the health care system provided to drug users in Germany. Conclusion In Germany, a history of substitution treatment spanning 20 years has meanwhile accumulated a wealth of experience, e.g. in the development of research on health care services, guidelines and the implementation of quality assurance measures. Implementing substitution treatment with concomitant effects and treatment elements such as drug history-taking, dosage setting, co-use of other psychoactive substances (alcohol, benzodiazepines, cocaine), management of 'difficult patient populations', and integration into the social environment has been arranged successfully. Also psychosocial counseling programmes adjuvant to substitution treatment have been established and, in the framework of a pilot project on heroin-based treatment, standardised manuals were developed. Research on allocating opioid users to the 'right' form of therapy at the 'right' point in time is still a challenge, though the pilot project 'heroin-based treatment' brought experience with patients who do not benefit from methadone treatment. There is also expertise in the treatment of specific co-morbidity such as HIV/AIDS, hepatitis and psychiatric disorders. The promotion and involvement of self-help groups plays an important part in the process of successful substitution treatment. PMID:17270059

  1. Initial response as a predictor of 12-week buprenorphine-naloxone treatment response in a prescription opioid dependent population

    PubMed Central

    McDermott, Katherine A.; Griffin, Margaret L.; Connery, Hilary S.; Hilario, E. Yvette; Fiellin, David A.; Fitzmaurice, Garrett M.; Weiss, Roger D.

    2015-01-01

    Objective Initial medication response has been shown to predict treatment outcome across a variety of substance use disorders, but no studies have examined the predictive power of initial response to buprenorphine-naloxone in the treatment of prescription opioid dependence. We therefore conducted a secondary analysis of data from the Prescription Opioid Addiction Treatment Study to determine whether initial response to buprenorphine-naloxone predicted 12-week treatment outcome in a prescription opioid-dependent population. Method Using data from a multi-site, randomized controlled trial of buprenorphine-naloxone plus counseling for DSM-IV prescription opioid dependence (June 2006–July 2009), we conducted a secondary analysis to investigate the relationship between initial medication response and 12-week treatment outcome to establish how soon the efficacy of buprenorphine-naloxone could be predicted. Outcomes were determined from the Substance Use Report, a self-report measure of substance use, and confirmatory urinalysis. Predictive values were calculated to determine the importance of abstinence vs. use at various time points within the first month of treatment (week 1, weeks 1–2, 1–3, or 1–4) in predicting successful vs. unsuccessful treatment outcome (based on abstinence or near-abstinence from opioids) in the last 4 weeks of buprenorphine-naloxone treatment (weeks 9–12). Results Outcome was best predicted by medication response after two weeks of treatment. Two weeks of initial abstinence was moderately predictive of treatment success (positive predictive value = 71%), while opioid use in both of the first two weeks was strongly predictive of unsuccessful treatment outcome (negative predictive value (NPV) = 84%), especially when successful outcome was defined as total abstinence from opioids in weeks 9–12 (NPV = 94%). Conclusion Evaluating prescription opioid-dependent patients after two weeks of buprenorphine-naloxone treatment may help determine the likelihood of successful outcome at completion of the current treatment regimen. Trial Registration ClinicalTrials.gov identifier: NCT00316277 PMID:25562462

  2. Buprenorphine versus methadone in the treatment of opioid dependence: self-reports, urinalysis, and addiction severity index.

    PubMed

    Strain, E C; Stitzer, M L; Liebson, I A; Bigelow, G E

    1996-02-01

    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. PMID:8834420

  3. The relative risk of fatal poisoning by methadone or buprenorphine within the wider population of England and Wales

    PubMed Central

    Marteau, Dave

    2015-01-01

    Objective To examine the population-wide overdose risk emerging from the prescription of methadone and buprenorphine for opioid substitution treatment in England and Wales. Design Retrospective administrative data study. Setting National databases for England and Wales. Participants/cases Drug-related mortality data were drawn from the Office for National Statistics, and prescription data for methadone and buprenorphine were obtained from the National Health Service for the years 2007–2012. During this 6-year period, a total of 2366 methadone-related deaths and 52 buprenorphine-related deaths were registered, corresponding to 17?333?163 methadone and 2?602?374 buprenorphine prescriptions issued. The analysis encompassed poisoning deaths among members of the wider population of England and Wales who consumed, but were not prescribed these medications, in addition to patients prescribed methadone or buprenorphine. Main outcome measures Mortality risk: substance-specific overdose rate per 1000 prescriptions issued; relative risk ratio of methadone in relation to buprenorphine. Results During the years 2007–2012, the pooled overdose death rate was 0.137/1000 prescriptions of methadone, compared to 0.022/1000 prescriptions of buprenorphine (including buprenorphine-naloxone). The analysis generated a relative risk ratio of 6.23 (95% CI 4.79 to 8.10) of methadone in relation to buprenorphine. UK Borders Agency data were taken into consideration and revealed that only negligible amounts of methadone and buprenorphine were seized on entering UK territory between 2007 and 2012, suggesting domestic diversion. Conclusions Our analysis of the relative safety of buprenorphine and methadone for opioid substitution treatment reveals that buprenorphine is six times safer than methadone with regard to overdose risk among the general population. Clinicians should be aware of the increased risk of prescribing methadone, and tighter regulations are needed to prevent its diversion. PMID:26024998

  4. Preliminary survey of office-based opioid treatment practices and attitudes among psychiatrists never receiving buprenorphine training to those who received training during residency

    PubMed Central

    Suzuki, Joji; Connery, Hilary S.; Ellison, Tatyana V.; Renner, John A.

    2015-01-01

    Objective To compare the characteristics, attitudes, and current prescribing practices of recently graduating psychiatrists who completed buprenorphine training during residency to those who never completed any training.. Methods A total of 359 psychiatrists completing residency training between 2008 and 2011 were recruited to complete an on-line survey. Results Responses from 93 psychiatrists were included for a response rate of 25.9%. Psychiatrists completing any buprenorphine training during residency were more likely to be male and report more favorable views of OBOT with buprenorphine than compared to those who never completed any training. Twenty (38.5%) of those psychiatrists who completed training during residency reported the current prescribing of buprenorphine. Conclusions Completion of buprenorphine training during residency may be a factor in shaping future attitudes towards OBOT and buprenorphine prescribing practices . Further research is needed to clarify the impact of buprenorphine training during residency. Scientific Significance Buprenorphine training during residency training may be a contributing factor in shaping future physician attitudes towards office-based opioid treatment and buprenorphine prescribing practices. PMID:25065457

  5. Sexual Dysfunction in Heroin Dependents: A Comparison between Methadone and Buprenorphine Maintenance Treatment

    PubMed Central

    Yee, Anne; Danaee, Mahmoud; Loh, Huai Seng; Sulaiman, Ahmad Hatim; Ng, Chong Guan

    2016-01-01

    Introduction 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. Methods 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. Results 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. Conclusions 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. PMID:26820154

  6. Growth In Buprenorphine Waivers For Physicians Increased Potential Access To Opioid Agonist Treatment, 2002-11.

    PubMed

    Dick, Andrew W; Pacula, Rosalie L; Gordon, Adam J; Sorbero, Mark; Burns, Rachel M; Leslie, Douglas; Stein, Bradley D

    2015-06-01

    Opioid use disorders are a significant public health problem, affecting two million people in the United States. Treatment with buprenorphine, methadone, or both is predominantly offered in methadone clinics, yet many people do not receive the treatment they need. In 2002 the Food and Drug Administration approved buprenorphine for prescription by physicians who completed a course and received a waiver from the Drug Enforcement Administration, exempting them from requirements in the Controlled Substances Act. To determine the waiver program's impact on the availability of opioid agonist treatment, we analyzed data for the period 2002-11 to identify counties with opioid treatment shortages. We found that the percentage of counties with a shortage of waivered physicians fell sharply, from 98.9 percent in 2002 to 46.8 percent in 2011. As a result, the percentage of the US population residing in what we classified as opioid treatment shortage counties declined from 48.6 percent in 2002 to 10.4 percent in 2011. These findings suggest that the increase in waivered physicians has dramatically increased potential access to opioid agonist treatment. Policy makers should focus their efforts on further increasing the number and geographical distribution of physicians, particularly in more rural counties, where prescription opioid misuse is rapidly growing. PMID:26056209

  7. Buprenorphine Treatment and 12-step Meeting Attendance: Conflicts, Compatibilities, and Patient Outcomes.

    PubMed

    Monico, Laura B; Gryczynski, Jan; Mitchell, Shannon Gwin; Schwartz, Robert P; O'Grady, Kevin E; Jaffe, Jerome H

    2015-10-01

    This analysis examines patient experiences and outcomes with 12-step recovery group attendance during buprenorphine maintenance treatment (BMT), two approaches with traditionally divergent philosophies regarding opioid medications for treatment of opioid use disorder. Using quantitative (n = 300) and qualitative (n = 20) data collected during a randomized trial of counseling services in buprenorphine treatment, this mixed-methods analysis of African Americans in BMT finds the number of NA meetings attended in the prior 6 months was associated with a higher rate of retention in BMT (p < .001) and heroin/cocaine abstinence at 6 month follow-up (p = .005). However, patients whose counselors required them to attend 12-step meetings did not have better outcomes than patients not required to attend such meetings. Qualitative narratives highlighted patients' strategies for managing dissonant viewpoints on BMT and disclosing BMT status in community 12-step meetings. Twelve-step meeting attendance is associated with better outcomes for BMT patients over the first 6 months of treatment. However, there is no benefit to requiring meeting attendance as a condition of treatment, and clinicians should be aware of potential philosophical conflicts between 12-step and BMT approaches. PMID:25986647

  8. [Buprenorphine transdermal patch (Norspan tape)].

    PubMed

    Hamaguchi, Shinsuke; Ikeda, Tomohito

    2013-07-01

    Buprenorphine is a chemically synthesized opioid characterized as the partial mu agonist and kappa antagonist, and transdermal buprenorphine patch will be considered useful as a strong analgesic with fewer psychological side effects in the treatment of chronic non-cancer pain. Use of transdermal buprenorphine should be limited for pain relief of intractable muscle skeletal pain that cannot be alleviated with other analgesics. To avoid severe complication and drug abuse or addiction, assessment of pain and medical history including drug dependence by medical team are important before administration of transdermal buprenorphine. Moreover, side effects such as nausea, vomiting, constipation, erythema and itching, loss of appetite should be treated appropriately. When transdermal buprenorphine is administered to chronic pain patients, physicians must examine the condition of patients regularly at an outpatient clinic. Moreover, decreasing and discontinuation of opioid including transdermal buprenorphine should always be considered during the treatment. Most important objective of chronic pain treatment is to improve QOL and ADL of patients. PMID:23905402

  9. Initiation of Buprenorphine During Incarceration and Retention in Treatment Upon Release

    PubMed Central

    Zaller, Nickolas; McKenzie, Michelle; Friedmann, Peter D.; Green, Traci C.; McGowan, Samuel; Rich, Josiah D.

    2013-01-01

    We report here on a feasibility study of initiating buprenorphine/naloxone prior to release from incarceration and linking participants to community treatment providers upon release. Study consisted of a small number of Rhode Island (RI) prisoners (N=44) diagnosed with opioid dependence. The study design is a single arm, open-label pilot study with a 6-month follow up interview conducted in the community. However, a natural experiment arose during the study comparing pre-release initiation of buprenorphone/naloxone to initiation post-release. Time to post-release prescriber appointment (mean days) for initiation of treatment Outside Rhode Island Department of Corrections (RIDOC) vs. Inside RIDOC was 8.8 and 3.9, respectively (p=.1). Median post release treatment duration (weeks) for Outside RIDOC vs. Inside RIDOC was 9 and 24, respectively (p=.007). We conclude that initiating buprenorphine/naloxone prior to release from incarceration may increase engagement and retention in community-based treatment. PMID:23541303

  10. Unusual false-positive case of urinary screening for buprenorphine.

    PubMed

    Lippi, Giuseppe; Romero, Araelsis; Cervellin, Gianfranco; Mercadanti, Mariella

    2011-01-01

    Buprenorphine is a centrally acting analgesic drug that is administered for the management of opioid dependence and as an analgesic drug for the treatment of chronic pain. The growing use of this substance has determined an increased need for laboratory testing for either detection and confirmation of the illicit use or monitoring compliance as a substitution therapy for opioid dependence. We describe here the case of urinary sample adulteration with exogenous buprenorphine (6,952?ng/ml), which has led to afalse-positive immunoassay test result (14.9?ng/ml) on a subsequent sample due to a phenomenon of instrumental carry-over. This unusual case confirms the importance to take into account adulteration when screening urines for buprenorphine in patients undergoing substitution therapy for opioid dependence, routinely perform a confirmation assay on positive samples, and rule out instrumental carry-over. PMID:21786326

  11. Predictors of Abstinence: National Institute of Drug Abuse Multisite Buprenorphine/Naloxone Treatment Trial in Opioid-Dependent Youth

    ERIC Educational Resources Information Center

    Subramaniam, Geetha A.; Warden, Diane; Minhajuddin, Abu; Fishman, Marc J.; Stitzer, Maxine L.; Adinoff, Bryon; Trivedi, Madhukar; Weiss, Roger; Potter, Jennifer; Poole, Sabrina A.; Woody, George E.

    2011-01-01

    Objective: To examine predictors of opioid abstinence in buprenorphine/naloxone (Bup/Nal)-assisted psychosocial treatment for opioid-dependent youth. Method: Secondary analyses were performed of data from 152 youth (15-21 years old) randomly assigned to 12 weeks of extended Bup/Nal therapy or up to 2 weeks of Bup/Nal detoxification with weekly…

  12. Predictors of Abstinence: National Institute of Drug Abuse Multisite Buprenorphine/Naloxone Treatment Trial in Opioid-Dependent Youth

    ERIC Educational Resources Information Center

    Subramaniam, Geetha A.; Warden, Diane; Minhajuddin, Abu; Fishman, Marc J.; Stitzer, Maxine L.; Adinoff, Bryon; Trivedi, Madhukar; Weiss, Roger; Potter, Jennifer; Poole, Sabrina A.; Woody, George E.

    2011-01-01

    Objective: To examine predictors of opioid abstinence in buprenorphine/naloxone (Bup/Nal)-assisted psychosocial treatment for opioid-dependent youth. Method: Secondary analyses were performed of data from 152 youth (15-21 years old) randomly assigned to 12 weeks of extended Bup/Nal therapy or up to 2 weeks of Bup/Nal detoxification with weekly…

  13. Supply of buprenorphine waivered physicians: the influence of state policies.

    PubMed

    Stein, Bradley D; Gordon, Adam J; Dick, Andrew W; Burns, Rachel M; Pacula, Rosalie Liccardo; Farmer, Carrie M; Leslie, Douglas L; Sorbero, Mark

    2015-01-01

    Buprenorphine, an effective opioid use disorder treatment, can be prescribed only by buprenorphine-waivered physicians. We calculated the number of buprenorphine-waivered physicians/100,000 county residents using 2008-11 Buprenorphine Waiver Notification System data, and used multivariate regression models to predict number of buprenorphine-waivered physicians/100,000 residents in a county as a function of county characteristics, state policies and efforts to promote buprenorphine use. In 2011, 43% of US counties had no buprenorphine-waivered physicians and 7% had 20 or more waivered physicians. Medicaid funding, opioid overdose deaths, and specific state guidance for office-based buprenorphine use were associated with more buprenorphine-waivered physicians, while encouraging methadone programs to promote buprenorphine use had no impact. Our findings provide important empirical information to individuals seeking to identify effective approaches to increase the number of physicians able to prescribe buprenorphine. PMID:25218919

  14. Supply of Buprenorphine Waivered Physicians: The Influence of State Policies

    PubMed Central

    Stein, Bradley D.; Gordon, Adam J.; Dick, Andrew W.; Burns, Rachel M.; Pacula, Rosalie Liccardo; Farmer, Carrie M.; Leslie, Douglas L.; Sorbero, Mark

    2015-01-01

    Buprenorphine, an effective opioid use disorder treatment, can be prescribed only by buprenorphine-waivered physicians. We calculated the number of buprenorphine-waivered physicians/100,000 county residents using 2008–11 Buprenorphine Waiver Notification System data, and used multivariate regression models to predict number of buprenorphine-waivered physicians/100,000 residents in a county as a function of county characteristics, state policies and efforts to promote buprenorphine use. In 2011, 43% of US counties had no buprenorphine-waivered physicians and 7% had 20 or more waivered physicians. Medicaid funding, opioid overdose deaths, and specific state guidance for office-based buprenorphine use were associated with more buprenorphine-waivered physicians, while encouraging methadone programs to promote buprenorphine use had no impact. Our findings provide important empirical information to individuals seeking to identify effective approaches to increase the number of physicians able to prescribe buprenorphine. PMID:25218919

  15. A model federal collaborative to increase patient access to buprenorphine treatment in HIV primary care.

    PubMed

    Cheever, Laura W; Kresina, Thomas F; Cajina, Adan; Lubran, Robert

    2011-03-01

    A Health Resources and Services Administration-Substance Abuse and Mental Health Services Administration collaboration was established to improve health outcomes for opiate-dependent HIV-infected patients through promotion of integrated models of HIV primary care and substance abuse treatment. The collaboration comprised 10 demonstration sites coordinated by a technical assistance/evaluation center that worked to refine planned interventions, address state-of-the-art treatment and policy issues relating to the use of buprenorphine opioid abuse treatment in HIV primary care settings, conduct local and multisite evaluations, and disseminate program findings. This article describes the goals and objectives of the collaborative as well as the interagency interactions and steps taken to establish the collaborative. PMID:21317591

  16. Factors associated with complicated buprenorphine inductions

    PubMed Central

    Whitley, Susan D.; Sohler, Nancy L.; Kunins, Hillary V.; Giovanniello, Angela; Li, Xuan; Sacajiu, Galit; Cunningham, Chinazo O.

    2016-01-01

    Despite data supporting its efficacy, barriers to implementation of buprenorphine for office-based treatment are present. Complications can occur during buprenorphine inductions, yet few published studies have examined this phase of treatment. To examine factors associated with complications during buprenorphine induction, we conducted a retrospective chart review of the first 107 patients receiving buprenorphine treatment in an urban community health center. The primary outcome, defined as complicated induction (precipitated or protracted withdrawal), was observed in 18 (16.8%) patients. Complicated inductions were associated with poorer treatment retention (than routine inductions) and decreased over time. Factors independently associated with complicated inductions included recent use of prescribed methadone, recent benzodiazepine use, no prior experience with buprenorphine, and a low initial dose of buprenorphine/naloxone. Findings from this study and further investigation of patient characteristics and treatment characteristics associated with complicated inductions can help guide buprenorphine treatment strategies. PMID:20682186

  17. Combined Abuse of Clonidine and Amitriptyline in a Patient on Buprenorphine Maintenance Treatment

    PubMed Central

    Dittmer, Trent; Sigman, Erika J.; Clemons, Holly; Johnson, J. Aaron

    2014-01-01

    Buprenorphine/naloxone maintenance therapy is often prescribed in primary care to treat opioid dependence. Previous reports have described concomitant abuse of opioids and clonidine. In this case, a primary care patient on buprenorphine/naloxone maintenance therapy demonstrating altered mental status, hallucinations, falls, and rebound hypertension was found to be concomitantly abusing clonidine and amitryptyline, which share metabolic pathways with buprenorphine. Clinicians should be aware of patients' combining amitryptyline, clonidine, and gabapentin with buprenorphine to achieve a mood altering state, avoid co-prescribing them if possible, and maintain communication with pharmacies and other providers when they are prescribed. PMID:25314340

  18. The Impact of Buprenorphine/Naloxone Treatment on HIV Risk Behaviors among HIV-Infected, Opioid-Dependent Patients*

    PubMed Central

    Edelman, E. Jennifer; Chantarat, Tongtan; Caffrey, Sarah; Chaudhry, Amina; O’Connor, Patrick; Weiss, Linda; Fiellin, David A.; Fiellin, Lynn E.

    2014-01-01

    Background Opioid dependence is a major risk factor for HIV infection, however, the impact of buprenorphine/naloxone treatment on HIV risk behaviors among HIV-infected opioid-dependent patients is unknown. Methods We conducted a longitudinal analysis of 303 HIV-infected opioid-dependent patients initiating buprenorphine/naloxone treatment. Outcomes included self-reported past 90-day needle-sharing and non-condom use. We assessed trends over the 12 months using the Cochran-Armitage trend test. Using Generalized Estimating Equations, after multiple imputation, we determined factors independently associated with needle-sharing and non-condom use, including time-updated variables. We then conducted a mediation analysis to determine whether substance use explained the relationship between time since treatment initiation and needle-sharing. Results Needle-sharing decreased from baseline to the fourth quarter following initiation of buprenorphine/naloxone (9% vs. 3%, p<0.001), while non-condom use did not (23% vs. 21%, p=0.10). HIV risk behaviors did not vary based on the presence of a detectable HIV-1 RNA viral load. Patients who were homeless and used heroin, cocaine/amphetamines or marijuana were more likely to report needle-sharing. Heroin use fully mediated the relationship between time since treatment initiation and needle-sharing. Women, patients who identified as being gay/lesbian/bisexual, those married or living with a partner and who reported heroin or alcohol use were more likely to report non-condom use. Older patients were less likely to report non-condom use. Conclusions While buprenorphine/naloxone is associated with decreased needle-sharing among HIV-infected opioid-dependent patients, sexual risk behaviors persist regardless of viral load. Targeted interventions to address HIV risk behaviors among HIV-infected opioid-dependent populations receiving buprenorphine/naloxone are needed. PMID:24726429

  19. Determination of buprenorphine, norbuprenorphine and naloxone in fingernail clippings and urine of patients under opioid substitution therapy.

    PubMed

    Tzatzarakis, Manolis N; Vakonaki, Elena; Kovatsi, Leda; Belivanis, Stamatis; Mantsi, Mary; Alegakis, Athanasios; Liesivuori, Jyrki; Tsatsakis, Aristidis M

    2015-05-01

    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. PMID:25663675

  20. Clinical experience with fortnightly buprenorphine/naloxone versus buprenorphine in Italy: preliminary observational data in an office-based setting.

    PubMed

    Amato, Patrizia

    2010-01-01

    Buprenorphine/naloxone is a new option for the management of opioid dependence. It has a reduced potential for abuse or misuse compared with methadone and buprenorphine alone, and has a long half-life allowing less frequent dosing. Buprenorphine/naloxone appears to be well suited for the management of opioid dependence in an office-based setting. The aim of this study was to evaluate the efficacy and safety of a buprenorphine/naloxone combination treatment in an office-based setting. Therefore, we evaluated the effect on misuse/diversion, quality of care, quality of life and service delivery. Seventy-eight patients were switched to buprenorphine/naloxone from either methadone or buprenorphine alone; the median duration of previous buprenorphine or methadone treatment was 10 years. Patients received buprenorphine/naloxone and were evaluated throughout a 1-year follow-up period. Treatment was self-administered by the patients every 2 weeks and the mean buprenorphine dosage at 1 year was 8 mg/day. Comparisons were made before and after the switch for patients who switched from buprenorphine alone to buprenorphine/naloxone. Switching to buprenorphine/naloxone was not associated with clinically relevant problems in 50% of patients studied. Buprenorphine/naloxone provided satisfactory coverage of withdrawal symptoms in 78.1% of patients, and 50% of patients were satisfied with buprenorphine/naloxone therapy. Seventy-eight per cent of patients reported improved psychosocial functioning. The majority of patients (approximately 85%) were negative for opioids during toxicological testing. A significantly higher proportion of treatment recipients were highly satisfied during buprenorphine/naloxone administration (p < 0.001 compared with buprenorphine given before the switch). Other outcomes were similar during buprenorphine and buprenorphine/naloxone administration. Fortnightly self-administration of buprenorphine/naloxone appeared to be cost saving for the clinic. Buprenorphine/naloxone is an effective and safe treatment option for the outpatient management of opioid dependence. PMID:20450244

  1. Genetic variation in OPRD1 and the response to treatment for opioid dependence with buprenorphine in European American females

    PubMed Central

    Clarke, Toni-Kim; Crist, Richard C.; Ang, Alfonso; Ambrose-Lanci, Lisa M.; Lohoff, Falk W.; Saxon, Andrew J.; Ling, Walter; Hillhouse, Maureen P.; Bruce, R. Douglas; Woody, George; Berrettini, Wade H.

    2013-01-01

    Two commonly prescribed treatments for opioid addiction are methadone and buprenorphine. While these drugs show some efficacy in treating opioid dependence, treatment response varies among individuals. It is likely that genetic factors play a role in determining treatment outcome. This study analyses the pharmacogenetic association of 6 polymorphisms in OPRD1, the gene encoding the delta-opioid receptor, on treatment outcome in 582 opioid addicted European Americans randomized to either methadone or buprenorphine/naloxone ((Suboxone®) over the course of a 24 week open-label clinical trial. Treatment outcome was assessed as the number of missed or opioid positive urine drug screens over the 24 weeks. In the total sample, no SNPs in OPRD1 were significantly associated with treatment outcome in either treatment arm. However, sex-specific analyses revealed 2 intronic SNPs (rs581111 and rs529520) that predicted treatment outcome in females treated with buprenorphine. Females with the AA or AG genotypes at rs581111 had significantly worse outcomes than those with the GG genotype when treated with buprenorphine (p=0.03, RR=1.67, 95% C.I.[1.06-2.1]). For rs529520, females with the AA genotype had a significantly worse outcome than those with the CC genotype when (p=0.006, RR=2.15, 95%C.I.[1.3-2.29]). No significant associations were detected in males. These findings suggest that rs581111 and rs52920 may be useful when considering treatment options for female opioid addicts, however confirmation in an independent sample is warranted. PMID:24126707

  2. Correlates of Nine-Month Retention following Interim Buprenorphine-Naloxone Treatment in Opioid Dependence: A Pilot Study

    PubMed Central

    HÃ¥kansson, A.; Widinghoff, C.; Abrahamsson, T.; Gedeon, C.

    2016-01-01

    Interim medication-only treatment has been suggested for the initiation of opioid maintenance treatment (OMT) in opioid-dependent subjects, but this rarely has been studied using buprenorphine instead of methadone. Following a pilot trial assessing interim buprenorphine-naloxone treatment in order to facilitate transfer into OMT, we here aimed to study retention, and potential correlates of retention, in full-scale treatment. Thirty-six patients successfully referred from a waiting list through an interim treatment phase were followed for nine months in OMT. Baseline characteristics, as well as urine analyses during the interim phase and during full-scale OMT, were studied as potential correlates of retention. The nine-month retention in OMT was 83 percent (n = 30). While interim-phase urine samples positive for benzodiazepines did not significantly predict dropout from full-scale OMT (p = 0.09), urine samples positive for benzodiazepines within full-scale OMT were significantly associated with dropout (p < 0.01), in contrast to other substances and baseline characteristics. Retention remained high through nine months in this pilot study sample of patients referred through buprenorphine-naloxone interim treatment, but use of benzodiazepines is problematic, and the present data suggest that it may be associated with treatment dropout. PMID:26904355

  3. Comparative treatment and mortality correlates and adverse event profile of implant naltrexone and sublingual buprenorphine.

    PubMed

    Reece, Albert Stuart

    2009-10-01

    There is increasing interest in the use of implantable naltrexone as a new treatment for opiate dependence. This center has been one of the leaders in this form of treatment in Australia and has recently completed a registry-controlled review of our mortality data. As part of the study of the safety profile of this therapy, we were interested to review both the treatment correlates of previously presented mortality data and of adverse events. A total of 255 naltrexone implant therapy (NIT) and 2,518 buprenorphine (BUP) patients were followed for 1,322.22 and 8,030.02 patient-years, respectively. NIT patients had significantly longer days in treatment per episode (mean +/- standard deviation, 238.32 +/- 110.11 vs. 46.96 +/- 109.79), total treatment duration (371.21 +/- 284.64 vs. 162.50 +/- 245.76), and mean treatment times but fewer treatment episodes than BUP (all p < .0001). Serious local tissue reaction or infection each occurred in 1% of 200 NIT episodes. These data show that NIT economizes treatment resources without compromising safety concerns. PMID:19394789

  4. Integrating Buprenorphine Maintenance Therapy into Federally Qualified Health Centers: Real World Substance Abuse Treatment Outcomes

    PubMed Central

    Haddad, Marwan S.; Zelenev, Alexei; Altice, Frederick L.

    2013-01-01

    Background Few studies have examined real world effectiveness of integrated buprenorphine maintenance treatment (BMT) programs in federally qualified health centers (FQHCs). Methods Opioid dependent patients (N=266) inducted on buprenorphine between July 2007 and December 2008 were retrospectively assessed at Connecticut’s largest FQHC network. Six-month BMT retention and opioid-free time were collected longitudinally from electronic health records; 136 (51.1%) of patients were followed for at least 12 months. Results Participants had a mean age of 40.1 years, were primarily male (69.2%) and treated by family practitioners (70.3%). Co-morbidity included HCV infection (59.8%), mood disorders (71.8%) and concomitant cocaine use (59%). Retention on BMT was 56.8% at 6 months and 61.6% at 12 months for the subset observed over 1 year. Not being retained on BMT at 12 months was associated with cocaine use (AOR=2.18; 95% CI=1.35–3.50) while prescription of psychiatric medication (AOR=0.36; 95% CI 0.20–0.62) and receiving on-site substance abuse counseling (AOR=0.34; 95% CI 0.19, 0.59) improved retention. Two thirds of the participants experienced at least one BMT gap of 2 or more weeks with a mean gap length of 116.4 days. Conclusions Integrating BMT in this large FQHC network resulted in retention rates similarly reported in clinical trials, but emphasizes the need for providing substance abuse counseling and screening and treating medical and psychiatric comorbidity. PMID:23332439

  5. Primary tumour growth in an orthotopic osteosarcoma mouse model is not influenced by analgesic treatment with buprenorphine and meloxicam.

    PubMed

    Husmann, K; Arlt, M J E; Jirkof, P; Arras, M; Born, W; Fuchs, B

    2015-10-01

    Little is known about the treatment of bone pain in animal models of bone cancer. In the present study, the orthotopic 143-B human osteosarcoma xenotransplantation model was used to address the following questions: (1) Can repetitive analgesic treatment extend the experimental period by prolonging the time to reach humane endpoints and (2) Does repetitive analgesic treatment affect bone tumour development and metastasis? The analgesics, buprenorphine and meloxicam, were either applied individually or in combination at 12?h intervals as soon as the animals began to avoid using the tumour cell injected leg. While control mice treated with NaCl showed continuous body weight loss, the major criterion previously for terminating the experiments, animals treated with analgesic substances did not. The control mice had to be sacrificed 26 days after tumour cell injection, whereas the groups of animals with the different pain treatments were euthanized after an additional eight days. Importantly, primary intratibial tumour growth was not affected in any of the experimental groups by any of the pain treatment procedures. Between days 26 and 34 after tumour cell injection an increase of about 100% of the number of lung metastases was found for the groups treated with buprenorphine alone or together with meloxicam, but not for the group treated with meloxicam alone. In summary, the results indicated that both buprenorphine and meloxicam are suitable analgesics for prolonging the experimental periods in an experimental intratibial osteosarcoma mouse model. PMID:25650386

  6. Buprenorphine, methadone, and morphine treatment during pregnancy: behavioral effects on the offspring in rats

    PubMed Central

    Chen, Hwei-Hsien; Chiang, Yao-Chang; Yuan, Zung Fan; Kuo, Chung-Chih; Lai, Mei-Dan; Hung, Tsai-Wei; Ho, Ing-kang; Chen, Shao-Tsu

    2015-01-01

    Methadone and buprenorphine are widely used for treating people with opioid dependence, including pregnant women. Prenatal exposure to opioids has devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. This study aimed at comparing the behavioral outcomes of young rats prenatally exposed to buprenorphine, methadone, and morphine. Pregnant Sprague-Dawley rats were administered saline, morphine, methadone, and buprenorphine during embryonic days 3–20. The cognitive function, social interaction, anxiety-like behaviors, and locomotor activity of offsprings were examined by novel object recognition test, social interaction test, light–dark transition test, elevated plus-maze, and open-field test between 6 weeks and 10 weeks of age. Prenatal exposure to methadone and buprenorphine did not affect locomotor activity, but significantly impaired novel object recognition and social interaction in both male and female offsprings in the same manner as morphine. Although prenatal exposure to methadone or buprenorphine increased anxiety-like behaviors in the light–dark transition in both male and female offsprings, the effects were less pronounced as compared to that of morphine. Methadone affected elevated plus-maze in both sex, but buprenorphine only affected the female offsprings. These findings suggest that buprenorphine and methadone maintenance therapy for pregnant women, like morphine, produced detrimental effects on cognitive function and social behaviors, whereas the offsprings of such women might have a lower risk of developing anxiety disorders. PMID:25834439

  7. Buprenorphine, methadone, and morphine treatment during pregnancy: behavioral effects on the offspring in rats.

    PubMed

    Chen, Hwei-Hsien; Chiang, Yao-Chang; Yuan, Zung Fan; Kuo, Chung-Chih; Lai, Mei-Dan; Hung, Tsai-Wei; Ho, Ing-Kang; Chen, Shao-Tsu

    2015-01-01

    Methadone and buprenorphine are widely used for treating people with opioid dependence, including pregnant women. Prenatal exposure to opioids has devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. This study aimed at comparing the behavioral outcomes of young rats prenatally exposed to buprenorphine, methadone, and morphine. Pregnant Sprague-Dawley rats were administered saline, morphine, methadone, and buprenorphine during embryonic days 3-20. The cognitive function, social interaction, anxiety-like behaviors, and locomotor activity of offsprings were examined by novel object recognition test, social interaction test, light-dark transition test, elevated plus-maze, and open-field test between 6 weeks and 10 weeks of age. Prenatal exposure to methadone and buprenorphine did not affect locomotor activity, but significantly impaired novel object recognition and social interaction in both male and female offsprings in the same manner as morphine. Although prenatal exposure to methadone or buprenorphine increased anxiety-like behaviors in the light-dark transition in both male and female offsprings, the effects were less pronounced as compared to that of morphine. Methadone affected elevated plus-maze in both sex, but buprenorphine only affected the female offsprings. These findings suggest that buprenorphine and methadone maintenance therapy for pregnant women, like morphine, produced detrimental effects on cognitive function and social behaviors, whereas the offsprings of such women might have a lower risk of developing anxiety disorders. PMID:25834439

  8. Patient Perspectives on Buprenorphine/Naloxone: A Qualitative Study of Retention During the Starting Treatment with Agonist Replacement Therapies (START) Study

    PubMed Central

    Teruya, Cheryl; Schwartz, Robert P.; Mitchell, Shannon Gwin; Hasson, Albert L.; Thomas, Christie; Buoncristiani, Samantha H.; Hser, Yih-Ing; Wiest, Katharina; Cohen, Allan J.; Glick, Naomi; Jacobs, Petra; McLaughlin, Paul; Ling, Walter

    2014-01-01

    This study examines the barriers and facilitators of retention among patients receiving buprenorphine/naloxone at eight community-based opioid treatment programs across the United States. Participants (n=105) were recruited up to three-and-a-half years after having participated in a randomized clinical trial comparing the effect of buprenorphine/naloxone and methadone on liver function. Semi-structured interviews were conducted with 67 patients provided with buprenorphine/naloxone who had terminated early and 38 patients who had completed at least 24 weeks of the trial. Qualitative data were analyzed using the constant comparison method. Barriers to buprenorphine/naloxone retention that emerged included factors associated with: (1) the design of the clinical trial, (2) negative medication or treatment experience, and (3) personal circumstances. The facilitators comprised: (1) positive experience with the medication, (2) personal determination and commitment to complete, and (3) staff encouragement and support. The themes drawn from interviews highlight the importance of considering patients’ prior experience with buprenorphine/naloxone and methadone, medication preference, personal circumstances, and motivation to abstain from illicit use or misuse of opioids, as these may influence retention. Ongoing education of patients and staff regarding buprenorphine/naloxone, especially in comparison to methadone, and support from staff and peers are essential. PMID:25364994

  9. Transdermal buprenorphine in the treatment of cancer and non-cancer pain - the results of multicenter studies in Poland.

    PubMed

    Przeklasa-Muszy?ska, Anna; Dobrogowski, Jan

    2011-01-01

    This was a multicenter, non-interventional, post-marketing study that aimed to evaluate the analgesic activity, safety of use, safety profile and adverse drug reactions of transdermal buprenorphine (Transtec 35, 52.5 and 70 ?g/h) during the treatment of moderate to severe chronic cancer and non-cancer pain. The study was performed in Poland by 339 doctors. The study involved 4,030 general practice outpatients (managed by primary care physicians), pain therapy center patients, specialist outpatient clinic patients as well as patients treated in inpatients units. The recruitment process began in September of 2007, and the study was completed in October of 2008. The study has been reported to the Central Register of Clinical Trials in Poland; it was also in accordance with the requirements of the Polish Pharmaceutical Law in force. The objective of the study was to evaluate the efficacy, safety of use and application of transdermal buprenorphine in patients with moderate to severe cancer pain and in patients with severe, non-malignant pain in the course of other diseases. Patients were enrolled if their pain was not well-controlled after using non-opioid analgesics. Another objective of the study was to monitor adverse drug reactions of transdermal buprenorphine reported by patients or noted by the doctors during the study visits. This first such multicenter study in Poland has confirmed high efficacy and good tolerability of buprenorphine and, therefore, confirmed its usefulness in the treatment of moderate to severe cancer pain as well as in the treatment of severe pain in patients with non-cancer pain that cannot be effectively treated with non-opioid analgesics. PMID:22001981

  10. Retention on Buprenorphine Treatment Reduces Emergency Department Utilization, But Not Hospitalization Among Treatment-Seeking Patients With Opioid Dependence

    PubMed Central

    Schwarz, Ryan; Zelenev, Alexei; Bruce, R. Douglas; Altice, Frederick L.

    2012-01-01

    Drug users are marginalized from typical primary care, often resulting in emergency department (ED) usage and hospitalization due to late-stage disease. Though data suggest methadone decreases such fragmented healthcare utilization (HCU), the impact of buprenorphine maintenance treatment (BMT) on HCU is unknown. Chart review was conducted on opioid dependent patients seeking BMT, comparing individuals (N=59) who left BMT ≤ 3 days with those retained on BMT (N=150), for ED use and hospitalization. Using negative binomial regressions, including comparison of time before BMT induction, ED utilization and hospitalization was assessed. Overall, ED utilization was 0.93 events per person year and was significantly reduced by BMT, with increasing time (retention) on BMT. BMT had no significant effect on hospitalizations or average length of stay. PMID:22534003

  11. Cost Effectiveness of Injectable Extended Release Naltrexone Compared to Methadone Maintenance and Buprenorphine Maintenance Treatment for Opioid Dependence

    PubMed Central

    Jackson, Heide; Mandell, Kara; Johnson, Kimberly; Chatterjee, Debanjana; Vanness, David J.

    2015-01-01

    Background The aim of this study was to estimate the cost-effectiveness of injectable extended release naltrexone (XR-NTX) compared to methadone maintenance and buprenorphine maintenance treatment (MMT and BMT respectively) for adult males enrolled in treatment for opioid dependence in the United States from the perspective of state-level addiction treatment payers. Methods We used a Markov model with daily time cycles to estimate the incremental cost per opioid-free day in a simulated cohort of adult males ages 18–65 over a six-month period from the state health program perspective. Results XR-NTX is predicted to be more effective and more costly than methadone or buprenorphine in our target population, with an incremental cost per opioid-free day gained relative to the next-most effective treatment (MMT) of $72. The cost-effectiveness of XR-NTX relative to MMT was driven by its effectiveness in deterring opioid use while receiving treatment. Conclusions XR-NTX is a cost-effective medication for treating opioid dependence if state addiction treatment payers are willing to pay at least $72 per opioid-free day. PMID:25775099

  12. Buprenorphine is protective against the depressive effects of norbuprenorphine on ventilation

    SciTech Connect

    Megarbane, Bruno . E-mail: bruno-megarbane@wanadoo.fr; Marie, Nicolas; Pirnay, Stephane; Borron, Stephen W.; Gueye, Papa N.; Risede, Patricia; Monier, Claire; Noble, Florence; Baud, Frederic J.

    2006-05-01

    High dose buprenorphine is used as substitution treatment in heroin addiction. However, deaths have been reported in addicts using buprenorphine. The role of norbuprenorphine, an N-dealkyl metabolite of buprenorphine, was hypothesized to explain these fatal cases. We determined the median intravenous lethal dose (LD{sub 5}) of norbuprenorphine in male Sprague-Dawley rats. The effects of a single intravenous dose of 3 or 9 mg/kg norbuprenorphine alone on arterial blood gases were studied. Finally, the effect of pre- and post-administrations of buprenorphine on norbuprenorphine-induced changes on arterial blood gases were analyzed. Norbuprenorphine's LD{sub 5} was 10 mg kg{sup -1}. Norbuprenorphine 3 mg kg{sup -1} produces the rapid onset of sustained respiratory depression, as demonstrated at 20 min by a maximal significant increase in PaCO{sub 2} (8.4 {+-} 0.9 versus 5.7 {+-} 0.1 kPa), decrease in arterial pH (7.25 {+-} 0.06 versus 7.44 {+-} 0.01), and hypoxia (8.3 {+-} 0.6 versus 11.1 {+-} 0.2 kPa). Buprenorphine not only protected against the effects of 3 mg kg{sup -1} norbuprenorphine in a dose-dependent manner but also reversed the effects when given afterward. Binding experiments suggest a role for mu- and to a lesser extent for delta-opioid receptors in buprenorphine protective effect against norbuprenorphine-induced respiratory depression. In conclusion, our data clearly show that norbuprenorphine alone causes important deleterious effects on ventilation in rats. However, buprenorphine protective effect calls into question the role for norbuprenorphine in respiratory toxicity associated with buprenorphine use.

  13. “The chief of the services is very enthusiastic about it”: A qualitative study of the adoption of buprenorphine for opioid addiction treatment

    PubMed Central

    Green, Carla A.; McCarty, Dennis; Mertens, Jennifer; Lynch, Frances L.; Hilde, Anadam; Firemark, Alison; Weisner, Constance M.; Pating, David; Anderson, Bradley M.

    2013-01-01

    Qualified physicians may prescribe buprenorphine to treat opioid dependence, but medication use remains controversial. We examined adoption of buprenorphine in two not-for-profit integrated health plans, over time, completing 101 semi-structured interviews with clinicians and clinician-administrators from primary and specialty care. Transcripts were reviewed, coded, and analyzed. A strong leader championing the new treatment was critical for adoption in both health plans. Once clinicians began using buprenorphine, patients’ and other clinicians’ experiences affected decisions more than did the champion. With experience, protocols developed to manage unsuccessful patients and changed to support maintenance rather than detoxification. Diffusion outside addiction and mental health settings was nonexistent; primary care clinicians cited scope-of-practice issues and referred patients to specialty care. With greater diffusion came questions about long-term use and safety. Recognizing how implementation processes develop may suggest where, when, and how to best expend resources to increase adoption of such treatments. PMID:24268947

  14. Safety, Tolerability, and Clinical Effect of Low-Dose Buprenorphine for Treatment-Resistant Depression in Mid-Life and Older Adults

    PubMed Central

    Karp, Jordan F.; Butters, Meryl A; Begley, Amy; Miller, Mark D.; Lenze, Eric J.; Blumberger, Daniel; Mulsant, Benoit; Reynolds, Charles F.

    2014-01-01

    Objective Describe the clinical effect and safety of low-dose buprenorphine, a kappa-opioid receptor antagonist, for treatment-resistant depression (TRD) in mid-life and older adults. Method Using an open-label protocol, buprenorphine was prescribed for 15 adults age 50 and older with TRD, diagnosed with the SCID for DSM-IV, between 6/2010-6/2011. The titrated dose of buprenorphine ranged from 0.2 mg-1.6 mg/day. We assessed clinical change in depression, anxiety, sleep, positive and negative affect, and quality of life. Tolerability was assessed by documenting change in vital signs, weight, cognitive function, and side effects. Clinical response durability was assessed 8 weeks after discontinuation of the buprenorphine. Results The average dose of buprenorphine was 0.4 mg/day (average maximum dose = 0.7 mg/day). The average depression score (MADRS) at baseline was 27.0 (SD=7.3); and at week 8, 9.5 (SD=9.5). There was a sharp decline in depression severity during the first three weeks of exposure (mean delta=?15.0 (SD=7.9)). Depression-specific items tapping pessimism and sadness improved during exposure, supporting a true antidepressant effect. Treatment emergent side effects (in particular nausea and constipation) were not sustained, vital signs and weight remained stable, and executive function and learning improved from pre- to post-treatment. Conclusion Low-dose buprenorphine may be a novel-mechanism medication that provides a rapid and sustained improvement for older adults with TRD. Placebo-controlled trials of longer duration are required to assess efficacy, safety, and physiological and psychological effects of extended exposure to this medication. PMID:25191915

  15. Use of conventional, complementary, and alternative treatments for pain among individuals seeking primary care treatment with buprenorphine-naloxone

    PubMed Central

    Barry, Declan T.; Savant, Jonathan D.; Beitel, Mark; Cutter, Christopher J.; Moore, Brent A.; Schottenfeld, Richard S.; Fiellin, David A.

    2012-01-01

    Previous studies have not examined patterns of pain treatment use among patients seeking office-based buprenorphine-naloxone treatment (BNT) for opioid dependence. Objectives To examine, among individuals with pain seeking BNT for opioid dependence, the use of pain treatment modalities, perceived efficacy of prior pain treatment, and interest in pursuing pain treatment while in BNT. Methods 244 patients seeking office-based BNT for opioid dependence completed measures of demographics, pain status (i.e. “chronic pain (CP)” [pain lasting at least 3 months] vs. “some pain (SP)” [pain in the past week not meeting the duration criteria for chronic pain]), pain treatment use, perceived efficacy of prior pain treatment, and interest in receiving pain treatment while in BNT. Results In comparison to the SP group (N = 87), the CP group (N = 88) was more likely to report past-week medical use of opioid medication (AOR 3.2, 95% CI 1.2–8.4), lifetime medical use of non-opioid prescribed medication (AOR 2.2, 95% CI 1.1–4.7), and lifetime use of prayer (AOR 2.8, 95% CI 1.2–6.5), and was less likely to report lifetime use of yoga (AOR 0.2, 95% CI 0.1–0.7) to treat pain. While the two pain groups did not differ on levels of perceived efficacy of prior lifetime pain treatments, in comparison to the SP group, the CP group was more likely to report interest in receiving pain treatment while in BNT (P < 0.001). Conclusions Individuals with pain seeking BNT for opioid dependence report a wide range of conventional, complementary, and alternative pain-related treatments and are interested (especially those with CP) in receiving pain management services along with BNT. PMID:23041680

  16. Treatment Retention among Patients Randomized to Buprenorphine/Naloxone Compared to Methadone in A Multi-site Trial

    PubMed Central

    Hser, Yih-Ing; Saxon, Andrew J.; Huang, David; Hasson, Al; Thomas, Christie; Hillhouse, Maureen; Jacobs, Petra; Teruya, Cheryl; McLaughlin, Paul; Wiest, Katharina; Cohen, Allan; Ling, Walter

    2013-01-01

    Aims To examine patient and medication characteristics associated with retention and continued illicit opioid use in methadone (MET) versus buprenorphine/naloxone (BUP) treatment for opioid dependence. Design/Settings/Participants This secondary analysis included 1,267 opioid-dependent individuals participating in 9 opioid treatment programs between 2006 and 2009 and randomized to receive open-label BUP or MET for 24 weeks. Measurements The analyses included measures of patient characteristics at baseline (demographics; use of alcohol, cigarettes, and illicit drugs; self-rated mental and physical health), medication dose and urine drug screens during treatment, and treatment completion and days in treatment during the 24 week trial. Findings The treatment completion rate was 74% for MET vs. 46% for BUP (p<.01); the rate among MET participants increased to 80% when the maximum MET dose reached or exceeded 60mg/day. With BUP, the completion rate increased linearly with higher doses, reaching 60% with doses of 30–32mg/day. Of those remaining in treatment, positive opioid urine results were significantly lower (OR=0.63, 95%CI=0.52–0.76, p<.01) among BUP relative to MET participants during the first 9 weeks of treatment. Higher medication dose was related to lower opiate use, more so among BUP patients. A Cox proportional hazards model revealed factors associated with dropout: (1) BUP (vs. MET, HR=1.61, CI:1.20–2.15), (2) lower medication dose (<16mg for BUP, <60mg for MET; HR=3.09, CI:2.19–4.37), (3) the interaction of dose and treatment condition (those with higher BUP dose were 1.04 times more likely to drop out than those with lower MET dose, and (4) being younger, Hispanic, and using heroin or other substances during treatment. Conclusions Provision of methadone appears to be associated with better retention in treatment for opioid dependence than buprenorphine, as does use of provision of higher doses of both medications. Provision of buprenorphine is associated with lower continued use of illicit opioids. PMID:23961726

  17. [The transdermal 7-day buprenorphine patch--an effective and safe treatment option, if tramadol or tilidate/naloxone is insufficient. Results of a non-interventional study].

    PubMed

    Schutter, U; Ritzdorf, I; Heckes, B

    2010-07-01

    The transdermal 7-day buprenorphine matrix patch provides a constant and user-friendly pain management when chronic musculoskeletal pain requires opioids. This analysis of clinical routine data evaluated the benefit of this treatment for patients previously receiving oral long-term treatment with weak opioids alone. Data of 310 patients previously treated with tramadol or tildate/naloxone and part of a multicentre observational study with 3295 patients were analyzed. In 89.7% of the 310 patients oral treatment with weak opioids was replaced by the 7-day buprenorphine patch due to insufficient analgesia. During treatment with the 7-day buprenorphine patch there was a clinically significant decrease of the mean pain intensity at rest during the day from 5.7 to 2.9, on physical effort during the day from 7.3 to 3.8 and at night from 5.2 to 2.3 (11-point NRS scale, p < or = 0.001). In addition, quality of life aspects such as mobility, self-reliance and quality of sleep improved, which are relevant for individual patient satisfaction with pain management. For patients with previous long-term tramadol or tilidate/naloxone treatment the switch to the 7-day buprenorphine matrix patch proved to be effective and safe for the management of chronic pain. The user-friendly 7-day application interval contributes to improving compliance and a reducing exposure to tablets. PMID:21591321

  18. Office-Based Opioid Treatment with Buprenorphine (OBOT-B): Statewide Implementation of the Massachusetts Collaborative Care Model in Community Health Centers.

    PubMed

    LaBelle, Colleen T; Han, Steve Choongheon; Bergeron, Alexis; Samet, Jeffrey H

    2016-01-01

    We describe a Massachusetts Bureau of Substance Abuse Services' (BSAS) initiative to disseminate the office-based opioid treatment with buprenorphine (OBOT-B) Massachusetts Model from its development at Boston Medical Center (BMC) to its implementation at fourteen community health centers (CHCs) beginning in 2007. The Massachusetts Collaborative Care Model for the delivery of opioid agonist therapy with buprenorphine, in which nurses working with physicians play a central role in the evaluation and monitoring of patients, holds promise for the effective expansion of treatment for opioid use disorders. The training of and technical assistance for the OBOT nurses as well as a limited program assessment are described. Data spanning 6years (2007-2013) report patient demographics, prior treatment for opioid use disorders, history of overdose, housing, and employment. The expansion of OBOT to the fourteen CHCs increased the number of physicians who were "waivered" (i.e., enabling their prescribing of buprenorphine) by 375%, from 24 to 114, within 3years. During this period the annual admissions of OBOT patients to CHCs markedly increased. Dissemination of the Massachusetts Model of the Office-Based Opioid Treatment with Buprenorphine employing a collaborative care model with a central role for nursing enabled implementation of effective treatment for patients with an opioid use disorder at community health centers throughout Massachusetts while effectively engaging primary care physicians in this endeavor. PMID:26233698

  19. Outcomes among buprenorphine-naloxone primary care patients after Hurricane Sandy

    PubMed Central

    2014-01-01

    Background The extent of damage in New York City following Hurricane Sandy in October 2012 was unprecedented. Bellevue Hospital Center (BHC), a tertiary public hospital, was evacuated and temporarily closed as a result of hurricane-related damages. BHC’s large primary care office-based buprenorphine clinic was relocated to an affiliate public hospital for three weeks. The extent of environmental damage and ensuing service disruption effects on rates of illicit drug, tobacco, and alcohol misuse, buprenorphine medication supply disruptions, or direct resource losses among office-based buprenorphine patients is to date unknown. Methods A quantitative and qualitative semi-structured survey was administered to patients in BHC’s primary care buprenorphine program starting one month after the hurricane. Survey domains included: housing and employment disruptions; social and economic support; treatment outcomes (buprenorphine adherence and ability to get care), and tobacco, alcohol, and drug use. Open-ended questions probed general patient experiences related to the storm, coping strategies, and associated disruptions. Results There were 132 patients enrolled in the clinic at the time of the storm; of those, 91 patients were recruited to the survey, and 89 completed (98% of those invited). Illicit opioid misuse was rare, with 7 respondents reporting increased heroin or illicit prescription opioid use following Sandy. Roughly half of respondents reported disruption of their buprenorphine-naloxone medication supply post-event, and self-lowering of daily doses to prolong supply was common. Additional buprenorphine was obtained through unscheduled telephone or written refills from relocated Bellevue providers, informally from friends and family, and, more rarely, from drug dealers. Conclusions The findings highlight the relative adaptability of public sector office-based buprenorphine treatment during and after a significant natural disaster. Only minimal increases in self-reported substance use were reported despite many disruptions to regular buprenorphine supplies and previous daily doses. Informal supplies of substitute buprenorphine from family and friends was common. Remote telephone refill support and a temporary back-up location that provided written prescription refills and medication dispensing for uninsured patients enabled some patients to maintain an adequate medication supply. Such adaptive strategies to ensure medication maintenance continuity pre/post natural disasters likely minimize poor treatment outcomes. PMID:24467734

  20. Timing of buprenorphine adoption by privately funded substance abuse treatment programs: The role of institutional and resource-based inter-organizational linkages

    PubMed Central

    Savage, Sarah A.; Abraham, Amanda J.; Knudsen, Hannah K.; Rothrauff, Tanja C.; Roman, Paul M.

    2011-01-01

    Identifying facilitators of more rapid buprenorphine adoption may increase access to this effective treatment for opioid dependence. Using a diffusion of innovations theoretical framework, we examine the extent to which programs’ inter-organizational institutional and resource-based linkages predict the likelihood of being an earlier, later, or non-adopter of buprenorphine. Data were derived from face-to-face interviews with administrators of 345 privately funded substance abuse treatment programs in 2007–2008. Results of multinomial logistic regression models show that inter-organizational and resource linkages were associated with timing of adoption. Programs reporting membership in provider associations were more likely to be earlier adopters of buprenorphine. Programs that relied more on resources linkages, such as the detailing activities by pharmaceutical companies and the NIDA website, were more likely to be earlier adopters of buprenorphine. These findings suggest that institutional and resource-based inter-organizational linkages may expose programs to effective treatments, thereby facilitating more rapid and sustained adoption of innovative treatment techniques. PMID:21831565

  1. Patients more likely to engage in treatment at 30 days when given buprenorphine in the ED, referred for follow-up.

    PubMed

    2015-08-01

    A new randomized trial shows patients who present to the ED with opioid dependence are much more likely to engage in treatment when they receive buprenorphine along with coordinated follow-up than when they just receive a brief intervention and a facilitated referral for treatment or just screening and referral. However, barriers to prescribing are robust, and many ED leaders are not persuaded they should be in the business of providing treatment for addiction. In the trial, at 30 days 78% of patients in the buprenorphine group (89 of 114 patients) were engaged in addiction treatment, compared with just 45% of the patients in the brief intervention group (50 of 111 patients) and 37% of patients in the referral group (38 of 102 patients). To prescribe buprenorphine for addiction disease, providers must undergo training and pass a test to obtain a DEA waiver; they are limited to treating 100 patients. While experts note there are not enough providers to prescribe buprenorphine and provide the follow-up needed to patients with addiction disease, they also acknowledge concerns about drug diversion as well as potential problems with capacity if EDs take a larger role in treating addiction. PMID:26258203

  2. Dosing considerations with transdermal formulations of fentanyl and buprenorphine for the treatment of cancer pain.

    PubMed

    Skaer, Tracy L

    2014-01-01

    Opioids continue to be first-line pharmacotherapy for patients suffering from cancer pain. Unfortunately, subtherapeutic dosage prescribing of pain medications remains common, and many cancer patients continue to suffer and experience diminished quality of life. A large variety of therapeutic options are available for cancer pain patients. Analgesic pharmacotherapy is based on the patient's self-report of pain intensity and should be tailored to meet the requirements of each individual. Most, if not all, cancer pain patients will ultimately require modifications in their opioid pharmacotherapy. When changes in a patient's medication regimen are needed, adequate pain control is best maintained through appropriate dosage conversion, scheduling immediate release medication for withdrawal prevention, and providing as needed dosing for breakthrough pain. Transdermal opioids are noninvasive, cause less constipation and sedation when compared to oral opioids, and may improve patient compliance. A relative potency of 100:1 is recommended when converting the patient from oral morphine to transdermal fentanyl. Based on the limited data available, there is significant interpatient variability with transdermal buprenorphine and equipotency recommendations from oral morphine of 75:1-110:1 have been suggested. Cancer patients may require larger transdermal buprenorphine doses to control their pain and may respond better to a more aggressive 75-100:1 potency ratio. This review outlines the prescribing of transdermal fentanyl and transdermal buprenorphine including how to safely and effectively convert to and use them for those with cancer pain. PMID:25170278

  3. Dosing considerations with transdermal formulations of fentanyl and buprenorphine for the treatment of cancer pain

    PubMed Central

    Skaer, Tracy L

    2014-01-01

    Opioids continue to be first-line pharmacotherapy for patients suffering from cancer pain. Unfortunately, subtherapeutic dosage prescribing of pain medications remains common, and many cancer patients continue to suffer and experience diminished quality of life. A large variety of therapeutic options are available for cancer pain patients. Analgesic pharmacotherapy is based on the patient’s self-report of pain intensity and should be tailored to meet the requirements of each individual. Most, if not all, cancer pain patients will ultimately require modifications in their opioid pharmacotherapy. When changes in a patient’s medication regimen are needed, adequate pain control is best maintained through appropriate dosage conversion, scheduling immediate release medication for withdrawal prevention, and providing as needed dosing for breakthrough pain. Transdermal opioids are noninvasive, cause less constipation and sedation when compared to oral opioids, and may improve patient compliance. A relative potency of 100:1 is recommended when converting the patient from oral morphine to transdermal fentanyl. Based on the limited data available, there is significant interpatient variability with transdermal buprenorphine and equipotency recommendations from oral morphine of 75:1–110:1 have been suggested. Cancer patients may require larger transdermal buprenorphine doses to control their pain and may respond better to a more aggressive 75–100:1 potency ratio. This review outlines the prescribing of transdermal fentanyl and transdermal buprenorphine including how to safely and effectively convert to and use them for those with cancer pain. PMID:25170278

  4. Update on the clinical use of buprenorphine

    PubMed Central

    Ducharme, Simon; Fraser, Ronald; Gill, Kathryn

    2012-01-01

    Abstract Objective To review the current evidence on buprenorphine-naloxone for the treatment of opioid-related disorders, with a focus on primary care settings. Quality of evidence MEDLINE and the Cochrane Database of Systematic Reviews were searched. Evidence is mainly level I. Main message Buprenorphine is a partial ?-opioid agonist and ?-opioid antagonist with a long half-life and less abuse potential than methadone. For detoxification, buprenorphine is at least equivalent to methadone and is superior to clonidine. For maintenance treatment, buprenorphine is clearly superior to placebo. Methadone has a slight advantage in terms of retention in treatment, but a stepped approach with initial use of buprenorphine-naloxone is as efficacious. Use of buprenorphine in the primary care setting is feasible, safe, and effective. Authorization to prescribe buprenorphine can be obtained after completing online training. Conclusion Buprenorphine is a safe and effective agent for detoxification from opioids. It can be used as a first-line agent in maintenance programs, owing to its lower abuse potential relative to other opioids. Its effectiveness in primary care settings makes it a useful therapeutic tool for family physicians. PMID:22267618

  5. Barriers to Primary Care Physicians Prescribing Buprenorphine

    PubMed Central

    Hutchinson, Eliza; Catlin, Mary; Andrilla, C. Holly A.; Baldwin, Laura-Mae; Rosenblatt, Roger A.

    2014-01-01

    PURPOSE Despite the efficacy of buprenorphine-naloxone for the treatment of opioid use disorders, few physicians in Washington State use this clinical tool. To address the acute need for this service, a Rural Opioid Addiction Management Project trained 120 Washington physicians in 2010–2011 to use buprenorphine. We conducted this study to determine what proportion of those trained physicians began prescribing this treatment and identify barriers to incorporating this approach into outpatient practice. METHODS We interviewed 92 of 120 physicians (77%), obtaining demographic information, current prescribing status, clinic characteristics, and barriers to prescribing buprenorphine. Residents and 7 physicians who were prescribing buprenorphine at the time of the course were excluded from the study. We analyzed the responses of the 78 remaining respondents. RESULTS Almost all respondents reported positive attitudes toward buprenorphine, but only 22 (28%) reported prescribing buprenorphine. Most (95%, n = 21) new prescribers were family physicians. Physicians who prescribed buprenorphine were more likely to have partners who had received a waiver to prescribe buprenorphine. A lack of institutional support was associated with not prescribing the medication (P = .04). A lack of mental health and psychosocial support was the most frequently cited barrier by both those who prescribe and who do not prescribe buprenorphine. CONCLUSION Interventions before and after training are needed to increase the number of physicians who offer buprenorphine for treatment of addiction. Targeting physicians in clinics that agree in advance to institute services, coupled with technical assistance after they have completed their training, their clinical teams, and their administrations is likely to help more physicians become active providers of this highly effective outpatient treatment. PMID:24615308

  6. The effectiveness of opioid substitution treatments for patients with opioid dependence: a systematic review and multiple treatment comparison protocol

    PubMed Central

    2014-01-01

    Background Opioids are psychoactive analgesic drugs prescribed for pain relief and palliative care. Due to their addictive potential, effort and vigilance in controlling prescriptions is needed to avoid misuse and dependence. Despite the effort, the prevalence of opioid use disorder continues to rise. Opioid substitution therapies are commonly used to treat opioid dependence; however, there is minimal consensus as to which therapy is most effective. Available treatments include methadone, heroin, buprenorphine, as well as naltrexone. This systematic review aims to assess and compare the effect of all available opioid substitution therapies on the treatment of opioid dependence. Methods/Design The authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. The title, abstract, and full-text screening will be completed in duplicate. When appropriate, multiple treatment comparison Bayesian meta-analytic methods will be performed to deduce summary statistics estimating the effectiveness of all opioid substitution therapies in terms of retention and response to treatment (as measured through continued opioid abuse). Discussion Using evidence gained from this systematic review, we anticipate disseminating an objective review of the current available literature on the effectiveness of all opioid substitution therapies for the treatment of opioid use disorder. The results of this systematic review are imperative to the further enhancement of clinical practice in addiction medicine. Systematic review registration PROSPERO CRD42013006507. PMID:25239213

  7. Outcome of heroin-dependent adolescents presenting for opiate substitution treatment.

    PubMed

    Smyth, Bobby P; Fagan, John; Kernan, Kathy

    2012-01-01

    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. PMID:21940134

  8. Therapeutic switch to buprenorphine/naloxone from buprenorphine alone: clinical experience in an Italian addiction centre.

    PubMed

    Montesano, Franco; Zaccone, Domenico; Battaglia, Egidio; Genco, Felice; Mellace, Vincenzo

    2010-01-01

    Pharmacological therapy has an important place in the management of opioid dependence. Methadone has been the mainstay of therapy but has a number of limitations. Buprenorphine monotherapy is another option, but misuse and diversion can have negative consequences. The opioid receptor antagonist, naloxone, has been added to buprenorphine to create a combination product with a reduced potential for misuse and diversion. This study evaluated the use of buprenorphine/naloxone for 24 weeks as a pharmacological management of opioid-dependent patients after therapeutic switch from buprenorphine alone. Patients (n = 43) received sublingual tablets of buprenorphine/naloxone. The buprenorphine dose was 2-24 mg (mean 16). Patients saw a physician, including an interview using a structured data sheet, and had counselling each week. Assessments were performed at week 2 (period 1), week 6 (period 2), week 16 (period 3) and week 24 (period 4). Laboratory immunoenzymatic testing was performed weekly to detect drugs in the urine. The management of withdrawal symptoms was rated as 'satisfactory' by 67% of patients during period 1 and 91% during period 4. The majority of patients was highly satisfied with therapy and considered that buprenorphine/naloxone provided good control of cravings. Two patients dropped out of therapy, but all others continued to receive buprenorphine throughout the study. Approximately 50% of patients stated that they disliked the sensory properties (taste, colour, odour and feel) of buprenorphine/naloxone. Adverse effects were as would be expected on the basis of the mechanism of action of buprenorphine (i.e. opioid-induced constipation) and for patients undergoing drug withdrawal. Only 2% of patients attempted the intravenous misuse of buprenorphine/naloxone, none of whom experienced any gratifying effects. Opioid-dependent patients maintained on buprenorphine monotherapy can be safely switched to a sublingual buprenorphine/naloxone tablet without any loss of treatment effectiveness. Buprenorphine/naloxone can be administered in an outpatient or primary care setting, and effectively controls cravings and withdrawal symptoms. Patient satisfaction was high, making retention in treatment more likely. PMID:20450241

  9. Buprenorphine in cancer pain.

    PubMed

    Davis, Mellar P

    2005-11-01

    Buprenorphine is a broad spectrum, highly lipophilic, and long-acting partial mu opioid receptor agonist that is noncross tolerant to other opioids. Buprenorphine can be given by several routes. Metabolism is through CYP3A4 and CYP2C8 and by conjugases. Constipation and sexual dysfunction appear to be less with buprenorphine than with other opioids. The recent development of a polymer matrix patch delivery system for buprenorphine prevents "dose dumping" and facilitates pain management in those unable to take oral analgesics. Sublingual buprenorphine has been combined with naloxone to prevent illicit conversion to parenteral administration. Buprenorphine has been used extensively to control cancer pain. In certain clinical situations, buprenorphine may have particular advantages over other opioids. PMID:16010532

  10. Adverse effects in children after unintentional buprenorphine exposure.

    PubMed

    Geib, Ann-Jeannette; Babu, Kavita; Ewald, Michele Burns; Boyer, Edward W

    2006-10-01

    Buprenorphine in sublingual formulation was recently introduced to the American market for treatment of opioid dependence. We report a series of 5 toddlers with respiratory and mental-status depression after unintentional buprenorphine exposure. Despite buprenorphine's partial agonist activity and ceiling effect on respiratory depression, all children required hospital admission and either opioid-antagonist therapy or mechanical ventilation. Results of routine urine toxicology screening for opioids were negative in all cases. Confirmatory testing was sent for 1 child and returned with a positive result. The increasing use of buprenorphine as a home-based therapy for opioid addiction in the United States raises public health concerns for the pediatric population. PMID:17015570

  11. Training HIV Physicians to Prescribe Buprenorphine for Opioid Dependence

    ERIC Educational Resources Information Center

    Sullivan, Lynn E.; Tetrault, Jeanette; Bangalore, Deepa; Fiellin, David A.

    2006-01-01

    Few HIV physicians are trained to provide buprenorphine treatment. We conducted a cross-sectional survey to assess the impact of an eight-hour course on the treatment of opioid dependence on HIV physicians' preparedness to prescribe buprenorphine. One hundred thirteen of 257 trained physicians (44%) provided HIV care. Post-course, the majority of…

  12. Training HIV Physicians to Prescribe Buprenorphine for Opioid Dependence

    ERIC Educational Resources Information Center

    Sullivan, Lynn E.; Tetrault, Jeanette; Bangalore, Deepa; Fiellin, David A.

    2006-01-01

    Few HIV physicians are trained to provide buprenorphine treatment. We conducted a cross-sectional survey to assess the impact of an eight-hour course on the treatment of opioid dependence on HIV physicians' preparedness to prescribe buprenorphine. One hundred thirteen of 257 trained physicians (44%) provided HIV care. Post-course, the majority of…

  13. Attitudes toward buprenorphine and methadone among opioid-dependent individuals

    PubMed Central

    Schwartz, Robert P.; Kelly, Sharon M.; O'Grady, Kevin E.; Mitchell, Shannon Gwin; Peterson, James A.; Reisinger, Heather Schacht; Agar, Michael H.; Brown, Barry S.

    2009-01-01

    Attitudes and beliefs about drug abuse treatment have long been known to shape response to that treatment. Two major pharmacological alternatives are available for opioid dependence: methadone, which has been available for the past 40 years, and buprenorphine, a recently-introduced medication. This mixed methods study examined the attitudes of opioid-dependent individuals toward methadone and buprenorphine. A total of 195 participants (n = 140 who were enrolling in one of 6 Baltimore area methadone programs and n = 55 who were out-of-treatment) were administered the Attitudes toward Methadone and toward Buprenorphine Scales and a subset (n = 46) received an ethnographic interview. In-treatment group had significantly more positive attitudes toward methadone than did the out-of-treatment group (p < .001), while they did not differ in their attitudes toward buprenorphine. Both groups had significantly more positive attitudes toward buprenorphine than methadone. Addressing these attitudes may increase treatment entry and retention. PMID:18770082

  14. Predictors of buprenorphine initial outpatient maintenance and dose taper response among non-treatment-seeking heroin dependent volunteers

    PubMed Central

    Woodcock, Eric A.; Lundahl, Leslie H.; Greenwald, Mark K.

    2014-01-01

    Background 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. Methods 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). Results 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 vs. 8 days to opioid-lapse) and nearly half (46.7%) refrained from opioid use during dose taper. Conclusions 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. PMID:25479914

  15. Buprenorphine and Buprenorphine/Naloxone Diversion, Misuse, and Illicit Use: An International Review

    PubMed Central

    Yokell, Michael A.; Zaller, Nickolas D.; Green, Traci C.; Rich, Josiah D.

    2011-01-01

    The diversion, misuse, and non-medically supervised use of buprenorphine and buprenorphine/naloxone by opioid users are reviewed. Buprenorphine and buprenorphine/naloxone are used globally as opioid analgesics and in the treatment of opioid dependency. Diversion of buprenorphine and buprenorphine/naloxone represents a complex medical and social issue, and has been widely documented in various geographical regions throughout the world. We first discuss the clinical properties of buprenorphine and its abuse potential. Second, we discuss its diversion and illicit use on an international level, as well as motivations for those activities. Third, we examine the medical risks and benefits of buprenorphine’s non-medically supervised use and misuse. These risks and benefits include the effect of buprenorphine’s use on HIV risk and the risk of its concomitant use with other medications and drugs of abuse. Finally, we discuss the implications of diversion, misuse, and non-medically supervised use (including potential measures to address issues of diversion); and potential areas for further research. PMID:21466501

  16. Buprenorphine in the workers' compensation setting.

    PubMed

    Colameco, Stephen; Pohl, Mel

    2014-01-01

    Buprenorphine is approved by the Food and Drug Administration for the treatment of chronic pain in low-dose transdermal patch formulations and for the treatment of addiction in high-dose sublingual tablets and films. Clinicians often prescribe these high-dose preparations "off label" for pain management. In the workers' compensation setting, it is particularly important to consider factors such as a) if the injured person has, and is being treated for co-occurring addiction as well as pain; b) if alternative therapies, including opioid withdrawal, were considered prior to initiating buprenorphine treatment; and c) the anticipated duration of treatment. This article reviews buprenorphine's approved indications, formulations, pharmacology, clinical efficacy, and special considerations in the workers' compensation setting. PMID:25162607

  17. Buprenorphine replacement therapy: a confirmed benefit.

    PubMed

    2006-04-01

    (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 consequences of sniffing crushed buprenorphine tablets have not been studied. (10) Deaths have been reported following buprenorphine overdose, but they appear to be less frequent than with methadone (0.2 and 0.7 deaths per 1000 users, respectively in 1998). (11) Approaches designed to help patients stop self-injecting have not been tested in comparative trials. Prescriptions of methadone syrup or an injection opiate may be worth trying when all other measures fail. PMID:16604748

  18. Abuse potential of intranasal buprenorphine versus buprenorphine/naloxone in buprenorphine-maintained heroin users.

    PubMed

    Jones, Jermaine D; Sullivan, Maria A; Vosburg, Suzanne K; Manubay, Jeanne M; Mogali, Shanthi; Metz, Verena; Comer, Sandra D

    2015-07-01

    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. PMID:25060839

  19. Buprenorphine/Naloxone and Methadone Maintenance Treatment Outcomes for Opioid Analgesic, Heroin, and Combined Users: Findings From Starting Treatment With Agonist Replacement Therapies (START)

    PubMed Central

    Potter, Jennifer S.; Marino, Elise N.; Hillhouse, Maureen P.; Nielsen, Suzanne; Wiest, Katharina; Canamar, Catherine P.; Martin, Judith A.; Ang, Alfonso; Baker, Rachael; Saxon, Andrew J.; Ling, Walter

    2013-01-01

    Objective: 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. Method: 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. Results: 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. Conclusions: 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. PMID:23739025

  20. Pain and Associated Substance Use among Opioid Dependent Individuals Seeking Office-Based Treatment with Buprenorphine-Naloxone: A Needs Assessment Study

    PubMed Central

    Barry, Declan T.; Savant, Jonathan D.; Beitel, Mark; Cutter, Christopher J.; Moore, Brent A.; Schottenfeld, Richard S.; Fiellin, David A.

    2012-01-01

    Background and Objectives A paucity of studies has examined the pain experiences of opioid dependent individuals seeking office-based buprenorphine-naloxone treatment (BNT). We set out to examine, among those seeking BNT: (a) the prevalence of pain types (i.e., recent pain, chronic pain), (b) the characteristics of pain (intensity, frequency, duration, interference, location, and genesis), and (c) substance use to alleviate pain. Methods We surveyed 244 consecutive individuals seeking office-based buprenorphine-naloxone treatment (BNT) for opioid dependence about physical pain and associated substance use. Results Thirty-six percent of respondents reported chronic pain (CP) (i.e., pain lasting at least 3 months) and 36% reported “some pain” (SP) (i.e., past week pain not meeting the threshold for CP). In comparison to SP respondents, those with CP were, on average, older; reported greater current pain intensity, pain frequency, typical pain duration, typical pain intensity, and typical pain interference; were more likely to report shoulder or pelvis and less likely to report stomach or arms as their most bothersome pain location; and were more likely to report accident or nerve damage and less likely to report opioid withdrawal as the genesis of their pain. Both pain subgroups reported similarly high rates of past-week substance use to alleviate pain. Conclusions and Scientific Significance The high rates of pain and self-reported substance use to manage pain suggest the importance of assessing and addressing pain in BNT patients. PMID:23617861

  1. Meloxicam and Buprenorphine Treatment after Ovarian Transplantation Does Not Affect Estrous Cyclicity and Follicular Integrity in Aged CBA/J Mice

    PubMed Central

    Le, Anna H.; Bonachea, Luis A.; Cargill, Shelley L.

    2014-01-01

    Angiogenesis, the formation of new blood vessels, is important for the survival of ovarian transplants and the restoration of ovarian functions. Without angiogenesis, transplanted ovarian tissue becomes more susceptible to tissue damage and necrosis. Administration of analgesics for pain management has been shown to decrease angiogenesis, which can influence transplant success especially in aged animals. Aging and the effects of hypoxia after transplantation decrease reproductive viability of the ovarian transplant; therefore, it is important to understand the additional effects of analgesics on aged animal models. The present study investigated the effects of two analgesics, buprenorphine, an opiate, and meloxicam, a non-steroidal anti-inflammatory drug (NSAID), on the reproductive indicators related to estrous cyclicity and follicular integrity after ovarian transplantation of young ovaries into aged CBA/J mice. These aged females did not show any different reproductive responses when treated with either buprenorphine or meloxicam. No significant differences were observed in estrous cycle length, the onset of estrous cycling, the regularity of estrous cycles, and the proportion of viable follicles and total number of follicles per ovarian sample across treatment groups. PMID:25153315

  2. A retrospective evaluation of patients switched from buprenorphine (subutex) to the buprenorphine/naloxone combination (suboxone)

    PubMed Central

    Simojoki, Kaarlo; Vorma, Helena; Alho, Hannu

    2008-01-01

    Background In Finland, buprenorphine (Subutex) is the most abused opioid. In order to curb this problem, many treatment centres transferred ("forced transfer") their buprenorphine patients to the buprenorphine plus naloxone (Suboxone) combination product in late 2003. Methods Data from a retrospective study involving five different treatment centers, examining the effects of switching patients to Suboxone, were gathered from 64 opioid-dependent patients who had undergone the medication transfer. Results Most patients (90.6%) switched to Suboxone at the same dose of buprenorphine that they had been receiving as Subutex (average 22 mg). The majority of these patients (71.9%) were maintained at the same dose of Suboxone throughout the 4-week study period. During the first 4 weeks, 50% of the patients reported adverse events and at the four month time point, 26.6% reported adverse events. However, due to adverse events one patient only discontinued treatment with Suboxone during the 4-week study period, and five during the four month follow-up period. Of the 26 patients in the follow-up period, Suboxone was misused intravenously once each by 4 patients and twice by 1 patient. These 5 patients all reported that injecting Suboxone was like injecting "nothing" with any euphoria, or that it was a bad experience. Conclusion We conclude that when patients are transferred from high doses (> 22 mg) of buprenorphine to the combination product, dose adjustments may be necessary especially in the later phase of the treatment. We recommend that a transfer from Subutex to Suboxone should be carefully discussed and planned in advance with the patients and after the transfer adverse events should be regularly monitored. With regard of buprenorphine IV abuse, the combination product seems to have a less abuse potential than buprenorphine alone. PMID:18559110

  3. Transdermal buprenorphine controls central neuropathic pain.

    PubMed

    Weiner, Michelle; Sarantopoulos, Constantine; Gordon, Eva

    2012-01-01

    A 53-year-old male with peripheral sensorimotor neuropathy suffered an intracerebral hemorrhage resulting in right hemiparesis and hemisensory loss. Three months later, he developed constant and burning pain within the entire right side of his body. He was diagnosed with central pain syndrome and treated with antiepileptics and tricyclic antidepressants. Minimal analgesia was achieved, which was limited by intractable sedation and drowsiness. Patient was then treated with oral opioids (morphine and hydrocodone with acetaminophen) in escalating doses that produced cognitive impairment. After an opioid rotation was attempted, by switching morphine to transdermal fentanyl, there was no pain reduction or improved quality of life. A trial of buprenorphine was initiated, by administering transdermal patches in escalating doses in weekly intervals. Patient's pain was eventually successfully controlled with buprenorphine patch 60 ?g/h every 7 days. His self-reported Visual Analogue Scale pain scores decreased from an average of 8/10 to 2/10 or less. Patient's overall function and participation in home activities increased. Buprenorphine is a partial ?-receptor and a ?-? receptor antagonist known to block NMDA receptors and reduce hyperalgesia secondary to central sensitization.(1) Buprenorphine is also a partial agonist at the opioid receptor-like (ORL-1) receptor, which is found to be analgesic and antinociceptive at the level of the spinal cord.(1,2) The difference in analgesic responses between buprenorphine and other opioids may be due to different receptor G protein interactions and/or selective activation of neuronal K(ATP) channels by buprenorphine.(3) Deficient opening of K(ATP) channels has been shown to mediate neuropathic pain(4); therefore, activation of these channels by buprenorphine may contribute to its analgesic effect in neuropathic pain states wherein other opioids fail. More recently, there have been two case reports in which patients with neuropathic pain of different central etiology were successfully treated with buprenorphine.(5) Despite advances in understanding the pathology related to central pain, effective treatment options are limited. Buprenorphine may be an analgesic option for central pain management when opioids fail to reduce hypersensitivity or when patients exhibit intolerable side effects to other medications. PMID:23264319

  4. Buprenorphine Sublingual and Buccal

    MedlinePLUS

    ... dependence (addiction to opioid drugs, including heroin and narcotic painkillers). Buprenorphine is in a class of medications ... and ritonavir (Norvir, in Kaletra, in Technivie); opiate (narcotic) medications for pain control; phenothiazines (medications used for ...

  5. Intravenous misuse of buprenorphine: characteristics and extent among patients undergoing drug maintenance therapy.

    PubMed

    Moratti, Enrico; Kashanpour, Hamid; Lombardelli, Tiziana; Maisto, Maria

    2010-01-01

    Sublingual buprenorphine [Subutex(R)] is used to treat opioid dependence. However, illicit intravenous (IV) injection of buprenorphine is a widespread problem. This survey investigated the IV misuse of buprenorphine among patients receiving drug replacement therapy at the Drug Addiction Centre in Udine, Italy. All patients who were receiving treatment with buprenorphine or methadone at the Drug Addiction Centre were invited to fill in a voluntary and anonymous questionnaire consisting of five questions. The questions asked if the patient had ever misused buprenorphine intravenously, when the misuse had occurred, the patient's reasons for misusing buprenorphine, the patient's perception of their experience, and the patient's perception of how widespread IV misuse of buprenorphine is. 307 patients completed the questionnaire, 93 and 214 of whom, respectively, were receiving buprenorphine and methadone. In total, 23.12% of patients admitted an IV misuse of buprenorphine, with a significantly greater prevalence among patients currently receiving buprenorphine (35.48%) than those receiving methadone (17.75%; p < 0.001). Younger patients were also more likely to have misused buprenorphine, and tended to have done so before coming to the Drug Addiction Centre. The most frequent motivation for IV misuse was treatment of heroin addiction or withdrawal symptoms (50.71%), while only 12.67% of patients reported that their motivation was to experience pleasure or euphoria. The majority of patients who had misused buprenorphine intravenously (53.52%) had a negative experience, and methadone recipients were significantly more likely to find the experience negative than buprenorphine recipients (68.42% vs 36.36%; p = 0.007). Almost half of the patients (45.93%) thought that at least 50% of patients had taken buprenorphine by IV injection. The results of our study confirm the widespread IV misuse of buprenorphine. Misuse was most common among patients currently receiving buprenorphine treatment and younger patients. For the majority of patients, the reason for IV misuse was to treat their dependence. We believe that the prevalence of buprenorphine misuse could be reduced by adopting appropriate clinical practices and treating patients with the buprenorphine/naloxone combination rather than buprenorphine alone. PMID:20450240

  6. Buprenorphine decreases the CCL2-mediated chemotactic response of monocytes.

    PubMed

    Carvallo, Loreto; Lopez, Lillie; Che, Fa-Yun; Lim, Jihyeon; Eugenin, Eliseo A; Williams, Dionna W; Nieves, Edward; Calderon, Tina M; Madrid-Aliste, Carlos; Fiser, Andras; Weiss, Louis; Angeletti, Ruth Hogue; Berman, Joan W

    2015-04-01

    Despite successful combined antiretroviral therapy, ∼ 60% of HIV-infected people exhibit HIV-associated neurocognitive disorders (HAND). CCL2 is elevated in the CNS of infected people with HAND and mediates monocyte influx into the CNS, which is critical in neuroAIDS. Many HIV-infected opiate abusers have increased neuroinflammation that may augment HAND. Buprenorphine is used to treat opiate addiction. However, there are few studies that examine its impact on HIV neuropathogenesis. We show that buprenorphine reduces the chemotactic phenotype of monocytes. Buprenorphine decreases the formation of membrane projections in response to CCL2. It also decreases CCL2-induced chemotaxis and mediates a delay in reinsertion of the CCL2 receptor, CCR2, into the cell membrane after CCL2-mediated receptor internalization, suggesting a mechanism of action of buprenorphine. Signaling pathways in CCL2-induced migration include increased phosphorylation of p38 MAPK and of the junctional protein JAM-A. We show that buprenorphine decreases these phosphorylations in CCL2-treated monocytes. Using DAMGO, CTAP, and Nor-BNI, we demonstrate that the effect of buprenorphine on CCL2 signaling is opioid receptor mediated. To identify additional potential mechanisms by which buprenorphine inhibits CCL2-induced monocyte migration, we performed proteomic analyses to characterize additional proteins in monocytes whose phosphorylation after CCL2 treatment was inhibited by buprenorphine. Leukosialin and S100A9 were identified and had not been shown previously to be involved in monocyte migration. We propose that buprenorphine limits CCL2-mediated monocyte transmigration into the CNS, thereby reducing neuroinflammation characteristic of HAND. Our findings underscore the use of buprenorphine as a therapeutic for neuroinflammation as well as for addiction. PMID:25716997

  7. Office-Based Buprenorphine for Patients with Opioid Dependence

    PubMed Central

    Sullivan, Lynn E.; Fiellin, David A.

    2013-01-01

    The profile of opioid dependence in the United States is changing. Abuse of prescription opioids is more common than that of illicit opioids. Recent data indicate that there are approximately 1.6 million individuals with prescription opioid abuse or dependence and 323,000 with heroin abuse or dependence. Despite this prevalence, nearly 80% of these individuals go untreated. One option for expanding treatment is the use of buprenorphine and the buprenorphine/naloxone combination. Buprenorphine is a partial opioid agonist that can be prescribed by trained Internists and dispensed at pharmacies. The case-based discussion in this paper addresses the clinical presentation of a patient with opioid dependence and describes the relatively new practice of office-based treatment with buprenorphine/naloxone. It examines the different components of treatment, the role of the Internist in providing this treatment, and the logistics of treating this growing and multi-faceted patient population. PMID:18458279

  8. The implementation of buprenorphine/naloxone in college health practice.

    PubMed

    DeMaria, Peter A; Patkar, Ashwin A

    2008-01-01

    Opiate abuse and dependence have become important concerns for college healthcare providers. The passage of the Drug Addiction Treatment Act of 2000 and the approval of the combination buprenorphine/naloxone for office-based treatment of opiate dependence have increased the options available for college students and their healthcare providers. The authors review the pharmacology of buprenorphine/naloxone and discuss how it can be implemented in college health practice. They also present a case report. PMID:18316282

  9. Predictors of Outcome after Short-term Stabilization with Buprenorphine

    PubMed Central

    Hillhouse, Maureen; Canamar, Catherine P.; Ling, Walter

    2012-01-01

    Using buprenorphine as a medication to treat opioid dependence is becoming more prevalent as illicit opiate use increases. Identifying the characteristics of opiate dependent individuals best suited to benefit from buprenorphine would improve guidelines for its administration. This study evaluates baseline and treatment participation variables for predicting positive response to short-term stabilization with buprenorphine. Data includes demographic, drug use, and other variables collected from participants undergoing stabilization over a 4-week period before being tapered off buprenorphine in a short-term detoxification process. Outcome variables include opioid use and retention. Logistic regression results indicate several characteristics associated with opioid use at the end of the stabilization period. These include being older, having no criminal history, and less opiate use. Criminal activity and opioid use in the last 30 days were significantly associated with shorter treatment stays. The benefits of identifying individual characteristics that may predict treatment response are discussed. PMID:23021099

  10. A woman's experience of tapering from buprenorphine during pregnancy.

    PubMed

    Welle-Strand, Gabrielle Katrine; Kvamme, Odd; Andreassen, Andreas; Ravndal, Edle

    2014-01-01

    Although opioid maintenance treatment (OMT) is the treatment of choice for pregnant opioid-dependent patients, some professionals argue that tapering the medication dose will reduce the severity of neonatal abstinence syndrome (NAS). This case description is based on the patient's detailed blog, and medical records from her general practitioner and the hospital. The patient is an employed, 32-year-old drug-abstinent woman in OMT. Her taper from 24 mg of buprenorphine started at 14 weeks' gestation and is slow, with withdrawal symptoms increasing gradually. In pregnancy week 31, she is off buprenorphine but she has severe withdrawal symptoms. She chose to go back on 4 mg of buprenorphine. The patient's son was born in pregnancy week 38+3, weighs 2950 g and does not require pharmacological treatment for NAS. The fetus most probably did experience fetal stress during the patient's tapering. It was the right decision by the patient to go back on buprenorphine. PMID:25540212

  11. Predictors of outcome after short-term stabilization with buprenorphine.

    PubMed

    Hillhouse, Maureen; Canamar, Catherine P; Ling, Walter

    2013-03-01

    Using buprenorphine as a medication to treat opioid dependence is becoming more prevalent as illicit opiate use increases. Identifying the characteristics of opiate dependent individuals best suited to benefit from buprenorphine would improve guidelines for its administration. This study evaluates baseline and treatment participation variables for predicting positive response to short-term stabilization with buprenorphine. Data include demographic, drug use, and other variables collected from participants undergoing stabilization over a 4-week period before being tapered off buprenorphine in a short-term detoxification process. Outcome variables include opioid use and retention. Logistic regression results indicate several characteristics associated with opioid use at the end of the stabilization period. These include being older, having no criminal history, and less opiate use. Criminal activity and opioid use in the last 30 days were significantly associated with shorter treatment stays. The benefits of identifying individual characteristics that may predict treatment response are discussed. PMID:23021099

  12. Transdermal buprenorphine in chronic pain: indications and clinical experience.

    PubMed

    Kusnik, Stefan; Likar, Rudolf; Sittl, Reinhard

    2008-11-01

    Transdermal buprenorphine has been shown to be effective in managing moderate-to-severe cancer pain and severe pain that is unresponsive to nonopioid analgesics. In clinical trials, it provided better pain relief than placebo, despite a higher consumption of rescue analgesia by placebo patients. Analgesia was rated as satisfactory or better by 90% of patients in a long-term follow-up study and 94.6% considered the buprenorphine matrix patch to be user friendly. Transdermal buprenorphine is well tolerated; most adverse events are transient local reactions to the patch or systemic effects typical of treatment with opioids. Even in opioid-experienced volunteers, buprenorphine does not cause respiratory depression at doses up to 70-times higher than those used for analgesia. No problems have been encountered when switching from another opioid to transdermal buprenorphine, or in combining the buprenorphine patch with intravenous morphine or tramadol for breakthrough pain. There is a growing body of evidence that transdermal buprenorphine may be particularly useful for managing neuropathic pain. Most notably, it appears to be effective in treating hyperalgesic states and syndromes characterized by pronounced central sensitization. PMID:24410602

  13. Current knowledge of buprenorphine and its unique pharmacological profile.

    PubMed

    Pergolizzi, Joseph; Aloisi, Anna Maria; Dahan, Albert; Filitz, Joerg; Langford, Richard; Likar, Rudolf; Mercadante, Sebastiano; Morlion, Bart; Raffa, Robert B; Sabatowski, Rainer; Sacerdote, Paola; Torres, Luis M; Weinbroum, Avi A

    2010-01-01

    Despite the increasing clinical use of transdermal buprenorphine, questions have persisted about the possibility of a ceiling effect for analgesia, its combination with other ?-opioid agonists, and the reversibility of side effects. In October 2008, a consensus group of experts met to review recent research into the pharmacology and clinical use of buprenorphine. The objective was to achieve consensus on the conclusions to be drawn from this work. It was agreed that buprenorphine clearly behaves as a full ?-opioid agonist for analgesia in clinical practice, with no ceiling effect, but that there is a ceiling effect for respiratory depression, reducing the likelihood of this potentially fatal adverse event. This is entirely consistent with receptor theory. In addition, the effects of buprenorphine can be completely reversed by naloxone. No problems are encountered when switching to and from buprenorphine and other opioids, or in combining them. Buprenorphine exhibits a pronounced antihyperalgesic effect that might indicate potential advantages in the treatment of neuropathic pain. Other beneficial properties are the compound's favorable safety profile, particularly in elderly patients and those with renal impairment, and its lack of effect on sex hormones and the immune system. The expert group agreed that these properties, as well as proven efficacy in severe pain and favorable tolerability, mean that buprenorphine can be considered a safe and effective option for treating chronic cancer and noncancer pain. PMID:20492579

  14. Transdermal buprenorphine, opioid rotation to sublingual buprenorphine, and the avoidance of precipitated withdrawal: a review of the literature and demonstration in three chronic pain patients treated with butrans.

    PubMed

    Kornfeld, Howard; Reetz, Heidi

    2015-01-01

    Buprenorphine is an opioid, used in the United States and abroad for both analgesia and addiction, with unique opioid receptor binding properties. There are several pharmacological features of buprenorphine that make it an emerging option for the long-term treatment of chronic pain-its respiratory suppression ceiling effect, its efficacy in neuropathic pain and hyperalgesic states, and its decreased suppression of the immune and endocrine systems compared with other long-acting opioids. Previous studies have shown that high-dose sublingual buprenorphine is an effective treatment of chronic pain patients not responding to other opioids. Guidelines for the introduction of sublingual buprenorphine, termed buprenorphine induction, include an opioid-free "withdrawal" period of 12-48 hours to avoid an anticipated and accelerated opioid withdrawal, a syndrome described in this article as precipitated withdrawal. The requirement of a period of opioid abstinence before buprenorphine use may present a significant barrier to its adoption for chronic pain. We present a case series of a novel method of sublingual buprenorphine introduction without an induction period, using the recently Food and Drug Administration-approved low-dose transdermal buprenorphine (Butrans; Purdue Pharma L.P.) as a bridge medication. In these cases, buprenorphine was started in opioid-dependent chronic noncancer pain patients who had taken short-acting opioid medications within hours of the initiation of the rotation. This method avoids the painful abstinence period and did not result in precipitated withdrawal or other significant adverse effects. PMID:23846520

  15. Buprenorphine Maintenance Therapy in Opioid-Addicted Health Care Professionals Returning to Clinical Practice: A Hidden Controversy

    PubMed Central

    Hamza, Heather; Bryson, Ethan O.

    2012-01-01

    It remains controversial whether it is safe for recovering health care professionals to return to clinical practice after treatment for drug addiction. One specific component of reentry that remains particularly contentious is the use of pharmacotherapeutics, specifically buprenorphine, as opioid substitution therapy for health care professionals who wish to return to clinical work. Because health care professionals are typically engaged in safety-sensitive work with considerable consequences when errors occur, abstinence-based recovery should be recommended until studies demonstrate that it is safe to allow this population to practice while undergoing opioid substitution therapy. PMID:22386182

  16. A combination of buprenorphine and naltrexone blocks compulsive cocaine intake in rodents without producing dependence.

    PubMed

    Wee, Sunmee; Vendruscolo, Leandro F; Misra, Kaushik K; Schlosburg, Joel E; Koob, George F

    2012-08-01

    Buprenorphine, a synthetic opioid that acts at both ? and ? opioid receptors, can decrease cocaine use in individuals with opioid addiction. However, the potent agonist action of buprenorphine at ? opioid receptors raises its potential for creating opioid dependence in non-opioid-dependent cocaine abusers. Here, we tested the hypothesis that a combination of buprenorphine and naltrexone (a potent ? opioid antagonist with weaker ? and ? antagonist properties) could block compulsive cocaine self-administration without producing opioid dependence. The effects of buprenorphine and various doses of naltrexone on cocaine self-administration were assessed in rats that self-administered cocaine under conditions of either short access (noncompulsive cocaine seeking) or extended access (compulsive cocaine seeking). Buprenorphine alone reproducibly decreased cocaine self-administration. Although this buprenorphine-alone effect was blocked in a dose-dependent manner by naltrexone in both the short-access and the extended-access groups, the combination of the lowest dose of naltrexone with buprenorphine blocked cocaine self-administration in the extended-access group but not in the short-access group. Rats given this low dose of naltrexone with buprenorphine did not exhibit the physical opioid withdrawal syndrome seen in rats treated with buprenorphine alone, and naltrexone at this dose did not block ? agonist-induced analgesia. The results suggest that the combination of buprenorphine and naltrexone at an appropriate dosage decreases compulsive cocaine self-administration with minimal liability to produce opioid dependence and may be useful as a treatment for cocaine addiction. PMID:22875830

  17. Rewarding or aversive effects of buprenorphine/naloxone combination (Suboxone) depend on conditioning trial duration.

    PubMed

    Canestrelli, Corinne; Marie, Nicolas; Noble, Florence

    2014-09-01

    Buprenorphine is used as a sublingual medication in the treatment of opioid dependence. However, its misuse by i.v. injection may limit its acceptability and dissemination. A buprenorphine/naloxone (ratio 4:1) combination has been developed to reduce diversion and abuse. So far, the relevance of this combination has not been investigated in the animal models traditionally used to study the reinforcing effects of drugs of abuse. The aim of this study was to compare the rewarding effects, assessed by conditioned place preference (CPP), of buprenorphine and buprenorphine/naloxone combination following i.v. administration in mice. Animals were treated with different doses of buprenorphine or buprenorphine/naloxone combination (ratio 4:1), and CPP conditioning trial duration was 5 or 30 min. At the longest trial duration, a bell-shaped dose-response curve was obtained with buprenorphine, which was shifted significantly to the right with naloxone combination. At the shortest trial duration, an aversive effect was observed with the buprenorphine/naloxone combination in animals, involving opioid receptor-like 1 (ORL1). These findings may explain the discrepancies reported in the literature as some authors have shown a reduced buprenorphine/naloxone misuse compared to buprenorphine in opioid abusers, while others have not. PMID:24606726

  18. Quantitation of Total Buprenorphine and Norbuprenorphine in Meconium by LC-MS/MS.

    PubMed

    Marin, Stephanie J; McMillin, Gwendolyn A

    2016-01-01

    Buprenorphine (Suboxone, Zubsolv, Buprenex, Butrans, etc.) is an opioid drug that has been used to treat opioid dependence on an outpatient basis, and is also prescribed for managing moderate to severe pain. Pregnant women may be prescribed buprenorphine as part of a treatment plan for opioid addiction. This chapter quantitates buprenorphine and norbuprenorphine in meconium by liquid chromatography tandem mass spectrometry (LC-MS/MS). PMID:26660174

  19. Safety and efficacy of buprenorphine/naloxone in opioid-dependent patients: an Italian observational study.

    PubMed

    Magnelli, Fernanda; Biondi, Lorita; Calabria, Roberto; Fiore, Angelo; Peluso, Eugenio; Vonella, Domenico; Rota, Amerigo Giuseppe

    2010-01-01

    Opioid dependence is a growing problem. Methadone is an established agent for the treatment of opioid dependence, but there is a risk of this agent being abused, a potential for interaction with antiretroviral agents and a risk of cardiac toxicity. Another option is the partial mu-opioid receptor opioid agonist buprenorphine, which has been used successfully to manage opioid dependence. While the risk of abuse is lower than that for methadone, there is still a risk. The sublingual combination formulation of buprenorphine and the opioid receptor antagonist naloxone (buprenorphine/naxolone) is a newer agent with reduced abuse potential, and has been shown to have promising efficacy for opioid dependence. We describe the results of an observational study investigating the safety and efficacy of buprenorphine/naloxone in opioid-dependent patients. A total of 77 patients were included and were switched from buprenorphine to sublingual tables of buprenorphine/naloxone; the buprenorphine dosage was titrated to achieve good control of withdrawal symptoms. The prevalence of withdrawal symptoms, craving, constipation, cramps, insomnia, sexual activity, depression, sweating, distress, bone/joint pain and drowsiness were compared over the first 30 days of treatment (period 1) and the total 120-day study duration (period 2). The average buprenorphine/naloxone dose in period 1 was 7.3 mg/day and 12.7 mg/day in period 2. Most patients did not experience any withdrawal symptoms in either period 1 or period 2. Fewer than 20% of patients experienced any cravings over the 120-day study period. Importantly, the adverse effects observed were usually mild, with very few patients experiencing significant adverse effects. This study shows that buprenorphine/naloxone is an effective and well tolerated treatment for opioid withdrawal when the dosage is titrated to achieve good control of withdrawal symptoms. Switching from buprenorphine alone to buprenorphine/naloxone was possible with very little discomfort for the patient and effective retained patients in treatment. PMID:20450242

  20. From research to the real world: buprenorphine in the decade of the Clinical Trials Network.

    PubMed

    Ling, Walter; Jacobs, Petra; Hillhouse, Maureen; Hasson, Albert; Thomas, Christie; Freese, Thomas; Sparenborg, Steven; McCarty, Dennis; Weiss, Roger; Saxon, Andrew; Cohen, Allan; Straus, Michele; Brigham, Gregory; Liu, David; McLaughlin, Paul; Tai, Betty

    2010-06-01

    The National Institute on Drug Abuse (NIDA) established the National Drug Abuse Treatment Clinical Trials Network (CTN) in 1999 to bring researchers and treatment providers together to develop a clinically relevant research agenda. Initial CTN efforts addressed the use of buprenorphine, a mu-opioid partial agonist, as treatment for opioid dependence. Strong evidence of buprenorphine's therapeutic efficacy was demonstrated in clinical trials involving several thousand opioid-dependent participants, and in 2002, the Food and Drug Administration approved buprenorphine for the treatment of opioid dependence. With the advent of a sublingual tablet containing both buprenorphine and naloxone to mitigate abuse and diversion (Suboxone), buprenorphine appeared poised to be the first-line treatment for opioid addiction. Notwithstanding its many attributes, certain implementation barriers remained to be addressed in CTN studies, and these efforts have brought a body of knowledge on buprenorphine to frontline clinicians. The purpose of this article is to review CTN-based buprenorphine research and related efforts to overcome challenges to the implementation of buprenorphine therapy in mainstream practice. Furthermore, this article explores current issues and future challenges that may require additional CTN efforts. PMID:20307796

  1. Effect of telaprevir on the pharmacokinetics of buprenorphine in volunteers on stable buprenorphine/naloxone maintenance therapy.

    PubMed

    Luo, Xia; Trevejo, Jose; van Heeswijk, Rolf P G; Smith, Frances; Garg, Varun

    2012-07-01

    This was an open-label, single-sequence trial in hepatitis C virus-negative volunteers on stable, individualized, buprenorphine maintenance therapy. Telaprevir at 750 mg every 8 h was coadministered with buprenorphine/naloxone (4:1 ratio as sublingual tablets) for 7 days with food. Pharmacokinetic profiles of buprenorphine, norbuprenorphine, and naloxone were measured over the 24-hour dosing interval on day -1 (buprenorphine/naloxone alone, reference) and day 7 of telaprevir coadministration (test). Geometric least-squares mean ratios and associated 90% confidence intervals of treatment ratios (test/reference) were calculated using log-transformed pharmacokinetic parameters. Opioid withdrawal symptoms were evaluated throughout the study (via questionnaires and pupillometry). Pharmacokinetic data were available for 14 and 13 volunteers on day -1 and day 7, respectively. The area under the concentration-time curve (AUC) for buprenorphine was unchanged and the maximum concentration of drug in serum (C(max)) for buprenorphine, C(max) and AUC for norbuprenorphine, and C(max) naxolone were modestly decreased during coadministration with telaprevir. Geometric least-squares mean ratios (90% confidence intervals) for buprenorphine were 0.80 (0.69, 0.93) for the C(max) and 0.96 (0.84, 1.10) for the AUC from 0 to 24 h (AUC(0-24)); for norbuprenorphine, values were 0.85 (0.66, 1.09) for C(max) and 0.91 (0.71, 1.16) for AUC(0-24); for naloxone, the C(max) was 0.84 (0.62, 1.13). Coadministration of telaprevir did not increase withdrawal symptom frequency, and there were no serious adverse events reported during or after completion of telaprevir coadministration. Results suggest dose adjustment may not be necessary when telaprevir and buprenorphine/naloxone are coadministered. PMID:22564847

  2. [Influencing hemostasis in substitute solution treatment].

    PubMed

    Máca, J; Kula, R; Chýlek, V

    2009-01-01

    Hemostasis is an important intricately regulated homeostatic process. During the hospitalization a critically ill patient is often subjected to various external and internal stimuli which have abilities to influence the hemostasis. Administration of substitute solutions could be related to such an adverse effect. This paper tries to describe main mechanisms leading to impair the hemostatic balance during the fluid therapy and outline possibilities of their monitoring. The work also deals with every basic arteficial substitute solutions individually in term of their influence on coagulation. The goal was as well to point out certain controversial conclusions and problems emerging from the effort of synthesis of all information acquired from clinical publications related to the main topic. Generally it is possible to conclude that all substitutes have a potential to disturb coagulation. Tromboelastography belongs between the most accurate ways to measure coagulation disturbances and has several substantial advantages compared to classic examination. Character and degree of the influence depends on quantity, velocity of administration and type of used solution. PMID:19227953

  3. Methadone and buprenorphine-naloxone are effective in reducing illicit buprenorphine and other opioid use, and reducing HIV risk behavior – Outcomes of a Randomized Trial

    PubMed Central

    Otiashvili, David; Piralishvili, Gvantsa; Sikharulidze, Zura; Kamkamidze, George; Poole, Sabrina; Woody, George E.

    2013-01-01

    Aims Determine the extent to which buprenorphine injectors continue treatment with buprenorphine-naloxone or methadone, and the impact of these treatments on substance use and HIV risk in the Republic of Georgia. Methods Randomized controlled 12-week trial of daily-observed methadone or buprenorphine-naloxone followed by a dose taper, referral to ongoing treatment, and follow-up at week 20 at the Uranti Clinic in Tbilisi, Republic of Georgia. Eighty consenting treatment-seeking individuals (40/group) aged 25 and above who met ICD-10 criteria for opioid dependence with physiologic features and reported injecting buprenorphine 10 or more times in the past 30 days. Opioid use according to urine tests and self-reports, treatment retention, and HIV risk behavior as determined by the Risk Assessment Battery. Results Mean age of participants was 33.7 (SD5.7), 4 were female, mean history of opioid injection use was 5.8 years (SD4.6), none were HIV+ at intake or at the 12-week assessment and 73.4% were HCV+. Sixty-eight participants (85%) completed the 12-week medication phase (33 from methadone and 35 from buprenorphine/naloxone group); 37 (46%) were in treatment at the 20-week follow-up (21 from methadone and 16 from the buprenorphine/naloxone group). In both study arms, treatment resulted in a marked reduction in unprescribed buprenorphine, other opioid use, and HIV injecting risk behavior with no clinically significant differences between the two treatment arms. Conclusions Daily observed methadone or buprenorphine-naloxone are effective treatments for non-medical buprenorphine and other opioid use in the Republic of Georgia and likely to be useful for preventing HIV infection. PMID:23916321

  4. Buprenorphine is a weak partial agonist that inhibits opioid receptor desensitization.

    PubMed

    Virk, Michael S; Arttamangkul, Seksiri; Birdsong, William T; Williams, John T

    2009-06-01

    Buprenorphine is a weak partial agonist at mu-opioid receptors that is used for treatment of pain and addiction. Intracellular and whole-cell recordings were made from locus ceruleus neurons in rat brain slices to characterize the actions of buprenorphine. Acute application of buprenorphine caused a hyperpolarization that was prevented by previous treatment of slices with the irreversible opioid antagonist beta-chlornaltrexamine (beta-CNA) but was not reversed by a saturating concentration of naloxone. As expected for a partial agonist, subsaturating concentrations of buprenorphine decreased the [Met](5)enkephalin (ME)-induced hyperpolarization or outward current. When the ME-induced current was decreased below a critical value, desensitization and internalization of mu-opioid receptors was eliminated. The inhibition of desensitization by buprenorphine was not the result of previous desensitization, slow dissociation from the receptor, or elimination of receptor reserve. Treatment of slices with subsaturating concentrations of etorphine, methadone, oxymorphone, or beta-CNA also reduced the current induced by ME but did not block ME-induced desensitization. Treatment of animals with buprenorphine for 1 week resulted in the inhibition of the current induced by ME and a block of desensitization that was not different from the acute application of buprenorphine to brain slices. These observations show the unique characteristics of buprenorphine and further demonstrate the range of agonist-selective actions that are possible through G-protein-coupled receptors. PMID:19494155

  5. Buprenorphine for chronic pain.

    PubMed

    Calderon, Raul; Copenhaver, David

    2013-12-01

    Questions from patients about pain conditions, analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The use of transdermal buprenorphine for chronic pain management is discussed. A brief history of the medication is provided. The use of the medication in opioid maintenance, and withdrawal and other concerns are discussed. Possible side effects are described. PMID:24245573

  6. New developments in the management of opioid dependence: focus on sublingual buprenorphine–naloxone

    PubMed Central

    Soyka, Michael

    2015-01-01

    Opioid maintenance therapy is a well-established first-line treatment approach in opioid dependence. Buprenorphine, a partial opioid agonist, has been found by numerous studies to be an effective and safe medication in the treatment of opioid dependence. At present, buprenorphine is available as a monodrug or in a fixed 4:1 ratio combination with naloxone. A diminished risk of diversion and abuse for the buprenorphine–naloxone combination is likely but not firmly established. Conventional formulations are given sublingually to avoid the hepatic first-pass effect. A novel film tablet is available only in the US and Australia. Other novel, sustained-release formulations (implant, depot) are currently being developed and tested. Recent studies, including a Cochrane meta-analysis, suggest that the retention with buprenorphine is lower than for methadone, but that buprenorphine may be associated with less drug use. Higher doses of buprenorphine are associated with better retention rates. Buprenorphine has a ceiling effect at the opioid receptor with regard to respiratory depression, and may cause fewer fatal intoxications than methadone. Possible antidepressant effects of buprenorphine and its use in comorbid psychiatric patients has not been studied in much detail. Clinical implications are discussed. PMID:25610012

  7. New developments in the management of opioid dependence: focus on sublingual buprenorphine-naloxone.

    PubMed

    Soyka, Michael

    2015-01-01

    Opioid maintenance therapy is a well-established first-line treatment approach in opioid dependence. Buprenorphine, a partial opioid agonist, has been found by numerous studies to be an effective and safe medication in the treatment of opioid dependence. At present, buprenorphine is available as a monodrug or in a fixed 4:1 ratio combination with naloxone. A diminished risk of diversion and abuse for the buprenorphine-naloxone combination is likely but not firmly established. Conventional formulations are given sublingually to avoid the hepatic first-pass effect. A novel film tablet is available only in the US and Australia. Other novel, sustained-release formulations (implant, depot) are currently being developed and tested. Recent studies, including a Cochrane meta-analysis, suggest that the retention with buprenorphine is lower than for methadone, but that buprenorphine may be associated with less drug use. Higher doses of buprenorphine are associated with better retention rates. Buprenorphine has a ceiling effect at the opioid receptor with regard to respiratory depression, and may cause fewer fatal intoxications than methadone. Possible antidepressant effects of buprenorphine and its use in comorbid psychiatric patients has not been studied in much detail. Clinical implications are discussed. PMID:25610012

  8. Opioid maintenance treatment as a harm reduction tool for opioid-dependent individuals in NYC: the need to expand access to buprenorphine in marginalized populations

    PubMed Central

    Stancliff, Sharon; Joseph, Herman; Furst, Terry; Fong, Chunki; Comer, Sandra D.; Roux, Perrine

    2013-01-01

    The aim of this pilot study was to assess the effectiveness of buprenorphine among marginalized opioid dependent individuals in terms of retention in and cycling in 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 buprenorphine could be successfully used to treat marginalized heroin users. PMID:22873189

  9. A meta-analysis of efficacy and tolerability of buprenorphine for the relief of cancer pain.

    PubMed

    Naing, Cho; Yeoh, Peng Nam; Aung, Kyan

    2014-01-01

    This study aimed to synthesize available evidence on the analgesic efficacy of buprenorphine in treating cancer pain and related adverse effects. We searched electronic databases for randomized controlled trials, assessing the efficacy of buprenorphine, regardless of delivery system. The primary endpoints were patient-reported 'pain intensity' and 'pain relief'. Statistical heterogeneity among included studies was assessed with the I (2) test. The summary relative risk (RR) and 95% CI were derived, if two or more studies reported the similar outcome. Sixteen RCTs (n?=?1329) with buprenorphine were included: 8 transdermal (TD), 5 sublingual (SL), 2 intramuscular injection (IM) and 1 subcutaneous infusion (SC) studies; with both SL and IM routes being assessed in one study. Only a few studies reported the same outcome in a similar way, creating difficulty for pooling of the outcome data. Many studies had a high risk of bias. In 2 studies (n?=?241), the 'global impression change' was significantly different between TD buprenorphine and the combined placebo and morphine (RR 1.35, 95% CI 1.14-1.59; I (2): 42%); the 'number-needed-to-treat' (NNT) was 4.9 (95% CI: 3.1-10.9). In 2 studies (n?=?331), 'requirement for rescue SL buprenorphine' was comparable between TD buprenorphine and placebo (RR 1.25, 95% CI 0.71-2.18; I (2) : 40%). In 2 studies (n?=?141), 'incidence of nausea' was less in TD buprenorphine (RR: 0.38, 95% CI: 0.2-0.71, I (2): 0%, NNT: 9.3, 5.6-28.5). Due to the small number of participants in a small number of studies, the results of the present review provide insufficient evidence to position adequately the use of buprenorphine in treatment of cancer pain. Large multicenter RCTs that compare TD buprenorphine with standard analgesic treatment is needed to position TD buprenorphine in the therapeutic armamentarium of cancer pain treatment. PMID:24600544

  10. Systematic review of adverse events of buprenorphine patch versus fentanyl patch in patients with chronic moderate-to-severe pain.

    PubMed

    Wolff, Robert F; Reid, Kim; di Nisio, Marcello; Aune, Dagfinn; Truyers, Carla; Hernandez, Adrian V; Misso, Kate; Riemsma, Rob; Kleijnen, Jos

    2012-07-01

    SUMMARY This systematic review compares convenience of administration, adverse events and tolerability of buprenorphine patch with fentanyl patch in patients with chronic pain. Methods of quantitative and qualitative research were combined. Seventeen databases were searched up to December 2010. A total of 49 unique trials (56 publications) were included. Patients regarded the use of patches, both transdermal buprenorphine and fentanyl, as easy and convenient. Compared with buprenorphine patch, fentanyl can cause more cases of constipation and could lead to a higher number of serious adverse events. There were no differences between buprenorphine patch and fentanyl patch regarding dizziness, somnolence, nausea and treatment discontinuation. Overall, transdermal administration of buprenorphine and fentanyl can be seen as an alternative pathway for delivering these drugs. Use of transdermal buprenorphine might be favorable in certain groups of patients, such as renally impaired, elderly and immunosuppressed patients. PMID:24654721

  11. The Implementation of Buprenorphine/Naloxone in College Health Practice

    ERIC Educational Resources Information Center

    DeMaria, Peter A., Jr.; Patkar, Ashwin A.

    2008-01-01

    Opiate abuse and dependence have become important concerns for college healthcare providers. The passage of the Drug Addiction Treatment Act of 2000 and the approval of the combination buprenorphine/naloxone for office-based treatment of opiate dependence have increased the options available for college students and their healthcare providers. The…

  12. The Implementation of Buprenorphine/Naloxone in College Health Practice

    ERIC Educational Resources Information Center

    DeMaria, Peter A., Jr.; Patkar, Ashwin A.

    2008-01-01

    Opiate abuse and dependence have become important concerns for college healthcare providers. The passage of the Drug Addiction Treatment Act of 2000 and the approval of the combination buprenorphine/naloxone for office-based treatment of opiate dependence have increased the options available for college students and their healthcare providers. The…

  13. A Combination of Buprenorphine and Naltrexone Blocks Compulsive Cocaine Intake in Rodents Without Producing Dependence

    PubMed Central

    Wee, Sunmee; Vendruscolo, Leandro F.; Misra, Kaushik K.; Schlosburg, Joel E.; Koob, George F.

    2012-01-01

    Buprenorphine, a synthetic opioid that acts at both μ and κ opioid receptors, can decrease cocaine use in individuals with opioid addiction. However, the potent agonist action of buprenorphine at μ opioid receptors raises its potential for creating opioid dependence in non–opioid-dependent cocaine abusers. Here, we tested the hypothesis that a combination of buprenorphine and naltrexone (a potent μ opioid antagonist with weaker δ and κ antagonist properties) could block compulsive cocaine self-administration without producing opioid dependence. The effects of buprenorphine and various doses of naltrexone on cocaine self-administration were assessed in rats that self-administered cocaine under conditions of either short access (noncompulsive cocaine seeking) or extended access (compulsive cocaine seeking). Buprenorphine alone reproducibly decreased cocaine self-administration. Although this buprenorphine-alone effect was blocked in a dose-dependent manner by naltrexone in both the short-access and the extended-access groups, the combination of the lowest dose of naltrexone with buprenorphine blocked cocaine self-administration in the extended-access group but not in the short-access group. Rats given this low dose of naltrexone with buprenorphine did not exhibit the physical opioid withdrawal syndrome seen in rats treated with buprenorphine alone, and naltrexone at this dose did not block κ agonist–induced analgesia. The results suggest that the combination of buprenorphine and naltrexone at an appropriate dosage decreases compulsive cocaine self-administration with minimal liability to produce opioid dependence and may be useful as a treatment for cocaine addiction. PMID:22875830

  14. The first three years of buprenorphine in the United States: experience to date and future directions.

    PubMed

    Fiellin, David A

    2007-06-01

    Buprenorphine, primarily as the buprenorphine/naloxone combination, has been available in the United States for office and specialty treatment program-based care since 2003. The existing evidence, collected primarily from federal sources, indicates that access to this type of treatment has expanded, that more than 50% of the 12,000 physicians able to provide this care are not addiction specialists, that buprenorphine diversion is low, that physician scrutiny by federal agents is infrequent, and among those receiving treatment patient acceptance is high. Implementation has been slowed because of physician training and support needs, reimbursement, and limits on the number of patients each physician can treat. As a result there are geographic variations in access and unmet treatment needs. The United States Congress has moved twice to loosen numerical limitations, now allowing each physician to treat up to 100 patients. Future research and evaluation are needed to ensure that opioid-dependent patients receive optimal care with buprenorphine. PMID:21768936

  15. To Be Free and Normal: Addiction, Governance, and the Therapeutics of Buprenorphine.

    PubMed

    Harris, Shana

    2015-12-01

    Methadone maintenance has dominated opiate addiction treatment in the United States for decades. Since 2002, opiate addiction has also been treated in general medical settings with a substance called buprenorphine. Based on interviews and participant observation conducted in northern California, this article analyzes how discourses of freedom and normalcy in patient and provider narratives reflect and affect experiences with this treatment modality. I discuss how buprenorphine treatment, in contrast to methadone maintenance, offers patients and providers a greater sense of autonomy and flexibility in how they receive and deliver treatment. It presents them with new obligations, responsibilities, and choices around care and conduct. It simultaneously perpetuates and shapes a desire to be "free" and "normal." I argue that the therapeutics of buprenorphine govern patients and providers through this desire for freedom and normalcy. Buprenorphine is thus a technology of governmentality that extends neoliberal discourses and values and produces self-governing subjects. PMID:26102240

  16. Utilizing buprenorphine–naloxone to treat illicit and prescription-opioid dependence

    PubMed Central

    Mauger, Sofie; Fraser, Ronald; Gill, Kathryn

    2014-01-01

    Objectives To review current evidence on buprenorphine–naloxone (bup/nx) for the treatment of opioid-use disorders, with a focus on strategies for clinical management and office-based patient care. Quality of evidence Medline and the Cochrane Database of Systematic Reviews were searched. Consensus reports, guidelines published, and other authoritative sources were also included in this review. Apart from expert guidelines, data included in this review constitute level 1 evidence. Findings Bup/nx is a partial ?-opioid agonist combined with the opioid antagonist naloxone in a 4:1 ratio. It has a lower abuse potential, carries less stigma, and allows for more flexibility than methadone. Bup/nx is indicated for both inpatient and ambulatory medically assisted withdrawal (acute detoxification) and long-term substitution treatment (maintenance) of patients who have a mild-to-moderate physical dependence. A stepwise long-term substitution treatment with regular monitoring and follow-up assessment is usually preferred, as it has better outcomes in reducing illicit opioid use, minimizing concomitant risks such as human immunodeficiency virus and hepatitis C transmission, retaining patients in treatment and improving global functioning. Conclusion Bup/nx is safe and effective for opioid detoxification and substitution treatment. Its unique pharmaceutical properties make it particularly suitable for office-based maintenance treatment of opioid-use disorder. PMID:24741316

  17. Opioid Abstinence Reinforcement Delays Heroin Lapse during Buprenorphine Dose Tapering

    ERIC Educational Resources Information Center

    Greenwald, Mark K.

    2008-01-01

    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…

  18. Management of opioid painkiller dependence in primary care: ongoing recovery with buprenorphine/naloxone.

    PubMed

    Hard, Bernadette

    2014-01-01

    Opioid painkiller dependence is a growing problem and best-practice management is not well defined. We report a case of a young woman exhibiting dependence on codeine, originally prescribed for myalgic encephalopathy, after escalating use over a 10-year period. In 2012, a consultation with a new general practitioner, who had extensive experience of patients with substance abuse, revealed the underlying dependence. After building trust for 6?months, she was able to admit to medication abuse, and was referred to the community drug and alcohol team. On presentation to the team, the patient had no pain issues and the dihydrocodeine use--600 tablets/week--solely reflected her dependence. The patient successfully underwent rapid induction with buprenorphine/naloxone as opioid substitution treatment over 2?days. She is currently stable, engaged with recovery support services and psychosocial counselling, and has just returned to work. She is maintained on a therapeutic dose of buprenorphine 10?mg/naloxone 2.5?mg. PMID:25432908

  19. [Analgesic management of acute pain in patients receiving methadone or buprenorphine].

    PubMed

    Zinck, Louise; Sonne, Nan M; Madsen, Sidsel Lægdsgaard; Nikolajsen, Lone

    2015-03-01

    In Denmark, approximately 7,600 patients receive maintenance therapy with methadone or buprenorphine because of opioid addiction. These patients have an increased risk of inadequate pain treatment during hospitalization, among others because of tolerance to opioids and poor communication with the staff. The present article describes four common misconceptions among health-care providers that underlie inadequate pain treatment and provides practical recommendations for the analgesic management of acute pain in patients receiving methadone or buprenorphine. PMID:25749118

  20. Urine specimen detection of concurrent nonprescribed medicinal and illicit drug use in patients prescribed buprenorphine.

    PubMed

    Guo, Alexander Y; Ma, Joseph D; Best, Brookie M; Atayee, Rabia S

    2013-01-01

    Patients being treated with buprenorphine usually have a history of opioid dependence and may be predisposed to misuse of drugs. Concurrent drug misuse increases the risk of life-threatening drug interactions. This retrospective data analysis observed which nonprescribed and illicit drugs were most commonly detected in the urine of patients from pain management clinics taking buprenorphine with or without a prescription. GC, LC/MS and LC-MS-MS were used to quantify 20,929 urine specimens. The most prevalent illicit drug used in both the groups (prescribed and nonprescribed buprenorphine) was marijuana, followed by cocaine. The most prevalent nonprescribed medications abused by both the groups were benzodiazepines, followed by oxycodone and hydrocodone. The overall prevalence of illicit and nonprescribed drug use was significantly higher in subjects who used buprenorphine without a prescription versus prescribed use. Of the concurrent use of marijuana and cocaine with buprenorphine, cocaine is most concerning since it decreases exposure to buprenorphine (lower area under the concentration-time curve and maximum concentration). The concurrent use of nonprescribed benzodiazepines with buprenorphine can cause excess sedation leading to respiratory depression and even death. These findings highlight the importance of educating patients about these potential toxicities. Furthermore, pain providers should consider expanding the spectrum of drugs that they monitor in patients under treatment. PMID:24080973

  1. The Impact of Prior Authorization on Buprenorphine Dose, Relapse Rates, and Cost for Massachusetts Medicaid Beneficiaries with Opioid Dependence

    PubMed Central

    Clark, Robin E; Baxter, Jeffrey D; Barton, Bruce A; Aweh, Gideon; O'Connell, Elizabeth; Fisher, William H

    2014-01-01

    Objective To assess the impact of a 2008 dose-based prior authorization policy for Massachusetts Medicaid beneficiaries using buprenorphine + naloxone for opioid addiction treatment. Doses higher than 16 mg required progressively more frequent authorizations. Data Sources Mediciaid claims for 2007 and 2008 linked with Department of Public Health (DPH) service records. Study Design We conducted time series for all buprenorphine users and a longitudinal cohort analysis of 2,049 individuals who began buprenorphine treatment in 2007. Outcome measures included use of relapse-related services, health care expenditures per person, and buprenorphine expenditures. Data Collection/Extraction Methods We used ICD-9 codes and National Drug Codes to identify individuals with opioid dependence who filled prescriptions for buprenorphine. Medicaid and DPH data were linked with individual identifiers. Principal Findings Individuals using doses >24 mg decreased from 16.5 to 4.1 percent. Relapses increased temporarily for some users but returned to previous levels within 3 months. Buprenorphine expenditures decreased but total expenditures did not change significantly. Conclusion Prior authorization policies strategically targeted by dose level appear to successfully reduce use of higher than recommended buprenorphine doses. Savings from these policies are modest and may be accompanied by brief increases in relapse rates. Lower doses may decrease diversion of buprenorphine. PMID:25040021

  2. Pharmacokinetics of buprenorphine: a comparison of sublingual tablet versus liquid after chronic dosing.

    PubMed

    Compton, Peggy; Ling, Walter; Chiang, C Nora; Moody, David E; Huber, Alice; Ling, Debbie; Charuvastra, Charles

    2007-06-01

    Although buprenorphine is approved for use in the outpatient treatment of opioid addiction in 2 tablet formulations, a monoproduct containing buprenorphine only (Subutex) and a buprenorphine/naloxone combination product (Suboxone), much of the clinical data that support the approval by the U.S. Food and Drug Administration were generated by using a sublingual liquid. To interpret the literature in prescribing parameters for tablet buprenorphine, this study was designed to determine steady state buprenorphine plasma levels for the 2 formulations and to assess the relative bioavailability of each. A randomized, double-blind, crossover study with dose increases was conducted during a 12-week period at an outpatient treatment clinic. Of the 184 subjects initially randomized to treatment, 133 (72.3%) were evaluated for the steady-state trough plasma concentration, 16 (8.7%) for relative bioavailability, and 31 (16.8%) for dose proportionality. At steady state, differences in the trough plasma concentrations of buprenorphine between the 2 formulations were found across all the dose levels. Average plasma concentration (Cavg) of the tablet at twice the milligram dose of the liquid was twice that of the liquid; intersubject variability was greater for the tablet. At double the dose of tablet, there is no difference in steady state plasma concentrations. The bioavailability seems equivalent for the 2 formulations across all the dose levels. PMID:21768940

  3. [Transdermal buprenorphine: a current overview of pharmacological and clinical data].

    PubMed

    Faymonville, M E; Libbrecht, D

    2008-11-01

    Our understanding of the pathophysiologic mechanisms of chronic pain progresses; the complexity of the problem justifies our need for new molecules and new ways of administration that will help to further optimise and better individualize our pharmacologic therapies. Whereas acute pain can be considered an alarm signal, chronic pain constitutes, per se, a syndrome that requires a meticulous selection of the analgesic drug(s). Since pain is permanent, the continuous administration of the analgesic is recommended rather than an on demand administration. Transdermic modes of administration are of value for the treatment of chronic pain because they allow a progressive delivery of the active compound together with the maintenance of stable plasma levels of the drug. Buprenorphine is a semi-synthetic opioid that is available in the sublingual, injectable, or transdermic forms. The matrix patch of buprenorphine represents a major asset for the treatment of chronic pain, whether it be cancerous in origin, or not. Its efficacy and safety have been clearly demonstrated in randomised double blind trials as well as in post-marketing surveillance observations. Buprenorphine, administered as a transdermal therapeutic system, induces a dose-related pain relief, whatever the nature of the pain and the age of the patient. Buprenorphine also exerts an analgesic action on neuropathic pain. It differs from other opioids by its affinity as a partial agonist on mu and kappa receptors, and as a complete agonist of ORL-1 receptors. Therefore, transdermal buprenorphine will be useful to all physicians having to control severe pain by powerful opioids. PMID:19112993

  4. Drug Interactions of Clinical Importance among the Opioids, Methadone and Buprenorphine, and other Frequently Prescribed Medications: A Review

    PubMed Central

    McCance-Katz, Elinore F.; Sullivan, Lynn; Nallani, Srikanth

    2012-01-01

    Drug interactions are a leading cause of morbidity and mortality. Methadone and buprenorphine are frequently prescribed for the treatment of opioid addiction. Patients needing treatment with these medications often have co-occurring medical and mental illnesses that require medication treatment. The abuse of illicit substances is also common in opioid-addicted individuals. These clinical realities place patients being treated with methadone and buprenorphine at risk for potentially toxic drug interactions. A substantial literature has accumulated on drug interactions between either methadone or buprenorphine with other medications when ingested concomitantly by humans. This review summarizes current literature in this area. PMID:20132117

  5. Buprenorphine therapy for opioid addiction in rural Washington: The experience of the early adopters

    PubMed Central

    Quest, Tyler L.; Merrill, Joseph O.; Roll, John; Saxon, Andrew J.; Rosenblatt, Roger A.

    2014-01-01

    Background The introduction of buprenorphine as office-based treatment for opioid dependence was designed to expand treatment capacity, but virtually there are no data about use of this medication in rural areas. Methods The survey of the first cohort of physicians in rural Washington State who obtained buprenorphine waivers (2002-2010) to determine the volume of treated patients, physician appraisal of the efficacy of this treatment, and perceived barriers to treatment was conducted. Twenty-four (73 percent) of the 33 rural buprenorphine-certified physicians practicing in the state were interviewed in 2010. Results Twenty physicians (83 percent) were actively prescribing buprenorphine/naloxone for treatment of addiction. Those currently prescribing averaged 23 active patients and had treated 125 patients since certification. All respondents reported that buprenorphine was efficacious in the treatment of addiction and 95 percent recommended that other rural colleagues adopt buprenorphine treatment. The following four major barriers were cited: 1) lack of adequate financial support from Medicaid, the largest source of third-party coverage for these patients; 2) unavailability of local mental health and behavioral addiction treatment services; 3) difficulty in finding consultants to assist in managing complex patients; and 4) shortages of other rural physicians providing this service. Conclusions Buprenorphine is viewed as a highly effective treatment of opioid addiction by early adopters in rural Washington State, but relatively few rural physicians currently provide this service. Inadequate insurance coverage, a shortage of effective links with consultants and colleagues, and the lack of mental health services are persistent barriers to the use of this modality in rural Washington State. PMID:22479882

  6. Low-dose naloxone provides an abuse-deterrent effect to buprenorphine.

    PubMed

    Webster, Lynn R; Smith, Michael D; Unal, Cemal; Finn, Andrew

    2015-01-01

    In developmental research, plasma buprenorphine concentrations comparable to a 2 mg buprenorphine-naloxone (BN) sublingual tablet have been achieved with a 0.75 mg dose of BN buccal film, a small, bioerodible polymer film for application to mucosal membranes. This was a randomized, double-blind, placebo-controlled, single-dose, four-period crossover study in opioid-dependent subjects with chronic pain receiving >100 mg oral morphine equivalents daily who experienced withdrawal following a naloxone challenge dose. The objective of the study was to determine if intravenous (IV) naloxone doses of 0.1 and 0.2 mg would produce a withdrawal response when coadministered with a 0.75 mg IV dose of buprenorphine. Fifteen subjects receiving 90-1,260 mg oral morphine equivalents per day enrolled and completed the study. Precipitated withdrawal occurred in 13% (2/15) of placebo-treated subjects and 47% (7/15) of buprenorphine-treated subjects. When combined with the 0.75 mg dose of buprenorphine, a 0.1 mg dose of naloxone increased the incidence of precipitated withdrawal to 60%, and a 0.2 mg dose of naloxone increased the incidence to 73%. By 15 minutes postdose, the mean change in Clinical Opioid Withdrawal Scale (COWS) score from predose was 3.0 for placebo, 6.9 for buprenorphine, 9.8 for BN 0.1 mg, and 12.4 for BN 0.2 mg. The mean COWS score with each active treatment was significantly greater than placebo (P<0.001), and the mean COWS score for each of the naloxone-containing treatments was significantly greater than for buprenorphine alone (P<0.001). Naloxone doses as low as 0.1 mg added an abuse-deterrent effect to a 0.75 mg IV dose of buprenorphine. PMID:26604818

  7. Discontinuation of buprenorphine maintenance therapy: perspectives and outcomes.

    PubMed

    Bentzley, Brandon S; Barth, Kelly S; Back, Sudie E; Book, Sarah W

    2015-05-01

    Buprenorphine maintenance therapy (BMT) is increasingly the preferred opioid maintenance agent due to its reduced toxicity and availability in an office-based setting in the United States. Although BMT has been shown to be highly efficacious, it is often discontinued soon after initiation. No current systematic review has yet investigated providers' or patients' reasons for BMT discontinuation or the outcomes that follow. Hence, provider and patient perspectives associated with BMT discontinuation after a period of stable buprenorphine maintenance and the resultant outcomes were systematically reviewed with specific emphasis on pre-buprenorphine-taper parameters predictive of relapse following BMT discontinuation. Few identified studies address provider or patient perspectives associated with buprenorphine discontinuation. Within the studies reviewed providers with residency training in BMT were more likely to favor long term BMT instead of detoxification, and providers were likely to consider BMT discontinuation in the face of medication misuse. Patients often desired to remain on BMT because of fear of relapse to illicit opioid use if they were to discontinue BMT. The majority of patients who discontinued BMT did so involuntarily, often due to failure to follow strict program requirements, and 1 month following discontinuation, rates of relapse to illicit opioid use exceeded 50% in every study reviewed. Only lower buprenorphine maintenance dose, which may be a marker for attenuated addiction severity, predicted better outcomes across studies. Relaxed BMT program requirements and frequent counsel on the high probability of relapse if BMT is discontinued may improve retention in treatment and prevent the relapse to illicit opioid use that is likely to follow BMT discontinuation. PMID:25601365

  8. Sublingual buprenorphine for chronic pain: A survey of clinician prescribing practices

    PubMed Central

    Rosen, Kristen; Gutierrez, Antonio; Haller, Deborah; Potter, Jennifer Sharpe

    2013-01-01

    Objectives Sublingual buprenorphine, with and without naloxone, is indicated for the treatment of opioid use disorders. Although not approved for pain, some evidence suggests it may be a safe and effective alternative to conventional opioid analgesics, particularly for those with addiction problems. This study surveyed pain specialists to examine the extent to which sublingual buprenorphine was prescribed for chronic pain and explore associated clinician attitudes and characteristics. Method A 36-item survey examining clinician attitudes and characteristics related to sublingual buprenorphine and other opioids was distributed to 1,307 members of the American Pain Society, a multi-disciplinary professional group. Members were provided a paper copy of the survey and URL to an on-line version. A follow up letter was mailed after 2 weeks. Results Overall, 230 completed surveys were returned (18.5%). Of clinicians who prescribed opioids for chronic pain (92.5%), 19.7% reported prescribing sublingual buprenorphine for chronic pain at least once; of these prescribers, 39.6% did not have a DEA X-waiver to prescribe sublingual buprenorphine for opioid dependance. Prescribers were more likely than non-prescribers to find sublingual buprenorphine effective for chronic pain. Prescribers were also significantly more likely to view sublingual buprenorphine as safer than full agonists in terms of addiction, overdose, and drug interaction. No differences emerged between prescribers and non-prescribers regarding perceptions of potential for drug diversion or in terms of overall opioid prescribing behaviors. Discussion Results suggest that sublingual buprenorphine is indeed being used to treat chronic pain; however, the circumstances when this occurs are not entirely clear. PMID:23727654

  9. Buprenorphine and methadone for opioid addiction during pregnancy.

    PubMed

    Mozurkewich, Ellen L; Rayburn, William F

    2014-06-01

    Buprenorphine and methadone are opioid-receptor agonists used as opioid substitution therapy during pregnancy to limit exposure of the fetus to cycles of opioid withdrawal and reduce the risk of infectious comorbidities of illicit opioid use. As part of a comprehensive care plan, such therapy may result in improved access to prenatal care, reduced illicit drug use, reduced exposure to infections associated with intravenous drug use, and improved maternal nutrition and infant birth weight. This article describes differences in patient selection between the two drugs, their relative safety during pregnancy, and changes in daily doses as a guide for prescribing clinicians. PMID:24845488

  10. BUPRENORPHINE-NALXONE THERAPY IN PAIN MANAGEMENT

    PubMed Central

    Chen, Kelly Yan; Chen, Lucy; Mao, Jianren

    2014-01-01

    Buprenorphine-naloxone (bup/nal in 4:1 ratio; Suboxone®, Reckitt Benckiser Pharmaceuticals Incorporation, Richmond, VA) is approved by the Food and Drug Administration for outpatient office-based addiction treatment. In the past few years, bup/nal has been increasingly prescribed off-label for chronic pain management. The current data suggests that bup/nal may provide pain relief in chronic pain patients with opioid dependence or addiction. However, the unique pharmacological profile of bup/nal confers it to be a weak analgesic that is unlikely to provide adequate pain relief for patients without opioid dependence or addiction. Possible mechanisms of pain relief by bup/nal therapy in opioid-dependent chronic pain patients may include reversal of opioid-induced hyperalgesia as well as improvement in opioid tolerance and addiction. Additional studies are needed to assess the implication of bup/nal therapy in clinical anesthesia and perioperative pain management. PMID:24509068

  11. Buprenorphine-naloxone therapy in pain management.

    PubMed

    Chen, Kelly Yan; Chen, Lucy; Mao, Jianren

    2014-05-01

    Buprenorphine-naloxone (bup/nal in 4:1 ratio; Suboxone; Reckitt Benckiser Pharmaceuticals Incorporation, Richmond, VA) is approved by the Food and Drug Administration for outpatient office-based addiction treatment. In the past few years, bup/nal has been increasingly prescribed off-label for chronic pain management. The current data suggest that bup/nal may provide pain relief in patients with chronic pain with opioid dependence or addiction. However, the unique pharmacological profile of bup/nal confers it to be a weak analgesic that is unlikely to provide adequate pain relief for patients without opioid dependence or addiction. Possible mechanisms of pain relief by bup/nal therapy in opioid-dependent patients with chronic pain may include reversal of opioid-induced hyperalgesia and improvement in opioid tolerance and addiction. Additional studies are needed to assess the implication of bup/nal therapy in clinical anesthesia and perioperative pain management. PMID:24509068

  12. Comparison of subcutaneous and transdermal administration of buprenorphine for pre-emptive analgesia in dogs undergoing elective ovariohysterectomy.

    PubMed

    Moll, Xavier; Fresno, Laura; García, Félix; Prandi, David; Andaluz, Anna

    2011-01-01

    The clinical efficacy of a 70 microg/h transdermal buprenorphine patch and of 20 microg/kg of buprenorphine administered subcutaneously (SC) for the relief of post-operative pain was determined in 24 healthy female dogs undergoing elective ovariohysterectomy (OHE). Dogs were randomly assigned to three groups: (1) a control group that received no analgesics, (2) a BSC group that received buprenorphine SC (20 microg/kg), and (3) a BP group that received buprenorphine by a 70 microg/h transdermal patch. Dogs were scored for signs of pain at 0, 2, 4, 6, 8, 10, 14, 20, 26, 32 and 38 h after extubation using the Numerical Rating Scale (NRS) and a modified University of Melbourne Pain Scale (UMPS). Mean NRS and UMPS scores for dogs in the BSC group (2.56 ± 0.23 and 3.05 ± 0.27, respectively) and the BP group (2.02 ± 0.24 and 2.67 ± 0.23, respectively) were significantly lower (P<0.05) compared with dogs in the control group (5.42 ± 0.38 and 7.89 ± 0.44, respectively), whereas differences between the two buprenorphine treatment groups were not significant. The results indicated that the analgesia produced by the 70 microg/h patch was similar to that induced by SC administration of 20 microg/kg of buprenorphine in dogs undergoing OHE, suggesting that the transdermal buprenorphine patch may be a useful alternative for pain management in dogs. PMID:20056555

  13. Abuse and diversion of buprenorphine sublingual tablets and film.

    PubMed

    Lavonas, Eric J; Severtson, S Geoffrey; Martinez, Erin M; Bucher-Bartelson, Becki; Le Lait, Marie-Claire; Green, Jody L; Murrelle, Lenn E; Cicero, Theodore J; Kurtz, Steven P; Rosenblum, Andrew; Surratt, Hilary L; Dart, Richard C

    2014-07-01

    Buprenorphine abuse is common worldwide. Rates of abuse and diversion of three sublingual buprenorphine formulations (single ingredient tablets; naloxone combination tablets and film) were compared. Data were obtained from the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System Poison Center, Drug Diversion, Opioid Treatment (OTP), Survey of Key Informants' Patients (SKIP), and College Survey Programs through December 2012. To control for drug availability, event ratios (rates) were calculated quarterly, based on the number of patients filling prescriptions for each formulation ("unique recipients of a dispensed drug," URDD) and averaged and compared using negative binomial regression. Abuse rates in the OTP, SKIP, and College Survey Programs were greatest for single ingredient tablets, and abuse rates in the Poison Center Program and illicit diversion rates were greatest for the combination tablets. Combination film rates were significantly less than rates for either tablet formulation in all programs. No geographic pattern could be discerned. PMID:24680219

  14. Low-dose naloxone provides an abuse-deterrent effect to buprenorphine

    PubMed Central

    Webster, Lynn R; Smith, Michael D; Unal, Cemal; Finn, Andrew

    2015-01-01

    In developmental research, plasma buprenorphine concentrations comparable to a 2 mg buprenorphine–naloxone (BN) sublingual tablet have been achieved with a 0.75 mg dose of BN buccal film, a small, bioerodible polymer film for application to mucosal membranes. This was a randomized, double-blind, placebo-controlled, single-dose, four-period crossover study in opioid-dependent subjects with chronic pain receiving >100 mg oral morphine equivalents daily who experienced withdrawal following a naloxone challenge dose. The objective of the study was to determine if intravenous (IV) naloxone doses of 0.1 and 0.2 mg would produce a withdrawal response when coadministered with a 0.75 mg IV dose of buprenorphine. Fifteen subjects receiving 90–1,260 mg oral morphine equivalents per day enrolled and completed the study. Precipitated withdrawal occurred in 13% (2/15) of placebo-treated subjects and 47% (7/15) of buprenorphine-treated subjects. When combined with the 0.75 mg dose of buprenorphine, a 0.1 mg dose of naloxone increased the incidence of precipitated withdrawal to 60%, and a 0.2 mg dose of naloxone increased the incidence to 73%. By 15 minutes postdose, the mean change in Clinical Opioid Withdrawal Scale (COWS) score from predose was 3.0 for placebo, 6.9 for buprenorphine, 9.8 for BN 0.1 mg, and 12.4 for BN 0.2 mg. The mean COWS score with each active treatment was significantly greater than placebo (P<0.001), and the mean COWS score for each of the naloxone-containing treatments was significantly greater than for buprenorphine alone (P<0.001). Naloxone doses as low as 0.1 mg added an abuse-deterrent effect to a 0.75 mg IV dose of buprenorphine. PMID:26604818

  15. Induction of opioid-dependent individuals onto buprenorphine and buprenorphine/naloxone soluble-films.

    PubMed

    Strain, E C; Harrison, J A; Bigelow, G E

    2011-03-01

    A sublingual soluble-film formulation of buprenorphine/naloxone (B/N) has been approved by the US Food and Drug Administration for the treatment of opioid dependency. This preparation provides unit-dose, child-resistant packaging amenable to tracking and accountability, offers more rapid dissolution, and has a potentially preferred taste vs. tablets. This study compared the ability of buprenorphine (B) and B/N films to suppress spontaneous withdrawal in opioid-dependent volunteers. Participants were maintained on morphine and underwent challenge sessions to confirm sensitivity to naloxone-induced opioid withdrawal. Subjects were randomized to receive either B (16 mg, n = 18) or B/N (16/4 mg, n = 16) soluble films for 5 days. The primary outcome measure was the Clinical Opiate Withdrawal Scale (COWS) score. Thirty-four subjects completed induction onto soluble films. There was a significant decrease in COWS scores but no significant differences between the groups. The results support the use of B and B/N soluble films as safe and effective delivery methods for opioid induction. PMID:21270789

  16. Management of opioid addiction with buprenorphine: French history and current management.

    PubMed

    Poloméni, Pierre; Schwan, Raymund

    2014-01-01

    The way in which opioid addiction is managed in France is unique, as it is based on the prescription of buprenorphine by general practitioners and is dispensed by retail pharmacies. This policy has had a direct, positive impact on the number of deaths caused by heroin overdose, which was reduced by four-fifths between 1994 and 2002. In addition, certain associated comorbidities, such as infection with the human immunodeficiency virus, have also been reduced; the incidence of acquired immune deficiency syndrome in intravenous drug users fell from 25% in the mid-1990s to 6% in 2010. Since the implementation of this French model of opioid management, major scientific progress has been made, leading to a better understanding of the pathophysiologic mechanisms of addiction and of the management modalities required for its treatment. However, despite notable advances in scientific knowledge and in the implementation of devices, opioid addiction remains a major public health care issue in France, with 275,000-360,000 "problem drug users" being reported in 2011. The situation is still particularly worrying due to psychoactive substance use and misuse of opioid substitution treatments. Since 2003, there has been a persistent increase in the number of deaths and comorbidities related to opioid addiction, principally hepatitis C virus infection, which affects up to 40% of intravenous drug users. In France, the direct involvement of general practitioners in the management of opioid addiction is indisputable. Nevertheless, management could be optimized through better understanding of the pathophysiologic mechanisms of the disease, better knowledge of the pharmacology of opioid substitution treatments, and clear definition of short-, medium- and long-term treatment objectives. Data related to the management of opioid addiction by general practitioners in France have been published in 2005. Since then, the context has changed, other drugs were launched on the market such as generics of buprenorphine, methadone capsule, and Suboxone. Thus, an update seems necessary. This paper provides a description of opioid addiction management objectives and treatment modalities for general practitioners, based on currently available knowledge. PMID:24623988

  17. Management of opioid addiction with buprenorphine: French history and current management

    PubMed Central

    Poloméni, Pierre; Schwan, Raymund

    2014-01-01

    The way in which opioid addiction is managed in France is unique, as it is based on the prescription of buprenorphine by general practitioners and is dispensed by retail pharmacies. This policy has had a direct, positive impact on the number of deaths caused by heroin overdose, which was reduced by four-fifths between 1994 and 2002. In addition, certain associated comorbidities, such as infection with the human immunodeficiency virus, have also been reduced; the incidence of acquired immune deficiency syndrome in intravenous drug users fell from 25% in the mid-1990s to 6% in 2010. Since the implementation of this French model of opioid management, major scientific progress has been made, leading to a better understanding of the pathophysiologic mechanisms of addiction and of the management modalities required for its treatment. However, despite notable advances in scientific knowledge and in the implementation of devices, opioid addiction remains a major public health care issue in France, with 275,000–360,000 “problem drug users” being reported in 2011. The situation is still particularly worrying due to psychoactive substance use and misuse of opioid substitution treatments. Since 2003, there has been a persistent increase in the number of deaths and comorbidities related to opioid addiction, principally hepatitis C virus infection, which affects up to 40% of intravenous drug users. In France, the direct involvement of general practitioners in the management of opioid addiction is indisputable. Nevertheless, management could be optimized through better understanding of the pathophysiologic mechanisms of the disease, better knowledge of the pharmacology of opioid substitution treatments, and clear definition of short-, medium- and long-term treatment objectives. Data related to the management of opioid addiction by general practitioners in France have been published in 2005. Since then, the context has changed, other drugs were launched on the market such as generics of buprenorphine, methadone capsule, and Suboxone. Thus, an update seems necessary. This paper provides a description of opioid addiction management objectives and treatment modalities for general practitioners, based on currently available knowledge. PMID:24623988

  18. Effect of buprenorphine on total intravenous anesthetic requirements during spine surgery.

    PubMed

    Khelemsky, Yury; Schauer, Jacob; Loo, Nathaniel

    2015-01-01

    Buprenorphine is a partial mu receptor agonist and kappa/delta antagonist commonly used for the treatment of opioid dependence or as an analgesic. It has a long plasma half-life and a high binding affinity for opioid receptors. This affinity is so high, that the effects are not easily antagonized by competitive antagonists, such as naloxone. The high affinity also prevents binding of other opioids, at commonly used clinical doses, to receptor sites - preventing their analgesic and likely minimum alveolar concentration (MAC) reducing benefits. This case report contrasts the anesthetic requirements of a patient undergoing emergency cervical spine surgery while taking buprenorphine with anesthetic requirements of the same patient undergoing a similar procedure after weaning of buprenorphine. Use of intraoperative neurophysiological monitoring prevented use of paralytics and inhalational anesthetics during both cases, therefore total intravenous anesthesia (TIVA) was maintained with propofol and remifentanil infusions. During the initial surgery, intraoperative patient movement could not be controlled with very high doses of propofol and remifentanil. The patient stopped moving in response to surgical stimulation only after the addition of a ketamine. Buprenorphine-naloxone was discontinued postoperatively. Five days later the patient underwent a similar cervical spine surgery. She had drastically reduced anesthetic requirements during this case, suggesting buprenorphine's profound effect on anesthetic dosing. This case report elegantly illustrates that discontinuation of buprenorphine is likely warranted for patients who present for major spine surgery, which necessitates the avoidance of volatile anesthetic and paralytic agents. The addition of ketamine may be necessary in patients maintained on buprenorphine in order to ensure a motionless surgical field. PMID:25794231

  19. A double blind, within subject comparison of spontaneous opioid withdrawal from buprenorphine versus morphine.

    PubMed

    Tompkins, D Andrew; Smith, Michael T; Mintzer, Miriam Z; Campbell, Claudia M; Strain, Eric C

    2014-02-01

    Preliminary evidence suggests that there is minimal withdrawal after the cessation of chronically administered buprenorphine and that opioid withdrawal symptoms are delayed compared with those of other opioids. The present study compared the time course and magnitude of buprenorphine withdrawal with a prototypical μ-opioid agonist, morphine. Healthy, out-of-treatment opioid-dependent residential volunteers (N = 7) were stabilized on either buprenorphine (32 mg/day i.m.) or morphine (120 mg/day i.m.) administered in four divided doses for 9 days. They then underwent an 18-day period of spontaneous withdrawal, during which four double-blind i.m. placebo injections were administered daily. Stabilization and spontaneous withdrawal were assessed for the second opioid using the same time course. Opioid withdrawal measures were collected eight times daily. Morphine withdrawal symptoms were significantly (P < 0.05) greater than those of buprenorphine withdrawal as measured by mean peak ratings of Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS), all subscales of the Profile of Mood States (POMS), sick and pain (0-100) Visual Analog Scales, systolic and diastolic blood pressure, heart rate, respiratory rate, and pupil dilation. Peak ratings on COWS and SOWS occurred on day 2 of morphine withdrawal and were significantly greater than on day 2 of buprenorphine withdrawal. Subjective reports of morphine withdrawal resolved on average by day 7. There was minimal evidence of buprenorphine withdrawal on any measure. In conclusion, spontaneous withdrawal from high-dose buprenorphine appears subjectively and objectively milder compared with that of morphine for at least 18 days after drug cessation. PMID:24227768

  20. Opioid Addiction and Pregnancy: Perinatal Exposure to Buprenorphine Affects Myelination in the Developing Brain

    PubMed Central

    SANCHEZ, EMILSE S.; BIGBEE, JOHN W.; FOBBS, WAMBURA; ROBINSON, SUSAN E.; SATO-BIGBEE, CARMEN

    2008-01-01

    Buprenorphine is a μ-opioid receptor partial agonist and κ-opioid receptor antagonist currently on trials for the management of pregnant opioid-dependent addicts. However, little is known about the effects of buprenorphine on brain development. Oligodendrocytes express opioid receptors in a developmentally regulated manner and thus, it is logical to hypothesize that perinatal exposure to buprenorphine could affect myelination. To investigate this possibility, pregnant rats were implanted with minipumps to deliver buprenorphine at 0.3 or 1 mg/kg/day. Analysis of their pups at different postnatal ages indicated that exposure to 0.3 mg/kg/day buprenorphine caused an accelerated and significant increase in the brain expression of all myelin basic protein (MBP) splicing isoforms. In contrast, treatment with the higher dose caused a developmental delay in MBP expression. Examination of corpus callosum at 26-days of age indicated that both buprenorphine doses cause a significant increase in the caliber of the myelinated axons. Surprisingly, these axons have a disproportionately thinner myelin sheath, suggesting alterations at the level of axon-glial interactions. Analysis of myelin associated glycoprotein (MAG) expression and glycosylation indicated that this molecule may play a crucial role in mediating these effects. Co-immunoprecipitation studies also suggested a mechanism involving a MAG-dependent activation of the Src-family tyrosine kinase Fyn. These results support the idea that opioid signaling plays an important role in regulating myelination in vivo and stress the need for further studies investigating potential effects of perinatal buprenorphine exposure on brain development. PMID:18381654

  1. A Double Blind, within Subject Comparison of Spontaneous Opioid Withdrawal from Buprenorphine versus Morphine

    PubMed Central

    Smith, Michael T.; Mintzer, Miriam Z.; Campbell, Claudia M.; Strain, Eric C.

    2014-01-01

    Preliminary evidence suggests that there is minimal withdrawal after the cessation of chronically administered buprenorphine and that opioid withdrawal symptoms are delayed compared with those of other opioids. The present study compared the time course and magnitude of buprenorphine withdrawal with a prototypical ?-opioid agonist, morphine. Healthy, out-of-treatment opioid-dependent residential volunteers (N = 7) were stabilized on either buprenorphine (32 mg/day i.m.) or morphine (120 mg/day i.m.) administered in four divided doses for 9 days. They then underwent an 18-day period of spontaneous withdrawal, during which four double-blind i.m. placebo injections were administered daily. Stabilization and spontaneous withdrawal were assessed for the second opioid using the same time course. Opioid withdrawal measures were collected eight times daily. Morphine withdrawal symptoms were significantly (P < 0.05) greater than those of buprenorphine withdrawal as measured by mean peak ratings of Clinical Opiate Withdrawal Scale (COWS), Subjective Opiate Withdrawal Scale (SOWS), all subscales of the Profile of Mood States (POMS), sick and pain (0–100) Visual Analog Scales, systolic and diastolic blood pressure, heart rate, respiratory rate, and pupil dilation. Peak ratings on COWS and SOWS occurred on day 2 of morphine withdrawal and were significantly greater than on day 2 of buprenorphine withdrawal. Subjective reports of morphine withdrawal resolved on average by day 7. There was minimal evidence of buprenorphine withdrawal on any measure. In conclusion, spontaneous withdrawal from high-dose buprenorphine appears subjectively and objectively milder compared with that of morphine for at least 18 days after drug cessation. PMID:24227768

  2. 40 CFR 148.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Dilution prohibited as a substitute for treatment. 148.3 Section 148.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) HAZARDOUS WASTE INJECTION RESTRICTIONS General § 148.3 Dilution prohibited as a substitute for treatment....

  3. Neonatal outcomes following in utero exposure to buprenorphine/naloxone or methadone

    PubMed Central

    Gawronski, Kristen M; Prasad, Mona R; Backes, Carl R; Lehman, K Joy; Gardner, Debra K

    2014-01-01

    Objectives: To study neonatal outcomes following buprenorphine/naloxone and methadone exposure during pregnancy. Methods: This study is a retrospective review of clinical and demographic information of 58 infants whose mothers were treated with buprenorphine/naloxone and 92 infants whose mothers were treated with methadone for opioid dependence during pregnancy. Results: Gestational age, birth weight, prematurity, admission to neonatal intensive care unit, and length of stay were similar between both groups of infants. Neonatal abstinence syndrome occurred less frequently among infants of mothers treated with buprenorphine/naloxone than those treated with methadone (64% and 80%, respectively, p = 0.03). All infants with neonatal abstinence syndrome were treated postnatally with methadone. There was a trend toward shorter duration of treatment and lower cumulative dosages of methadone among the buprenorphine/naloxone–exposed infants. Conclusions: No apparent significant adverse neonatal outcomes were detected following treatment with either maintenance medication; however, further prospective research is necessary to examine the safety and efficacy of buprenorphine/naloxone in pregnancy and its effects on the neonate. PMID:26770721

  4. A preliminary study comparing methadone and buprenorphine in patients with chronic pain and coexistent opioid addiction.

    PubMed

    Neumann, Anne M; Blondell, Richard D; Jaanimägi, Urmo; Giambrone, Amanda K; Homish, Gregory G; Lozano, Jacqueline R; Kowalik, Urszula; Azadfard, Mohammadreza

    2013-01-01

    Patients with opioid addiction who receive prescription opioids for treatment of nonmalignant chronic pain present a therapeutic challenge. Fifty-four participants with chronic pain and opioid addiction were randomized to receive methadone or buprenorphine/naloxone. At the 6-month follow-up examination, 26 (48.1%) participants who remained in the study noted a 12.75% reduction in pain (P = 0.043), and no participants in the methadone group compared to 5 in the buprenorphine group reported illicit opioid use (P = 0.039). Other differences between the two conditions were not found. Long-term, low-dose methadone or buprenorphine/naloxone treatment produced analgesia in participants with chronic pain and opioid addiction. PMID:23480249

  5. Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: implications for clinical use and policy

    PubMed Central

    Greenwald, Mark K.; Comer, Sandra D.; Fiellin, David A.

    2014-01-01

    Background Sublingual formulations of buprenorphine (BUP) and BUP/naloxone have well-established pharmacokinetic and pharmacodynamic profiles, and are safe and effective for treating opioid use disorder. Since approvals of these formulations, their clinical use has increased. Yet, questions have arisen as to how BUP binding to mu-opioid receptors (?ORs), the neurobiological target for this medication, relate to its clinical application. BUP produces dose- and time-related alterations of ?OR availability but some clinicians express concern about whether doses higher than those needed to prevent opioid withdrawal symptoms are warranted, and policymakers consider limiting reimbursement for certain BUP dosing regimens. Methods We review scientific data concerning BUP-induced changes in ?OR availability and their relationship to clinical efficacy. Results Withdrawal suppression appears to require ?50% ?OR availability, associated with BUP trough plasma concentrations ?1 ng/mL; for most patients, this may require single daily BUP doses of 4-mg to defend against trough levels, or lower divided doses. Blockade of the reinforcing and subjective effects of typical doses of abused opioids require <20% ?OR availability, associated with BUP trough plasma concentrations ?3 ng/mL; for most individuals, this may require single daily BUP doses >16-mg, or lower divided doses. For individuals attempting to surmount this blockade with higher-than-usual doses of abused opioids, even larger BUP doses and <10% ?OR availability would be required. Conclusion For these reasons, and given the complexities of studies on this issue and comorbid problems, we conclude that fixed, arbitrary limits on BUP doses in clinical care or limits on reimbursement for this care are unwarranted. PMID:25179217

  6. Transdermal buprenorphine – a critical appraisal of its role in pain management

    PubMed Central

    Hans, Guy; Robert, Dominique

    2009-01-01

    This paper reviews the current clinical data for the role of transdermal buprenorphine (BUP TDS) in the treatment of diverse acute and chronic pain syndromes. Literature searches were carried out using PubMed (1988 to June 2009). The published findings seem to support hypotheses regarding the rather unique analgesic mechanisms of buprenorphine as compared with pure ?-opioids like morphine and fentanyl. However, the exact mechanism of this analgesic efficacy still remains largely unknown despite recent advances in preclinical pharmacological studies. Such assessments have demonstrated the sustained antihyperalgesic effect of buprenorphine in diverse animal pain models. These findings are supported in a growing number of clinical studies of oral, intrathecal, intravenous, and Bup TDS. This review paper focuses almost entirely on the clinical experience concerning the transdermal administration of buprenorphine, although preclinical aspects are also addressed in order to provide a complete picture of the unique pharmacological properties of this analgesic drug. Mounting evidence indicates the appropriateness of Bup TDS in the treatment of diverse acute and chronic pain syndromes which have been less or not responsive to other opioids. Additionally, BUP TDS seems to hold great promise for other difficult-to-treat (pain) conditions, such as patients in the intensive care setting. However, its use is somewhat tempered by the occurrence of local skin reactions which have been shown to be often therapy resistant. Further studies are certainly warranted to identify even more precisely the clinical syndromes that are most sensitive to buprenorphine treatment, and to compare buprenorphine to other opioids in head-to-head trials of acute and chronic pain conditions. PMID:21197300

  7. Hepatotoxicity in a 52-week randomized trial of short-term versus long-term treatment with buprenorphine/naloxone in HIV-negative injection opioid users in China and Thailand*

    PubMed Central

    Lucas, Gregory M.; Young, Alicia; Donnell, Deborah; Richardson, Paul; Aramrattana, Apinun; Shao, Yiming; Ruan, Yuhua; Liu, Wei; Fu, Liping; Ma, Jun; Celentano, David D.; Metzger, David; Jackson, J. Brooks; Burns, David

    2014-01-01

    Background Buprenorphine/naloxone (BUP/NX), an effective treatment for opioid dependence, has been implicated in hepatic toxicity. However, as persons taking BUP/NX have multiple hepatic risk factors, comparative data are needed to quantify the risk of hepatoxicity with BUP/NX. Methods We compared rates of alanine aminotransferase (ALT) elevation ? grade 3 (ALT ? 5.1 times the upper limit of normal) and graded bilirubin elevations in HIV-negative opioid injectors randomized to long-term (52 weeks) or short-term (18 days) medication assisted treatment (LT-MAT and ST-MAT, respectively) with BUP/NX in a multisite trial conducted in China and Thailand. ALT and bilirubin were measured at baseline, 12, 26, 40 and 52 weeks, times temporally remote from BUP/NX exposure in the ST-MAT participants. Results Among1036 subjects with at least one laboratory follow-up measurement, 76 (7%) participants experienced ALT elevation ? grade 3. In an intent-to-treat analysis, the risk of ALT events was similar in participants randomized to LT-MAT compared with ST-MAT (adjusted hazard ratio 1.25, 95% confidence interval 0.79 to 1.98). This finding was supported by an as-treated analysis, in which actual exposure to BUP/NX was considered. Hepatitis C seroconversion during follow-up was strongly associated with ALT events. Bilirubin elevations ? grade 2 occurred in 2% of subjects, with no significant difference between arms. Conclusions Over 52-week follow-up, the risk of hepatotoxicity was similar in opioid injectors receiving brief and prolonged treatment with BUP/NX. These data suggest that most hepatotoxic events observed during treatment with BUP/NX are due to other factors. PMID:24999060

  8. Management of opioid-dependent patients: comparison of the cost associated with use of buprenorphine/naloxone or methadone, and their interactions with concomitant treatments for infectious or psychiatric comorbidities.

    PubMed

    Roncero, Carlos; Domínguez-Hernández, Raquel; Díaz, Tomás; Fernández, José Manuel; Forcada, Rafael; Martínez, José Manuel; Seijo, Pedro; Terán, Antonio; Oyagüez, Itziar

    2015-01-01

    The objective was to estimate the annual interaction management cost of agonist opioid treatment (AOT) for opioid-dependent (OD) patients with buprenorphine-naloxone (Suboxone®) (B/N) or methadone associated with concomitant treatments for infectious (HIV) or psychiatric comorbidities. A costs analysis model was developed to calculate the associated cost of AOT and interaction management. The AOT cost included pharmaceutical costs, drug preparation, distribution and dispensing, based on intake regimen (healthcare center or take-home) and type and frequency of dispensing (healthcare center or pharmacy), and medical visits. The cost of methadone also included single-dose bottles, monthly costs of custody at pharmacy, urine toxicology drug screenings and nursing visits. Potential interactions between AOT and concomitant treatments (antivirals, antibacterials/antifungals, antipsychotics, anxiolytics, antidepressant and anticonvulsants), were identified to determine the additional use of healthcare resources for each interaction management. The annual cost per patient of AOT was €1,525.97 for B/N and €1,467.29 for methadone. The average annual cost per patient of interaction management was €257.07 (infectious comorbidities), €114.03 (psychiatric comorbidities) and €185.55 (double comorbidity) with methadone and €7.90 with B/N in psychiatric comorbidities. Total annual costs of B/N were €1,525.97, €1,533.87 and €1,533.87 compared to €1,724.35, €1,581.32 and €1,652.84 for methadone per patient with infectious, psychiatric or double comorbidity respectively.Compared to methadone, the total cost per patient with OD was lower with B/N (€47.45-€198.38 per year). This is due to the differences in interaction management costs associated with the concomitant treatment of infectious and/or psychiatric comorbidities. PMID:26437312

  9. Effects of regulation on methadone and buprenorphine provision in the wake of Hurricane Sandy.

    PubMed

    McClure, Bridget; Mendoza, Sonia; Duncan, Laura; Rotrosen, John; Hansen, Helena

    2014-10-01

    Hurricane Sandy led to the closing of many major New York City public hospitals including their substance abuse clinics and methadone programs, and the displacement or relocation of thousands of opioid-dependent patients from treatment. The disaster provided a natural experiment that revealed the relative strengths and weaknesses of methadone treatment in comparison to physician office-based buprenorphine treatment for opioid dependence, two modalities of opioid maintenance with markedly different regulatory requirements and institutional procedures. To assess these two modalities of treatment under emergency conditions, semi-structured interviews about barriers to and facilitators of continuity of care for methadone and buprenorphine patients were conducted with 50 providers of opioid maintenance treatment. Major findings included that methadone programs presented more regulatory barriers for providers, difficulty with dose verification due to impaired communication, and an over reliance on emergency room dosing leading to unsafe or suboptimal dosing. Buprenorphine treatment presented fewer regulatory barriers, but buprenorphine providers had little to no cross-coverage options compared to methadone providers, who could refer to alternate methadone programs. The findings point to the need for well-defined emergency procedures with flexibility around regulations, the need for a central registry with patient dose information, as well as stronger professional networks and cross-coverage procedures. These interventions would improve day-to-day services for opioid-maintained patients as well as services under emergency conditions. PMID:25163931

  10. Randomized, Placebo-Controlled Pilot Trial of Gabapentin During an Outpatient, Buprenorphine-Assisted Detoxification Procedure1

    PubMed Central

    Sanders, Nichole C.; Mancino, Michael J.; Gentry, W. Brooks; Guise, J. Benjamin; Bickel, Warren K.; Thostenson, Jeff; Oliveto, Alison H.

    2014-01-01

    This pilot study examined the efficacy of the N-type calcium channel blocker gabapentin to improve outcomes during a brief detoxification protocol with buprenorphine. Treatment-seeking opioid-dependent individuals were enrolled in a 5-wk, double blind, placebo-controlled trial examining the effects of gabapentin during a 10-day outpatient detoxification from buprenorphine. Participants were inducted onto buprenorphine sublingual tablets during week 1, were randomized and inducted onto gabapentin or placebo during week 2, underwent a 10-day buprenorphine taper during weeks 3–4 and then were tapered off gabapentin/placebo during week 5. Assessments included thrice-weekly opioid withdrawal scales, vitals, and urine drug screens. Twenty-four individuals (13 male, 17 Caucasian, 3 African American, 4 Latino, mean age 29.7 yrs) participated in the detoxification portion of the study (gabapentin, N=11; placebo, N=13). Baseline characteristics did not differ significantly between groups. Self-reported and observer-rated opioid withdrawal ratings were relatively low and did not differ between groups during the buprenorphine taper. Urine results showed a drug x time interaction, such that the probability of opioid-positive urines significantly decreased over time in the gabapentin versus placebo groups during weeks 3–4 (OR=0.73, p=0.004). These results suggest that gabapentin reduces opioid use during a 10-day buprenorphine detoxification procedure. PMID:23855333

  11. Clinical Application of Antimicrobial Bone Graft Substitute in Osteomyelitis Treatment: A Systematic Review of Different Bone Graft Substitutes Available in Clinical Treatment of Osteomyelitis

    PubMed Central

    van Vugt, T. A. G.; Geurts, J.; Arts, J. J.

    2016-01-01

    Osteomyelitis is a common occurrence in orthopaedic surgery, which is caused by different bacteria. Treatment of osteomyelitis patients aims to eradicate infection by debridement surgery and local and systemic antibiotic therapy. Local treatment increases success rates and can be performed with different antimicrobial bone graft substitutes. This review is performed to assess the level of evidence of synthetic bone graft substitutes in osteomyelitis treatment. According to the PRISMA statement for reporting systematic reviews, different types of clinical studies concerning treatment of osteomyelitis with bone graft substitutes are included. These studies are assessed on their methodological quality as level of evidence and bias and their clinical outcomes as eradication of infection. In the fifteen included studies, the levels of evidence were weak and in ten out of the fifteen studies there was a moderate to high risk of bias. However, first results of the eradication of infection in these studies showed promising results with their relatively high success rates and low complication rates. Due to the low levels of evidence and high risks of bias of the included studies, these results are inconclusive and no conclusions regarding the performed clinical studies of osteomyelitis treatment with antimicrobial bone graft substitutes can be drawn. PMID:26904683

  12. Pharmacokinetic/pharmacodynamic relationships of transdermal buprenorphine and fentanyl in experimental human pain models.

    PubMed

    Andresen, Trine; Upton, Richard N; Foster, David J R; Christrup, Lona L; Arendt-Nielsen, Lars; Drewes, Asbjørn M

    2011-04-01

    Pharmacokinetic/pharmacodynamic (PK/PD) modelling can be used to characterize the relationship between dose regimen of opioids, plasma concentration and effect of opioids, which in turn can lead to more rational treatment regimens of pain. The aim of this study was to investigate the concentration-effect relationship for transdermal buprenorphine and fentanyl in experimentally induced pain. Twenty-two healthy volunteers were randomized to receive transdermal patches with fentanyl (25 ?g/hr, 72 hr), buprenorphine (20 ?g/hr, 144 hr) or placebo. The experimental pain tests were pressure at the tibial bone, cutaneous thermal stimulation, cold pressor test (conditioning stimulus (3 ± 0.3°C cold water), nerve growth factor-induced muscle soreness and intradermal capsaicin-induced hyperalgesia and allodynia. Experiments were carried out at baseline, 24, 48, 72 and 144 hr after application of patches. Time-course of placebo was described first and was afterwards added to the description of the time-courses of buprenorphine and fentanyl. This was either described by zero (no drug effect), linear or E(max) model concentration-effect relationships. Time-dependent changes in pain measures in the placebo arm were described by linear or quadratic functions. The time-course of fentanyl and buprenorphine plasma concentrations was complex but could be represented by cubic spline interpolation in the models. Buprenorphine significantly attenuated bone-associated pain, heat pain, nerve growth factor-induced soreness and cold pressor pain. Fentanyl significantly attenuated cold pressor pain for the administered dose regimens. Although the PK/PD relationship for both drugs could be described with similar models, tissue-differentiated analgesic effects between buprenorphine and fentanyl was shown. PMID:21138531

  13. The Reinforcing and Subjective Effects of Intravenous and Intranasal Buprenorphine in Heroin Users

    PubMed Central

    Jones, Jermaine D.; Madera, Gabriela; Comer, Sandra D.

    2014-01-01

    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. PMID:24793093

  14. Parenteral buprenorphine-naloxone abuse is a major cause of fatal buprenorphine-related poisoning.

    PubMed

    Häkkinen, Margareeta; Heikman, Pertti; Ojanperä, Ilkka

    2013-10-10

    Buprenorphine (BPN) medication for opioid maintenance treatment in Finland consists predominantly of buprenorphine-naloxone (BNX). Both BPN and BNX are associated with diversion, abuse and non-medically supervised use worldwide. Our purpose was to estimate the proportion of BNX to all BPN-related fatalities. The material consisted of 225 deceased drug abusers in Finland from January 2010 to June 2011 with a positive BPN and/or norbuprenorphine (NOR) and/or naloxone (NX) finding in urine. The data were divided into three groups based on the urine NX and BPN concentrations. The "Parenteral BNX" group (>100 ?g/l NX) was presumed to consist of injecting or snorting BNX abusers and the "Parenteral BPN" group (>50 ?g/l BPN, 0 ?g/l NX) of injecting or snorting BPN abusers, while the "Other BNX or BPN" group (?100 ?g/l NX, or ?50 ?g/l BPN combined with 0 ?g/l NX) was presumed to consist of mainly sublingual BNX or BPN users. In 12.4% of cases the NX urine concentration was higher than the threshold 100 ?g/l. In fatal BPN poisonings, the proportion of parenteral BNX was 28.4%. In the "Parenteral BNX", "Parenteral BPN" and "Other BNX or BPN" groups, the proportion of fatal BPN poisonings was 67.9, 31.0 and 22.6%, respectively. BNX abuse can be fatal. Among the 225 BPN-related fatalities, parenteral abuse of BNX was shown to be common (12.4%) and BNX poisoning was the underlying cause of death in 8.4%. Parenteral BNX caused fatal BPN poisoning proportionally more often than parenteral BPN. PMID:24053859

  15. A review of buprenorphine diversion and misuse: the current evidence base and experiences from around the world.

    PubMed

    Lofwall, Michelle R; Walsh, Sharon L

    2014-01-01

    Outpatient opioid addiction treatment with sublingual buprenorphine pharmacotherapy has rapidly expanded in the United States and abroad, and, with this increase in medication availability, there have been increasing concerns about its diversion, misuse, and related harms. This narrative review defines the behaviors of diversion and misuse, examines how the pharmacology of buprenorphine alone and in combination with naloxone influence its abuse liability, and describes the epidemiological data on buprenorphine diversion and intravenous misuse, risk factors for its intravenous misuse, and the unintended consequences of misuse and diversion. Physician practices to prevent, screen for, and therapeutically respond to these behaviors, which are a form of medication nonadherence, are discussed, and gaps in knowledge are identified. Outpatient opioid addiction treatment with sublingual buprenorphine pharmacotherapy experiences from other countries that have varied health care systems, public policies, and access to addiction treatment are shared to make clear that diversion and misuse occur across the world in various contexts, for many different reasons, and are not limited to buprenorphine. Comparisons are made with other opioids with known abuse liability and medications with no known abuse. The objective was to facilitate understanding of diversion and misuse so that all factors influencing their expression (patient and provider characteristics and public policy) can be appreciated within a framework that also recognizes the benefits of addiction treatment. With this comprehensive perspective, further careful work can help determine how to minimize these behaviors without eroding the current benefits realized through improved addiction treatment access and expansion. PMID:25221984

  16. 40 CFR 268.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... restricted waste or the residual from treatment of a restricted waste as a substitute for adequate treatment... specified in § 268.40 as the treatment standard, or unless the waste is a D003 reactive cyanide wastewater or nonwastewater. (c) Combustion of the hazardous waste codes listed in Appendix XI of this part...

  17. Messages about methadone and buprenorphine in reality television: a content analysis of celebrity rehab with Dr. Drew.

    PubMed

    Roose, Robert; Fuentes, Liza; Cheema, Mandeep

    2012-08-01

    Medication-assisted treatment for opioid dependence is safe and effective, yet negative perceptions about methadone and buprenorphine may discourage patients from entering treatment. One source of information that may influence viewers' perceptions is television. We performed a content analysis of a popular reality television program on addiction treatment. Although many patients had histories of opioid use, there were no positive messages about methadone or buprenorphine. The two main messages were that they (1) are primarily drugs of abuse, and (2) not acceptable treatment options. These messages reinforce negative stereotypes and may perpetuate stigma. There were multiple missed opportunities to provide evidence-based information. PMID:22587811

  18. A new highly specific buprenorphine immunoassay for monitoring buprenorphine compliance and abuse.

    PubMed

    Melanson, Stacy E F; Snyder, Marion L; Jarolim, Petr; Flood, James G

    2012-04-01

    Urine buprenorphine screening is utilized to assess buprenorphine compliance and to detect illicit use. Robust screening assays should be specific for buprenorphine without cross-reactivity with other opioids, which are frequently present in patients treated for opioid addiction and chronic pain. We evaluated the new Lin-Zhi urine buprenorphine enzyme immunoassay (EIA) as a potentially more specific alternative to the Microgenics cloned enzyme donor immunoassay (CEDIA) by using 149 urines originating from patients treated for chronic pain and opioid addiction. The EIA methodology offered specific detection of buprenorphine use (100%) (106/106) and provided superior overall agreement with liquid chromatography-tandem mass spectrometry, 95% (142/149) and 91% (135/149) using 5 ng/mL (EIA[5]) and 10 ng/mL (EIA[10]) cutoffs, respectively, compared to CEDIA, 79% (117/149). CEDIA generated 27 false positives, most of which were observed in patients positive for other opioids, providing an overall specificity of 75% (79/106). CEDIA also demonstrated interference from structurally unrelated drugs, chloroquine and hydroxychloroquine. CEDIA and EIA[5] yielded similar sensitivities, both detecting 96% (22/23) of positive samples from patients prescribed buprenorphine, and 88% (38/43) and 81% (35/43), respectively, of all positive samples (illicit and prescribed users). The EIA methodology provides highly specific and sensitive detection of buprenorphine use, without the potential for opioid cross-reactivity. PMID:22417836

  19. Inpatient initiation of buprenorphine maintenance vs. detoxification: can retention of opioid-dependent patients in outpatient counseling be improved?

    PubMed

    Caldiero, Ryan M; Parran, Theodore V; Adelman, Christopher L; Piche, Betty

    2006-01-01

    Buprenorphine-naloxone is an office-based opioid agonist released in 2003 in the United States for the maintenance of heroin- and other opioid-dependent patients. Concern has been raised that the medication will distract or otherwise inhibit patients from participating in a holistic recovery program or abstinence-based counseling. Using a retrospective chart review, the first thirty opioid-dependent patients induced on buprenorphine maintenance therapy in an inpatient detoxification unit were compared to thirty age- and gender-matched patients who underwent detoxification (with a tramadol taper) and referral to intensive outpatient treatment. The clinical outcomes were a comparison of completion rates for an intensive outpatient program (IOP) and retention in treatment after twelve weeks of aftercare therapy. Patients induced on buprenorphine maintenance over three days had similar relief of withdrawal symptoms to patients detoxified from opioids over five days with tramadol. Patients maintained on buprenorphine had a markedly increased initiation of IOP and remained in outpatient treatment longer than patients who were detoxified (8.5 wks vs. 0.4 wks, p < 0.001). This study indicates that induction and maintenance on buprenorphine may be more effective than detoxification for engaging and retaining patients in abstinence-based comprehensive outpatient addiction treatment. PMID:16449087

  20. Pronociceptive and Antinociceptive Effects of Buprenorphine in the Spinal Cord Dorsal Horn Cover a Dose Range of Four Orders of Magnitude

    PubMed Central

    Gerhold, Katharina J.; Drdla-Schutting, Ruth; Honsek, Silke D.; Forsthuber, Liesbeth

    2015-01-01

    Due to its distinct pharmacological profile and lower incidence of adverse events compared with other opioids, buprenorphine is considered a safe option for pain and substitution therapy. However, despite its wide clinical use, little is known about the synaptic effects of buprenorphine in nociceptive pathways. Here, we demonstrate dose-dependent, bimodal effects of buprenorphine on transmission at C-fiber synapses in rat spinal cord dorsal horn in vivo. At an analgesically active dose of 1500 μg·kg−1, buprenorphine reduced the strength of spinal C-fiber synapses. This depression required activation of spinal opioid receptors, putatively μ1-opioid receptors, as indicated by its sensitivity to spinal naloxone and to the selective μ1-opioid receptor antagonist naloxonazine. In contrast, a 15,000-fold lower dose of buprenorphine (0.1 μg·kg−1), which caused thermal and mechanical hyperalgesia in behaving animals, induced an enhancement of transmission at spinal C-fiber synapses. The ultra-low-dose buprenorphine-induced synaptic facilitation was mediated by supraspinal naloxonazine-insensitive, but CTOP-sensitive μ-opioid receptors, descending serotonergic pathways, and activation of spinal glial cells. Selective inhibition of spinal 5-hydroxytryptamine-2 receptors (5-HT2Rs), putatively located on spinal astrocytes, abolished both the induction of synaptic facilitation and the hyperalgesia elicited by ultra-low-dose buprenorphine. Our study revealed that buprenorphine mediates its modulatory effects on transmission at spinal C-fiber synapses by dose dependently acting on distinct μ-opioid receptor subtypes located at different levels of the neuraxis. PMID:26134641

  1. Effects of Buprenorphine and Hepatitis C on Liver Enzymes in Adolescents and Young Adults

    PubMed Central

    Bogenschutz, Michael P.; Abbott, Patrick J.; Kushner, Robert; Tonigan, J. Scott; Woody, George E.

    2010-01-01

    Objective The purpose of this study was to explore changes in transaminase values associated with buprenorphine treatment and hepatitis C status among opioid dependent subjects aged 15–21. Methods 152 subjects seeking treatment for opioid dependence were randomized to 2-week detoxification with buprenorphine/naloxone (DETOX) or 12 weeks buprenorphine/naloxone (BUP). Liver chemistries including transaminases were obtained baseline and at 4, 8, and 12 weeks. 111 patients had at least one set of transaminases during treatment and were included in analyses of treatment effects. Results Overall, 8/60 BUP participants vs. 12/51 DETOX participants had at least one elevated ALT value during follow-up (Chi-square n.s.). 5/60 BUP participants vs. 11/51 DETOX participants had at least one elevated AST value (Chi-square = 3.194, p = .048). Twenty-eight out of 152 participants were hepatitis C (HCV) positive at baseline, and 4 seroconverted within 12 weeks, 2 in each group. HCV status was significantly associated with transaminase abnormalities (p = .009 and p = .006 for ALT an AST, respectively). HCV status had a strong effect on transaminase abnormalities among participants assigned to DETOX, but not among those assigned to BUP. Conclusions No evidence was found for hepatotoxicity of buprenorphine in this exploratory analysis. HCV was present in a significant minority of participants and was a significant predictor of transaminase elevation. Results suggest that stabilization on buprenorphine may decrease the frequency of transaminase abnormalities associated with HCV in opioid dependent young people. The high rate of seroconversion underscores the importance of effective treatment and prevention. PMID:21170166

  2. Comparison of the Efficacy of Buprenorphine and Clonidine in Detoxification of Opioid-Dependents

    PubMed Central

    Ziaaddini, Hassan; Nasirian, Mansooreh; Nakhaee, Nouzar

    2012-01-01

    Background Since the number of drug users is increasing, applying a method of detoxification with fewer side effects during withdrawal from opioids and greater reliability seems to be necessary. In addition, without maintenance treatment, there will be limited success of treatment. This study aimed to compare success rates of detoxification with sublingual buprenorphine and clonidine and to evaluate addiction relapse in patients using naltrexone in a six-month follow-up. Methods This double-blind trial was carried out on opioid dependent patients in a psychiatric hospital in Kerman (Iran) during 2007-09. The subjects were randomly selected from individuals who had referred for detoxification. They were allocated to two groups to receive either clonidine (n = 21) or buprenorphine (n = 14). The success rates of the two methods were assessed at the end of the course and patients were discharged while prescribed with 25 mg daily use of naltrexone. They were followed up for six months and the continuous use of naltrexone and relapse of substance abuse were evaluated. Findings A total number of 35 patients entered the study. Success of detoxification with naltrexone was confirmed in all cases. One person (8.4%) in the clonidine group and no patient in the buprenorphine group had a clinical opiate withdrawal scale (COWS) score of more than 12 (P > 0.05). The mean levels of objective signs and subjective symptoms of withdrawal and the desire for drug abuse had significant reductions during detoxification period in both groups (P < 0.001). However, the difference in these variables between the two groups was not statistically significant (P > 0.05). Naltrexone was used for an average of one month in 43% and 64% of subjects in the clonidine and buprenorphine groups, respectively. In addition, 62% of patients in the clonidine group and 92.8% of subjects in the buprenorphine group received maintenance treatment. Nevertheless, the mean number of days staying in treatment was not significantly difference between the two groups (P > 0.05). Conclusion Buprenorphine is as effective as clonidine in controlling withdrawal symptoms. A greater percentage of patients detoxified by buprenorphine received maintenance treatment, but there was not a significant difference in relapse rates between the two methods. PMID:24494140

  3. [Skin substitutes reconstructed in the laboratory: application in burn treatment].

    PubMed

    Braye, F; Hautier, A; Bouez, C; Damour, O

    2005-12-01

    The development of skin substitutes started 25 years ago with the cultivation of keratinocytes to replace the epidermis of extensively burned patients. It is now possible to reproduce in vitro the two layers of skin, epidermis and dermis. Cultured epidermises are now usually used in burn centers dealing with the more severe patients. They are provided by hospital or private laboratories. Dermal substrates are some collagen matrices, which act in vivo as a guide for the reconstruction of a neodermis. Living dermis include living fibroblasts. Different models are now available for clinical use. Living skin equivalent is obtained by coculturing fibroblast and keratinocytes on a collagen support. Clinical essays are going on for chronic wounds. We present the different skin equivalent models and their clinical applications. PMID:16364813

  4. Training rural practitioners to use buprenorphine; using The Change Book to facilitate technology transfer.

    PubMed

    McCarty, Dennis; Rieckmann, Traci; Green, Carla; Gallon, Steve; Knudsen, Jeff

    2004-04-01

    The Opiate Medication Initiative for Rural Oregon Residents trained physicians and counselors in Central and Southwestern Oregon to use buprenorphine and develop service models that supported patient participation in drug abuse counseling. The Change Book from Addiction Technology Transfer Centers was used to structure the change process. Fifty-one individuals (17 physicians, 4 pharmacists, 2 nurse practitioners, and 28 drug abuse counselors and administrators) from seven counties completed the training and contributed to the development of community treatment protocols. A pre-post measure of attitudes and beliefs toward the use of buprenorphine suggested significant improvements in attitude after training, especially among counselors. Eight months after training, 10 of 17 physicians trained had received waivers to use buprenorphine and 29 patients were in treatment with six of the physicians. The Change Book facilitated development of county change teams and structured the planning efforts. The initiative also demonstrated the potential to concurrently train physicians, pharmacists, and counselors on the use of buprenorphine. PMID:15063914

  5. Endocrine and behavioural effects of transdermal buprenorphine in pain-suffering women of different reproductive ages.

    PubMed

    Aurilio, Caterina; Ceccarelli, Ilaria; Pota, Vincenzo; Sansone, Pasquale; Massafra, Cosimo; Barbarisi, Manlio; Pace, Maria Caterina; Passavanti, Maria Beatrice; Bravi, Fabio; Aloisi, Anna Maria

    2011-01-01

    Chronic pain is a common problem in clinical practice and women are affected more often than men. Morphine is often used for long-term pain relief, but it induces side effects including endocrine alterations. The aim of the present study was to assess the behavioural and hormonal effects of transdermal buprenorphine in women suffering from persistent non-malignant pain. Hormones (LH, FSH, total and free testosterone, estradiol, cortisol) and pain measures (visual analogue scale, McGill Pain questionnaire, present pain intensity test) were evaluated at baseline and after 1, 3 and 6 months. Subjects were recruited in the Second University of Naples Pain Research Centre. Eighteen chronic pain women were included in the study, divided into pre- and post-menopausal groups. A transdermal buprenorphine patch (Buprenorphine TDS, 35 µg/h) was administered every 72 h. As expected, buprenorphine administration led to a decrease in pain intensity and no side effects suggestive of hypogonadism were recorded. Pain measures decreased at the first control visit (T1) in both groups. Total and free testosterone were not reduced by treatment (they tended to increase in both groups) while cortisol progressively recovered from the quite low levels detected at the beginning of treatment. These data confirm that buprenorphine is a safe and effective drug for pain relief in women. It is free from the adverse effects on gonadal hormones frequently associated with other opioid treatments. The lack of opioid-induced effects on gonadal hormones (i.e., hypogonadism) is important to guarantee safe long-term pain treatment. PMID:21937837

  6. Benzodiazepines increase the reward effects of buprenorphine in a conditioned place preference test in the mouse.

    PubMed

    Ma, Lin-Lin; Freret, Thomas; Lange, Mathilde; Bourgine, Joanna; Coquerel, Antoine; Lelong-Boulouard, Véronique

    2014-12-01

    Buprenorphine (BPN) is widely used as a substitution treatment for opioid addiction. Some cases of abuse and misuse, especially associated with various benzodiazepines (BZDs), have been described, and a previous study has shown that BZDs increase the sedative effect of BPN and decrease its anxiogenic properties. To investigate the reward effect that may lead to the abusive combination of BPN and BZD, we studied the influence of different doses of three BZDs extensively used with BPN by drug addicts on conditioned place preference behavior in mice. BPN (0.3, 1, 3 mg/kg) was injected subcutaneously into male mice alone or in combination with a BZD administered intraperitoneally: dipotassium clorazepate (CRZ; 1, 4, 16 mg/kg), diazepam (DAZ; 0.5, 1, 5 mg/kg), or bromazepam (BMZ; 0.5, 1, 3 mg/kg). Amphetamine (8 mg/kg) was used as a reference drug. Reward effects of BPN alone or in combination were measured in a conditioned place preference paradigm using an unbiased procedure. Our results showed that groups treated with BPN associated with different doses of diazepam and clorazepate, but not bromazepam, spent significantly more time in the drug-paired compartment compared to the group treated with BPN alone. Our study shows that joint consumption of diazepam and clorazepate, but not bromazepam, can increase the reward properties of BPN alone in mice. These results could help to explain the use of this type of drug combination in the drug addict population. PMID:24617653

  7. [Transdermal System-Buprenorphine and Fentanyl].

    PubMed

    Sakurai, Hiroki

    2015-11-01

    Pain management with transdermal opioids is a useful choice in light of longer duration of action, being not affected by oral intake, and with less adverse effect Recently, transdermal fentanyl and buprenorphine are permitted for musculoskeletal non-malignant pain as a new indication. In Japan, one of the world's fastest aging society, it is a welcome step in terms of pain control. However, proper monitoring and management are required. This article reviews the pharmacology, therapeutic efficacy and adverse effect of buprenorphine transdermal patch, and clinical application in cancer pain management of fentanyl patch. PMID:26689065

  8. Patient Perspectives Associated with Intended Duration of Buprenorphine Maintenance Therapy.

    PubMed

    Bentzley, Brandon S; Barth, Kelly S; Back, Sudie E; Aronson, Garrett; Book, Sarah W

    2015-09-01

    Patients with opioid use disorders frequently discontinue opioid maintenance therapy (OMT) prematurely, reducing retention and possibly limiting the efficacy of OMT. The current study is a cross-sectional survey of patients (N=69) enrolled in buprenorphine maintenance therapy (BMT). We examined patient demographics, BMT characteristics (e.g., dose, time in BMT), and patient perspectives regarding intended duration of BMT. In addition, patients' reasons for continuing or discontinuing BMT were investigated. Results revealed that the majority (82%) of participants reported wanting to continue BMT for at least 12months. Age at first drug use, time in BMT, concern about pain, and concern about relapse were all positively associated with intended duration of BMT. The following were negatively associated with intended duration of BMT: recent discussion with a treatment provider about BMT discontinuation, prior attempt to discontinue BMT, concern about withdrawal symptoms, experiencing pleasurable effects from taking buprenorphine, and perceived conflicts of BMT with life, work, or school obligations. The most common reasons for wanting to continue BMT included concerns about withdrawal symptoms, relapse, and pain. Although preliminary, the findings highlight key issues with regard to patients' perspectives of BMT. The results of this study provide information that may be useful in improving OMT programs and treatment outcomes. PMID:25899872

  9. [When is testosterone substitution a medically necessary treatment?].

    PubMed

    Hakimi, Rainer

    2012-06-01

    The expert questioning of when a treatment with testosterone is medically necessary has increased by several 100% in the daily work of the insurance medical expert in the past years. The reason for this is that testosterone is prescribed a lot more often nowadays than it was 10 years ago. One can suspect that testosterone has become part of a popular lifestyle medication. However, the clinical meaning of the age-dependent decrease of testosterone in men is controversial. Unfortunately, there are only few study data about hypogonadism in ageing men. Testosterone treatment has a very narrow application field and is only medically necessary if the low testosterone level has been clinically proven as well as in a medical lab examination. This is decisive because testosterone treatment has numerous limitations of application and has a wide range of side effects. This article shows the controversy surrounding the discussion on testosterone treatment and the pitfalls of issuing the insurance medical expert's report. PMID:22808644

  10. A Preliminary Study Comparing Methadone and Buprenorphine in Patients with Chronic Pain and Co-existent Opioid Addiction

    PubMed Central

    Neumann, Anne M.; Blondell, Richard D.; Jaanimägi, Urmo; Giambrone, Amanda K.; Homish, Gregory G.; Lozano, Jacqueline R.; Kowalik, Urszula; Azadfard, Mohammadreza

    2013-01-01

    Patients with opioid addiction who receive prescription opioids for treatment of chronic non-malignant pain present a therapeutic challenge. Fifty-four patients with chronic pain and opioid addiction were randomized to receive methadone or buprenorphine/naloxone. At the 6-month follow-up, 26 (48.1%) participants who remained in the study noted a 12.75% reduction in pain (P = 0.043) and compared to 5 in the buprenorphine group, none in the methadone group reported illicit opioid use (P = 0.039). Other differences between the two conditions were not found. Long-term low-dose methadone or buprenorphine/naloxone treatment produced analgesia in patients with chronic pain and opioid addiction. PMID:23480249

  11. Effects of Dexmedetomidine and Ketamine–Dexmedetomidine with and without Buprenorphine on Corticoadrenal Function in Rabbits

    PubMed Central

    González-Gil, Alfredo; Villa, Alberto; Millán, Pilar; Martínez-Fernández, Leticia; Illera, Juan Carlos

    2015-01-01

    Anesthetics may influence adrenal function and consequently alter serum glucocorticoid concentrations, leading to erroneous interpretations of results from anesthetized rabbits. However, decreases in glucocorticoid concentrations may be advantageous in protocols designed to minimize the stress response to surgery. This study characterized the variations in adrenocortical function based on changes in corticosterone and cortisol levels after various doses and combinations of dexmedetomidine, ketamine, and buprenorphine. Each rabbit received all treatments with a minimal interexperiment interval of 10 d. Rabbits were allocated to 7 groups (n = 10 per group) and received either 1 mL saline solution; dexmedetomidine at 0.05, 0.15, or 0.25 mg/kg; ketamine (35 mg/kg) and dexmedetomidine (0.25 mg/kg) without or with buprenorphine (0.03 mg/kg); or ketamine (35 mg/kg) and buprenorphine (0.03 mg/kg). Blood was sampled before drug administration and at 10, 30, 60, and 120 min and 24 h afterward. Serum glucocorticoid levels fell in all treatment groups except the one receiving ketamine–dexmedetomidine; in that group, serum glucocorticoids increased. Rabbits that received ketamine–dexmedetomidine–buprenorphine had the lowest serum glucocorticoid levels overall. In conclusion, dexmedetomidine reduces glucocorticoid secretion in rabbits but, when combined with ketamine, increases corticosterone and cortisol levels as well as heart and respiratory rates. The addition of buprenorphine to the ketamine–dexmedetomidine mixture reduces serum glucocorticoid levels. The influence of anesthetic drugs should be considered when designing a protocol to minimize the glucocorticoid response to surgery or when measuring glucocorticoid levels in rabbits. PMID:26045456

  12. Retention rate and substance use in methadone and buprenorphine maintenance therapy and predictors of outcome: results from a randomized study.

    PubMed

    Soyka, Michael; Zingg, Christina; Koller, Gabriele; Kuefner, Heinrich

    2008-08-01

    This was a 6-month, randomized, flexible-dose study comparing the effects of methadone (Meth) and buprenorphine (Bup) on retention rate and substance use in a sample of 140 opioid-dependent, primarily heroin-addicted, patients who had been without opioid substitution therapy in the 4 weeks prior to the study. The major aims were to compare the efficacy of Bup and Meth in a flexible dosing regimen and to identify possible predictors of outcome. There were no major inhomogeneities between treatment groups. All patients also received standardized psychosocial interventions. Mean daily dosages after the induction phase were 44-50 mg for Meth and 9-12 mg for Bup. Results from this study indicate a favourable outcome, with an overall retention rate of 52.1% and no significant differences between treatment groups (55.3% vs. 48.4%). Substance use decreased significantly over time in both groups and was non-significantly lower in the Bup group. Predictors of outcome were length of continuous opioid use and age at onset of opioid use, although these were only significant in the Bup group. Mean dosage and other parameters were not significant predictors of outcome. Overall, the results of this study give further evidence that substitution treatment is a safe and effective treatment for drug dependence. Meth and Bup are equally effective. Duration of continuous opioid use and age at onset were found to have predictive value for negative outcome. The intensity of withdrawal symptoms showed the strongest correlation with drop-out. Future studies are warranted to further address patient profiles and outcome under different substitution regimens. PMID:18205978

  13. Prenatal buprenorphine exposure decreases neurogenesis in rats.

    PubMed

    Wu, Chih-Cheng; Hung, Chih-Jen; Shen, Ching-Hui; Chen, Wen-Ying; Chang, Cheng-Yi; Pan, Hung-Chuan; Liao, Su-Lan; Chen, Chun-Jung

    2014-02-10

    Perinatal opioid exposure has a negative effect on neurogenesis and produces neurological consequences. However, its mechanisms of action are incompletely understood. Buprenorphine, a mixed opioid agonist/antagonist, is an alternative medication for managing pregnant opioid addicts. This study provides evidence of decreased neurogenesis and depression-like consequences following prenatal exposure to buprenorphine and sheds light on mechanisms of action in a rat model involving administration of intraperitoneal injection to pregnant rats starting from gestation day 7 and lasting for 14 days and a cultured neurosphere model. Results of forced swimming test and tail suspension test showed that pups at postnatal day 21 had worse parameters of depression-like neurobehaviors, independent of gender. Neurobehavioral changes were accompanied by reduction of neuronal composition, biochemical parameters of neural stem/progenitor cells, brain-derived neurotrophic factor (BDNF) expression, tropomyosin-related kinase receptor type B phosphorylation, protein kinase A (PKA) activity, and cAMP response element-binding protein phosphorylation. Results of parallel cell studies further demonstrated a negative impact of buprenorphine on cultured neurospheres, including proliferation, differentiation, BDNF expression and signaling, and PKA activity. Taken together, our results suggest that prenatal exposure to buprenorphine might result in depression-like phenotypes associated with impaired BDNF action and decreased neurogenesis in the developing brain of weanlings. PMID:24321744

  14. Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial

    PubMed Central

    Wright, Nat MJ; Sheard, Laura; Tompkins, Charlotte NE; Adams, Clive E; Allgar, Victoria L; Oldham, Nicola S

    2007-01-01

    Background Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with dihydrocodeine for detoxification from illicit opiates in primary care. Methods Open label randomised controlled trial in NHS Primary Care (General Practices), Leeds, UK. Sixty consenting adults using illicit opiates received either daily sublingual buprenorphine or daily oral dihydrocodeine. Reducing regimens for both interventions were at the discretion of prescribing doctor within a standard regimen of not more than 15 days. Primary outcome was abstinence from illicit opiates at final prescription as indicated by a urine sample. Secondary outcomes during detoxification period and at three and six months post detoxification were recorded. Results Only 23% completed the prescribed course of detoxification medication and gave a urine sample on collection of their final prescription. Risk of non-completion of detoxification was reduced if allocated buprenorphine (68% vs 88%, RR 0.58 CI 0.35–0.96, p = 0.065). A higher proportion of people allocated to buprenorphine provided a clean urine sample compared with those who received dihydrocodeine (21% vs 3%, RR 2.06 CI 1.33–3.21, p = 0.028). People allocated to buprenorphine had fewer visits to professional carers during detoxification and more were abstinent at three months (10 vs 4, RR 1.55 CI 0.96–2.52) and six months post detoxification (7 vs 3, RR 1.45 CI 0.84–2.49). Conclusion Informative randomised trials evaluating routine care within the primary care setting are possible amongst drug using populations. This small study generates unique data on commonly used treatment regimens. PMID:17210079

  15. Bone graft substitutes for the treatment of traumatic fractures of the extremities

    PubMed Central

    Hagen, Anja; Gorenoi, Vitali; Schönermark, Matthias P.

    2012-01-01

    Health political and scientific background Bone graft substitutes are increasingly being used as supplements to standard care or as alternative to bone grafts in the treatment of traumatic fractures. Research questions The efficacy and cost-effectiveness of bone graft substitutes for the treatment of traumatic fractures as well as the ethical, social and legal implications of their use are the main research questions addressed. Methods A systematic literature search was conducted in electronic medical databases (MEDLINE, EMBASE etc.) in December 2009. Randomised controlled trials (RCT), where applicable also containing relevant health economic evaluations and publications addressing the ethical, social and legal aspects of using bone graft substitutes for fracture treatment were included in the analysis. After assessment of study quality the information synthesis of the medical data was performed using metaanalysis, the synthesis of the health economic data was performed descriptively. Results 14 RCT were included in the medical analysis, and two in the heath economic evaluation. No relevant publications on the ethical, social and legal implications of the bone graft substitute use were found. In the RCT on fracture treatment with bone morphogenetic protein-2 (BMP-2) versus standard care without bone grafting (RCT with an elevated high risk of bias) there was a significant difference in favour of BMP-2 for several outcome measures. The RCT of calcium phosphate (CaP) cement and bone marrow-based composite materials versus autogenous bone grafts (RCT with a high risk of bias) revealed significant differences in favour of bone graft substitutes for some outcome measures. Regarding the other bone graft substitutes, almost all comparisons demonstrated no significant difference. The use of BMP-2 in addition to standard care without bone grafting led in the study to increased treatment costs considering all patients with traumatic open fractures. However, cost savings through the additional use of BMP-2 were calculated in a patient subgroup with high-grade open fractures (Gustilo-Anderson grade IIIB). Cost-effectiveness for BMP-2 versus standard care with autologous bone grafts as well as for other bone graft substitutes in fracture treatment has not been determined yet. Discussion Although there were some significant differences in favour of BMP-2, due to the overall poor quality of the studies the evidence can only be interpreted as suggestive for efficacy. In the case of CaP cements and bone marrow-based bone substitute materials, the evidence is only weakly suggestive for efficacy. From an overall economic perspective, the transferability of the results of the health economic evaluations to the current situation in Germany is limited. Conclusions The current evidence is insufficient to evaluate entirely the use of different bone graft substitutes for fracture treatment. From a medical point of view, BMP-2 is a viable alternative for treatment of open fractures of the tibia, especially in cases where bone grafting is not possible. Autologous bone grafting is preferable comparing to the use of OP-1. Possible advantages of CaP cements and composites containing bone marrow over autogenous bone grafting should be taken into account in clinical decision making. The use of the hydroxyapatite material and allograft bone chips compared to autologous bone grafts cannot be recommended. From a health economic perspective, the use of BMP-2 in addition to standard care without bone grafting is recommended as cost-saving in patients with high-grade open fractures (Gustilo-Anderson grade IIIB). Based on the current evidence no further recommendations can be made regarding the use of bone graft substitutes for the treatment of fractures. To avoid legal implications, use of bone graft substitutes outside their approved indications should be avoided. PMID:22984371

  16. 12 CFR 217.36 - Guarantees and credit derivatives: substitution treatment.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 2 2014-01-01 2014-01-01 false Guarantees and credit derivatives: substitution treatment. 217.36 Section 217.36 Banks and Banking FEDERAL RESERVE SYSTEM BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM CAPITAL ADEQUACY OF BOARD-REGULATED INSTITUTIONS Risk-Weighted Assets-Standardized...

  17. Quantitation of Buprenorphine, Norbuprenorphine, Buprenorphine Glucuronide, Norbuprenorphine Glucuronide, and Naloxone in Urine by LC-MS/MS.

    PubMed

    Marin, Stephanie J; McMillin, Gwendolyn A

    2016-01-01

    Buprenorphine is an opioid drug that has been used to treat opioid dependence on an outpatient basis, and is also prescribed for managing moderate to severe pain. Some formulations of buprenorphine also contain naloxone to discourage misuse. The major metabolite of buprenorphine is norbuprenorphine. Both compounds are pharmacologically active and both are extensively metabolized to their glucuronide conjugates, which are also active metabolites. Direct quantitation of the glucuronide conjugates in conjunction with free buprenorphine, norbuprenorphine, and naloxone in urine can distinguish compliance with prescribed therapy from specimen adulteration intended to mimic compliance with prescribed buprenorphine.This chapter quantitates buprenorphine, norbuprenorphine, their glucuronide conjugates and naloxone directly in urine by liquid chromatography tandem mass spectrometry (LC-MS/MS). Urine is pretreated with formic acid and undergoes solid phase extraction (SPE) prior to analysis by LC-MS/MS. PMID:26660175

  18. The pharmacodynamic and pharmacokinetic profile of intranasal crushed buprenorphine and buprenorphine/naloxone tablets in opioid abusers

    PubMed Central

    Middleton, L.S.; Nuzzo, P.A.; Lofwall, M.R.; Moody, D.E.; Walsh, S.L.

    2011-01-01

    Aims Sublingual buprenorphine and buprenorphine/naloxone are efficacious opioid dependence pharmacotherapies, but there are reports of their diversion and misuse by the intranasal route. The study objectives were to characterize and compare their intranasal pharmacodynamic and pharmacokinetic profiles. Design A randomized, double-blind, placebo-controlled, crossover study. Setting An in-patient research unit at the University of Kentucky. Participants Healthy adults (n=10) abusing, but not physically dependent on, intranasal opioids. Measurements Six sessions (72 hours apart) tested five intranasal doses [0/0, crushed buprenorphine (2, 8 mg), crushed buprenorphine/naloxone (2/0.5, 8/2 mg)] and one intravenous dose (0.8 mg buprenorphine/0.2 mg naloxone for bioavailability assessment). Plasma samples, physiological, subject- and observer-rated measures were collected before and for up to 72 hours after drug administration. Findings Both formulations produced time- and dose-dependent increases on subjective and physiological mu-opioid agonist effects (e.g. ‘liking’, miosis). Subjects reported higher subjective ratings and street values for 8 mg compared to 8/2 mg, but these differences were not statistically significant. No significant formulation differences in peak plasma buprenorphine concentration or time-course were observed. Buprenorphine bioavailability was 38–44% and Tmax was 35–40 minutes after all intranasal doses. Naloxone bioavailability was 24% and 30% following 2/0.5 and 8/2 mg, respectively. Conclusions It is difficult to determine if observed differences in abuse potential between intranasal buprenorphine and buprenorphine/naloxone are clinically relevant at the doses tested. Greater bioavailability and faster onset of pharmacodynamic effects compared to sublingual administration suggests a motivation for intranasal misuse in non-dependent opioid abusers. However, significant naloxone absorption from intranasal buprenorphine/naloxone administration may deter the likelihood of intranasal misuse of buprenorphine/naloxone, but not buprenorphine, in opioid-dependent individuals. PMID:21395892

  19. A non-rewarding, non-aversive buprenorphine/naltrexone combination attenuates drug-primed reinstatement to cocaine and morphine in rats in a conditioned place preference paradigm.

    PubMed

    Cordery, Sarah F; Taverner, Alistair; Ridzwan, Irna E; Guy, Richard H; Delgado-Charro, M Begoña; Husbands, Stephen M; Bailey, Christopher P

    2014-07-01

    Concurrent use of cocaine and heroin is a major public health issue with no effective relapse prevention treatment currently available. To this purpose, a combination of buprenorphine and naltrexone, a mixed very-low efficacy mu-opioid receptor agonist/kappa-opioid receptor antagonist/nociceptin receptor agonist, was investigated. The tail-withdrawal and the conditioned place preference (CPP) assays in adult Sprague Dawley rats were used to show that naltrexone dose-dependently blocked the mu-opioid receptor agonism of buprenorphine. Furthermore, in the CPP assay, a combination of 0.3?mg/kg buprenorphine and 3.0?mg/kg naltrexone was aversive. A combination of 0.3?mg/kg buprenorphine and 1.0?mg/kg naltrexone was neither rewarding nor aversive, but still possessed mu-opioid receptor antagonist properties. In the CPP extinction and reinstatement method, a combination of 0.3?mg/kg buprenorphine and 1.0?mg/kg naltrexone completely blocked drug-primed reinstatement in cocaine-conditioned rats (conditioned with 3?mg/kg cocaine, drug prime was 3?mg/kg cocaine) and attenuated drug-primed reinstatement in morphine-conditioned rats (conditioned with 5?mg/kg morphine, drug prime was 1.25?mg/kg morphine). These data add to the growing evidence that a buprenorphine/naltrexone combination may be protective against relapse in a polydrug abuse situation. PMID:23240906

  20. The effects of the opioid pharmacotherapies methadone, LAAM and buprenorphine, alone and in combination with alcohol, on simulated driving.

    PubMed

    Lenné, Michael G; Dietze, Paul; Rumbold, Greg R; Redman, Jennifer R; Triggs, Thomas J

    2003-12-11

    While methadone is currently the primary pharmacotherapy used in the treatment of heroin dependence in Australia, levo-alpha-acetyl-methodol (LAAM) and buprenorphine are new pharmacotherapies that are being examined as alternatives to methadone maintenance treatment. The aim of this research is to consider the effects of the methadone, buprenorphine and LAAM, as used in maintenance pharmacotherapy for heroin dependence, upon simulated driving. Clients stabilised in methadone, LAAM and buprenorphine treatment programs for 3 months, and a control group of non-drug-using participants, took part in this study which involved operating a driving simulator over a 75 min period. All participants attended one session without alcohol and one session with alcohol at around the 0.05% blood alcohol level. Simulated driving skill was measured through standard deviations of lateral position, speed and steering wheel angle, and reaction time to a subsidiary task was also measured. While alcohol impaired all measures of driving performance, there were no differences in driving skills across the four participant groups. These findings suggest that typical community standards around driving safety should be applied to clients stabilised in methadone, LAAM and buprenorphine treatment. The findings are important in terms of the widespread implementation of these treatment options in Victoria given that a large proportion of pharmacotherapy clients drive. PMID:14643944

  1. Oral buprenorphine and aspirin analgesia in rats undergoing liver transplantation.

    PubMed

    Jablonski, P; Howden, B O

    2002-04-01

    The objective of this study was to establish effective postoperative analgesia for Dark Agouti rats undergoing liver transplantation with minimal additional stress due to handling and no adverse effect on transplant outcome. Oral administration of buprenorphine (0.5 mg/kg/dose) or aspirin (100 mg/kg/dose) in raspberry-flavoured gelatine were compared to controls receiving no treatment or plain gelatine. The drugs were presented five times: immediately on recovery from anaesthesia and at 12 h intervals thereafter. All rats underwent right nephrectomy and replacement of their liver by an arterialized liver isograft preserved optimally for 24 h. All groups had reversible hepatic damage, lost weight and demonstrated severely reduced dark cycle activity after surgery. Neither treatment appeared to ameliorate the loss of body weight that probably reflected hepatic insufficiency during the first week as well as pain and surgical stress. In the second week, when liver function was 'normal', rats began to regain weight at the pre-transplant rate. Aspirin treatment significantly increased activity during the first and second dark cycles after surgery, whereas buprenorphine significantly increased activity during the second dark cycle only. Neither drug had any apparent adverse effects on the rats or on graft function. Postoperative oral administration of aspirin should be incorporated into future programmes of liver transplantation in rodents. More effective treatment in the immediate postoperative period may require oral administration of analgesia prior to surgery or a single subcutaneous injection of an analgesic agent on completion of surgery in addition to postoperative oral administration of aspirin. PMID:11943077

  2. A Review of Buprenorphine Diversion and Misuse: The Current Evidence Base and Experiences from Around the World

    PubMed Central

    Lofwall, Michelle R.; Walsh, Sharon L.

    2014-01-01

    Outpatient opioid addiction treatment with sublingual buprenorphine pharmacotherapy (OBOT) has rapidly expanded in the United States and abroad, and, with this increase in medication availability, there have been increasing concerns about its diversion, misuse and related harms. This narrative review defines the behaviors of diversion and misuse, examines how the pharmacology of buprenorphine alone and in combination with naloxone influence its abuse liability, and describes the epidemiological data on buprenorphine diversion and intravenous misuse, risk factors for its intravenous misuse and the unintended consequences of misuse and diversion. Physician practices to prevent, screen for, and therapeutically respond to these behaviors, which are a form of medication non-adherence, are discussed and gaps in knowledge are identified. OBOT experiences from other countries that have varied health care systems, public policies, and access to addiction treatment are shared in order to make clear that diversion and misuse occur across the world in various contexts, for many different reasons, and are not limited to buprenorphine. Comparisons are made with other opioids with known abuse liability as well as medications with no known abuse. The objective is to facilitate understanding of diversion and misuse so that all factors influencing their expression (patient and provider characteristics and public policy) can be appreciated within a framework that also recognizes the benefits of addiction treatment. With this comprehensive perspective, further careful work can help determine how to minimize these behaviors without eroding the current benefits realized through improved addiction treatment access and expansion. PMID:25221984

  3. Dosing adjustments in postpartum patients maintained on buprenorphine or methadone.

    PubMed

    Jones, Hendrée E; Johnson, Rolley E; O'Grady, Kevin E; Jasinski, Donald R; Tuten, Michelle; Milio, Lorraine

    2008-06-01

    Scant scientific attention has been given to examining the need for agonist medication dose changes in the postpartum period. Study objectives were: 1) to determine the need for medication dose adjustments in participants stabilized on buprenorphine or methadone 3 weeks before and 4 weeks after delivery, and 2) to evaluate the need for methadone dose adjustments during the first 7 days in participants transferred from buprenorphine to methadone at 5 weeks postpartum. Participants were opioid-dependent pregnant women who had completed a randomized, double-blind, double-dummy, flexible dosing comparison of buprenorphine to methadone. Participants received a stable dose of methadone (N = 10) or buprenorphine (N = 8) before and 4 weeks after delivery. Buprenorphine-maintained participants were transferred to methadone at 5 weeks postpartum. There were no significant differences predelivery and/or postdelivery between the buprenorphine and methadone conditions in the mean ratings of dose adequacy, "liking," "hooked," and "craving" of heroin or cocaine. Patient response to the conversion from buprenorphine to methadone seems variable. Buprenorphine-maintained participants required dose changes postpartum only after they transferred to methadone. Regardless of type of medication, postpartum patients should be monitored for signs of overmedication. PMID:21768979

  4. Do methadone and buprenorphine have the same impact on psychopathological symptoms of heroin addicts?

    PubMed Central

    2011-01-01

    Background The idea that the impact of opioid agonist treatment is influenced by the psychopathological profile of heroin addicts has not yet been investigated, and is based on the concept of a specific therapeutic action displayed by opioid agents on psychopathological symptoms. In the present report we compared the effects of buprenorphine and methadone on the psychopathological symptoms of 213 patients (106 on buprenorphine and 107 on methadone) in a follow-up study lasting 12 months. Methods Drug addiction history was collected by means of the Drug Addiction History Rating Scale (DAH-RS) and psychopathological features were collected by means of the Symptom Checklist-90 (SCL-90), using a special five-factor solution. Toxicological urinalyses were carried out for each patient during the treatment period. Results No statistically significant differences were detected in psychopathological symptoms, including 'worthlessness-being trapped', 'somatization', and 'panic-anxiety'. Methadone proved to be more effective on patients characterized by 'sensitivity-psychoticism', whereas buprenorphine was more effective on patients displaying a 'violence-suicide' symptomatology. Conclusions Heroin-dependent patients with psychiatric comorbidities may benefit from opioid agonist treatment not only because it targets their addictive problem, but also, precisely due to this, because it is effective against their mental disorder too. PMID:21569624

  5. Chemical profile of counterfeit buprenorphine vials seized in Tehran, Iran.

    PubMed

    Soltaninejad, Kambiz; Faryadi, Mansoor; Akhgari, Maryam; Bahmanabadi, Leila

    2007-10-25

    Buprenorphine, commonly known by the trademark Temgesic, is one of the most popular drugs of abuse among the opioid-addicted young individuals in Iran. Temgesic, Bungesic, etc. are the most popular and important illicit opioid drugs in Tehran's illicit drugs black market, and are now among the most widely abused by opioid addicts. Because of this, counterfeiting of this drug has increased in Tehran. In this study, the qualitative analysis of counterfeit buprenorphine by gas chromatography-mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) demonstrates the presence of diacetylmorphine, acetylcodeine and pheniramine, as well as the absence of buprenorphine. In conclusion, due to the absence of quality control and difficulties in differentiating counterfeit buprenorphine from genuine products, the use of counterfeit buprenorphine leads the opioid abusers to health risks. PMID:17646070

  6. Comparison of Intravenous Morphine with Sublingual Buprenorphine in Management of Postoperative Pain after Closed Reduction Orthopedic Surgery

    PubMed Central

    Soltani, Ghasem; Khorsand, Mahmood; Shamloo, Alireza Sepehri; Jarahi, Lida; Zirak, Nahid

    2015-01-01

    Background: Postoperative pain is a common side effect following surgery that can significantly reduce surgical quality and patient’s satisfaction. Treatment options are morphine and buprenorphine. We aimed to compare the efficacy of a single dose of intravenous morphine with sublingual buprenorphine in postoperative pain control following closed reduction surgery. Methods: This triple blind clinical trial was conducted on 90 patients referred for closed reduction orthopedic surgery. They were older than 18 years and in classes I and II of the American Society of Anesthesiologists (ASA) with an operation time of 30-90 minutes. Patients were divided into two groups of buprenorphine (4.5µg/kg sublingually) and morphine (0.2mg/kg intravenously). Baseline characteristics, vital signs, pain score, level of sedation and pharmacological side effects were recorded in the recovery room (at 0 and 30 minutes), and in the ward (at 3, 6 and 12 hours). SPSS version 19 software was used for data analysis and the significance level was set at P<0.05. Results: Ninety patients were studied, 60 males and 30 females with a mean age of 37.7±16.2 years. There was no significant difference between the two groups in terms of baseline characteristics. Pain score in the morphine group was significantly higher than the buprenorphine group with an average score of 2.5 (P<0.001). Postoperative mean heart rate in the buprenorphine group was four beats lower than the morphine group (P<0.001). Also, in the buprenorphine 48.6% and in the morphine group 86.7% of cases were conscious in recovery (P=0.001) with a higher rate of pruritus in the latter group (P=0.001). Conclusion: Sublingual buprenorphine administration before anesthesia induction in closed reduction surgery can lead to better postoperative pain control in comparison to intravenous morphine. Due to simple usage and longer postoperative sedation, sublingual buprenorphine is recommended as a suitable drug in closed reduction surgery. PMID:26550594

  7. Assessment of Drug-Drug Interactions between Daclatasvir and Methadone or Buprenorphine-Naloxone

    PubMed Central

    Wang, R.; Luo, W.-L.; Wastall, P.; Kandoussi, H.; DeMicco, M.; Bruce, R. D.; Hwang, C.; Bertz, R.; Bifano, M.

    2015-01-01

    Hepatitis C virus (HCV) infection is common among people who inject drugs, including those managed with maintenance opioids. Pharmacokinetic interactions between opioids and emerging oral HCV antivirals merit evaluation. Daclatasvir is a potent pangenotypic inhibitor of the HCV NS5A replication complex recently approved for HCV treatment in Europe and Japan in combination with other antivirals. The effect of steady-state daclatasvir (60 mg daily) on stable plasma exposure to oral opioids was assessed in non-HCV-infected subjects receiving methadone (40 to 120 mg; n = 14) or buprenorphine plus naloxone (8 to 24 mg plus 2 to 6 mg; n = 11). No relevant interaction was inferred if the 90% confidence interval (CI) of the geometric mean ratio (GMR) of opioid area under the plasma concentration-time curve over the dosing interval (AUCτ) or maximum concentration in plasma (Cmax) with versus without daclatasvir was within literature-derived ranges of 0.7 to 1.43 (R- and S-methadone) or 0.5 to 2.0 (buprenorphine and norbuprenorphine). Dose-normalized AUCτ for R-methadone (GMR, 1.08; 90% CI, 0.94 to 1.24), S-methadone (1.13; 0.99 to 1.30), and buprenorphine (GMR, 1.37; 90% CI, 1.24 to 1.52) were within the no-effect range. The norbuprenorphine AUCτ was slightly elevated in the primary analysis (GMR, 1.62; 90% CI, 1.30 to 2.02) but within the no-effect range in a supplementary analysis of all evaluable subjects. Dose-normalized Cmax for both methadone enantiomers, buprenorphine and norbuprenorphine, were within the no-effect range. Standardized assessments of opioid pharmacodynamics were unchanged throughout daclatasvir administration with methadone or buprenorphine. Daclatasvir pharmacokinetics were similar to historical data. Coadministration of daclatasvir and opioids was generally well tolerated. In conclusion, these data suggest that daclatasvir can be administered with buprenorphine or methadone without dose adjustments. PMID:26124175

  8. Assessment of drug-drug interactions between daclatasvir and methadone or buprenorphine-naloxone.

    PubMed

    Garimella, T; Wang, R; Luo, W-L; Wastall, P; Kandoussi, H; DeMicco, M; Bruce, R D; Hwang, C; Bertz, R; Bifano, M

    2015-09-01

    Hepatitis C virus (HCV) infection is common among people who inject drugs, including those managed with maintenance opioids. Pharmacokinetic interactions between opioids and emerging oral HCV antivirals merit evaluation. Daclatasvir is a potent pangenotypic inhibitor of the HCV NS5A replication complex recently approved for HCV treatment in Europe and Japan in combination with other antivirals. The effect of steady-state daclatasvir (60 mg daily) on stable plasma exposure to oral opioids was assessed in non-HCV-infected subjects receiving methadone (40 to 120 mg; n = 14) or buprenorphine plus naloxone (8 to 24 mg plus 2 to 6 mg; n = 11). No relevant interaction was inferred if the 90% confidence interval (CI) of the geometric mean ratio (GMR) of opioid area under the plasma concentration-time curve over the dosing interval (AUC?) or maximum concentration in plasma (C max) with versus without daclatasvir was within literature-derived ranges of 0.7 to 1.43 (R- and S-methadone) or 0.5 to 2.0 (buprenorphine and norbuprenorphine). Dose-normalized AUC? for R-methadone (GMR, 1.08; 90% CI, 0.94 to 1.24), S-methadone (1.13; 0.99 to 1.30), and buprenorphine (GMR, 1.37; 90% CI, 1.24 to 1.52) were within the no-effect range. The norbuprenorphine AUC? was slightly elevated in the primary analysis (GMR, 1.62; 90% CI, 1.30 to 2.02) but within the no-effect range in a supplementary analysis of all evaluable subjects. Dose-normalized C max for both methadone enantiomers, buprenorphine and norbuprenorphine, were within the no-effect range. Standardized assessments of opioid pharmacodynamics were unchanged throughout daclatasvir administration with methadone or buprenorphine. Daclatasvir pharmacokinetics were similar to historical data. Coadministration of daclatasvir and opioids was generally well tolerated. In conclusion, these data suggest that daclatasvir can be administered with buprenorphine or methadone without dose adjustments. PMID:26124175

  9. Efficacy and safety of transdermal buprenorphine: a randomized, placebo-controlled trial in 289 patients with severe cancer pain.

    PubMed

    Poulain, Philippe; Denier, Willy; Douma, Joep; Hoerauf, Klaus; Samija, Mirko; Sopata, Maciej; Wolfram, Gernot

    2008-08-01

    Strong opioids are recommended for treating severe cancer pain in the advanced stages of the disease. Few data are available concerning the efficacy of buprenorphine in cancer pain. We compared transdermal buprenorphine 70 microg/h (BUP TDS) to placebo in an enriched design study. Opioid-tolerant patients with cancer pain requiring strong opioids in the dose range of 90-150 mg/d oral morphine equivalents entered a two-week run-in phase, during which they were converted to BUP TDS. Patients who could be stabilized on BUP TDS were randomized to BUP TDS or placebo patch for a two-week maintenance phase. Rescue medication (buprenorphine sublingual tablets 0.2mg) was allowed as required. Response was defined as a mean pain intensity of <5 (0-10 scale) and a mean daily buprenorphine sublingual tablet intake of < or =2 tablets during the maintenance phase. Of 289 patients who entered the run-in phase, 100 discontinued treatment due to lack of efficacy or adverse events; 189 patients continued treatment in the maintenance phase (94 BUP TDS, 95 placebo), of whom 31 discontinued treatment (7 BUP TDS, 24 placebo). A significant difference in the number of treatment responders was observed: 70 BUP TDS (74.5%, 65.7-83.3) vs. 47 placebo (50%, 39.9-60.1) (P=0.0003). This result was supported by a lower daily pain intensity, lower intake of buprenorphine sublingual tablets and fewer dropouts in the BUP TDS group. The incidence of adverse events was slightly higher for BUP TDS. In conclusion, BUP TDS 70 microg/h is an efficacious and safe treatment for patients with severe cancer pain. PMID:18411010

  10. A Randomized, Double-blind Evaluation of Buprenorphine Taper Duration in Primary Prescription Opioid Abusers

    PubMed Central

    Sigmon, Stacey C.; Dunn, Kelly E.; Saulsgiver, Kathryn; Patrick, Mollie E.; Badger, Gary J.; Heil, Sarah H.; Brooklyn, John R.; Higgins, Stephen T.

    2014-01-01

    IMPORTANCE Although abuse of prescription opioids (POs) is a significant public health problem, few experimental studies have investigated the treatment needs of this growing population. OBJECTIVE To evaluate, following brief stabilization with a combination of buprenorphine hydrochloride and naloxone hydrochloride dihydrate, the relative efficacy of 1-, 2-, and 4-week buprenorphine tapering regimens and subsequent naltrexone hydrochloride therapy in PO-dependent outpatients. DESIGN, SETTING, AND PARTICIPANTS A double-blind, 12-week randomized clinical trial was conducted in an outpatient research clinic. Following a brief period of buprenorphine stabilization, 70 PO-dependent adults were randomized to receive 1-, 2-, or 4-week tapers followed by naltrexone therapy. INTERVENTION During phase 1 (weeks 1–5 after randomization), participants visited the clinic daily; during phase 2 (weeks 6–12), visits were reduced to thrice weekly. Participants received behavioral therapy and urine toxicology testing throughout the trial. MAIN OUTCOMES AND MEASURES The percentage of participants negative for illicit opioid use, retention, naltrexone ingestion, and favorable treatment response (ie, retained in treatment, opioid abstinent, and receiving naltrexone at the end of the study). RESULTS Opioid abstinence at the end of phase 1 was greater in the 4-week compared with the 2- and 1-week taper conditions (P = .02), with 63% (n = 14), 29% (n = 7), and 29% (n = 7) of participants abstinent in the 4-, 2-, and 1-week conditions, respectively. Abstinence at the end of phase 2 was also greater in the 4-week compared with the 2- and 1-week conditions (P = .03), with 50% (n = 11), 16% (n = 4), and 20% (n = 5) of participants abstinent in the 4-, 2-, and 1-week conditions, respectively. There were more treatment responders in the 4-week condition (P = .03), with 50% (n = 11), 17% (n = 4), and 21% (n = 5) of participants in the 4-, 2-, and 1-week groups considered responders at the end of treatment, respectively. Retention and naltrexone ingestion also were superior in the 4-week vs briefer tapers (both P = .04). Experimental condition (ie, taper duration) was the strongest predictor of treatment response, followed by buprenorphine stabilization dose. CONCLUSIONS AND RELEVANCE This study represents a rigorous experimental evaluation of outpatient buprenorphine stabilization, brief taper, and naltrexone maintenance for treatment of PO dependence. Results suggest that a meaningful subset of PO-dependent outpatients may respond positively to a 4-week taper plus naltrexone maintenance intervention. PMID:24153411

  11. Indicators of Buprenorphine and Methadone Use and Abuse: What Do We Know?

    PubMed Central

    Maxwell, Jane Carlisle; McCance-Katz, Elinore F.

    2013-01-01

    Abuse of prescription opioids is a growing problem. The number of methadone pain pills distributed now exceeds liquid methadone used in opioid treatment, and the increases in buprenorphine indicators provide evidence of the need to monitor and intervene to decrease the abuse of this drug. The need for additional and improved data to track trends is discussed, along with findings as to the characteristics of the users and combinations of drugs. Data on toxicities related to methadone or buprenorphine, particularly in combination with other prescribed drugs, are presented and clinical implications and considerations are offered. These findings underscore the need for physicians to be aware of potential toxicities and to educate their patients regarding these issues. PMID:20132124

  12. [Understanding Oral and Nasal Mucosal Absorption of Fentanyl, and Rectal Absorption of Buprenorphine].

    PubMed

    Shimoyama, Naohito; Shimoyama, Megumi; Kubota, Yukino; Kato, Yoko

    2015-11-01

    One of the key issues in the treatment of pain is to choose the appropriate route and dosage form of analgesics for each individual patient in pain. New drug forms of fentanyl absorbed by oral or nasal mucosa, and buprenorphine absorbed by rectal mucosa are described in this chapter. Only lipophilic opioids such as fentanyl and buprenorphine can be absorbed via the mucosa of oral or nasal cavity of the human body. The T max of rapid onset opioids (ROO) such as fentanyl buccal or sublingual tablets is the fastest among various dosage forms of opioid analgesics. However, such rapid increase in plasma concentration of fentanyl by ROO formulations may cause the risk of respiratory depression. Safe ways to use ROO analgesics are described. PMID:26689067

  13. Psychiatric comorbidity, red flag behaviors, and associated outcomes among office-based buprenorphine patients following Hurricane Sandy.

    PubMed

    Williams, Arthur R; Tofighi, Babak; Rotrosen, John; Lee, Joshua D; Grossman, Ellie

    2014-04-01

    In October 2012, Bellevue Hospital Center (Bellevue) in New York City was temporarily closed as a result of Hurricane Sandy, the largest hurricane in US history. Bellevue's primary care office-based buprenorphine program was temporarily closed and later relocated to an affiliate public hospital. Previous research indicates that the relationships between disaster exposure, substance use patterns, psychiatric symptoms, and mental health services utilization is complex, with often conflicting findings regarding post-event outcomes (on the individual and community level) and antecedent risk factors. In general, increased use of tobacco, alcohol, and illicit drugs is associated with both greater disaster exposure and the development or exacerbation of other psychiatric symptoms and need for treatment. To date, there is limited published information regarding post-disaster outcomes among patients enrolled in office-based buprenorphine treatment, as the treatment modality has only been relatively approved recently. Patients enrolled in the buprenorphine program at the time of the storm were surveyed for self-reported buprenorphine adherence and illicit substance and alcohol use, as well as disaster-related personal consequences and psychiatric sequelae post-storm. Baseline demographic characteristics and insurance status were available from the medical record. Analysis was descriptive (counts and proportions) and qualitative, coding open-ended responses for emergent themes. There were 132 patients enrolled in the program at the time of the storm; of those, 91 were contacted and 89 completed the survey. Almost half of respondents reported disruption of their buprenorphine supply. Unexpectedly, patients with psychiatric comorbidity were no more likely to report increased use/relapse as a result. Rather, major risk factors associated with increased use or relapse post-storm were: (1) shorter length of time in treatment, (2) exposure to storm losses such as buprenorphine supply disruption, (3) a pre-storm history of red flag behaviors (in particular, repeat opioid-positive urines), and (4) new-onset post-storm psychiatric symptoms. Our findings highlight the relative resilience of buprenorphine as an office-based treatment modality for patients encountering a disaster with associated unanticipated service disruption. In responding to future disasters, triaging patient contact and priority based on a history of red-flag behaviors, rather than a history of psychiatric comorbidity, will likely optimize resource allocation, especially among recently enrolled patients. Additionally, patients endorsing new-onset psychiatric manifestations following disasters may be an especially high-risk group for poor outcomes, warranting further study. PMID:24619775

  14. Uptake and delivery of hepatitis C treatment in opiate substitution treatment: perceptions of clients and health professionals.

    PubMed

    Treloar, C; Newland, J; Rance, J; Hopwood, M

    2010-12-01

    Uptake of treatment for hepatitis C virus (HCV) infection is very low particularly among people who have injected drugs. Opiate substitution treatment (OST) programs, with a high prevalence of people living with HCV, have been a site of growing interest in the delivery of hepatitis C treatment. There has been no exploration of OST clients' and health professionals' perceptions of the barriers and facilitators to uptake and delivery of HCV treatment in OST clinics from personal and organizational perspectives. This qualitative study involved interviews with 27 OST clients in New South Wales and a focus group and interviews with 22 Australian OST health professionals. Clients and health professionals viewed hepatitis C treatment in OST as a 'one-stop-shop' model which could increase access to and uptake of treatment and build on existing relationships of trust between OST client and health professional. Elements of the organizational culture were also noted as barriers to HCV treatment delivery including concerns about confidentiality, lack of discussion of HCV treatment and that HCV treatment was not perceived by clinicians as a legitimate activity of OST clinics. OST client participants also reported a number of personal barriers to engaging with HCV treatment including family responsibilities (and concerns about treatment side effects), unstable housing, comorbidities and perceptions of the unsatisfactory level of treatment efficacy. These findings emphasize the need for future research and delivery of services which addresses the complexity of care and treatment for people in marginalized social circumstances. PMID:20070504

  15. Methadone and buprenorphine prescribing and referral practices in US prison systems: results from a nationwide survey.

    TOXLINE Toxicology Bibliographic Information

    Nunn A; Zaller N; Dickman S; Trimbur C; Nijhawan A; Rich JD

    2009-11-01

    BACKGROUND: 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.OBJECTIVE AND METHODS: 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.RESULTS: 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.CONCLUSION: 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.

  16. The analgesic effect of buprenorphine, etorphine and pethidine in the pig: a randomized double blind cross-over study.

    TOXLINE Toxicology Bibliographic Information

    Hermansen K; Pedersen LE; Olesen HO

    1986-07-01

    In order to find a suitable analgesic for the treatment of postoperative pain in pigs the analgesic effect of buprenorphine, etorphine and pethidine has been compared in 8 domestic pigs. For assessment of the analgesic action on thermal (hot plate) and two mechanical (cannulation of ear vein, needle prick) noxious stimuli have been employed. In a pilot experiment on 2 pigs in which methadone was included the maximal effective doses were estimated for each drug. Methadone was found unsuitable because of unacceptable side effects (respiratory dysfunction, hyperactivity) at effective dose levels. Next buprenorphine 120 micrograms/kg, etorphine 3 micrograms/kg and pethidine 20 mg/kg all given intramuscularly were compared in a randomized blind trial with a balanced cross-over design on 6 pigs. Etorphine proved to have the highest and pethidine the lowest maximal analgesic effect which was especially evident in the needle-prick test. Buprenorphine proved to have the longest duration of action in all three analgesic tests, in the hot plate test lasting between 7 and 24 hrs. Etorphine had a duration of 3 to 5 hrs whereas the effect of pethidine was short, only lasting about 2 hrs. Etorphine provides a complete analgesia but has a small safety margin for which reason it should be used with caution in the pig. The experimental results indicate that buprenorphine should be the first drug of choice in the treatment of pain after surgical intervention due to its long duration of action and lack of side effects.

  17. Safety and clinical effectiveness of a compounded sustained-release formulation of buprenorphine for postoperative analgesia in New Zealand White rabbits.

    PubMed

    DiVincenti, Louis; Meirelles, Luiz A D; Westcott, Robin A

    2016-04-01

    OBJECTIVE To determine the clinical effectiveness and safety of a compounded sustained-release formulation of buprenorphine, compared with effects of regular buprenorphine, for postoperative analgesia in rabbits. DESIGN Blinded randomized controlled clinical trial. ANIMALS 24 purpose-bred adult male New Zealand White rabbits. PROCEDURES Rabbits received titanium implants in each tibia as part of another study. Immediately prior to surgery, each rabbit received regular buprenorphine hydrochloride (0.02 mg/kg [0.009 mg/lb], SC, q 12 h for 3 days) or 1 dose of a compounded sustained-release formulation of buprenorphine (0.12 mg/kg [0.055 mg/lb], SC) followed by an equal volume of saline (0.9% NaCl) solution (SC, q 12 h for 3 days) after surgery. For 7 days after surgery, rabbits were evaluated for signs of pain by means of rabbit grimace and activity scoring and for adverse effects. RESULTS No significant differences were identified between treatment groups in grimace and activity scores at any point. No major adverse effects were detected for either drug. However, 3 rabbits that received regular buprenorphine had pain scores suggestive of moderate to severe pain by the time dose admininistration was due (ie, within the 12-hour administration interval). No clinically important differences were detected in intraoperative anesthetic or postoperative recovery variables. CONCLUSIONS AND CLINICAL RELEVANCE Sustained-release buprenorphine administered SC at 0.12 mg/kg was at least as effective as regular buprenorphine in providing analgesia for rabbits following orthopedic surgery without any major adverse effects. This sustained-release formulation represents an important alternative for rabbit analgesia with potential to improve rabbit welfare over existing analgesic standards. (J Am Vet Med Assoc 2016;248:795-801). PMID:27003021

  18. Atipamezole Reverses Ketamine–Dexmedetomidine Anesthesia without Altering the Antinociceptive Effects of Butorphanol and Buprenorphine in Female C57BL/6J Mice

    PubMed Central

    Izer, Jenelle M; Whitcomb, Tiffany L; Wilson, Ronald P

    2014-01-01

    Butorphanol and buprenorphine are common analgesics used in laboratory mice. Inadvertent attenuation of the antinociceptive effects of these analgesics via the administration of an anesthetic reversal agent could result in postprocedural pain and distress, with subsequent negative effects on animal welfare, study outcomes, and regulatory compliance. This study was undertaken to determine whether atipamezole reverses ketamine–dexmedetomidine anesthesia and alters the antinociceptive effects of butorphanol and buprenorphine in female C57BL/6J mice. Atipamezole reliably reversed the anesthetic effects of ketamine–dexmedetomidine, and mice were ambulatory 17.4 ± 30.6 min after administration of the ?2-adrenoreceptor antagonist. Atipamezole alone had no significant effect on tail-flick latency and did not alter the antinociceptive properties of butorphanol or low-dose (0.05 mg/kg) or high-dose (0.1 mg/kg) buprenorphine in female C57BL/6J mice. After reversal of ketamine–dexmedetomidine anesthesia, tail-flick latency at 30, 60, and 150 min after analgesic treatment differed significantly between mice treated with atipamezole alone and those given atipamezole followed by butorphanol or high-dose buprenorphine. These results suggest that the analgesic effects of butorphanol and buprenorphine are not affected by atipamezole. Buprenorphine (0.1 mg/kg) administered 30 min prior to or at the time of anesthesia resulted in a greater magnitude of antinociception after antagonism of anesthesia than when given at the time of reversal. Given these results, we recommend the use of ketamine–dexmedetomidine anesthesia with buprenorphine administered either preemptively or at the time of anesthetic induction to provide a defined period of surgical anesthesia that is effectively reversed by atipamezole. PMID:25650975

  19. High-dose buprenorphine: perioperative precautions and management strategies.

    PubMed

    Roberts, D M; Meyer-Witting, M

    2005-02-01

    Buprenorphine has been in clinical use in anaesthesia for several decades. Recently, the high-dose sublingual formulation (Subutex, Reckitt Benckiser, Slough, U.K.) has been increasingly used as maintenance therapy in opioid dependence, as an alternative to methadone and other pharmacological therapies. Buprenorphine has unique pharmacological properties making it well suited for use as a maintenance therapy in opioid dependence. However, these same properties may cause difficulty in the perioperative management of pain. Buprenorphine is a partial opioid agonist, attenuating the effects of supplemental illicit or therapeutic opioid agonists. As a result of its high receptor affinity, supplemental opioids do not readily displace buprenorphine from the opioid receptor in standard doses. High-dose buprenorphine has an extended duration of action that prolongs both of these effects. The perioperative management of patients stabilized on high-dose buprenorphine and undergoing surgery requires consideration of the likely analgesic requirements. Where possible the buprenorphine should be continued. Pain management should focus on maximizing non-opioid analgesia, local anaesthesia and non-pharmacological techniques. Where pain may not be adequately relieved by these methods, the addition of a full opioid agonist such as fentanyl or morphine at appropriate doses should be considered, accompanied by close monitoring in a high dependency unit. In situations where this regimen is unlikely to be effective, preoperative conversion to morphine or methadone may be an option. Where available, liaison with a hospital-based alcohol and drug service should always be considered. PMID:15957687

  20. The use of high dosages of transdermal buprenorphine for pain management in palliative cancer patients: a case study.

    PubMed

    M J Clement, Paul; Beuselinck, Benoit; Van Beek, Karen; Georgette Mertens, P; Cornelissen, Paul; Menten, Johan

    2013-01-01

    Pain is a prevalent condition in patients with cancer, particularly in advanced stages of cancer. Although strong opioids are the mainstay of cancer pain management protocols, patients are often undertreated. Transdermal buprenorphine is currently available for the treatment of moderate to severe cancer pain and severe pain which does not respond to nonopioid analgesics; patch doses of 35, 52.5 and 70 µg/h are available (applied for up to 96 h), with no more than 2 transdermal patches at the same time, regardless of the strength. To date, there are no published reports in the literature of the use of high-dose transdermal buprenorphine (>140 µg/h). Herein, we present 2 cases of palliative cancer patients who received transdermal buprenorphine at doses titrated up to 210 and 175 µg/h, respectively, for the management of pain. Transdermal buprenorphine titrated to doses >140 µg/h provided adequate pain control and was well tolerated. Future studies to confirm these initial observations are warranted. PMID:23626556

  1. Buprenorphine for cancer pain: is it ready for prime time?

    PubMed

    Prommer, Eric

    2015-12-01

    Buprenorphine (BUP) is a semisynthetic derivative of the opium alkaloid thebaine found in the poppy Papaver somniferum. Its chemical structure contains the morphine structure but differs by having a cyclopropylmethyl group. Buprenorphine is a potent µ opioid agonist. Buprenorphine undergoes extensive first-pass metabolism in the liver and gut. The development of a transdermal BUP formulation in 2001 led to its evaluation in cancer pain. This article provides the practitioner with an update on the current role of BUP in cancer care. It highlights data suggesting effectiveness in various types of cancer pain. The article reviews pharmacology, routes of administration, adverse effects, drug interactions, and cost considerations. PMID:25163678

  2. Voltammetric study and determination of buprenorphine in pharmaceuticals.

    PubMed

    García-Fernández, M A; Fernández-Abedul, M T; Costa-García, A

    1999-12-01

    The oxidation of buprenorphine on a carbon paste electrode has been studied using voltammetric techniques under both semi-infinite linear diffusion and hydrodynamic conditions. By applying a simple electrode pretreatment a good reproducibility of the current signal is obtained (R.S.D. = 0.85%, n = 6 for a 1.0 x 10(-5) M buprenorphine concentration). The limit of detection was found to be 2.0 x 10(-7) M. The voltammetric method developed for the determination of buprenorphine in pharmaceutical preparations was examined for its applicability to liquid and solid preparations. PMID:10701946

  3. The Effects of Maternally Administered Methadone, Buprenorphine and Naltrexone on Offspring: Review of Human and Animal Data

    PubMed Central

    Farid, W.O; Dunlop, S.A; Tait, R.J; Hulse, G.K

    2008-01-01

    Most women using heroin are of reproductive age with major risks for their infants. We review clinical and experimental data on fetal, neonatal and postnatal complications associated with methadone, the current “gold standard”, and compare these with more recent, but limited, data on developmental effects of buprenorphine, and naltrexone. Methadone is a µ-opioid receptor agonist and is commonly recommended for treatment of opioid dependence during pregnancy. However, it has undesired outcomes including neonatal abstinence syndrome (NAS). Animal studies also indicate detrimental effects on growth, behaviour, neuroanatomy and biochemistry, and increased perinatal mortality. Buprenorphine is a partial µ-opioid receptor agonist and a ?-opioid receptor antagonist. Clinical observations suggest that buprenorphine during pregnancy is similar to methadone on developmental measures but is potentially superior in reducing the incidence and prognosis of NAS. However, small animal studies demonstrate that low doses of buprenorphine during pregnancy and lactation lead to changes in offspring behaviour, neuroanatomy and biochemistry. Naltrexone is a non-selective opioid receptor antagonist. Although data are limited, humans treated with oral or sustained-release implantable naltrexone suggest outcomes potentially superior to those with methadone or buprenorphine. However, animal studies using oral or injectable naltrexone have shown developmental changes following exposure during pregnancy and lactation, raising concerns about its use in humans. Animal studies using chronic exposure, equivalent to clinical depot formulations, are required to evaluate safety. While each treatment is likely to have maternal advantages and disadvantages, studies are urgently required to determine which is optimal for offspring in the short and long term. PMID:19305793

  4. Stakeholders in opioid substitution treatment policy: similarities and differences in six European countries.

    PubMed

    Thom, Betsy; Duke, Karen; Frank, Vibeke Asmussen; Bjerge, Bagga

    2013-08-01

    Based on the research papers within this special issue, this overview discusses similarities and differences in stakeholding in drug user opioid substitution treatment policy in Britain, Denmark, Italy, Austria, Poland, and Finland. It explores factors that have influenced stakeholder activity, including the importance of crisis, the impact of evidence, the availability of resources, the wider political context, the influence of moral frameworks and ideologies, and the pressure of external influences. The paper highlights the important differences in the emergence and evolution of stakeholder groups and in the political, cultural, and economic circumstances, which both constrain and enable their activities. PMID:23952506

  5. The use of transdermal buprenorphine to relieve radiotherapy-related pain in head and neck cancer patients.

    PubMed

    Menten, Johan; Carpentier, Isabelle; Deschutter, Harlinde; Nuyts, Sandra; Van Beek, Karen

    2013-07-01

    Many head and neck cancer (HNC) patients experience painful therapy-related mucositis and dermatitis. This prospective observational study evaluated transdermal buprenorphine use in HNC patients to relieve treatment-related pain. During treatment with paracetamol or tramadol, visual analogue scale (VAS)-pain scores >30/100 occurred in 26/45 patients 4 weeks after starting cancer therapy, persisting for ?2 weeks after treatment. These patients subsequently received transdermal buprenorphine. Pain therapy should be more accurately up-titrated to the maximum recommended dose (140 ?g/hr) where necessary to maintain pain scores ?30/100 and, for some patients, should be continued for 6 weeks after the last cancer treatment day. PMID:23758187

  6. Changes in Quality of Life (WHOQOL-BREF) and Addiction Severity Index (ASI) among participants in Opioid Substitution Treatment (OST) in Low and Middle Income Countries: An International Systematic Review

    PubMed Central

    Feelemyer, Jonathan P; Jarlais, Don C Des; Arasteh, Kamyar; Phillips, Benjamin W; Hagan, Holly

    2013-01-01

    Background Opioid substitution treatment (OST) can increase quality of life (WHOQOL-BREF) and reduce addiction severity index (ASI) scores among participants over time. OST program participants have noted that improvement in quality of life is one of the most important variables to their reduction in drug use. However, there is little systematic understanding of WHOQOL-BREF and ASI domain changes among OST participants in low and middle-income countries (LMIC). Methods Utilizing PRISMA guidelines we conducted a systematic literature search to identify OST program studies documenting changes in WHOQOL-BREF or ASI domains for participants in buprenorphine or methadone programs in LMIC. Standardized mean differences for baseline and follow-up domain scores were compared along with relationships between domain scores, OST dosage, and length of follow-up. Results There were 13 OST program studies with 1801 participants from seven countries eligible for inclusion in the review. Overall, statistically significant changes were noted in all four WHOQOL-BREF domain and four of the seven ASI domain scores (drug, psychological, legal, and family) documented in studies. Dosage of pharmacologic medication and length of follow-up did not affect changes in domain scores. Conclusion WHOQOL-BREF and ASI domain scoring is a useful tool in measuring overall quality of life and levels of addiction among OST participants. Coupled with measurements of blood-borne infection, drug use, relapse, and overdose, WHOQOL-BREF and ASI represent equally important tools for evaluating the effects of OST over time and should be further developed as integrated tools in the evaluation of participants in LMIC. PMID:24200104

  7. Clinician Beliefs and Attitudes about Buprenorphine/Naloxone Diversion

    PubMed Central

    Schuman-Olivier, Zev; Connery, Hilary; Griffin, Margaret L.; Wyatt, Steve A.; Wartenberg, Alan A.; Borodovsky, Jacob; Renner, John A.; Weiss, Roger D.

    2013-01-01

    Background and Objectives Concern about diversion of buprenorphine/naloxone (B/N) in the U.S. may affect prescribing patterns and policy decisions. This study examines addiction treatment clinician beliefs and attitudes regarding B/N diversion. Methods Participants (n=369) completed a 34-item survey in 2010 during two national symposia on opioid dependence. We conducted multivariable regression, examining the relationship of perceived danger from B/N diversion with clinician characteristics and their beliefs about B/N treatment and diversion. We compared causal beliefs about diversion among clinicians with and without B/N treatment experience. Results Forty percent of clinicians believed that B/N diversion is a dangerous problem. The belief that B/N diversion increases accidental overdoses in the community was strongly associated with perceived danger from B/N diversion. Conclusions and Scientific Significance Attitudes and beliefs, not education level, were associated with clinician’s perceived danger from B/N diversion. Clinicians with greater B/N patient experience were more likely to believe treatment access barriers are the major cause of B/N diversion. PMID:24131165

  8. Opioid-induced respiratory effects: new data on buprenorphine.

    PubMed

    Dahan, Albert

    2006-01-01

    When selecting the appropriate long-acting opioid to treat cancer pain, both analgesic efficacy and safety need consideration. Generally, opioids are well tolerated. However, of opioid-typical adverse events, respiratory depression is especially important because of the risk of a fatal outcome. Although all potent opioid analgesics act via the micro-opioid receptor system, they differ in how they affect respiratory control. Recently, the respiratory effects of fentanyl (1 7 microg/kg) and buprenorphine (0.7-9 microg g/kg) were compared in healthy opioid-naïve volunteers. Fentanyl produced dose-dependent depression of respiration with apnoea at doses > or = 3 microg/kg, while buprenorphine caused depression that levelled at approximately 50% of baseline with doses > or = 2 microg/kg. These findings indicate the occurrence of a ceiling in the respiratory depression induced by buprenorphine but not by fentanyl. Surprisingly few studies have addressed the clinically important ability to reverse the respiratory effects of opioids. A recent assessment of the naloxone dose required to reverse 0.2 mg intravenous buprenorphine-induced respiratory depression in healthy opioid-naïve volunteers, found that the accumulated naloxone dose causing 50% reversal of respiratory depression was 1.20 +/- 0.32 mg/70 kg (given in 30 min); 80% reversal was observed at 2.50 +/- 0.60 mg/70 kg (given in 30 min). At greater buprenorphine doses, full reversal is observed when the duration of naloxone infusion is increased. These findings indicate the need for a continuous rather than bolus administration of naloxone to reverse the respiratory effects of buprenorphine. In conclusion, buprenorphine is more favourable compared with fentanyl in respect to ventilatory control. Buprenorphine causes limited respiratory depression with a ceiling effect at higher doses, while fentanyl causes dose-dependent respiratory depression with apnoea at high dose levels. In the rare instance of respiratory depression, reversal is possible with a sufficient and continuous infusion of naloxone. PMID:16764215

  9. Clonazepam as Agonist Substitution Treatment for Benzodiazepine Dependence: A Case Report

    PubMed Central

    Maremmani, Angelo Giovanni Icro; Rovai, Luca; Rugani, Fabio; Bacciardi, Silvia; Pacini, Matteo; Dell'Osso, Liliana; Maremmani, Icro

    2013-01-01

    Nowadays, the misuse of benzodiazepines (BZDs) is a cause for a serious concern among pharmacologically inexperienced patients, whether treated or untreated, that could lead to significant complications, including tolerance, dependence, and addiction. We present a case report in which an Italian patient affected by anxiety disorder and treated with BZDs presented a severe case of dependence on BZDs. We treated him according to an agonist substitution approach, switching from the abused BZD to a slow-onset, long-acting, high potency agonist (clonazepam), and looking at the methadone treatment model as paradigm. We decided to use clonazepam for its pharmacokinetic properties. The advantage of choosing a slow-onset, long-lasting BZD for the treatment of our patient was that it led us to a remarkable improvement in the clinical situation, including the cessation of craving, absence of withdrawal symptoms, reduced anxiety, improvements in social functioning, and a better cognition level. PMID:23424702

  10. Clonazepam as agonist substitution treatment for benzodiazepine dependence: a case report.

    PubMed

    Maremmani, Angelo Giovanni Icro; Rovai, Luca; Rugani, Fabio; Bacciardi, Silvia; Pacini, Matteo; Dell'osso, Liliana; Maremmani, Icro

    2013-01-01

    Nowadays, the misuse of benzodiazepines (BZDs) is a cause for a serious concern among pharmacologically inexperienced patients, whether treated or untreated, that could lead to significant complications, including tolerance, dependence, and addiction. We present a case report in which an Italian patient affected by anxiety disorder and treated with BZDs presented a severe case of dependence on BZDs. We treated him according to an agonist substitution approach, switching from the abused BZD to a slow-onset, long-acting, high potency agonist (clonazepam), and looking at the methadone treatment model as paradigm. We decided to use clonazepam for its pharmacokinetic properties. The advantage of choosing a slow-onset, long-lasting BZD for the treatment of our patient was that it led us to a remarkable improvement in the clinical situation, including the cessation of craving, absence of withdrawal symptoms, reduced anxiety, improvements in social functioning, and a better cognition level. PMID:23424702

  11. Opioid agonist and antagonist behavioural effects of buprenorphine.

    PubMed Central

    Leander, J. D.

    1983-01-01

    1 The agonist and antagonist effects of a range of buprenorphine doses (0.08-20 mg/kg) were studied on the responding of pigeons under a multiple fixed-ratio, fixed-interval schedule of grain presentation. Various doses (0.02-10 mg/kg) of buprenorphine were also tested in pigeons trained to discriminate between injections of 0.05 mg/kg of fentanyl and injections of distilled water. 2 Buprenorphine, over a broad dose range (0.08-5 mg/kg), increased the rates of responding in the fixed-interval component of the multiple schedule and disrupted patterning of responding within the fixed-interval, without affecting fixed-ratio responding even at a dose of 40 mg/kg. The effects of some of the high doses on fixed-interval responding were still evident one and two days after buprenorphine injection. 3 Doses of buprenorphine which produced increases in fixed-interval responding were also effective as antagonists of the behavioural depression produced by 40 mg/kg of morphine, and were discriminated as fentanyl-like by pigeons trained to discriminate between injections of fentanyl and injections of water. 4 These results show that buprenorphine produces marked agonist and antagonist effects over an extremely broad dose range without producing behavioural depressant effects. PMID:6850163

  12. Psychological Barriers to Tobacco Cessation in Indian Buprenorphine-Naloxone Maintained Patients: A Pilot Study

    PubMed Central

    Mandal, Piyali; Jain, Raka; Jhanjee, Sonali; Sreenivas, V.

    2015-01-01

    Context: The prevalence of smoking in opioid agonist treatment programmes remains high, leading to significant tobacco related health hazards and mortality. This is the first study from India addressing tobacco cessation and related barriers among recipients of buprenorphine-naloxone maintenance treatment. Aims: The purpose of the study was to investigate Indian buprenorphine-naloxone maintained patients’ willingness to quit tobacco use, to determine its possible association with demographic, agonist maintenance treatment, tobacco use related variables and personal health and risk perceptions related to health hazards associated with tobacco use. Settings and Design: The study was cross-sectional, observational. It was conducted in the out-patient department of a national level de-addiction centre in India. Materials and Methods: Fifty-five males on buprenorphine-naloxone treatment were assessed using Tobacco Use Characteristics, Fagerstrom Test for Nicotine Dependence (FTND and FTND-ST), Readiness to Change questionnaire (RCQ), Smoker's Perceived Health Risk Evaluation (SPHERE), Importance of Intervention scale and a semi-structured questionnaire. Statistical Analysis: Descriptive statistics, Kruskal-Wallis Chi-square test, Spearman rank order correlation, paired-t test, ANOVA (STATA 9.2 statistical package). Results: Around 65.4% of the subjects were smokers, 9% were using smokeless tobacco only whereas 25.6% were using both. Mean duration of tobacco use was 20 ± 1.5 years. Only 20% had past quit attempts. Only 24% were in action phase of change. Personal health and risk perceptions were poor and only 61.62% considered intervention tobacco smoking cessation important. Conclusions: Higher severity of nicotine dependence, low perception of harm from tobacco warrant immediate attention and need for on-site treatment opportunity. PMID:26664077

  13. Role of buprenorphine in prolonging the duration of post-operative analgesia in percutaneous nephrolithotomy: Comparison between bupivacaine versus bupivacaine and buprenorphine combination

    PubMed Central

    Nirmala, Jonnavithula; Kumar, Anil; Devraj, Rahul; Vidyasagar, Sriramoju; Ramachandraiah, Gunta; Murthy, Pisapati V. L. N.

    2015-01-01

    Introduction: Percutaneous nephrolithotomy (PCNL) is the treatment of choice for large renal calculi. Pain around the nephrostomy tube is a clinical problem and we have previously reported alleviation of pain by peritubal block with bupivacaine, which lasted for 14 hours. The present study aimed to investigate the role of buprenorphine and bupivacaine combination in prolonging the duration of analgesia in peritubal block. Materials and Methods: A prospective, randomized controlled study was undertaken in 40 American Society of Anesthesiologists (ASA) grade I and II patients who were scheduled for PCNL. Group I patients received 20 mL of 0.25% bupivacaine and group II patients received 20 mL of 0.25% bupivacaine with 100 ?g of buprenorphine. Peritubal infiltration was given under fluoroscopic guidance along the nephrostomy tube from the renal capsule to the skin. Post-operative pain was assessed by Visual Analog Score (VAS), dynamic VAS (DVAS), sedation score, duration of analgesia and number of rescue analgesic demands. Rescue analgesia was inj tramadol 1 mg/kg IV if pain score exceeded 3. Results: Demographic data were comparable between the groups. Median duration of analgesia was 16 h in group I and 20 h in group II (P = 0.002). The maximum median VAS was 4 in group I and 2 in group II (P = 0.002). The median area under curve (AUC) for VAS was 7 and 5 in groups I and II, respectively (P = 0.047). The median maximum DVAS in group I was 6 and 4 in group II. The median AUC for DVAS in 24 h was 16 in group I and 15 in group II (P = 0.017). Conclusions: Peritubal infiltration of 0.25% bupivacaine with 100 ?g buprenorphine around a nephrostomy tube increased the duration of analgesia following PCNL without any side-effects. PMID:25878415

  14. A successful switch from transdermal fentanyl to transdermal buprenorphine in a patient with neuropathic pain: a case report.

    PubMed

    Leppert, Wojciech

    2014-02-01

    Buprenorphine is a frequently used opioid in the treatment of neuropathic pain component that is often present in patients with cancer. A case of a 41-year-old patient was depicted whose pain syndrome was associated with the chondrosarcoma growth originating from the sacral bone and numerous surgical interventions and radiotherapy. Improvement in analgesia and good toleration of therapy were observed after switching from transdermal fentanyl to transdermal buprenorphine while maintaining treatment with antidepressants and anticonvulsants. This case report indicates a possibility of a safe switch of transdermal opioids at home, which may provide benefits in terms of analgesia and adverse effects and in consequence have positive impact on the patients' quality of life. This is also accompanied by constant psychological, social, and spiritual support provided to the patient and family. PMID:23349342

  15. Treatment with a dietary fat substitute decreased Arochlor 1254 contamination in an obese diabetic male.

    PubMed

    Redgrave, Trevor G; Wallace, Peter; Jandacek, Ronald J; Tso, Patrick

    2005-06-01

    A case manifesting symptoms due to organochlorine toxicity was treated with the fat substitute olestra in his diet. Before treatment, the patient was obese, with severe type 2 diabetes mellitus and mixed hyperlipidemia, chloracne, frequent headaches, and numbness and paraesthesias of his trunk and lower limbs. Earlier attempts at weight loss had been unsuccessful due to worsening of his symptoms. After inclusion of olestra in his diet for 2 years, weight loss was successful without aggravation of his symptoms, and the patient reverted to normoglycemia and normolipidemia. Olestra may have assisted weight loss and amelioration of his diabetes by increasing fecal elimination of organochlorines, rather than by preventing the partitioning of these pollutants into tissues, where they have been reported to exert antimetabolic effects on substrate oxidation. PMID:15936651

  16. Epidural analgesia with morphine or buprenorphine in ponies with lipopolysaccharide (LPS)-induced carpal synovitis

    PubMed Central

    Freitas, Gabrielle C.; Carregaro, Adriano B.; Gehrcke, Martielo I.; De La Côrte, Flávio D.; Lara, Valéria M.; Pozzobon, Ricardo; Brass, Karin E.

    2011-01-01

    This study evaluated the analgesia effects of the epidural administration of 0.1 mg/kg bodyweight (BW) of morphine or 5 ?g/kg BW of buprenorphine in ponies with radiocarpal joint synovitis. Six ponies were submitted to 3 epidural treatments: the control group (C) received 0.15 mL/kg BW of a 0.9% sodium chloride (NaCl) solution; group M was administered 0.1 mg/kg BW of morphine; and group B was administered 5 ?g/kg BW of buprenorphine, both diluted in 0.9% NaCl to a total volume of 0.15 mL/kg BW administered epidurally at 10 s/mL. The synovitis model was induced by injecting 0.5 ng of lipopolysaccharide (LPS) in the left or right radiocarpal joint. An epidural catheter was later introduced in the lumbosacral space and advanced up to the thoracolumbar level. The treatment started 6 h after synovitis induction. Lameness, maximum angle of carpal flexion, heart rate, systolic arterial pressure, respiratory rate, temperature, and intestinal motility were evaluated before LPS injection (baseline), 6 h after LPS injection (time 0), and 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 h after treatments. Although the model of synovitis produced clear clinical signs of inflammation, the lameness scores in group C were different from the baseline for only up to 12 h. Both morphine and buprenorphine showed a reduction in the degree of lameness starting at 0.5 and 6 h, respectively. Reduced intestinal motility was observed at 0.5 h in group M and at 0.5 to 1 h in group B. Epidural morphine was a more effective analgesic that lasted for more than 12 h and without side effects. It was concluded that morphine would be a valuable analgesic option to alleviate joint pain in the thoracic limbs in ponies. PMID:21731186

  17. HIV Testing Practices Among Buprenorphine-Prescribing Physicians

    PubMed Central

    Edelman, E. Jennifer; Dinh, An; Moore, Brent A.; Schottenfeld, Richard; Fiellin, David A.; Fiellin, Lynn E.

    2012-01-01

    Background Despite the Centers for Disease Control and Prevention recommendations for annual HIV testing of at-risk populations, including those with substance use disorders, there are no data on the HIV testing practices of buprenorphine-prescribing physicians. Objective To describe HIV testing practices among buprenorphine-prescribing physicians. Methods We conducted a cross-sectional survey of physicians enrolled in a national system to support buprenorphine prescribing between July and August 2008. The electronic survey included questions on demographics; clinical training and experience; clinical practice; patient characteristics; and physician screening practices, including HIV testing. Results Only 46% of 382 respondent physicians conducted HIV testing. On univariate analysis, physicians who conducted HIV testing were more likely to report addiction specialty training (33% vs. 19%, p=.001), practicing in addiction settings (28% vs. 16%, p=.006), and having treated more than 50 patients with buprenorphine (50% vs. 31%, p<.0001) compared to those who did not. Compared to physicians who did not conduct HIV testing, physicians who conducted HIV testing had a lower proportion of buprenorphine patients who were White (75% vs. 82%, p=.01) or dependent upon prescription opioids (57% vs. 70%, p<.0001). In multivariate analysis, physicians who conducted HIV testing were more likely to have treated more than 50 patients with buprenorphine (OR 1.777, 95%CI 1.011 – 3.124) and had fewer patients dependent upon prescription opioids (OR 0.986 95% CI 0.975 – 0.998) than physicians who did not. Conclusion Interventions to increase HIV testing among physicians prescribing buprenorphine are needed. PMID:22367499

  18. Considerations on the role of buprenorphine in recovery from heroin addiction from a UK perspective.

    PubMed

    Nutt, David J

    2015-01-01

    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. PMID:25389219

  19. Implementation of a collaborative care management program with buprenorphine in primary care: A comparison between opioid-dependent patients and chronic pain patients using opioids non-medically

    PubMed Central

    Suzuki, Joji; Matthews, Michele L.; Brick, David; Nguyen, Minh-Thuy; Jamison, Robert N.; Ellner, Andrew L.; Tishler, Lori W.; Weiss, Roger D.

    2014-01-01

    Objective To implement a collaborative care management program with buprenorphine in a primary care clinic. Design Prospective observational study. Setting A busy urban academic primary care clinic affiliated with a tertiary care hospital. Participants Opioid dependent patients or chronic pain patients using opioids non-medically were recruited for the study. A total of 45 participants enrolled. Interventions Patients were treated with buprenorphine and managed by a supervising psychiatrist, pharmacist care manager and health coaches. The care manager conducted buprenorphine inductions and all follow-ups visits. Health coaches offered telephonic support. The psychiatrist supervised both the care manager and health coaches. Main outcome measures Primary outcomes were treatment retention at 6 months, and change in the proportion of aberrant toxicology results and opioid craving scores from baseline to 6 months. After data collection, clinical outcomes were compared between opioid dependent patients and chronic pain patients using opioids non-medically. Overall, 55.0% (25/45) of participants remained in treatment at 6 months. PCPs’ attitudes about opioid dependence treatment were surveyed at baseline and at 18-months. Results Forty-three patients (95.6%) accepted treatment and 25 (55.0%) remained in treatment at 6 months. The proportion of aberrant urine toxicology results decreased significantly from baseline to 6 months (p<0.01). Craving scores significantly decreased from baseline to 6 months (p<0.01). Opioid dependent patients, as opposed to chronic pain patients using opioids non-medically, were significantly more likely to complete 6 months of treatment (p<0.05). PCPs’ confidence in treating opioid dependence in primary care increased significantly from baseline to 18-months post-implementation (p<0.01). Conclusion Collaborative care management for opioid dependence with buprenorphine may be feasible in a primary care clinic. More research is needed to understand the role of buprenorphine in managing chronic pain patients using opioids non-medically. PMID:24944066

  20. Predictors of Dropout from Inpatient Opioid Detoxification with Buprenorphine: A Chart Review

    PubMed Central

    Hallén, Emma

    2014-01-01

    Inpatient withdrawal treatment (detoxification) is common in opioid dependence, although dropout against medical advice often limits its outcome. This study aimed to assess baseline predictors of dropout from inpatient opioid detoxification with buprenorphine, including age, gender, current substance use, and type of postdetoxification planning. A retrospective hospital chart review was carried out for inpatient standard opioid detoxifications using buprenorphine taper, in a detoxification ward in Malmö, Sweden (N = 122). Thirty-four percent of patients (n = 42) dropped out against medical advice. In multivariate logistic regression, dropout was significantly associated with younger age (OR 0.93 [0.89–0.97]) and negatively predicted by inpatient postdetoxification plan (OR 0.41 [0.18–0.94]), thus favouring an inpatient plan as opposed to outpatient treatment while residing at home. Dropout was unrelated to baseline urine toxicology. In opioid detoxification, patients may benefit from a higher degree of postdetoxification planning, including transition to residential treatment, in order to increase the likelihood of a successful detoxification and treatment entry. Young opioid-dependent patients may need particular attention in the planning of detoxification. PMID:25530903

  1. Photocatalytic Properties of Layered Metal Oxides Substituted with Silver by a Molten AgNO3 Treatment.

    PubMed

    Horie, Hirotaka; Iwase, Akihide; Kudo, Akihiko

    2015-07-15

    K4Nb6O17 (BG: 3.67 eV) and Na2W4O13 (BG: 3.12 eV) layered oxide photocatalysts with wide band gaps were treated with a molten AgNO3 to substitute K+ and Na+ with Ag+, resulting in red-shifts of absorption edges in diffuse reflectance spectra. A part of Na+ ions in the interlayer of Na2W4O13 was substituted with Ag+ ions by the molten AgNO3 treatment with keeping the layered structure. Both Ag(I)-substituted K4Nb6O17 and Na2W4O13 showed photocatalytic activities for O2 evolution from aqueous solutions containing a sacrificial reagent utilizing the absorption bands newly formed by the Ag(I)-substitution. Notably, the Ag(I)-substituted Na2W4O13 produced O2 under visible light irradiation. When ball-milled Na2W4O13 was treated with a molten AgNO3, the Ag(I)-substitution rate increased. The Ag(I)-substituted Na2W4O13 with ball-milling showed higher photocatalytic activity for O2 evolution than that without ball-milling. Z-schematic water splitting proceeded under visible light irradiation by combining the Ag(I)-substituted Na2W4O13 of an O2-evolving photocatalyst with Ru-loaded SrTiO3 doped with Rh of a H2-evolving photocatalyst. PMID:26099451

  2. 'Diversion’ of methadone or buprenorphine: 'harm’ versus 'helping’

    PubMed Central

    2013-01-01

    Background '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. Findings 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. Conclusions 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. PMID:24131626

  3. Withdrawal from Buprenorphine/Naloxone and Maintenance with a Natural Dopaminergic Agonist: A Cautionary Note

    PubMed Central

    Blum, Kenneth; Oscar-Berman, Marlene; Femino, John; Waite, Roger L; Benya, Lisa; Giordano, John; Borsten, Joan; Downs, William B; Braverman, Eric R; Loehmann, Raquel; Dushaj, Kristina; Han, David; Simpatico, Thomas; Hauser, Mary; Barh, Debmalya; McLaughlin, Thomas

    2013-01-01

    Background While numerous studies support the efficacy of methadone and buprenorphine for the stabilization and maintenance of opioid dependence, clinically significant opioid withdrawal symptoms occur upon tapering and cessation of dosage. Methods We present a case study of a 35 year old Caucasian female (Krissie) who was prescribed increasing dosages of prescription opioids after carpel tunnel surgery secondary to chronic pain from reflex sympathetic dystrophy and fibromyalgia. Over the next 5 years, daily dosage requirements increased to over 80 mg of Methadone and 300 ug/hr Fentanyl transdermal patches, along with combinations of 12–14 1600 mcg Actig lollipop and oral 100 mg Morphine and 30 mg oxycodone 1–2 tabs q4-6hr PRN for breakthrough pain. Total monthly prescription costs including supplemental benzodiazepines, hypnotics and stimulants exceeded $50,000. The patient was subsequently transferred to Suboxone® in 2008, and the dosage was gradually tapered until her admission for inpatient detoxification with KB220Z a natural dopaminergic agonist. We carefully documented her withdrawal symptoms when she precipitously stopped taking buprenorphine/naloxone and during follow-up while taking KB220Z daily. We also genotyped the patient using a reward gene panel including (9 genes 18 alleles): DRD 2,3,4; MOA-A; COMT; DAT1; 5HTTLLR; OPRM1; and GABRA3. Findings At 432 days post Suboxone® withdrawal the patient is being maintained on KB220Z, has been urine tested and is opioid free. Genotyping data revealed a moderate genetic risk for addiction showing a hypodopaminergic trait. This preliminary case data suggest that the daily use of KB220Z could provide a cost effective alternative substitution adjunctive modality for Suboxone®. We encourage double-blind randomized –placebo controlled studies to test the proposition that KB220Z may act as a putative natural opioid substitution maintenance adjunct. PMID:24273683

  4. Buprenorphine Response as a Function of Neurogenetic Polymorphic Antecedents: Can Dopamine Genes Affect Clinical Outcomes in Reward Deficiency Syndrome (RDS)?

    PubMed Central

    Blum, Kenneth; Oscar-Berman, Marlene; Jacobs, William; McLaughlin, Thomas; Gold, Mark S.

    2014-01-01

    There is a plethora of research indicating the successful treatment of opioid dependence with either buprenorphine alone or in combination with naloxone (Suboxone®). However, we encourage caution in long-term maintenance with these drugs, albeit, lack of any other FDA approved opioid maintenance compound to date. Our concern has been supported by severe withdrawal (even with tapering of the dosage of for example Suboxone® which is 40 times more potent than morphine) from low dose of buprenorphine (alone or with naloxone). In addition our findings of a long-term flat affect in chronic Suboxone® patients amongst other unwanted side effects including diversion and suicide attempts provides impetus to reconsider long-term utilization. However, it seems prudent to embrace genetic testing to reveal reward circuitry gene polymorphisms especially those related to dopaminergic pathways as well as opioid receptor(s) as a way of improving treatment outcomes. Understanding the interaction of reward circuitry involvement in buprenorphine effects and respective genotypes provide a novel framework to augment a patient's clinical experience and benefits during opioid replacement therapy. PMID:25664200

  5. Buprenorphine - the unique opioid adjuvant in regional anesthesia.

    PubMed

    Kosel, Juliusz; Bobik, Piotr; Tomczyk, Micha?

    2016-03-01

    Regional anesthesia techniques are commonly used for many surgical procedures alone or as an addition to general anesthesia, because they offer many advantages over general anesthesia. Unfortunately these techniques are partially limited by the time of action of local anesthetics. One of the methods of overcoming this limitation is adding to the local anesthetic solution additional drug - so called adjuvant. Among many adjuvants to local anesthetic drugs tested so far one seems to be particularly interesting - buprenorphine. The aim of this paper is to present pharmacological background for using buprenorphine for regional anesthesia and to review clinical trials of using buprenorphine for all regional anesthesia techniques: spinal and epidural anesthesia, peripheral nerves blocks, local anesthesia and intravenous regional anesthesia. PMID:26758991

  6. Reversal of opioid overdose syndrome in morphine-dependent rats using buprenorphine.

    PubMed

    Zamani, Nasim; Hassanian-Moghaddam, Hossein; Bayat, Amir Hossein; Haghparast, Abbas; Shadnia, Shahin; Rahimi, Mitra; Hashemi Demaneh, Behrouz; Assar, Nasim

    2015-02-01

    The method of choice for reversal of opioid-toxicity is administration of naloxone. This treatment can be accompanied by complications including acute lung-injury, myocardial infarction, or withdrawal-syndrome (in dependent-patients). We aimed to evaluate the efficacy of buprenorphine in reversal of opioid-overdose syndrome in dependent-rats. A prospective case-control study was designed, in which a total of 30 rats were put on opioid-dependency protocol with 10 mg/kg of intra-peritoneal morphine twice daily for 10 days. After confirmation of dependency by naloxone administration, the rats were overdosed by giving 16 mg/kg of intra-peritoneal methadone. They were divided into four groups receiving naloxone (n=7; 2 mg/kg) and buprenorphine(n=8, 8, and 7 with doses of 3 mg/kg, 6 mg/kg, and 10 mg/kg), respectively. These four groups were compared regarding reversal of opioid signs/symptoms and development of withdrawal-syndrome. Rats in the first group showed signs/symptoms of opioid-withdrawal severely and with a higher frequency (P<0.001). In the groups 2-4, all doses recovered the intoxicated-rats without inducing signs/symptoms of withdrawal; however, the 3mg/kg dose reversed toxicity slower (P<0.001) and one rat in this group died later due to the re-development of signs of toxicity. Buprenorphine recovers opioid-overdose in morphine-dependent rats and bypasses the withdrawal-syndrome due to administration of naloxone. PMID:25510513

  7. Effects of Buprenorphine, Meloxicam, and Flunixin Meglumine as Postoperative Analgesia in Mice

    PubMed Central

    Tubbs, Jacquelyn T; Kissling, Grace E; Travlos, Greg S; Goulding, David R; Clark, James A; King-Herbert, Angela P; Blankenship-Paris, Terry L

    2011-01-01

    C57BL/6NCrl male mice (n = 60; age, 6 to 7 wk) underwent partial hepatectomy or no surgery and were given 1 of 3 analgesics pre- and postoperatively. Food and water consumption, body weight, running wheel activity, locomotor activity, and serum corticosterone concentrations were measured before and after surgery. Mice that were surgically manipulated weighed significantly less on days 1 through 3 after surgery than did mice not manipulated surgically. On the day of surgery, the surgery groups consumed significantly less feed (–1.5 ± 0.35 g) than did nonsurgery groups. There were no differences in water consumption on any day between surgery and nonsurgery groups or among the 3 analgesic groups. For running wheel activity, significant decreases in the surgery groups were seen at day 1 after surgery compared with baseline. Surgery groups that received buprenorphine and meloxicam returned to baseline activity levels on day 2 after surgery. Open-field testing revealed no significant differences in locomotor activity in any groups; however, posttreatment locomotor activity in the buprenorphine nonsurgery group was increased compared with baseline, and posttreatment locomotor activity in the flunixin meglumine surgery group was decreased compared with baseline. Serum corticosterone concentrations were within normal limits regardless of treatment in all groups. Comparison of the overall results indicated that meloxicam and buprenorphine, at the dose given, appear to be suitable postoperative analgesics for partial hepatectomy in mice. Flunixin meglumine at the given dosage (2.5 mg/kg) may not provide adequate analgesia for partial hepatectomy. PMID:21439211

  8. Pattern of buprenorphine abuse among opioid abusers in Nepal

    PubMed Central

    Aich, Tapas Kumar; Dhungana, Manoj; Khanal, Roshija

    2010-01-01

    Background: Although buprenorphine abusers are a common clinical entity, literature on them is rare in Nepal. Aim: To assess whether injectable opioid abusers are any different a subgroup vis-a-vis brown sugar abusers in relation to their demographic and clinical profiles. Materials and Methods: Seventy-six opioid abusers, who were admitted over a period of one year, in our de-addiction center, were included in the present study. They were divided into two groups based on the history of the presence or absence of buprenorphine injection abuse in them. The demographic and clinical profiles of these two groups were studied and compared. Results: The most characteristic opioid abuse pattern was the abuse of brown sugar through inhalation (chasing). A total of 32 (42.1%) among them had a history of injectable drug abuse (IDU). Most characteristic buprenorphine abuse pattern seen was an evolution from injectable buprenorphine to triple injection to brown sugar abuse (Reverse Transition). Injection buprenorphine abusers, who attended our clinic, were older in age and had a history of a longer duration of abuse than their counterparts who abused opioid drugs through the inhalational route only. Their lifetime diagnosis revealed a polysubstance abuse pattern. They were more unstable, impulsive, and disorganized in their behavior pattern, suggestive of the presence of inadequate personality traits. There were high instances of injection-related side effects in the form of the presence of thrombophlebitis, HIV positivity, and clinical AIDS in them. Conclusion: Findings of the current research indicate the presence of a subgroup of patient population among opioid abusers with a history of injectable buprenorphine abuse, with characteristic personality traits, pattern of drug abuse, and associated physical complications resulting from it. PMID:21180410

  9. Induction of opioid-dependent individuals onto buprenorphine and buprenorphine/naloxone soluble films

    PubMed Central

    Strain, Eric C.; Harrison, Joseph A.; Bigelow, George E.

    2011-01-01

    A sublingual soluble film formulation of buprenorphine and naloxone (B/N) has been approved by the Food and Drug Administration. This preparation provides unit dose child resistant packaging amenable to tracking and accountability, offers more rapid dissolution, and has potentially preferred taste versus tablets. This study compared the ability of buprenorphine (B) and B/N films to suppress spontaneous withdrawal in opioid dependent volunteers. Methods Participants were maintained on morphine and underwent challenge sessions to confirm sensitivity to naloxone induced opioid withdrawal. Subjects were randomized onto either B (16mg, n=18) or B/N (16/4 mg, n=16) soluble films for five days. Primary outcome measure was the Clinical Opiate Withdrawal Scale (COWS) score. Results Thirty-four subjects completed induction onto soluble films. There was a significant decrease in COWS scores but no significant differences between groups. Conclusions Results support use of B and B/N soluble films as safe and effective delivery methods for opioid induction. PMID:21270789

  10. The role of skin substitutes in the treatment of burn injuries.

    PubMed

    Shakespeare, Peter G

    2005-01-01

    Extensive burn wounds are difficult to manage and repair. Several engineered skin substitutes have been developed to aid in this process. These substitutes are designed with particular objectives in mind which dictate the circumstances under which they can, and should, be employed to promote healing or prepare the burn wound for final closure with autograft. This article discusses some of the rationale behind the use of skin substitutes and reviews some of the substitutes in use at the present time. Current perspectives suggest that skin substitute use is still in its infancy and that there is some way to go before their role in clinical practice becomes clear. Nevertheless the prospect of being able to supply new wound repair components and to influence the healing process to modify outcome and improve the quality of the healed burn wound will ensure a continuing high degree of interest in these potentially useful and beneficial medical devices. PMID:16023937

  11. The causal effect of opioid substitution treatment on HAART medication refill adherence

    PubMed Central

    Nosyk, Bohdan; Min, Jeong E.; Colley, Guillaume; Lima, Viviane D.; Yip, Benita; Milloy, M.-J.S.; Wood, Evan; Montaner, Julio S.G.

    2015-01-01

    Background People who inject drugs (PWID) account for roughly 13% of the prevalent HIV/AIDS population outside of sub-Saharan Africa, and access to opioid substitution treatment (OST) is limited in many settings globally. OST likely facilitates access to HAART, yet sparse evidence is available to support this hypothesis. Our objective was to determine the causal impact of OST exposure on HAART adherence among HIV-positive PWID in a Canadian setting. Methods We executed a retrospective cohort study using linked population-level data for British Columbia, Canada (January 1996–March 2010). We considered HIV-positive PWID after meeting HAART initiation criteria. A marginal structural model was estimated on a monthly timescale using inverse probability of treatment weights. The primary outcome was 95% HAART adherence, according to pharmacy refill compliance. Exposure to OST was defined as 95% of OST receipt, and we controlled for a range of fixed and time-varying covariates. Results Our study included 1852 (63.3%) HIV-positive PWID with a median follow-up of 5.5 years; 34% were female and 39% had previously accessed OST. The baseline covariate-adjusted odds of HAART adherence following OST exposure was 1.96 (95% confidence interval: 1.72–2.24), although the adjusted odds estimated within the marginal structural model was 1.68 (1.48–1.92). Findings were robust to sensitivity analyses on model specification. Conclusion In a setting characterized by universal healthcare and widespread access to both office-based OST and HAART, OST substantially increased the odds of HAART adherence. This underlines the need to address barriers to OST globally to reduce the disease burden of both opioid dependence and HIV/AIDS. PMID:25915170

  12. [Application of a seven-day buprenorphine transdermal patch in multimorbid patients on long-term ibuprofen or diclofenac].

    PubMed

    Böhme, K; Heckes, B; Thomitzek, K

    2011-01-13

    The objective of this study was to evaluate the benefit of a seven-day buprenorphine transdermal patch for patients with chronic musculoskeletal pain previously receiving long-term treatment with ibuprofen or diclofenac alone. Data of a subgroup of 703 patients were analysed which were part of a multicenter observational study with 3,295 patients. These patients had previously received ibuprofen or diclofenac and were characterized by older age,the presence of gastrointestinal, cardiovascular, and renal risk factors and the existence of chronic musculoskeletal pain. The switch to the seven-day buprenorphine patch resulted in a clinically significant decrease of the mean pain intensity at rest during the day from 5.3 to 2.9, on physical effort during the day from 7.1 to 3.3, and at night from 4.9 to 1.9 at the end of the study (11-point NRS scale, pbuprenorphine due to the lack of cardiac, renal and gastrointestinal toxicity. Constant analgesia, improvement of daily activities and reduction of tablets were reported as important advantages of the seven-day patch. In conclusion, the seven-day buprenorphine patch is a valuable therapeutic option for patients with insufficient analgesia on long-term ibuprofen or diclofenac. PMID:21598463

  13. Buprenorphine Outpatient Outcomes Project: can Suboxone be a viable outpatient option for heroin addiction?

    PubMed Central

    Sittambalam, Charmian D.; Vij, Radhika; Ferguson, Robert P.

    2014-01-01

    Background Opioid dependence treatment traditionally involves methadone clinics, for which dispensing schedules can be cumbersome. Buprenorphine, a partial agonist of the mu receptor and antagonist of the kappa receptor, is a potential outpatient alternative to methadone. Funded by a grant from the State of Maryland's Community Health Resources Commission (CHRC), the Buprenorphine Outpatient Outcomes Project (BOOP) evaluates the outcome of Suboxone (buprenorphine/naloxone) treatment on abstinence from heroin use, rates of emergency room visits and hospitalizations, legal issues, and quality of life. Methods Active heroin users were recruited between June 2007 and June 2010 and induction therapy with Suboxone was instituted during hospitalization. Once discharged, patients were followed as outpatients for maintenance treatment and counseling. Data were collected from electronic medical records, Maryland state legal records, and SF-36® Health Surveys regarding several parameters and patients were categorized according to duration of treatment with Suboxone into one of three groups: <1 month, 1–3 months, and >3 months. Results A total of 220 participants were included in the study. The age range of participants was 18–67 years with most being African American males. Eighty-three (38%) remained in the study for at least 1 month, with 37 of the 83 (45%) remaining in treatment for >3 months. Ten of the 37 (27%) never relapsed after their longest period of abstinence from heroin. During the first year after initiating treatment with Suboxone, hospitalization and emergency room visit rates for all 220 participants decreased by 45 and 23%, respectively, as compared to the year prior to starting treatment. The number of legal charges for drug possession decreased from 70 to 62. Anecdotally, the quality of life seemed to improve in those who were treated with Suboxone for longer periods of time and received regular counseling. Conclusion Overall, Suboxone is an effective treatment method for heroin addiction and is a viable outpatient therapy option. Individualized treatment plans and counseling must be implemented for maximum benefits to be seen. Retention of patients for a long duration of therapy was difficult, but for those who did remain, benefits were seen in overall health, abstinence from heroin use, cognition, and quality of life. PMID:24765257

  14. Pharmacokinetics and pharmacodynamics of multiple sublingual buprenorphine tablets in dose-escalation trials.

    PubMed

    Ciraulo, Domenic A; Hitzemann, Robert J; Somoza, Eugene; Knapp, Clifford M; Rotrosen, John; Sarid-Segal, Ofra; Ciraulo, Ann Marie; Greenblatt, David J; Chiang, C Nora

    2006-02-01

    In this investigation, the pharmacokinetic and pharmacodynamic properties were determined of multiple doses of sublingual tablets containing either buprenorphine alone or buprenorphine and naloxone. Subjects were experienced opiate users who received escalating doses (4-24 mg) of buprenorphine either alone or in combination with naloxone. Peak concentration (Cmax) and area under the concentration-time curves (AUCs) increased for both buprenorphine and naloxone with escalating doses. Significant differences were found across the range of doses administered for dose-adjusted Cmax for both tablet formulations and for the dose-adjusted AUCs for the buprenorphine-naloxone tablets. For both formulations, the maximal buprenorphine-induced decreases in respiratory rate and pupil diameter did not vary significantly across doses. Several of the subjective effects of buprenorphine did not increase as the dose of buprenorphine administered was increased. These findings are consistent with the ceiling effect associated with the partial agonist actions of buprenorphine. They also indicate a lack of dose proportionality for buprenorphine sublingual tablets, at least during the times at which levels of this agent are highest. PMID:16432270

  15. Hepatitis C testing and status among opioid substitution treatment clients in New South Wales

    PubMed Central

    Shand, Fiona L; Day, Carolyn; Rawlinson, William; Degenhardt, Louisa; Martin, Nicholas G.; Nelson, Elliot C.

    2015-01-01

    Background In Australia approximately half of the people who inject drugs (PWID) are hepatitis C (HCV) antibody positive (anti-HCV+). The prevalence among opioid substitution treatment (OST) clients specifically is unclear, despite OST clinics being a potential setting for HCV care. The aims of this study were to report the prevalence of HCV among a large sample of NSW OST clients, understand whether HCV testing is translating into knowledge of status, and identify the correlates of inaccurate self-reporting of HCV status. Methods Participants completed an interview which included self-reported HCV status. Participants also provided a blood sample which was tested for HCV IgG antibodies; and for viral load using a quantitative real-time reverse-transcriptase polymerase chain reaction. Valid interviews and viable blood sample were provided by 1484 participants. Logistic regression modelling was used to identify independent predictors of knowledge of HCV antibody status. Results Overall, 84% of participants were anti-HCV+. Of these, 65% were RNA+. Four per cent of anti-HCV negative participants were RNA+. One-quarter of anti-HCV+ participants did not know or reported their status incorrectly, compared with 14.5% of anti-HCV negative participants. Conclusion The prevalence of HCV in this sample was higher than that found amongst other samples of people who inject drugs, suggesting the need for greater prevention efforts with OST clients. Anti-HCV+ individuals are less accurate at reporting their HCV status than those who are anti-HCV−. Inaccurate knowledge is associated with different variables for anti-HCV+ vs. anti-HCV− individuals. There are opportunities to improve knowledge of HCV status and to therefore improve health outcomes and reduce transmission amongst this at-risk population. PMID:24690055

  16. Uses of diverted methadone and buprenorphine by opioid-addicted individuals in Baltimore, Maryland

    PubMed Central

    Mitchell, Shannon Gwin; Kelly, Sharon M.; Brown, Barry S.; Reisinger, Heather Schacht; Peterson, James A.; Ruhf, Adrienne; Agar, Michael H.; O'Grady, Kevin E.; Schwartz, Robert P.

    2009-01-01

    This study examined the uses of diverted methadone and buprenorphine among opiate-addicted individuals recruited from new admissions to methadone programs and from out-of-treatment individuals recruited from the streets. Self-report data regarding diversion were obtained from surveys and semi-structured qualitative interviews. Approximately 16% (n=84) of the total sample (N=515) reported using diverted (street) methadone 2–3 times per week for six months or more, and for an average of 7.8 days (SD=10.3) within the past month. The group reporting lifetime use of diverted methadone as compared to the group that did not report such use was less likely to use heroin and cocaine in the 30 days prior to admission (ps < .01) and had lower ASI Drug Composite scores (p < .05). Participants in our qualitative sub-sample (n=22) indicated that street methadone was more widely used than street buprenorphine and that both drugs were largely used as self-medication for detoxification and withdrawal symptoms. Participants reported using low dosages and no injection of either medication was reported. PMID:19874152

  17. Development of an enhanced formulation for delivering sustained release of buprenorphine hydrochloride.

    PubMed

    Koocheki, S; Madaeni, S S; Niroomandi, P

    2011-10-01

    To control the minimum effective dose, and reduce the number and quantity of administered potent drugs are unique features of advanced drug delivery in situ forming gel formulation. The efficacy, consistency, and increasing the application of existing injection therapies can be enhanced through optimization of controlled released systems by using FDA approved biodegradable PLGA (poly-d,l-lactide-co-glycolide) polymer. The purpose of this study was to develop different in situ forming implant (ISFI) formulations of buprenorphine hydrochloride for post treatment of drug addicts, acute and chronic pains. The drug releases from different ISFIs membranes with and without Tween 80 were compared over a period of time. Kinetic equation followed the Korsmeyer-Peppas model, as the plots showed high linearity. The influence of this additive on polymer properties was investigated using differential scanning calorimetry (DSC), and the membranes structure was studied by X-ray diffractometry (XRD) and scanning electron microscope (SEM). Data revealed that Tween 80 modified the drug release pattern using diffusion mechanism and decreased the glass transition temperature (T g) significantly. The degree of crystallinity was decreased after phase inversion which helps the dissolution of drug from membrane. The porosity of modified membranes was in accordance with release profiles. These findings suggest four different in situ forming implant formulations which can release various dose of the buprenorphine hydrochloride in a prolonged time. Also this surfactant can be an attractive additive for modifying the release rate of drugs from PLGA-based membrane drug delivery systems. PMID:23960766

  18. Blockade of IL-18 signaling diminished neuropathic pain and enhanced the efficacy of morphine and buprenorphine.

    PubMed

    Pilat, Dominika; Piotrowska, Anna; Rojewska, Ewelina; Jurga, Agnieszka; ?lusarczyk, Joanna; Makuch, Wioletta; Basta-Kaim, Agnieszka; Przewlocka, Barbara; Mika, Joanna

    2016-03-01

    Currently, the low efficacy of antinociceptive drugs for the treatment of neuropathic pain is a major therapeutic problem. Here, we show the potential role of interleukin (IL)-18 signaling in this phenomenon. IL-18 is an important molecule that performs various crucial functions, including the alteration of nociceptive transmission in response to neuropathic pain. We have studied the changes in the mRNA and protein levels (qRT-PCR and Western blot analysis, respectively) of IL-18, IL-18-binding protein (IL-18BP) and the IL-18 receptor (IL-18R) over time in rats following chronic constriction injury (CCI) of the sciatic nerve. Our study demonstrated that the spinal levels of IL-18BP were slightly downregulated at days 7 and 14 in the rats subjected to CCI. In contrast, the IL-18 and IL-18R mRNA expression and protein levels were elevated in the ipsilateral spinal cord on days 2, 7 and 14. Moreover, in rats exposed to a single intrathecal administration of IL-18BP (50 and 100ng) 7 or 14days following CCI, symptoms of neuropathic pain were attenuated, and the analgesia pursuant to morphine and buprenorphine (0.5 and 2.5?g) was enhanced. In summary, the restoration of the analgesic activity of morphine and buprenorphine via the blockade of IL-18 signaling suggests that increased IL-18 pathway may account for the decreased analgesic efficacy of opioids for neuropathic pain. PMID:26763728

  19. Development of an enhanced formulation for delivering sustained release of buprenorphine hydrochloride

    PubMed Central

    Koocheki, S.; Madaeni, S.S.; Niroomandi, P.

    2011-01-01

    To control the minimum effective dose, and reduce the number and quantity of administered potent drugs are unique features of advanced drug delivery in situ forming gel formulation. The efficacy, consistency, and increasing the application of existing injection therapies can be enhanced through optimization of controlled released systems by using FDA approved biodegradable PLGA (poly-d,l-lactide-co-glycolide) polymer. The purpose of this study was to develop different in situ forming implant (ISFI) formulations of buprenorphine hydrochloride for post treatment of drug addicts, acute and chronic pains. The drug releases from different ISFIs membranes with and without Tween 80 were compared over a period of time. Kinetic equation followed the Korsmeyer–Peppas model, as the plots showed high linearity. The influence of this additive on polymer properties was investigated using differential scanning calorimetry (DSC), and the membranes structure was studied by X-ray diffractometry (XRD) and scanning electron microscope (SEM). Data revealed that Tween 80 modified the drug release pattern using diffusion mechanism and decreased the glass transition temperature (Tg) significantly. The degree of crystallinity was decreased after phase inversion which helps the dissolution of drug from membrane. The porosity of modified membranes was in accordance with release profiles. These findings suggest four different in situ forming implant formulations which can release various dose of the buprenorphine hydrochloride in a prolonged time. Also this surfactant can be an attractive additive for modifying the release rate of drugs from PLGA-based membrane drug delivery systems. PMID:23960766

  20. Effect of steady-state faldaprevir on the pharmacokinetics of steady-state methadone and buprenorphine-naloxone in subjects receiving stable addiction management therapy.

    PubMed

    Joseph, David; Schobelock, Michael J; Riesenberg, Robert R; Vince, Bradley D; Webster, Lynn R; Adeniji, Abidemi; Elgadi, Mabrouk; Huang, Fenglei

    2015-01-01

    The effects of steady-state faldaprevir on the safety, pharmacokinetics, and pharmacodynamics of steady-state methadone and buprenorphine-naloxone were assessed in 34 healthy male and female subjects receiving stable addiction management therapy. Subjects continued receiving a stable oral dose of either methadone (up to a maximum dose of 180 mg per day) or buprenorphine-naloxone (up to a maximum dose of 24 mg-6 mg per day) and also received oral faldaprevir (240 mg) once daily (QD) for 8 days following a 480-mg loading dose. Serial blood samples were taken for pharmacokinetic analysis. The pharmacodynamics of the opioid maintenance regimens were evaluated by the objective and subjective opioid withdrawal scales. Coadministration of faldaprevir with methadone or buprenorphine-naloxone resulted in geometric mean ratios for the steady-state area under the concentration-time curve from 0 to 24 h (AUC(0-24,ss)), the steady-state maximum concentration of the drug in plasma (C(max,ss)), and the steady-state concentration of the drug in plasma at 24 h (C(24,ss)) of 0.92 to 1.18 for (R)-methadone, (S)-methadone, buprenorphine, norbuprenorphine, and naloxone, with 90% confidence intervals including, or very close to including, 1.00 (no effect), suggesting a limited overall effect of faldaprevir. Although individual data showed moderate variability in the exposures between subjects and treatments, there was no evidence of symptoms of opiate overdose or withdrawal either during the coadministration of faldaprevir with methadone or buprenorphine-naloxone or after faldaprevir dosing was stopped. Similar faldaprevir exposures were observed in the methadone- and buprenorphine-naloxone-treated subjects. In conclusion, faldaprevir at 240 mg QD can be coadministered with methadone or buprenorphine-naloxone without dose adjustment, although given the relatively narrow therapeutic windows of these agents, monitoring for opiate overdose and withdrawal may still be appropriate. (This study has been registered at ClinicalTrials.gov under registration no. NCT01637922.). PMID:25385094

  1. Effect of Steady-State Faldaprevir on the Pharmacokinetics of Steady-State Methadone and Buprenorphine-Naloxone in Subjects Receiving Stable Addiction Management Therapy

    PubMed Central

    Joseph, David; Schobelock, Michael J.; Riesenberg, Robert R.; Vince, Bradley D.; Webster, Lynn R.; Adeniji, Abidemi; Elgadi, Mabrouk

    2014-01-01

    The effects of steady-state faldaprevir on the safety, pharmacokinetics, and pharmacodynamics of steady-state methadone and buprenorphine-naloxone were assessed in 34 healthy male and female subjects receiving stable addiction management therapy. Subjects continued receiving a stable oral dose of either methadone (up to a maximum dose of 180 mg per day) or buprenorphine-naloxone (up to a maximum dose of 24 mg-6 mg per day) and also received oral faldaprevir (240 mg) once daily (QD) for 8 days following a 480-mg loading dose. Serial blood samples were taken for pharmacokinetic analysis. The pharmacodynamics of the opioid maintenance regimens were evaluated by the objective and subjective opioid withdrawal scales. Coadministration of faldaprevir with methadone or buprenorphine-naloxone resulted in geometric mean ratios for the steady-state area under the concentration-time curve from 0 to 24 h (AUC0–24,ss), the steady-state maximum concentration of the drug in plasma (Cmax,ss), and the steady-state concentration of the drug in plasma at 24 h (C24,ss) of 0.92 to 1.18 for (R)-methadone, (S)-methadone, buprenorphine, norbuprenorphine, and naloxone, with 90% confidence intervals including, or very close to including, 1.00 (no effect), suggesting a limited overall effect of faldaprevir. Although individual data showed moderate variability in the exposures between subjects and treatments, there was no evidence of symptoms of opiate overdose or withdrawal either during the coadministration of faldaprevir with methadone or buprenorphine-naloxone or after faldaprevir dosing was stopped. Similar faldaprevir exposures were observed in the methadone- and buprenorphine-naloxone-treated subjects. In conclusion, faldaprevir at 240 mg QD can be coadministered with methadone or buprenorphine-naloxone without dose adjustment, although given the relatively narrow therapeutic windows of these agents, monitoring for opiate overdose and withdrawal may still be appropriate. (This study has been registered at ClinicalTrials.gov under registration no. NCT01637922.) PMID:25385094

  2. Buprenorphine from detox and beyond: preliminary evaluation of a pilot program to increase heroin dependent individuals' engagement in a full continuum of care.

    PubMed

    Donovan, Dennis M; Knox, Patricia C; Skytta, Jenny A F; Blayney, Jessica A; DiCenzo, Jessica

    2013-04-01

    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. PMID:23007109

  3. Buprenorphine + naloxone: new combination. Opiate dependence: no proof of reduced risk of self-administered injection.

    PubMed

    2007-12-01

    (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. PMID:18087797

  4. Trends of People Using Drugs and Opioid Substitute Treatment Recorded in England and Wales General Practice (1994-2012)

    PubMed Central

    Davies, Hilary R.; Nazareth, Irwin; Petersen, Irene

    2015-01-01

    Background Illicit drug use is a multifaceted public-health problem with potentially serious impacts. The United Kingdom has one of the highest prevalence of illegal drug use in Europe. Reduction of overall illegal drug use in England and Wales has decreased from 11% to 8.2% (2012/13) over the past 10 years. People who use drugs often seek help from their family doctors. Aims To investigate General Practitioners (family doctors) first recording of drug use and opioid substitute treatment in primary care settings. Design A descriptive study design. Males and females (16-64 years old) were extracted from The Health Improvement Network (THIN) database. Setting England and Wales primary care. Method The first recording of drug use and opioid substitution treatment in primary care was estimated for the period (1994-2012). Poisson regressions were conducted to estimate incidence risk ratios (IRR). Results We identified 33,508 first recordings of drug use and 10,869 individuals with prescriptions for opioid substitute treatment. Overall, males (IRR 2.02, 95% CI:1.97–2.07), people in the age-group; 16-24 (IRR 6.7, 95% CI:6.4–6.9) compared to those over 25 years and the most deprived (IRR 4.2, 95% CI:3.9–4.4) were more likely to have a recording of drug use. Males (IRR 1.2 95% CI:1.2–1.3), in the age-group; 25-34 (IRR 1.8 95% CI:1.7–1.9) and the most deprived (IRR 3.9 95% CI:3.6–4.3) were the groups more likely to have a opioid substitute treatment prescription. Conclusion It is evident from this study that there is little recording of drug use and opioid substitute treatment in primary care. Most drug users do not receive treatment in primary care. PMID:25923806

  5. Pharmacokinetics of buprenorphine hydrochloride following intramuscular and intravenous administration to American kestrels (Falco sparverius)

    USGS Publications Warehouse

    Gustavsen, Kate A.; Guzman, David Sanchez-Migallon; Knych, Heather K.; Petritz, Olivia A.; Olsen, Glenn H.; Paul-Murphy, Joanne R.

    2014-01-01

    Conclusions and Clinical Relevance—Buprenorphine was rapidly absorbed, and bioavailability was good after IM administration to American kestrels. Plasma buprenorphine concentrations were > 1 ng/mL for 9 hours after both IM and IV administration. These results, in combination with those of a pharmacodynamic study, suggested that the analgesic effects of buprenorphine could last at least 6 to 9 hours in this species. Further investigations of the duration of analgesic effects, multiple-dose protocols, and potential adverse effects of buprenorphine are warranted in American kestrels and other raptors.

  6. Therapeutic substitutions in the midst of new technology diffusion: The case of treatment for localized prostate cancer.

    PubMed

    Shen, Chan; Tina Shih, Ya-Chen

    2016-02-01

    Robotic surgical systems have become increasingly popular worldwide. Robotic assisted radical prostatectomies have been widely adopted in the treatment of localized prostate cancer, replacing the conventional open surgeries. However, it is not clear whether this was achieved by substitution within the same treatment type (i.e., replacing open surgeries with robotic-assisted surgeries) or substitution across treatment types (i.e., expanding the proportion of patients receiving surgery while crowding out other forms of treatment for localized prostate cancer). Given the large number of patients undergoing these procedures each year, it is important to study the impact of the fast diffusion of robotic surgical systems on the overall treatment pattern of localized prostate cancer. We addressed this question using state-level cancer epidemiology data (256 observations) extracted from 2002 to 2010 National Cancer Database, and supply-side variables (e.g. density of robotic surgical systems, urologists) obtained from Area Resource File as well as investor presentations posted at the website of the manufacturer of robotic surgical systems. Recognizing that the purchase decision of robotic systems is potentially endogenous, we used an optimal instrumental variables panel estimation method to examine the impact while taking into account of the panel structure and the potential endogeneity of the density of robotic surgical systems and its quadratic term. We found that the density of robotic systems at state-level had a significantly positive impact on the rate of surgery and a significantly negative impact on the rate of radiation therapy. Further, our age-stratified analysis showed that the increase in surgery rate was most pronounced in the younger population. In conclusion, our findings suggest that part of the increase in the rate of surgery was driven by substitution across treatment types with a large proportion originating from the younger population. PMID:26799678

  7. Opioid Dependence Treatment: Options In Pharmacotherapy

    PubMed Central

    Stotts, Angela L.; Dodrill, Carrie L.; Kosten, Thomas R.

    2010-01-01

    The development of effective treatments for opioid dependence is of great importance given the devastating consequences of the disease. Pharmacotherapies for opioid addiction include opioid agonists, partial agonists, opioid antagonists, and alpha-2-adrenergic agonists, which are targeted toward either detoxification or long-term agonist maintenance. Agonist maintenance therapy is currently the recommended treatment for opioid dependence due to its superior outcomes relative to detoxification. Detoxification protocols have limited long term efficacy and patient discomfort remains a significant therapy challenge. Buprenorphine’s effectiveness relative to methadone remains a controversy and may be most appropriate for patients in need of low doses of agonist treatment. Buprenorphine appears superior to alpha-2 agonists, however, and office-based treatment with buprenorphine in the US is gaining support. Studies of sustained-release formulations of naltrexone suggest improved effectiveness for retention and sustained abstinence, however, randomized clinical trials are needed. PMID:19538000

  8. Enzyme immunoassay validation for the detection of buprenorphine in urine.

    PubMed

    Cirimele, V; Kintz, P; Lohner, S; Ludes, B

    2003-03-01

    A solid-phase enzyme immunoassay involving microtiter plates was proposed by Microgenics to screen buprenorphine in urine. The intra-assay precision at 10 ng/mL was 7.7% (coefficient of variation). The immunoassay was determined to have no cross-reactivity with codeine, dihydrocodeine, morphine, ethylmorphine, 6-monoacetylmorphine, methadone, pholcodine, propoxyphene, dextromoramide, and dextromethorphan at 1 and 10 mg/L. A low cross-reactivity (3% at 1 ng/mL) was observed at low concentrations of norbuprenorphine. After comparing this new immunological test (Singlestep ELISA) for 76 urine specimens with our validated high-performance liquid chromatography-electrospray mass spectrometry (HPLC-ES-MS) procedure, an optimum cutoff concentration of 2 ng/mL was determined for the kit. At this cutoff, the screening assay was able to determine more than 90% of true results with 43.4% true positives and 48.7% true negatives. Four positive urines (5.3%) were not confirmed by HPLC-ES-MS. In only one case, the negative urine test was confirmed as positive by HPLC-ES-MS (buprenorphine: 62.5 ng/mL). Buprenorphine concentrations determined by HPLC-ES-MS ranged from 1.2 to 1052 ng/mL. Of the four potential adulterants (hypochloride 50 mL/L, sodium nitrite 50 g/L, liquid soap 50 mL/L, and sodium chloride 50 g/L) that might be added to a positive urine specimen, none were able to cause a false-negative response by the immunoassay. The results of this study support the concept that the Singlestep ELISA for buprenorphine determination in urine should be considered as a new, valided screening procedure. PMID:12670004

  9. Fulminant hepatic failure after intravenous injection of sublingual buprenorphine in a patient with hepatitis C.

    PubMed

    French, Janine; Mujumdar, Avik; Angus, Peter; Gow, Paul

    2015-08-01

    A 20-year-old indigenous Australian male was admitted to the intensive care unit with fulminant hepatic failure secondary to intravenous use of buprenorphine, which had been prescribed sublingually for opioid dependence. Intravenous buprenorphine-induced hepatitis is well recognized, however, life-threatening fulminant hepatic failure has not previously been reported. PMID:26331017

  10. Fulminant hepatic failure after intravenous injection of sublingual buprenorphine in a patient with hepatitis C

    PubMed Central

    French, Janine; Mujumdar, Avik; Angus, Peter; Gow, Paul

    2015-01-01

    Key Clinical Message A 20-year-old indigenous Australian male was admitted to the intensive care unit with fulminant hepatic failure secondary to intravenous use of buprenorphine, which had been prescribed sublingually for opioid dependence. Intravenous buprenorphine-induced hepatitis is well recognized, however, life-threatening fulminant hepatic failure has not previously been reported. PMID:26331017

  11. False-positive buprenorphine by CEDIA in patients prescribed amisulpride or sulpiride.

    PubMed

    Birch, M A; Couchman, L; Pietromartire, S; Karna, T; Paton, C; McAllister, R; Marsh, A; Flanagan, R J

    2013-05-01

    Buprenorphine is a potent partial opioid agonist that is analyzed in urine to (i) monitor adherence to maintenance or detoxification therapy and (ii) detect illicit use. Buprenorphine analysis is commonly conducted on urine by immunoassay, but is subject to cross-reactivity from other drugs/drug metabolites, including morphine, codeine and dihydrocodeine. This study reports false-positive buprenorphine analysis [Thermo Fisher Scientific cloned enzyme donor immunoassay (CEDIA)] in patients who denied unauthorized buprenorphine use prior to sampling, but who had been prescribed amisulpride. In two cases, confirmatory analysis by liquid chromatography-tandem mass spectrometry was negative (<0.5 µg/L) for buprenorphine and metabolites and positive for amisulpride. Although the cross-reactivity of amisulpride and sulpiride in the CEDIA buprenorphine assay is low (estimated at 0.003 and 0.002%, respectively), it remains a significant consideration given the likely high concentrations of these compounds in urine relative to the low cutoff of the buprenorphine assay. Neither amisulpride nor sulpiride was listed as potential sources of interference on the CEDIA data sheet when this work was performed. These findings highlight the importance of confirming immunoassay-positive buprenorphine results using a more selective analytical technique. PMID:23471956

  12. False-positive buprenorphine EIA urine toxicology results due to high dose morphine: a case report.

    PubMed

    Tenore, Peter L

    2012-01-01

    In monitoring a patient with chronic pain who was taking high-dose morphine and oxycodone with weekly urine enzymatic immunoassay (EIA) toxicology testing, the authors noted consistent positives for buprenorphine. The patient was not taking buprenorphine, and gas chromatography/mass spectroscopy (GCMS) testing on multiple samples revealed no buprenorphine, indicating a case of false-positive buprenorphine EIAs in a high-dose opiate case. The authors discontinued oxycodone for a period of time and then discontinued morphine. Urine monitoring with EIAs and GCMS revealed false-positive buprenorphine EIAs, which remained only when the patient was taking morphine. When taking only oxycodone and no morphine, urine samples became buprenorphine negative. When morphine was reintroduced, false-positive buprenorphine results resumed. Medical practitioners should be aware that high-dose morphine (with morphine urine levels turning positive within the 15,000 to 28,000 mg/mL range) may produce false-positive buprenorphine EIAs with standard urine EIA toxicology testing. PMID:23244551

  13. Evaluation of a Combined Online and in Person Training in the Use of Buprenorphine

    ERIC Educational Resources Information Center

    Gunderson, Erik W.; Levin, Frances R.; Kleber, Herbert D.; Fiellin, David A.; Sullivan, Lynn E.

    2006-01-01

    To evaluate buprenorphine training methodology, we surveyed physicians who had completed a combined online and in person buprenorphine curriculum. Of 53/70 (76%) survey respondents, 57% were psychiatrists and 40% generalists. On a scale of 1 (very poor) to 7 (superlative), the overall training rated a mean of 5.8. The online course (5.0) rated…

  14. [High-dose buprenorphine for outpatient palliative pain therapy].

    PubMed

    Gastmeier, K; Freye, E

    2009-04-01

    The case of a 78-year-old patient with cancer-related pain and additionally mixed-pain syndrome is presented. Pain therapy with buprenorphine TTS 210 microg/h every 3 days was sufficient in the beginning, later the therapy was changed because of increasing problems of tape fixing during fever periods under chemotherapy to a continuous infusion of buprenorphine intravenously via an external medication pump. During the course of therapy it became necessary to increase the dose to 99.9 mg/day buprenorphine. Under this medication a sufficient pain reduction (median NRS 2-3) over a period of 135 days could be achieved. At the same time the patient was vigilant and cooperative without signs of intoxication until the end of life at home in the presence of his family.If no signs of intoxication occur under extreme opioid therapy and a sufficient pain therapy can be achieved, a rotation to another opioid is not necessary. However, outpatient palliative care requires a frequent adaptation to the individually varying opioid demand of the patient and time-consuming nursing care. PMID:19066981

  15. Long-term administration of high doses of transdermal buprenorphine in cancer patients with severe neuropathic pain

    PubMed Central

    Leppert, Wojciech; Kowalski, Grzegorz

    2015-01-01

    Background Buprenorphine is often administered by the transdermal route (transdermal buprenorphine [TB]) in cancer patients with severe neuropathic pain. However, high doses of TB of 140 µg/h are rarely used. Patients and methods Three cancer patients with severe neuropathic Numeric Rating Scale (NRS) pain scores of 8–10 who were successfully treated with high doses of TB up to 140 µg/h along with other opioids and adjuvant analgesics. Results TB was administered for a long period of follow-up (9 months to 4 years, including 34–261 days of treatment with the dose of 140 µg/h), which allowed achievement of satisfactory analgesia (NRS 3–5) and good treatment tolerance. In all three patients, TB dose was gradually titrated from 35 to 140 µg/h, and all patients used morphine at least for some time for breakthrough and background pain management along with adjuvant analgesics. Two patients continued the treatment with TB until the end of life, and one patient is still receiving the treatment. Conclusion TB at doses of up to 140 µg/h in cancer patients with severe neuropathic pain seems to be effective and safe in combination with other opioids and with adjuvant analgesics, and may significantly improve patients’ quality of life. Clinical studies may explore higher than maximal 140 µg/h TB doses recommended by a manufacturer, and also in combination with other opioids and adjuvant analgesics. PMID:26675083

  16. IL-1 receptor antagonist improves morphine and buprenorphine efficacy in a rat neuropathic pain model.

    PubMed

    Pilat, Dominika; Rojewska, Ewelina; Jurga, Agnieszka M; Piotrowska, Anna; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2015-10-01

    An interesting research and therapeutic problem is the reduced beneficial efficacy of opioids in the treatment of neuropathic pain. The present study sought to investigate the potential role of IL-1 family members in this phenomenon. We studied the time course of changes in IL-1alpha, IL-1beta, IL-1 receptor type I and IL-1 receptor antagonist mRNA and protein levels experienced by rats after chronic constriction injury (CCI) of the sciatic nerve using qRT-PCR and Western blot analysis. In CCI-exposed rats, spinal levels of IL-1alpha mRNA were slightly downregulated on the 7th day, and protein levels were not changed on the 7th and 14th days. Levels of IL-1 receptor antagonist and IL-1 receptor type I were slightly upregulated in the ipsilateral part of the spinal cord on the 7th and 14th days; however, protein levels were not changed at those time points. Interestingly, we observed that IL-1beta mRNA and protein levels were strongly elevated in the ipsilateral part of the dorsal spinal cord on the 7th and 14th days following CCI. Moreover, in rats exposed to a single intrathecal administration of an IL-1 receptor antagonist (100 ng i.t.) on the 7th and 14th day following CCI, symptoms of neuropathic pain were attenuated, and the analgesic effects of morphine (2.5 µg i.t.) and buprenorphine (2.5 µg i.t.) were enhanced. In summary, restoration of the analgesic activity of morphine and buprenorphine by blockade of IL-1 signaling suggests that increased IL-1beta responses may account for the decreased analgesic efficacy of opioids observed in the treatment of neuropathy. PMID:26043968

  17. Solvent substitution

    SciTech Connect

    Not Available

    1990-01-01

    The DOE Environmental Restoration and Waste Management Office of Technology Development and the Air Force Engineering and Services Center convened the First Annual International Workshop on Solvent Substitution on December 4--7, 1990. The primary objectives of this joint effort were to share information and ideas among attendees in order to enhance the development and implementation of required new technologies for the elimination of pollutants associated with industrial use of hazardous and toxic solvents; and to aid in accelerating collaborative efforts and technology transfer between government and industry for solvent substitution. There were workshop sessions focusing on Alternative Technologies, Alternative Solvents, Recovery/Recycling, Low VOC Materials and Treatment for Environmentally Safe Disposal. The 35 invited papers presented covered a wide range of solvent substitution activities including: hardware and weapons production and maintenance, paint stripping, coating applications, printed circuit boards, metal cleaning, metal finishing, manufacturing, compliance monitoring and process control monitoring. This publication includes the majority of these presentations. In addition, in order to further facilitate information exchange and technology transfer, the US Air Force and DOE solicited additional papers under a general Call for Papers.'' These papers, which underwent review and final selection by a peer review committee, are also included in this combined Proceedings/Compendium. For those involved in handling, using or managing hazardous and toxic solvents, this document should prove to be a valuable resource, providing the most up-to-date information on current technologies and practices in solvent substitution. Individual papers are abstracted separated.

  18. Effects of Multimodal Analgesia with Low-Dose Buprenorphine and Meloxicam on Fecal Glucocorticoid Metabolites after Surgery in New Zealand White Rabbits (Oryctolagus cuniculus)

    PubMed Central

    Goldschlager, Gregg B; Gillespie, Virginia L; Palme, Rupert; Baxter, Mark G

    2013-01-01

    Despite the increasing use of rabbits as companion animals and models for biomedical research, rabbits have not been extensively studied to identify an efficacious postsurgical analgesic that does not cause systemic complications. The synergy of NSAID and systemic opioids is well-documented, and their combined use reduces the amount of either drug required for adequate analgesia. We measured fecal corticosterone metabolites (FCM) in rabbits after a minimally invasive vascular cut-down procedure. Rabbits received buprenorphine (0.03 mg/kg SC every 12 h for 3 d), meloxicam (0.2 mg/kg SC every 24 h for 3 d), buprenorphine–meloxicam (0.01 mg/kg–0.1 mg/kg SC every 24 h for 3 d), or a single dose of 0.5% bupivacaine (0.5 mL) infused locally at the incision site. By day 3 after surgery, buprenorphine, meloxicam, and bupivacaine groups showed elevated FCM levels, which continued to rise until day 7 and then gradually returned to baseline by day 28. In the buprenorphine–meloxicam group, FCM was relatively unchanged until day 3, when treatment was discontinued, and then began to rise. Rabbits in the buprenorphine–meloxicam group gained more weight over the 28-d study than did those in the other 3 treatment groups. This study shows that in rabbits low-dose buprenorphine administered with meloxicam effectively mitigates the FCM response that develops after surgery without the adverse effects associated with higher doses. PMID:24041213

  19. Pharmacokinetic Interactions Between Buprenorphine/Naloxone and Tipranavir/Ritonavir in HIV-Negative Subjects Chronically Receiving Buprenorphine/Naloxone

    PubMed Central

    Bruce, R. Douglas; Altice, Frederick L.; Moody, David E.; Lin, Shen-Nan; Fang, Wenfang B.; Sabo, John P.; Wruck, Jan M.; Piliero, Peter J.; Conner, Carolyn; Andrews, Laurie; Friedland, Gerald H.

    2009-01-01

    HIV-infected patients with opioid dependence often require opioid replacement therapy. Pharmacokinetic interactions between HIV therapy and opioid-dependence treatment medications can occur. HIV-seronegative subjects stabilized on at least 3 weeks of buprenorphine/naloxone (BUP/NLX) therapy sequentially underwent baseline and steady-state pharmacokinetic evaluation of open-label, twice daily tipranavir 500 mg co-administered with ritonavir 200 mg (TPV/r). Twelve subjects were enrolled and 10 completed the study. Prior to starting TPV/r, the geometric mean BUP AUC0-24h and Cmax were 43.9 ng?hr/mL and 5.61 ng/mL, respectively. After achieving steady-state with TPV/r (?7 days), these values were similar at 43.7 ng?hr/mL and 4.84 ng/mL, respectively. Similar analyses for norBUP, the primary metabolite of BUP, demonstrated a reduction in geometric mean for AUC0-24h [68.7 to 14.7 ng?hr/mL; ratio=0.21 (90% CI 0.19–0.25)] and Cmax [4.75 to 0.94 ng/mL; ratio=0.20 (90% CI 0.17–0.23)]. The last measurable NLX concentration (Clast) in the concentration-time profile, never measured in previous BUP/NLX interaction studies with antiretroviral medications, was decreased by 20%. Despite these pharmacokinetic effects on BUP metabolites and NLX, no clinical opioid withdrawal symptoms were noted. TPV steady-state AUC0-12h and Cmax decreased 19% and 25% respectively, and Cmin was relatively unchanged when compared to historical control subjects receiving TPV/r alone. No dosage modification of BUP/NLX is required when co-administered with TPV/r. Though mechanistically unclear, it is likely that decreased plasma RTV levels while on BUP/NLX contributed substantially to the decrease in TPV levels. BUP/NLX and TPV/r should therefore be used cautiously to avoid decreased efficacy of TPV in patients taking these agents concomitantly. PMID:19726139

  20. Treatment of intractable skin ulcers caused by vascular insufficiency with allogeneic cultured dermal substitute: a report of eight cases.

    PubMed

    Taniguchi, Tomonori; Amoh, Yasuyuki; Tanabe, Kenichi; Katsuoka, Kensei; Kuroyanagi, Yoshimitsu

    2012-03-01

    Chronic leg ulcers have various causes and can be difficult to treat, although topical treatments, including basic fibroblast growth factor and PGE1, have been used. We applied an allogeneic cultured dermal substitute (CDS) to eight patients with intractable ulcers. The patients had various underlying diseases, including diabetes mellitus, systemic lupus erythematosus, antiphospholipid syndrome, necrobiosis lipoidica, stasis dermatitis, livedo vasculopathy, and rheumatoid arthritis. The CDS was prepared by seeding cultured human fibroblasts on a spongy matrix consisting of hyaluronic acid and atelocollagen. Good clinical results were achieved, as demonstrated by reepithelization, healthy granulation tissue formation, and a subsequent decrease in wound size. Daily dressing changes became unnecessary when the allogeneic CDS was used. Based on these results, we suggest that CDS may be useful for the treatment of intractable skin ulcers. PMID:21861088

  1. Sustained-Release Buprenorphine (RBP-6000) Blocks the Effects of Opioid Challenge With Hydromorphone in Subjects With Opioid Use Disorder.

    PubMed

    Nasser, Azmi F; Greenwald, Mark K; Vince, Bradley; Fudala, Paul J; Twumasi-Ankrah, Philip; Liu, Yongzhen; Jones, J P; Heidbreder, Christian

    2016-02-01

    A major goal for the treatment of opioid use disorder is to reduce or eliminate the use of illicit opioids. Buprenorphine, a ?-opioid receptor partial agonist and kappa opioid receptor antagonist, is now being developed as a monthly, sustained-release formulation (RBP-6000). The objective of this study was to demonstrate that RBP-6000 blocks the subjective effects and reinforcing efficacy of the ?-opioid receptor agonist hydromorphone (intramuscularly administered) in subjects with moderate or severe opioid use disorder. Subjects were first inducted and dose stabilized on sublingual buprenorphine/naloxone (8-24 mg daily; dose expressed as the buprenorphine component), then received two subcutaneous injections of RBP-6000 (300 mg) on Day 1 and Day 29. Hydromorphone challenges (6 mg, 18 mg or placebo administered in randomized order) occurred on 3 consecutive days of each study week before and after receiving RBP-6000. Subjects reported their responses to each challenge on various 100-mm Visual Analogue Scales (VAS). Subjects also completed a choice task to assess the reinforcing efficacy of each hydromorphone dose relative to money. At baseline, mean "drug liking" VAS scores for hydromorphone 18 mg and 6 mg versus placebo were 61 mm (95% confidence interval, 52.3-68.9) and 45 mm (95% confidence interval, 37.2-53.6), respectively. After 300 mg RBP-6000 was administered, mean VAS score differences from placebo were less than 10 mm through week 12. The reinforcing efficacy of hydromorphone decreased in a parallel manner. This study demonstrated that RBP-6000 at a 300 mg dose provides durable and potent blockade of the subjective effects and reinforcing efficacy of hydromorphone in subjects with moderate or severe opioid use disorder. PMID:26650971

  2. Opioid withdrawal, craving, and use during and after outpatient buprenorphine stabilization and taper: A discrete survival and growth mixture model

    PubMed Central

    Stotts, Angela L.; Green, Charles; Potter, Jennifer S.; Marino, Elise N.; Walker, Robrina; Weiss, Roger D.; Trivedi, Madhukar

    2014-01-01

    Most patients relapse to opioids within one month of opioid agonist detoxification, making the antecedents and parallel processes of first use critical for investigation. Craving and withdrawal are often studied in relationship to opioid outcomes, and a novel analytic strategy applied to these two phenomena may indicate targeted intervention strategies. Specifically, this secondary data analysis of the Prescription Opioid Addiction Treatment Study used a discrete-time mixture analysis with time-to-first opioid use (survival) simultaneously predicted by craving and withdrawal growth trajectories. This analysis characterized heterogeneity among prescription opioid-dependent individuals (N=653) into latent classes (i.e., latent class analysis [LCA]) during and after buprenorphine/naloxone stabilization and taper. A 4-latent class solution was selected for overall model fit and clinical parsimony. In order of shortest to longest time-to-first use, the 4 classes were characterized as 1) high craving and withdrawal 2) intermediate craving and withdrawal 3) high initial craving with low craving and withdrawal trajectories and 4) a low initial craving with low craving and withdrawal trajectories. Odds ratio calculations showed statistically significant differences in time-to-first use across classes. Generally, participants with lower baseline levels and greater decreases in craving and withdrawal during stabilization combined with slower craving and withdrawal rebound during buprenorphine taper remained opioid-free longer. This exploratory work expanded on the importance of monitoring craving and withdrawal during buprenorphine induction, stabilization, and taper. Future research may allow individually tailored and timely interventions to be developed to extend time-to-first opioid use. PMID:25282598

  3. Clinical effects of buprenorphine on open field behaviour and gait symmetry in healthy and lame weaned piglets.

    PubMed

    Meijer, Ellen; van Nes, Arie; Back, Willem; van der Staay, Franz Josef

    2015-12-01

    Lameness in pigs decreases animal welfare and economic profit for the farmer. An important reason for impaired welfare in lame animals is pain due to lameness. No direct measurement of pain is possible in animals, and methods to indirectly detect and quantify the amount of pain an animal is experiencing are urgently needed. In this study, two methods to assess pain associated with lameness in pigs were evaluated to determine if they were sensitive enough to detect a lameness reduction as an effect of an experimental analgesic medication. Asymmetry associated with lameness was objectively quantified using pressure mat kinetic parameters: peak vertical force (PVF), load rate (LR), vertical impulse (VI) and peak vertical pressure (PVP). Locomotor activity was assessed in an open field test. A dose of 0.04?mg/kg buprenorphine, a strong analgesic, was used to treat 10 lame pigs, while eight other lame pigs, treated with physiological saline solution, served as controls. Buprenorphine decreased lameness-associated asymmetry for pressure mat LR (P?=?0.002), VI (P?=?0.003) and PVP (P?=?0.001) and increased activity of the lame pigs in the open field (P?=?0.023), while saline-treated animals did not show any changes in asymmetry and became less active in the open field (P?<0.001). It was concluded that measurement of gait asymmetry by pressure mat analysis and locomotor activity in an open field test are both sensitive enough to detect the analgesic effects of buprenorphine when used to treat moderate to severe clinical pain in a relatively small group of affected pigs. The methods used in this study may also provide promising additional tools for future research into early pain recognition and lameness treatment in pigs. PMID:26521014

  4. Budgetary impact analysis of buprenorphine-naloxone combination (Suboxone®) in Spain

    PubMed Central

    2012-01-01

    Background Opioid addiction is a worldwide problem. Agonist opioid treatment (AOT) is the most widespread and frequent pharmacotherapeutic approach. Methadone has been the most widely used AOT, but buprenorphine, a partial ?-opiod agonist and a ?-opiod antagonist, is fast gaining acceptance. The objective was to assess the budgetary impact in Spain of the introduction of buprenorphine-naloxone (B/N) combination. Methods A budgetary impact model was developed to estimate healthcare costs of the addition of B/N combination to the therapeutic arsenal for treating opioid dependent patients, during a 3-year period under the National Health System perspective. Inputs for the model were obtained from the specialized scientific literature. Detailed information concerning resource consumption (drug cost, logistics, dispensing, medical, psychiatry and pharmacy supervision, counselling and laboratory test) was obtained from a local expert panel. Costs are expressed in euros (€, 2010). Results The number of patients estimated to be prescribed B/N combination was 2,334; 2,993 and 3,589 in the first, second and third year respectively. Total budget is €85,766,129; €79,855,471 and €79,137,502 in the first, second and third year for the scenario without B/N combination. With B/N combination the total budget would be €86,589,210; €80,398,259 and €79,708,964 in the first, second and third year of the analyses. Incremental cost/patient comparing the addition of the B/N combination to the scenario only with methadone is €10.58; €6.98 and €7.34 in the first, second and third year respectively. Conclusion Addition of B/N combination would imply a maximum incremental yearly cost of €10.58 per patient compared to scenario only with methadone and would provide additional benefits. PMID:22828157

  5. Production and validation of model iron-tannate dyed textiles for use as historic textile substitutes in stabilisation treatment studies

    PubMed Central

    2012-01-01

    Background For millennia, iron-tannate dyes have been used to colour ceremonial and domestic objects shades of black, grey, or brown. Surviving iron-tannate dyed objects are part of our cultural heritage but their existence is threatened by the dye itself which can accelerate oxidation and acid hydrolysis of the substrate. This causes many iron-tannate dyed textiles to discolour and decrease in tensile strength and flexibility at a faster rate than equivalent undyed textiles. The current lack of suitable stabilisation treatments means that many historic iron-tannate dyed objects are rapidly crumbling to dust with the knowledge and value they hold being lost forever. This paper describes the production, characterisation, and validation of model iron-tannate dyed textiles as substitutes for historic iron-tannate dyed textiles in the development of stabilisation treatments. Spectrophotometry, surface pH, tensile testing, SEM-EDX, and XRF have been used to characterise the model textiles. Results On application to textiles, the model dyes imparted mid to dark blue-grey colouration, an immediate tensile strength loss of the textiles and an increase in surface acidity. The dyes introduced significant quantities of iron into the textiles which was distributed in the exterior and interior of the cotton, abaca, and silk fibres but only in the exterior of the wool fibres. As seen with historic iron-tannate dyed objects, the dyed cotton, abaca, and silk textiles lost tensile strength faster and more significantly than undyed equivalents during accelerated thermal ageing and all of the dyed model textiles, most notably the cotton, discoloured more than the undyed equivalents on ageing. Conclusions The abaca, cotton, and silk model textiles are judged to be suitable for use as substitutes for cultural heritage materials in the testing of stabilisation treatments. PMID:22616934

  6. Crushed and Injected Buprenorphine Tablets: Characteristics of Princeps and Generic Solutions

    PubMed Central

    Bouquié, Régis; Wainstein, Laura; Pilet, Paul; Mussini, Jean-Marie; Deslandes, Guillaume; Clouet, Johann; Dailly, Eric; Jolliet, Pascale; Victorri-Vigneau, Caroline

    2014-01-01

    Self-injection of high-dose buprenorphine is responsible for well-described complications. In 2011, we have been alerted by unusual but serious cutaneous complication among injection buprenorphine users. A prospective data collection identified 30 cases of necrotic cutaneous lesions after injection of filtered buprenorphine solution, among which 25 cases occurred following injection of buprenorphine generics. The main goal of our study was to put forward particularities that could explain the cutaneous complications, by qualitatively and quantitatively confronting particles present in Subutex and generics solutions. We used the same protocol that injected-buprenorphine users: generic or subutex tablets were crushed in sterile water and filtered through 2 filters commonly used (cotton-pad and sterifilt). Solutions were analyzed by laser granulometry, flow cytometry and scanning electron microscopy. We have highlighted the wide variation of the quantity and the size of the particles present in solution between the two drugs after cotton-pad filtration. The proportion of particles <10 µm is systematically higher in the generic solutions than with Subutex. All of the insoluble particles found in generic solutions contain silica, whereas non- organic element was to be identified in the insoluble particles of Subutex. One skin biopsy obtained from one patient who developed a necrotic lesion after intravenous injection of filtrated solution of buprenorphine generic, shows non-organic elements. Identification of particles in situ enables us to confirm the presence of silica in the biopsy. Actually the monitoring of patient receiving generic of buprenorphine must be strengthened. PMID:25474108

  7. Availability of buprenorphine on the Internet for purchase without a prescription

    PubMed Central

    Bachhuber, Marcus A.; Cunningham, Chinazo O.

    2012-01-01

    Background Use of illicit buprenorphine is increasingly recognized, but it is unknown if the Internet currently represents an accessible source. Methods A series of Internet searches were conducted. Twenty searches were performed on two different search engines. The first 100 results of each search were classified into categories based on content. All Internet pharmacies were searched for buprenorphine preparations and if available, sites were examined to determine if a prescription was required for purchase, for the cost of buprenorphine, the geographical origin of the pharmacy, and evidence of validation by an online pharmacy verification service. Results Of the 2,000 links examined, 1422 were unique. Six percent of links were to illicit commercial sites, 2% were to legitimate commercial sites, and 2% were to illicit portal sites, which contained links to many illicit commercial sites. Twenty pharmacies offering buprenorphine for purchase without a prescription were identified. The monthly cost of a typical starting dose of 2 mg buprenorphine daily ranged between $232 and $1,163 USD. No pharmacies were listed by online pharmacy verification services. Conclusion Twenty online pharmacies advertising buprenorphine formulations for sale without a prescription were identified. Prices varied widely between illicit pharmacies but were uniformly more expensive than legitimate pharmacies. Illicitly obtained buprenorphine formulations appear to be relatively inaccessible and at high cost on the Internet. PMID:23201172

  8. Structural barriers in the context of opiate substitution treatment in Germany - a survey among physicians in primary care

    PubMed Central

    2013-01-01

    Background Opiate substitution treatment (OST) is the most widely used treatment for opioid dependence in Germany with substantial long-term benefits for the patient and for society. Due to lessened restrictive admission criteria, the number of registered OST patients in Germany has increased continuously in the recent years, whereas the number of physicians providing OST has remained constant. Previous data already indicated a deteriorating situation in the availability or quality of OST delivered and that structural barriers impede physicians in actively providing OST. The present survey among a sample of primary care physicians in Germany aimed to identify and assess potential structural barriers for the provision of health care in the context of OST. Methods An anonymous written questionnaire was sent out to a sample of 2,332 physicians across Germany providing OST. Physicians contacted were identified through databases of the Federal State Chambers of Physicians and/or of the Federal Associations of Statutory Health Insurance Physicians. Data obtained were analysed descriptively. Results The response rate was 25,5% and the majority of 596 physicians sampled viewed substantial problems in terms of the regulatory framework of OST care in the German context. Furthermore, financial remuneration, insufficient qualification, as well as inadequate interdisciplinary cooperation in the treatment of comorbidities of opiate substituted patients were regarded as problematic. The number of physicians providing OST in Germany is expected to substantially decrease in the near future. Conclusion Despite less restrictive admission criteria for OST in Germany, the legal regulation framework for OST is still a limiting factor through raising concerns on the provider and consumer side to be unable to adhere to the strict rules. To avoid future shortages in the provision of OST care on the system level in Germany, revisions to the legal framework seem to be necessary. In regards to adequate care for drug use-related infectious diseases and psychiatric comorbidities commonly found in opiate substituted patients, efforts are required to improve professional qualifications of physicians providing OST as well as respective interdisciplinary collaboration. PMID:23875627

  9. Buprenorphine During Pregnancy Reduces Neonate Distress

    MedlinePLUS

    ... Consequences Mental Health Pain Prevention Substance Abuse in Military Life Treatment Trends & Statistics Women and Drugs Publications ... Genetics HIV or AIDS Medical Consequences Mental Health Military and Veterans Pain Prevention Research Training Treatment Research ...

  10. BU08073 a buprenorphine analogue with partial agonist activity at ?-receptors in vitro but long-lasting opioid antagonist activity in vivo in mice

    PubMed Central

    Khroyan, T V; Wu, J; Polgar, W E; Cami-Kobeci, G; Fotaki, N; Husbands, S M; Toll, L

    2015-01-01

    BACKGROUND AND PURPOSE Buprenorphine is a potent analgesic with high affinity at ?, ? and ? and moderate affinity at nociceptin opioid (NOP) receptors. Nevertheless, NOP receptor activation modulates the in vivo activity of buprenorphine. Structure activity studies were conducted to design buprenorphine analogues with high affinity at each of these receptors and to characterize them in in vitro and in vivo assays. EXPERIMENTAL APPROACH Compounds were tested for binding affinity and functional activity using [35S]GTP?S binding at each receptor and a whole-cell fluorescent assay at ? receptors. BU08073 was evaluated for antinociceptive agonist and antagonist activity and for its effects on anxiety in mice. KEY RESULTS BU08073 bound with high affinity to all opioid receptors. It had virtually no efficacy at ?, ? and NOP receptors, whereas at ? receptors, BU08073 has similar efficacy as buprenorphine in both functional assays. Alone, BU08073 has anxiogenic activity and produces very little antinociception. However, BU08073 blocks morphine and U50,488-mediated antinociception. This blockade was not evident at 1 h post-treatment, but is present at 6 h and remains for up to 3–6 days. CONCLUSIONS AND IMPLICATIONS These studies provide structural requirements for synthesis of ‘universal’ opioid ligands. BU08073 had high affinity for all the opioid receptors, with moderate efficacy at ? receptors and reduced efficacy at NOP receptors, a profile suggesting potential analgesic activity. However, in vivo, BU08073 had long-lasting antagonist activity, indicating that its pharmacokinetics determined both the time course of its effects and what receptor-mediated effects were observed. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24903063

  11. Effects of Buprenorphine and Estrous Cycle in a Murine Model of Cecal Ligation and Puncture

    PubMed Central

    Kennedy, Lucy H; Hwang, Haejin; Wolfe, A Marissa; Hauptman, Joseph; Nemzek-Hamlin, Jean A

    2014-01-01

    The effect of opioids on the immunopathology of sepsis models in mice has been controversial. In previous work, we showed that mortality and various inflammatory parameters did not differ between female mice given saline or buprenorphine after cecal ligation and puncture. To investigate further, we hypothesized that buprenorphine would not affect outcomes of sepsis at any stage of estrous. Female mice were allocated into 4 groups (n = 20 per group) according to stage of estrous. Mice then underwent cecal ligation and puncture and received either buprenorphine or saline. In 3-wk survival studies, overall survival did not differ between buprenorphine- and saline-treated mice. When mice were stratified according to stage of estrous, survival did not vary among saline-treated groups but was lower in buprenorphine-treated mice in metestrus compared with proestrus. To investigate inflammation as a potential mechanism for survival, we measured cell counts and cytokine levels in the peripheral blood and peritoneal lavage fluid at 12 and 24 h after cecal ligation and puncture. At 24 h, buprenorphine-treated mice in proestrus had more circulating neutrophils and monocytes than did saline-treated mice in proestrus and more circulating WBC than did mice in any other stage with or without buprenorphine. Our current results suggest that the effects of buprenorphine on a 50% survival model of sepsis in BALB/c female mice are minimal overall but that the stage of estrous has various effects in this model. Investigators should consider the effects of buprenorphine and estrous cycle when using female mice in sepsis research. PMID:25296014

  12. 40 CFR 268.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... specified in § 268.40 as the treatment standard, or unless the waste is a D003 reactive cyanide wastewater...) The waste consists of organic, debris-like materials (e.g., wood, paper, plastic, or...

  13. 40 CFR 268.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... specified in § 268.40 as the treatment standard, or unless the waste is a D003 reactive cyanide wastewater...) The waste consists of organic, debris-like materials (e.g., wood, paper, plastic, or...

  14. Dexamethasone hepatic induction in rats subsequently treated with high dose buprenorphine does not lead to respiratory depression

    SciTech Connect

    Hreiche, Raymond; Megarbane, Bruno . E-mail: bruno-megarbane@wanadoo.fr; Pirnay, Stephane; Borron, Stephen W.; Monier, Claire; Risede, Patricia; Milan, Nathalie; Descatoire, Veronique; Pessayre, Dominique; Baud, Frederic J.

    2006-12-15

    In humans, asphyxic deaths and severe poisonings have been attributed to high-dosage buprenorphine, a maintenance therapy for heroin addiction. However, in rats, intravenous buprenorphine at doses up to 90 mg kg{sup -1} was not associated with significant effects on arterial blood gases. In contrast, norbuprenorphine, the buprenorphine major cytochrome P450 (CYP) 3A-derived metabolite, is a potent respiratory depressant. Thus, our aim was to study the consequences of CYP3A induction on buprenorphine-associated effects on resting ventilation in rats. We investigated the effects on ventilation of 30 mg kg{sup -1} buprenorphine alone or following cytochrome P450 (CYP) 3A induction with dexamethasone, using whole body plethysmography (N = 24) and arterial blood gases (N = 12). Randomized animals in 4 groups received sequential intraperitoneal dosing with: (dexamethasone [days 1-3] + buprenorphine [day 4]), (dexamethasone solvent [days 1-3] + buprenorphine [day 4]), (dexamethasone [days 1-3] + buprenorphine solvent [day 4]), or (dexamethasone solvent [days 1-3] + buprenorphine solvent [day 4]). Buprenorphine alone caused a significant rapid and sustained increase in the inspiratory time (P < 0.001), without significant effects on the respiratory frequency, the tidal volume, the minute volume, or arterial blood gases. In dexamethasone-pretreated rats, there was no significant alteration in the respiratory parameters, despite CYP3A induction and significant increase of the ratio of plasma norbuprenorphine-to-buprenorphine concentrations. In conclusion, dexamethasone did not modify the effects of 30 mg kg{sup -1} buprenorphine on rat ventilation. Our results suggest a limited role of drug-mediated CYP3A induction in the occurrence of buprenorphine-attributed respiratory depression in addicts.

  15. Safety studies of post-surgical buprenorphine therapy for mice.

    PubMed

    Traul, Karl A; Romero, Jennell B; Brayton, Cory; DeTolla, Louis; Forbes-McBean, Nadine; Halquist, Matthew S; Karnes, H Thomas; Sarabia-Estrada, Rachel; Tomlinson, Michael J; Tyler, Betty M; Ye, Xiaobu; Zadnik, Patricia; Guarnieri, Michael

    2015-04-01

    The use of appropriate analgesia in laboratory mice may be suboptimal because of concerns about adverse events (AE). Target Animal Safety trials were conducted to determine the safety of an extended-release suspension of buprenorphine. Drug or control suspensions were injected subcutaneously in surgically-treated BALB/c mice anesthetized with ketamine-xylazine to mimic post-operative conditions in which the compound might commonly be administered. Single and repeat five-fold (5×) excesses of the 3.25 mg/kg intended dose were used to provoke potential AE. Trials included prospective measurements of weight changes, blood chemistry, hematology, and histopathology. Clinical and histopathology findings were similar in drug-treated and control mice in a four-day trial using a single 16.25 mg/kg, 5× overdose of the drug. In a 12-day trial, which used a total buprenorphine dose of 48.75 mg/kg, clinical and histopathology values were also similar in control and drug-treated female mice. In the male arm of the repeat-overdose trial, two of eight mice died on the morning of day 12, three days following the third 16.25 mg/kg overdose administration. Histopathology did not reveal a cause of death. In a 14-month trial using a single 3.25 mg/kg dose of the drug, no significant findings identified potential AE. These findings indicate a high tolerance to an extended-release buprenorphine suspension administered post-operatively in mice with appropriate husbandry. PMID:25305141

  16. Intravenous use of illicit buprenorphine/naloxone to reverse an acute heroin overdose.

    PubMed

    Yokell, Michael A; Zaller, Nickolas D; Green, Traci C; McKenzie, Michelle; Rich, Josiah D

    2012-01-01

    A case of heroin overdose reversed through the intravenous (IV) administration of a crushed sublingual tablet of buprenorphine/naloxone (Suboxone) by a lay responder is described. Although the sublingual administration of buprenorphine/naloxone to reverse an overdose has been reported elsewhere, this is the first report of IV administration. Healthcare professionals should be aware that injection drug users may respond to an opioid overdose by injecting buprenorphine/naloxone and should consequently counsel all opioid-using patients on the proper response to an overdose. Physicians should also consider prescribing naloxone to at-risk patients. The work of community-based naloxone distribution programs should be expanded. PMID:22479887

  17. Substitutes or complements? Diagnosis and treatment with non-conventional and conventional medicine

    PubMed Central

    Tavares, Aida Isabel

    2015-01-01

    Background: Portugal has a strong tradition of conventional western healthcare. So it provides a natural case study for the relationship between Complementary/Alternative Medicine (CAM) and Western Medicine (WM). This work aims to test the relationship between CAM and WM users in the diagnosis and treatment stages and to estimate the determinants of CAM choice. Methods: The forth Portuguese National Health Survey is employed to estimate two single probit models and obtain the correlation between the consumption of CAM and WM medicines in the diagnosis and treatment stages. Results: Firstly, both in the diagnosis and the treatment stage, CAM and WM are seen to be complementary choices for individuals. Secondly, self-medication also shows complementarity with the choice of CAM treatment. Thirdly, education has a non-linear relationship with the choice of CAM. Finally, working status, age, smoking and chronic disease are determinant factors in the decision to use CAM. Conclusion: The results of this work are relevant to health policy-makers and for insurance companies. Patients need freedom of choice and, for the sake of safety and efficacy of treatment, WM and CAM healthcare ought to be provided in a joint and integrated health system. PMID:25844385

  18. Who benefits from additional drug counseling among prescription opioid dependent patients receiving buprenorphine-naloxone and standard medical management?

    PubMed Central

    Weiss, Roger D.; Griffin, Margaret L.; Potter, Jennifer Sharpe; Dodd, Dorian R.; Dreifuss, Jessica A.; Connery, Hilary S.; Carroll, Kathleen M.

    2014-01-01

    Background In the multi-site Prescription Opioid Addiction Treatment Study (POATS), conducted within the National Drug Abuse Clinical Trials Network, participants randomly assigned to receive individual drug counseling in addition to buprenorphine-naloxone and medical management did not have superior opioid use outcomes. However, research with other substance dependent populations shows that subgroups of participants may benefit from a treatment although the entire population does not. Method We conducted a secondary analysis of POATS data to determine whether a subgroup of participants benefited from drug counseling in addition to buprenorphine-naloxone and medical management, either due to greater problem severity or more exposure to counseling as a result of greater treatment adherence. Problem severity was measured by a history of heroin use, higher Addiction Severity Index drug composite score, and chronic pain. Adequate treatment adherence was defined a priori as attending at least 60% of all offered sessions. Results Patients who had ever used heroin and received drug counseling were more likely to be successful (i.e., abstinent or nearly abstinent from opioids) than heroin users who received medical management alone, but only if they were adherent to treatment and thus received adequate exposure to counseling (OR=3.7, 95% CI=1.1-11.8, p=0.03). The association between severity and outcome did not vary by treatment condition for chronic pain or ASI drug severity score. Conclusions These findings emphasize the importance of treatment adherence, and suggest that patients with prescription opioid dependence are a heterogeneous group, with different optimal treatment strategies for different subgroups. PMID:24831754

  19. 40 CFR 268.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... prohibited, unless the waste, at the point of generation, or after any bona fide treatment such as cyanide...) contaminated with an inorganic metal-bearing hazardous waste; (3) The waste, at point of generation, has... dilution, and therefore prohibited, to add iron filings or other metallic forms of iron to...

  20. 40 CFR 268.3 - Dilution prohibited as a substitute for treatment.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... prohibited, unless the waste, at the point of generation, or after any bona fide treatment such as cyanide...) contaminated with an inorganic metal-bearing hazardous waste; (3) The waste, at point of generation, has... dilution, and therefore prohibited, to add iron filings or other metallic forms of iron to...

  1. Effects of buprenorphine on balance of oxidant/antioxidant system in the different ages of male rat liver.

    PubMed

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Afshari, Reza; Farkhondeh, Tahereh; Karimnezhad, Fatemeh

    2015-06-01

    Our knowledge about a link between buprenorphine and hepatotoxicity is controversial. This study evaluated the effects of buprenorphine on the liver of young, adult, and aged rats. For this reason, young, adult, and aged rats received intraperitoneally 0.25, 0.5, and 1 mg/kg buprenorphine for 30 days. The present results revealed that the normal aging was associated with a significant decrease in the activities of antioxidant enzymes, and an increase in the liver lipid peroxidation, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities in the aged rats. This study also demonstrated that buprenorphine led to a significant increase in the serum activities of ALT, AST, and LDH as well as liver lipid peroxidation content with a decrease in the antioxidant enzymes in the liver of buprenorphine-treated aged rat versus the aged matched control animals. In conclusion, the present results demonstrate that buprenorphine deteriorated oxidative damage in the aged livers. PMID:25683329

  2. The Anti-Suicidal Potential of Buprenorphine: A Case Report

    PubMed Central

    Striebel, Joan M.; Kalapatapu, Raj K.

    2014-01-01

    The very strong relationship between suicide, depressive disorders and substance use disorders is well recognized. Certain pain syndromes are significantly associated with suicide, irrespective of co-occurring medical or psychiatric diagnosis. Chronic pain, depression, substance use disorders and suicide appear to involve overlapping neural pathways and brain regions that function in the processing of emotional and physical pain, as well as maintaining reward and anti-reward circuitry. In this article, we employ a clinical case to illustrate how various stressors disrupted the balance between pain and opioid-facilitated analgesia. This disruption resulted in excessive use of short-acting opioids to treat pain with ensuing allostatic overload and culmination in chronic suicidal ideation with a suicide attempt. Sublingual buprenorphine was selected to treat the opioid use disorder. We propose that the unique pharmacodynamics of this drug served to stabilize dysregulated neural circuits, neurotransmitters and neuropeptides, allowing the mitigation of pain, assuaging opioid cravings, easing depression and resolving suicidal ideation. To our knowledge, this is the first case report to describe the possible anti-suicidal effect of sublingual buprenorphine. PMID:25084802

  3. Comparative assessment of cultured skin substitutes and native skin autograft for treatment of full-thickness burns.

    PubMed Central

    Boyce, S T; Goretsky, M J; Greenhalgh, D G; Kagan, R J; Rieman, M T; Warden, G D

    1995-01-01

    OBJECTIVE: Comparison of cultured skin substitutes (CSSs) and split-thickness autograft (STAG) was performed to assess whether the requirement for autologous skin grafts may be reduced in the treatment of massive burns. SUMMARY BACKGROUND DATA: Cultured skin substitutes consisting of collagen-glycosaminoglycan substrates populated with autologous fibroblasts and keratinocytes have been demonstrated to close full-thickness skin wounds in athymic mice and to express normal skin antigens after closure of excised wounds in burn patients. METHODS: Data were collected from 17 patients between days 2 and 14 to determine incidence of exudate, incidence of regrafting, coloration, keratinization, and percentage of site covered by graft (n = 17). Outcome was evaluated on an ordinal scale (0 = worst; 10 = best) beginning at day 14, with primary analyses at 28 days (n = 10) and 1 year (n = 4) for erythema, pigmentation, epithelial blistering, surface roughness, skin suppleness, and raised scar. RESULTS: Sites treated with CSSs had increased incidence of exudate (p = 0.06) and decreased percentage of engraftment (p < 0.05) compared with STAG. Outcome parameters during the first year showed no differences in erythema, blistering, or suppleness. Pigmentation was greater, scar was less raised, but regrafting was more frequent in CSS sites than STAG. No differences in qualitative outcomes were found after 1 year, and antibodies to bovine collagen were not detected in patient sera. CONCLUSIONS: These results suggest that outcome of engrafted CSSs is not different from STAG and that increased incidence of regrafting is related to decreased percentage of initial engraftment. Increased rates of engraftment of CSSs may lead to improved outcome for closure of burn wounds, allow greater availability of materials for grafting, and reduce requirements for donor skin autograft. Images Figure 1. Figure 2. PMID:8526581

  4. Challenges to Implementing Opioid Substitution Therapy in Ukrainian Prisons: Personnel Attitudes Toward Addiction, Treatment, and People With HIV/AIDS

    PubMed Central

    Polonsky, Maxim; Azbel, Lyuba; Wickersham, Jeffrey A.; Taxman, Faye S.; Grishaev, Evgeny; Dvoryak, Sergey; Altice, Frederick L.

    2015-01-01

    Background Ukraine is experiencing one of the most volatile HIV epidemics globally, fueled primarily by people who inject drugs (PWIDs), and a parallel incarceration epidemic. Opioid substitution therapy (OST) is internationally recognized as one of the most effective forms of treatment for opioid dependence and is among the most effective HIV prevention strategies available, yet efforts to adopt it in Ukraine’s Criminal Justice System (CJS) have been thwarted. Methods To understand the reluctance of the Ukrainian CJS to adopt OST despite the overwhelming evidence pointing to its health benefits and improved criminal justice outcomes, we conducted the first survey of Ukrainian prison administrative, medical and custodial staff (N=243) attitudes towards addiction in general, OST, and people living with HIV/AIDS (PLWHA) in representative regions of Ukraine. Results Results revealed that Ukrainian CJS workers’ attitudes toward OST, PLWHA, and drug addiction were universally negative, but differed substantially along geographic and occupational lines. Whereas geographic and cultural proximity to the European Union drove positive attitudes in the west, in the southern region we observed an identifiability effect, as workers who worked directly with prisoners held the most positive attitudes. We also found that knowledge mediated the effect of drug intolerance on OST attitudes. Conclusion In Ukraine, adoption of OST is more influenced by ideological biases and prejudices than by existing scientific evidence. By elucidating existing attitudes among CJS personnel, this assessment will help direct subsequent interventions to address the barriers to implementing evidence-based HIV prevention treatments. PMID:25620732

  5. On drug treatment and social control: Russian narcology's great leap backwards.

    PubMed

    Elovich, Richard; Drucker, Ernest

    2008-01-01

    The medical discipline of narcology in Russia is a subspecialty of psychiatry from the Soviet era and it is given warrant to define the scope of health activities with regard to alcohol and other drug use, drug users, and related problems. Narcological practice is in turn constrained by the State. The emergence of widespread injection opiate use and associated HIV morbidities and mortalities during the first decade following the collapse of the Soviet Union has brought the contradictions in Russian narcological discourse into high relief. Narcology officials in the Russian Federation have consistently opposed substitution treatment for opiate dependence--the replacement of a short-acting illegal substance with a longer acting prescribed drug with similar pharmacological action but lower degree of risk. Thus, despite the addition of methadone and buprenorphine to WHO's list of essential medicines in 2005 and multiple position papers by international experts calling for substitution treatment as a critical element in the response to HIV (IOM, 2006; UNODC, UNAIDS, and WHO, 2005), methadone or buprenorphine remain prohibited by law in Russia. The authors detail Russian opposition to the prescription of methadone and buprenorphine, describing four phenomena: (1) the dominance of law enforcement and drug control policy over public health and medical ethics; (2) the conflation of Soviet era alcoholism treatment with treatment for opiate dependence; (3) the near universal representation of detoxification from drugs as treatment for dependence; and (4) a framework for judging treatment efficacy that is restricted to "cure" versus "failure to cure," and does not admit its poor outcomes or recognize alternative frameworks for gauging treatment of opiate dependence. In keeping with this position, Russian narcology officials have taken an implacable ideological stance toward illicit drug use, the people who use drugs, and their treatment. By adopting policies and practices totally unsupported by scientific evidence and inquiry, officials in Russia have rendered narcology (and medical practice) insensitive to the alarming rates and continued spread of HIV, with its dire morbidity and mortality rates in the Russian Federation, turning their backs on all the other health problems posed by opiate use and dependence itself. PMID:18577225

  6. On drug treatment and social control: Russian narcology's great leap backwards

    PubMed Central

    Elovich, Richard; Drucker, Ernest

    2008-01-01

    The medical discipline of narcology in Russia is a subspecialty of psychiatry from the Soviet era and it is given warrant to define the scope of health activities with regard to alcohol and other drug use, drug users, and related problems. Narcological practice is in turn constrained by the State. The emergence of widespread injection opiate use and associated HIV morbidities and mortalities during the first decade following the collapse of the Soviet Union has brought the contradictions in Russian narcological discourse into high relief. Narcology officials in the Russian Federation have consistently opposed substitution treatment for opiate dependence – the replacement of a short-acting illegal substance with a longer acting prescribed drug with similar pharmacological action but lower degree of risk. Thus, despite the addition of methadone and buprenorphine to WHO's list of essential medicines in 2005 and multiple position papers by international experts calling for substitution treatment as a critical element in the response to HIV (IOM, 2006; UNODC, UNAIDS, and WHO, 2005), methadone or buprenorphine remain prohibited by law in Russia. The authors detail Russian opposition to the prescription of methadone and buprenorphine, describing four phenomena: (1) the dominance of law enforcement and drug control policy over public health and medical ethics ; (2) the conflation of Soviet era alcoholism treatment with treatment for opiate dependence; (3) the near universal representation of detoxification from drugs as treatment for dependence; and (4) a framework for judging treatment efficacy that is restricted to "cure" versus "failure to cure," and does not admit its poor outcomes or recognize alternative frameworks for gauging treatment of opiate dependence. In keeping with this position, Russian narcology officials have taken an implacable ideological stance toward illicit drug use, the people who use drugs, and their treatment. By adopting policies and practices totally unsupported by scientific evidence and inquiry, officials in Russia have rendered narcology ( and medical practice) insensitive to the alarming rates and continued spread of HIV, with its dire morbidity and mortality rates in the Russian Federation, turning their backs on all the other health problems posed by opiate use and dependence itself. PMID:18577225

  7. Facts about Buprenorphine for Treatment of Opioid Addiction

    MedlinePLUS

    ... dizziness —Stand up slowly. Call your doctor if problems persist. Constipation —Drink more water and juice. Eat food with fiber. Exercise more. Sweating —Shower often. Dress in layers. Sleep problems, including tiredness —Take the pill in the morning. ...

  8. Plasma buprenorphine concentrations after the application of a 70 microg/h transdermal patch in dogs. Preliminary report.

    PubMed

    Andaluz, A; Moll, X; Ventura, R; Abellán, R; Fresno, L; García, F

    2009-10-01

    The objective of the present study was to evaluate the plasma concentrations and pharmacokinetics of buprenorphine after transdermal application in dogs (n = 4). A 70 microg/h transdermal buprenorphine patch was applied to the ventral abdomen of four healthy beagles. Blood samples were collected through a preplaced jugular catheter before and at 1, 2, 4, 8, 12, 24, 36, 48 and every 6 h until 108 h after the patch application. Plasma buprenorphine concentrations were measured using a (125)I-labelled radioimmunoassay (RIA) assay. No adverse effects were observed in any of the dogs. Concentrations of buprenorphine were detected in plasma after the application of the transdermal buprenorphine patch on the four experimental animals. Buprenorphine plasma concentrations increased during the first 36 h and then remained in the 0.7-1.0 ng/mL range during the study period. A decrease in plasma buprenorphine concentration was not observed during the study. Although analgesia could not be demonstrated the present study shows the ability of buprenorphine transdermal delivery systems developed for human use to deliver measurable concetrations of buprenorphine in dogs. PMID:19754919

  9. Simultaneous quantification of buprenorphine, norbuprenorphine, buprenorphine glucuronide, and norbuprenorphine glucuronide in human placenta by liquid chromatography mass spectrometry

    PubMed Central

    Concheiro-Guisan, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.

    2011-01-01

    A LCMS method was developed and validated for the determination of buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc), and norbuprenorphine glucuronide (NBUP-Gluc) in placenta. Quantification was achieved by selected ion monitoring of m/z 468.4 (BUP), 414.3 (NBUP), 644.4 (BUP-Gluc), and 590 (NBUP-Gluc). BUP and NBUP were identified monitoring MS2 fragments m/z 396, 414 and 426 for BUP, and 340, 364 and 382 for NBUP, and glucuronide conjugates monitoring MS3 fragments m/z 396 and 414 for BUP-Gluc, and 340 and 382 for NBUP-Gluc. Linearity was 1–50 ng/g. Intra-day, inter-day and total assay imprecision (% RSD) were <13.4%, and analytical recoveries were 96.2–113.1%. Extraction efficiencies ranged from 40.7–68%, process efficiencies 38.8–70.5%, and matrix effect 1.3–15.4%. Limits of detection were 0.8 ng/g for all compounds. An authentic placenta from an opioid-dependent pregnant woman receiving BUP pharmacotherapy was analyzed. BUP was not detected but metabolite concentrations were NBUP-Gluc 46.6, NBUP 15.7 and BUP-Gluc 3.2 ng/g. PMID:19247639

  10. Comparative pharmacokinetics of intravenous fentanyl and buprenorphine in healthy greyhound dogs.

    PubMed

    KuKanich, B; Allen, P

    2014-12-01

    The purpose of this study was to compare the pharmacokinetics of two highly protein-bound, lipophilic opioid drugs. Fentanyl (10 ?g/kg) and buprenorphine (20 ?g/kg) were administered intravenously (IV) to six healthy greyhound dogs (three males and three females). The doses were based on clinically administered doses for dogs. Plasma drug concentrations were determined using liquid chromatography with mass spectrometry, and noncompartmental pharmacokinetics were estimated with computer software. The volume of distribution (area) was larger for fentanyl (7.42 L/kg) compared to buprenorphine (3.54 L/kg). The plasma clearance of fentanyl (38.6 mL·min/kg) was faster than buprenorphine (10.3 mL·min/kg). The terminal half-life of fentanyl (2.22 h) was shorter than buprenorphine (3.96 h). Despite similar physicochemical properties including octanol-water partition coefficient and pKa, the pharmacokinetics of fentanyl and buprenorphine were not similar. Both fentanyl (84%) and buprenorphine (95-98%) are considered highly protein bound, but the differences in protein binding may contribute to the lack of similarity of pharmacokinetics in healthy dogs. PMID:24684621

  11. Antinociceptive actions of morphine and buprenorphine given intrathecally in the conscious rat.

    PubMed Central

    Bryant, R. M.; Olley, J. E.; Tyers, M. B.

    1983-01-01

    1 The antinociceptive effects of morphine and buprenorphine given intrathecally and subcutaneously have been compared in the conscious rat. 2 In the paw pressure test, when given subcutaneously buprenorphine 0.001-0.1 mg/kg s.c., was approximately 100 times more potent than morphine 0.1-3 mg/kg s.c., but in the hot plate test, buprenorphine 0.03-3.0 mg/kg s.c., produced a bell-shaped dose-response curve of low maximum effect and was about equipotent with morphine 0.03-3 mg/kg s.c. 3 When given intrathecally buprenorphine 10 micrograms and morphine, 10-60 micrograms, were approximately equipotent in both paw pressure and hot plate tests. Furthermore, morphine produced these effects at 1/25th of the minimum effective parenteral dose while the dose of buprenorphine exceeded the parenteral dose. 4 It is concluded that the predominant site of the analgesic action of buprenorphine is supraspinal. The significance of these findings in relation to the role of spinal opiate receptors is discussed. PMID:6687818

  12. Comparative pharmacokinetics of intravenous fentanyl and buprenorphine in healthy Greyhound dogs

    PubMed Central

    KuKanich, Butch; Allen, Philip

    2014-01-01

    The purpose of this study was to compare the pharmacokinetics of two highly protein bound, lipophilic opioid drugs. Fentanyl (10 ?g/kg) and buprenorphine (20 ?g/kg) were administered intravenously (IV) to six healthy Greyhound dogs (3 males and 3 females). The doses were based on clinically administered doses for dogs. Plasma drug concentrations were determined using liquid chromatography with mass spectrometry and noncompartmental pharmacokinetics were estimated with computer software. The volume of distribution (area) was larger for fentanyl (7.42 L/kg) compared to buprenorphine (3.54 L/kg). The plasma clearance of fentanyl (38.6 mL/min/kg) was faster than buprenorphine (10.3 mL/min/kg). The terminal half-life of fentanyl (2.22 h) was shorter than buprenorphine (3.96 h). Despite similar physicochemical properties including: octanol:water partition coefficient and pKa the pharmacokinetics of fentanyl and buprenorphine were not similar. Both fentanyl (84%) and buprenorphine (95-98%) are considered highly protein bound, but the differences in protein binding may contribute to the lack of similarity of pharmacokinetics in healthy dogs. PMID:24684621

  13. Combined effects of post-growth thermal treatment and chemical substitution on physical properties of CaFe2As2

    SciTech Connect

    Ran, Sheng

    2014-12-01

    This thesis summarizes experimental work using process of postgrowth thermal treatment and chemical substitution as tuning parameters in the study of physical properties of CaFe2As2. Details of sample preparation and characterization are given as well as various phase diagrams.

  14. Clinical and radiographic evaluation of intrabony periodontal defect treatment by open flap debridement alone or in combination with nanocrystalline hydroxyapatite bone substitute.

    PubMed

    Pietruska, Ma?gorzata; Skurska, Anna; Pietruski, Jan; Doli?ska, Ewa; Arweiler, Nicole; Milewski, Robert; Duraj, Ewa; Sculean, Anton

    2012-11-01

    The aim of this study has been to compare the clinical and radiographic outcome of periodontal intrabony defect treatment by open flap debridement alone or in combination with nanocrystalline hydroxyapatite bone substitute application. Thirty patients diagnosed with advanced periodontits were divided into two groups: the control group (OFD), in which an open flap debridement procedure was performed and the test group (OFD+NHA), in which defects were additionally filled with nanocrystalline hydroxyapatite bone substitute material. Plaque index (PI), gingival index (GI), bleeding on probing (BOP), pocket depth (PD), gingival recession (GR) and clinical attachment level (CAL) were measured prior to, then 6 and 12months following treatment. Radiographic depth and width of defects were also evaluated. There were no differences in any clinical and radiographic parameters between the examined groups prior to treatment. After treatment, BOP, GI, PD, CAL, radiographic depth and width parameter values improved statistically significantly in both groups. The PI value did not change, but the GR value increased significantly after treatment. There were no statistical differences in evaluated parameters between OFD and OFD+NHA groups 6 and 12months after treatment. Within the limits of the study, it can be concluded that the additional use of nanocrystalline hydroxyapatite bone substitute material after open flap procedure does not improve clinical and radiographic treatment outcome. PMID:22727935

  15. Human Split-Thickness Skin Allograft: Skin Substitute in the Treatment of Burn

    PubMed Central

    Mahdavi-Mazdeh, M.; Nozary Heshmati, B.; Tavakoli, S. A. H.; Ayaz, M.; Azmoudeh Ardalan, F.; Momeni, M.

    2013-01-01

    Background: Human skin allograft has been used as wound coverage for a long time; it is one of the most successful and widely used dressings for burn wounds in the world. Objective: To prepare a freeze-dried human split-thickness skin allograft and evaluate its cytotoxicity, the structure and physical properties after processing methods and clinical efficacy in burn patients. Methods: After ensuring tissue safety, we lyophilized human cadaveric partial thickness skin and exposed it to gamma radiation. Histopathological and immunohistochemical properties, tensile strength and in vitro cytotoxicity were assayed for the skin samples. Then, we tested the samples in 11 patients with deep skin burn. Results: On histological and histopathological examinations, we found a normal skin structure. The tensile strength of the rehydrated freeze-dried human skin allograft was not lesser than the fresh human skin. Cell viability in MTT testing was more than 95%. None of our patients showed any signs of immunological reactions or complications. Conclusion: Gamma-irradiated freeze-dried human split-thickness skin is safe and non-toxic and can be used for the treatment of patients with deep skin burn. PMID:25013660

  16. Development of nanofibrous cellulose acetate/gelatin skin substitutes for variety wound treatment applications.

    PubMed

    Vatankhah, Elham; Prabhakaran, Molamma P; Jin, Guorui; Mobarakeh, Laleh Ghasemi; Ramakrishna, Seeram

    2014-02-01

    The major component of fibrous extracellular matrix of dermis is composed of a complex combination of proteins and polysaccharides. Electrospun cellulose acetate/gelatin might be an effective simulator of the structure and composition of native skin and during this study, we electrospun cellulose acetate/gelatin membranes in various compositions and their performance as a scaffold for either skin tissue engineering or as a wound dressing was evaluated. Skin treatment products, whether tissue-engineered scaffolds or wound dressings, should be sufficiently hydrophilic to allow for gas and fluid exchange and absorb excess exudates while controlling the fluid loss. However, a wound dressing should be easily removable without causing tissue damage and a tissue-engineered scaffold should be able to adhere to the wound, and support cell proliferation during skin regeneration. We showed that these distinct adherency features are feasible just by changing the composition of cellulose acetate and gelatin in composite cellulose acetate/gelatin scaffolds. High proliferation of human dermal fibroblasts on electrospun cellulose acetate/gelatin 25:75 confirmed the capability of cellulose acetate/gelatin 25:75 nanofibers as a tissue-engineered scaffold, while the electrospun cellulose acetate/gelatin 75:25 can be a potential low-adherent wound dressing. PMID:23640859

  17. A Clinical Trial Comparing Tapering Doses of Buprenorphine with Steady Doses for Chronic Pain and Co-existent Opioid Addiction

    PubMed Central

    Blondell, Richard D.; Ashrafioun, Lisham; Dambra, Christina M.; Foschio, Elisa M.; Zielinski, Amy L.; Salcedo, Daniel M.

    2009-01-01

    Objectives Effective strategies are needed to manage individuals with chronic non-cancer pain and coexistent opioid addiction. This study compared opioid discontinuation and opioid replacement protocols. Methods We planned to enroll 60 individuals into an open-label trial who had been treated with opioids for chronic non-cancer pain, and who also had opioid addiction. Participants were randomly assigned to one of two 6-month treatment protocols of buprenorphine/naloxone sublingual tablets: 1) tapering doses for opioid weaning or “detoxification” (active comparator group) or 2) steady doses for opioid replacement (experimental group). They were followed monthly for the study outcomes: completion of the 6-month treatment protocol and self-reported pain control, physical functioning, alcohol consumption and illicit drug use. Results Enrollment was terminated after enrolling 12 participants because none of the 6 assigned to receive tapering doses could successfully complete the protocol (5 were given steady doses and 1 was admitted to an inpatient chemical dependency treatment program); whereas, of the 6 assigned to receive steady doses, 5 completed the protocol (1 withdrew). This difference between the 2 treatment conditions was significant (P = 0.015). Of the 10 participants who completed the 6 month follow-up, 8 reported improved pain control and physical functioning and 5 used alcohol and/or illicit drugs. Conclusions We conclude that over 6 months, these participants with chronic pain and co-existent opioid addiction were more likely to adhere to an opioid replacement protocol than an opioid weaning protocol and that opioid replacement therapy with steady doses of buprenorphine/naloxone is associated with improved pain control and physical functioning. PMID:20959867

  18. Systematic strontium substitution in hydroxyapatite coatings on titanium via micro-arc treatment and their osteoblast/osteoclast responses.

    PubMed

    Chung, Chi-Jen; Long, Han-Yun

    2011-11-01

    This study attempts to enhance the osseointegration of titanium implants by adopting a micro-arc treatment (MAT) capable of replacing calcium (Ca) with different percentages of strontium (Sr) in order to fabricate strontium-containing hydroxyapatite (Sr-HAp) coatings. Sr, regarded as a significant therapy promoting bone mass and bone strength, has a dual mechanism, enhancing osteoblast differentiation and inhibiting osteoclast differentiation. This study also investigates how Sr content affects the microstructure of and osteoblast/osteoclast growth on the coatings. Experimental results indicate that an increase in the Sr content in the electrolyte bath results in a greater degree of Sr substitution at Ca sites within the HAp phase, facilitating the formation of Sr-HAp coatings with Sr fully solid soluble in the HAp phase. Irrespective of the Sr content, most coatings are similar in porous morphology and pore size. Additionally, the Sr-HAp coating shows higher osteoblast compatibility than raw titanium metal and the HAp coating. Moreover, cell adhesion and proliferation after 48 h was greater than that after 4 h, indicating that Sr can stimulate osteoblast adhesion and proliferation. Further, Sr significantly inhibits osteoclast differentiation when the Sr-HAp coatings exceed 38.9 at.% Sr. PMID:21784178

  19. New insights into the pharmacological chaperone activity of c2-substituted glucoimidazoles for the treatment of Gaucher disease.

    PubMed

    Li, Zhonghua; Li, Tiehai; Dai, Shaoxing; Xie, Xiaoli; Ma, Xiaofeng; Zhao, Wei; Zhang, Weimin; Li, Jing; Wang, Peng George

    2013-07-01

    Mutations in acid β-glucocerebrosidase (GCase) lead to the accumulation of the sphingolipid glucosylceramide, thereby resulting in Gaucher disease (GD). Active-site-specific competitive GCase inhibitors are effective pharmacological chaperones (PCs) that act as folding agents for mutant GCase folding in the endoplasmic reticulum. In this study, we prepared a series of glucoimidazole C2-substituent derivatives, and evaluated their inhibition and PC properties with GCase. A cell-based assay with patient-derived lymphoblasts (N370S or L444P mutations) demonstrated that administration of these compounds can significantly increase GCase activity. Interestingly, the 3,3-dimethyl-N-phenyl-4-amide-1-butyl-substituted moderate inhibitor 11 had the greatest effect on activity: 2.1-fold increase in N370S lymphoblasts at 2.5 μM and 1.2-fold increase in L444P at 0.5 μM following a three-day incubation. Computer docking studies and a protease protection assay were used to elucidate the ligand-enzyme interactions responsible for the chaperone activity of 11. Western blot and immuno-fluorescence assays verified restoration of GCase trafficking to the lysosome. Together, these results indicate that 11 is a promising PC for GD treatment and provide direct evidence of the mechanism of GCase chaperoning. PMID:23775891

  20. Illicit Use of Buprenorphine in a Community Sample of Young Adult Non-Medical Users of Pharmaceutical Opioids

    PubMed Central

    Daniulaityte, Raminta; Falck, Russel; Carlson, Robert G.

    2011-01-01

    BACKGROUND There is growing evidence about illicit use of buprenorphine in the U.S. The study aims to: 1) identify prevalence and predictors of illicit buprenorphine use in a community sample of 396 young adult (18-23 years old) non-medical users of pharmaceutical opioids; 2) describe knowledge, attitudes and behaviors linked to illicit buprenorphine use as reported by a qualitative sub-sample (n=51). METHODS Participants were recruited using respondent-driven sampling. Qualitative interview participants were selected from the larger sample. The sample (n=396) was 54% male and 50% white; 7.8% reported lifetime illicit use of buprenorphine. RESULTS Logistic regression analysis results indicate that white ethnicity, intranasal inhalation of pharmaceutical opioids, symptoms of opioid dependence, and a greater number of pharmaceutical opioids used in lifetime were statistically significant predictors of illicit buprenorphine use. Qualitative interviews revealed that buprenorphine was more commonly used by more experienced users who were introduced to it by their “junkie friends.” Those who used buprenorphine to self-medicate withdrawal referred to it as a “miracle pill.” When used to get high, reported experiences ranged from “the best high ever” to “puking for days.” Participants reported using buprenorphine/naloxone orally or by intranasal inhalation. Injection of buprenorphine without naloxone was also reported. CONCLUSION Our findings suggest that illicit buprenorphine use is gaining ground primarily among whites and those who are more advanced in their drug use careers. Continued monitoring is needed to better understand evolving patterns and trends of illicit buprenorphine use. PMID:22036303

  1. Clinical relevance of substitutions in the connection subdomain and RNase H domains of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naïve patients

    PubMed Central

    Hachiya, Atsuko; Shimane, Kazuki; Sarafianos, Stefan G.; Kodama, Eiichi N.; Sakagami, Yasuko; Negishi, Fujie; Koizumi, Hirokazu; Gatanaga, Hiroyuki; Matsuoka, Masao; Takiguchi, Masafumi; Oka, Shinichi

    2012-01-01

    Some mutations in the connection subdomain of the polymerase domain and in the RNase H domain of HIV-1 reverse transcriptase (RT) have been shown to contribute to resistance to RT inhibitors. However, the clinical relevance of such mutations is not well understood. To address this point we determined the prevalence of such mutations in a cohort of antiretroviral treatment-naïve patients (n=123) and assessed whether these substitutions are associated with drug resistance in vitro and in vivo. We report here significant differences in the prevalence of substitutions among subtype B, and non-subtype B HIV isolates. Specifically, the E312Q, G333E, G335D, V365I, A371V and A376S substitutions were present in 2–6% of subtype B, whereas the G335D and A371V substitutions were commonly observed in 69 and 75% of non-B HIV-1 isolates. We observed a significant decline in the viral loads of patients that were infected with HIV-1 carrying these substitutions and were subsequently treated with triple drug regimens, even in the case where zidovudine (AZT) was included in such regimens. We show here that generally, such single substitutions at the connection subdomain or RNase H domain have no influence on drug susceptibility in vitro by themselves. Instead, they generally enhance AZT resistance in the presence of excision-enhancing mutations (EEMs, also known as thymidine analogue-associated mutations, TAMs). However, N348I, A376S and Q509L did confer varying amounts of nevirapine resistance by themselves, even in the absence of EEMs. Therefore, our cohort establishes that several connection subdomain and RNase H domain substitutions typically act as pre-therapy polymorphisms. PMID:19428602

  2. Vitreous Substitutes

    PubMed Central

    Foster, William Joseph

    2008-01-01

    Modern vitreoretinal surgery is a young science. While tremendous developments have occurred in instrument design and technique since Machemer first described vitrectomy surgery in 1973[1], the application of advanced materials concepts to the development of intra-ocular compounds is a particularly exciting area of research. To date, the development of vitreous substitutes has played a significant role in enabling the dramatic and progressive improvement in surgical outcome, but perhaps no other area of research has the potential to further improve the treatment of retinal detachment and other retinal disorders. While prior research has focused solely upon the ability of a compound to re-attach the retina, future research should seek to enable the surgeon to inhibit the development of proliferative vitreoretinopathy and re-detachment, the integration of stem-cell therapies with surgical retina, long-term delivery of medications to the posterior segment, and the promotion of more rapid and complete visual rehabilitation. PMID:19343097

  3. Spontaneous Reductions in Smoking during Double-blind Buprenorphine Detoxification

    PubMed Central

    Patrick, Mollie E.; Dunn, Kelly E.; Badger, Gary J.; Heil, Sarah H.; Higgins, Stephen T.; Sigmon, Stacey C.

    2014-01-01

    Evidence suggests a positive association between administration of psychoactive drugs and rates of cigarette smoking. Prevalence of smoking among opioid-dependent individuals, for example, is four times greater than the general population. We recently completed a randomized double-blind trial evaluating outpatient buprenorphine taper for prescription opioid (PO) abusers, which provided an unique opportunity to examine naturalistic changes in smoking among participants who detoxified without resumption of illicit opioid use. Participants received no smoking-cessation services and were not encouraged to alter their smoking in any way. A subset of 10 opioid-dependent smokers, who were randomized to receive the same 4-week buprenorphine taper and successfully completed detoxification, were included in the present study. They provided staff-observed urine specimens thrice-weekly throughout the 12-week trial. Specimens were analyzed onsite via enzyme-multiplied immunoassay for urinary cotinine, a metabolite of nicotine that provides a sensitive biochemical measure of smoking status. Mean cotinine levels were significantly different across study phases, with significantly lower cotinine levels during taper (1317.5 ng/ml) and post-taper (1015.8 ng/ml) vs. intake (1648.5 ng/ml) phases (p’s<.05). Overall, mean cotinine levels decreased by 38% between intake and end-of-study, reflecting a reduction of approximately eight cigarettes per day. These data provide additional evidence that opioids influence smoking and extend prior findings to include primary PO abusers, rigorous double-blind opioid dosing conditions and urinary cotinine. These results also suggest that, while likely insufficient for complete cessation, patients who successfully taper from opioids may also experience concurrent reductions in smoking and thus may be ideal candidates for smoking cessation services. PMID:24845165

  4. Comparative Trial to Study the Effectiveness of Clonidine Hydrochloride and Buprenorphine-Naloxone in Opioid Withdrawal – A Hospital Based Study

    PubMed Central

    Farhat, Samina; Rather, Yasir Hassan; Abbas, Zaffar

    2015-01-01

    Objectives: Prevalence of opioid addiction has alarmingly increased over the recent years. In South Asian region alone there are more than 10 million opioid abusers amounting to 2% of world population. Detoxification remains to be the first step for the successful treatment of opioid addiction. The present study was carried out to compare the relative efficacy and safety of buprenorphine –naloxone and clonidine hydrochloride in the detoxification of opioid-dependents. Materials and Methods: Present trial was conducted at De- addiction centre of Institute of Mental and Neurosciences (IMNS), GMC Srinagar. Fifty four (54) treatment seeking subjects, 15-50 years of age, fulfilling DSM-1V TR (American Psychiatric association`s Mental Disorders-1V text revision) criteria for opioid dependence were included and randomized into two groups. The groups received either clonidine hydrochloride (Group A) or buprenorphine- naloxone (Bup-Nax) (Group B) for the duration of 10 days. The efficacy of the two drugs in controlling the opioid withdrawal was evaluated by Clinical Opioid Withdrawal Scale (COWS) and their effect on the desire for the abused substance was measured by Visual Analogue Scale (VAS). The safety of the two drugs was measured by taking the side effect profile of the two compared drugs into consideration. Results: There was significant difference of COWS-score between the two groups which was evident from day 3 (14.85 ± 3.43 vs. 11.67 ± 2.40, p<0.005) and continued till day 6 (2.56 ± 1.40 vs. 0.30 ± 0.61, p<0.005), for Group A and group B respectively. The effect of two drugs in controlling the craving for the abused substance also showed significant difference from day 2 (66.30 ± 10.80 vs. 47.40 ± 12.90, p<0.005) till day 5 (7.78 ± 6.41 vs. 1.85 ± 6.22, p<0.005), for Group A and Group B respectively. Conclusion: Administration of buprenorphine-naloxone was more efficient in reducing the signs and symptoms of opioid withdrawal and in controlling the craving for the abused substance during the first few days of detoxification. PMID:25738001

  5. Pharmacokinetics of sustained-release and transdermal buprenorphine in Göttingen minipigs (Sus scrofa domestica).

    PubMed

    Thiede, Allison J; Garcia, Kelly D; Stolarik, DeAnne F; Ma, Junli; Jenkins, Gary J; Nunamaker, Elizabeth A

    2014-11-01

    The opioid buprenorphine has been shown to provide adequate postoperative analgesia in both companion and laboratory animals. However, its use is still hindered by the need for multiple parenteral injections to achieve continuous analgesia. The purpose of the current study was to conduct a pharmacokinetic analysis of 2 new long-acting formulations of buprenorphine-an injectable sustained-release buprenorphine (SRB) and a transdermal buprenorphine (TDB) patch-in healthy Göttingen minipigs by using liquid chromatography-electrospray ionization-tandem mass spectrometry. Administration of 0.18 mg/kg SC SRB and 30 ? g/h TDB achieved AUC(0-Tlast) of 221.6 ± 26.8 and 25.2 ± 3.9 ng × h/mL, respectively, compared with 9.7 ± 1.4 ng*h/mL for 0.02 mg/kg IV buprenorphine. By using a hypothesized therapeutic plasma buprenorphine concentration threshold of 0.1 ng/mL, therapeutic concentrations were achieved at the first study time point (5 to 30 min) and lasted an average of 8.0 ± 1.3 h for intravenous buprenorphine and 264.0 ± 32.2 h for SRB. TDB achieved therapeutic concentrations in 12 to 24 h after patch application, which lasted until the patch was removed at 72 h. The results of this study suggest that SRB and TDB are long-acting alternatives for pain management, and their use could decrease animal handling and stress, thereby simplifying pain management and improving welfare in laboratory swine. PMID:25650977

  6. Opioid partial agonist buprenorphine dampens responses to psychosocial stress in humans.

    PubMed

    Bershad, Anya K; Jaffe, Jerome H; Childs, Emma; de Wit, Harriet

    2015-02-01

    Pre-clinical and clinical evidence indicates that opioid drugs have stress-dampening effects. In animal models, opioid analgesics attenuate responses to isolation distress, and in humans, opioids reduce stress related to anticipation of physical pain. The stress-reducing effects of opioid drugs may contribute to their abuse potential. Despite this evidence in laboratory animals, the effects of opioids on responses to psychosocial stress have not been determined in humans. Here we examined the effects of buprenorphine, a μ-opioid partial agonist used to treat opioid dependence and pain, on subjective and physiological responses to a stressful public speaking task in healthy adults. We hypothesized that buprenorphine would reduce subjective and physiological stress responses. Healthy adult volunteers (N=48) were randomly assigned to receive placebo, 0.2mg sublingual buprenorphine, or 0.4mg sublingual buprenorphine in a two-session study with a stressful speaking task (Trier Social Stress Test; TSST) and a non-stressful control task. During the sessions, the participants reported on their mood states, provided subjective appraisals of the task, and measures of salivary cortisol, heart rate, and blood pressure at regular intervals. Stress produced its expected effects, increasing heart rate, blood pressure, salivary cortisol, and subjective ratings of anxiety and negative mood. In line with our hypothesis, both doses of buprenorphine significantly dampened salivary cortisol responses to stress. On self-report ratings, buprenorphine reduced how threatening participants found the tasks. These results suggest that enhanced opioid signaling dampens responses to social stress in humans, as it does in laboratory animals. This stress-dampening effect of buprenorphine may contribute to the non-medical use of opioid drugs. PMID:25544740

  7. Opioid partial agonist buprenorphine dampens responses to psychosocial stress in humans

    PubMed Central

    Bershad, Anya K.; Jaffe, Jerome H.; Childs, Emma; de Wit, Harriet

    2014-01-01

    Preclinical and clinical evidence indicates that opioid drugs have stress-dampening effects. In animal models, opioid analgesics attenuate responses to isolation distress, and in humans, opioids reduce stress related to anticipation of physical pain. The stress-reducing effects of opioid drugs may contribute to their abuse potential. Despite this evidence in laboratory animals, the effects of opioids on responses to psychosocial stress have not been determined in humans. Here we examined the effects of buprenorphine, a μ-opioid partial agonist used to treat opioid dependence and pain, on subjective and physiological responses to a stressful public speaking task in healthy adults. We hypothesized that buprenorphine would reduce subjective and physiological stress responses. Healthy adult volunteers (N = 48) were randomly assigned to receive placebo, 0.2mg sublingual buprenorphine, or 0.4mg sublingual buprenorphine in a two-session study with a stressful speaking task (Trier Social Stress Test; TSST) and a non-stressful control task. During the sessions, the participants reported on their mood states, provided subjective appraisals of the task, and measures of salivary cortisol, heart rate, and blood pressure at regular intervals. Stress produced its expected effects, increasing heart rate, blood pressure, salivary cortisol, and subjective ratings of anxiety and negative mood. In line with our hypothesis, both doses of buprenorphine significantly dampened salivary cortisol responses to stress. On self-report ratings, buprenorphine reduced how threatening participants found the tasks. These results suggest that enhanced opioid signaling dampens responses to social stress in humans, as it does in laboratory animals. This stress-dampening effect of buprenorphine may contribute to the non-medical use of opioid drugs. PMID:25544740

  8. Buprenorphine/Naloxone and Methadone Effects on Laboratory Indices of Liver Health: a Randomized Trial

    PubMed Central

    Saxon, Andrew J.; Ling, Walter; Hillhouse, Maureen; Thomas, Christie; Hasson, Albert; Ang, Alfonso; Doraimani, Geetha; Tasissa, Gudaye; Lokhnygina, Yuliya; Leimberger, Jeff; Bruce, R. Douglas; McCarthy, John; Wiest, Katharina; McLaughlin, Paul; Bilangi, Richard; Cohen, Allan; Woody, George; Jacobs, Petra

    2012-01-01

    BACKGROUND Buprenorphine/naloxone (BUP) and methadone (MET) are efficacious treatments for opioid dependence, although concerns about a link between BUP and drug-induced hepatitis have been raised. This study compares the effects of BUP and MET on liver health in opioid-dependent participants. METHODS This was a randomized controlled trial of 1269 opioid-dependent participants seeking treatment at 8 federally licensed opioid treatment programs and followed for up to 32 weeks between May 2006 and August 2010; 731 participants met “evaluable” criteria defined as completing 24 weeks of medication and providing at least 4 blood samples for transaminase testing. Participants were randomly assigned to receive BUP or MET for 24 weeks. Shift table analysis determined how many evaluable participants moved between categories of low and elevated transaminase levels. Predictors of moving from low to high transaminase levels were identified. RESULTS Changes in transaminase levels did not differ by medication condition. Baseline infection with hepatitis C or B was the only significant predictor of moving from low to elevated transaminase levels; 9 BUP and 15 MET participants showed extreme liver test elevations and were more likely than those without extreme elevations to have seroconverted to both hepatitis B and C during the study, or to use illicit drugs during the first 8 weeks of treatment. MET participants were retained longer in treatment than BUP participants. CONCLUSIONS This study demonstrated no evidence of liver damage during the initial 6 months of treatment in either condition. Physicians can prescribe either medication without major concern for liver injury. PMID:22921476

  9. The effectiveness of a long-acting transdermal fentanyl solution compared to buprenorphine for the control of postoperative pain in dogs in a randomized, multicentered clinical study.

    PubMed

    Linton, D D; Wilson, M G; Newbound, G C; Freise, K J; Clark, T P

    2012-08-01

    A prospective, double-blinded, positive-controlled, multicenter, noninferiority clinical study was conducted to evaluate the safety and effectiveness of a long-acting transdermal fentanyl solution (TFS) for the control of postoperative pain. Four hundred forty-five client-owned dogs of various breeds were randomly assigned to receive a single dose of TFS (2.6 mg/kg [?50 ?L/kg]) (N = 223) applied 2-4 h prior to surgery or buprenorphine (20 ?g/kg) (N = 222) administered intramuscularly 2-4 h prior to surgery and every 6 h through 90 h. There were 159 (35.7%) males and 286 (64.3%) females ranging from 0.5 to 16 years of age and 3 to 98.5 kg enrolled. Pain was scored using the modified Glasgow Composite Pain Scale with an a priori dropout criteria of ? 8 (20 maximum score). The one-sided upper 95% confidence interval of the mean difference between fentanyl and buprenorphine treatment failures was 5.6%, which was not greater than the a priori selected margin difference of 15%. Adverse events attributed to either treatment were minimal in impact and were approximately equal between groups. Sustained plasma fentanyl concentrations provided by a single pre-emptive dose of TFS are safe and effective and are noninferior to repeated injections of buprenorphine in controlling postoperative pain over 4?days. This long-acting fentanyl formulation provides veterinarians with a novel, registered option for the control of postoperative pain in dogs that improves dosing compliance and potentially mitigates the disadvantages of oral, parenteral, and patch delivered opioids. PMID:22731776

  10. The unique role of transdermal buprenorphine in the global chronic pain epidemic.

    PubMed

    Pergolizzi, Joseph V; Scholten, Willem; Smith, Kevin J; Leighton-Scott, James; Willis, Jenna C; Henningfield, Jack E

    2015-06-01

    Pain is a global epidemic, exacerbated by barriers to access of opioid analgesics. Regulations about opioids attempt to protect public health from the risks of harmful use of opioids, diversion, and dependence. Transdermal buprenorphine is an effective opioid analgesic agent with unique properties that may make it particularly well suited for more widespread use. It is a versatile analgesic product with demonstrated safety and effectiveness in cancer and noncancer pain populations. Its pharmacological properties make it a first-line opioid analgesic for geriatric patients and patients with renal dysfunction; no dosing adjustments need to be made. The 7-day transdermal delivery system is convenient for patients and promotes compliance. A low dose of buprenorphine can provide effective and well-tolerated pain relief. Although buprenorphine has been associated with certain opioid-related adverse effects, such as dizziness and nausea, it is associated with a lower rate of constipation than many other opioid analgesics. The potential for nonmedical use of buprenorphine is relatively low compared with other opioid agents. Buprenorphine has a relatively low likeability for nonmedical use and the transdermal matrix patch renders the substance particularly difficult to extract for illicit purposes. PMID:26205326

  11. Postoperative pain relief with epidural buprenorphine versus epidural butorphanol in laparoscopic hysterectomies: A comparative study

    PubMed Central

    Jose, Dona Elsa; Ganapathi, P.; Anish Sharma, N. G.; Shankaranarayana, P.; Aiyappa, D. S.; Nazim, Mohammed

    2016-01-01

    Background: The purpose of this study was to compare the safety and efficacy of postoperative analgesia with epidural buprenorphine and butorphanol tartrate. Methods: Sixty patients who were scheduled for elective laparoscopic hysterectomies were randomly enrolled in the study. At the end of the surgery, in study Group A 1 ml (0.3 mg) of buprenorphine and in Group B 1 ml (1 mg) of butorphanol tartrate both diluted to 10 ml with normal saline was injected through the epidural catheter. Visual analog pain scales (VAPSs) were assessed every hour till the 6th h, then 2nd hourly till the 12th h. To assess sedation, Ramsay sedation score was used. The total duration of postoperative analgesia was taken as the period from the time of giving epidural drug until the patients first complain of pain and the VAPS is more than 6. Patients were observed for any side effects such as respiratory depression, nausea, vomiting, hypotension, bradycardia, pruritus, and headache. Results: Buprenorphine had a longer duration of analgesia when compared to butorphanol tartrate (586.17 ± 73.64 vs. 342.53 ± 47.42 [P < 0.001]). Nausea, vomiting (13% vs. 10%), and headache (20% vs. 13%) were more in buprenorphine group; however, sedation score and pruritus (3% vs. 6%) were found to be more with butorphanol. Conclusion: Epidural buprenorphine significantly reduced pain and increased the quality of analgesia with a longer duration of action and was a better alternative to butorphanol for postoperative pain relief. PMID:26957696

  12. Pharmacokinetics of a single subcutaneous dose of sustained release buprenorphine in northern elephant seals (Mirounga angustirostris).

    PubMed

    Molter, Christine M; Barbosa, Lorraine; Johnson, Shawn; Knych, Heather K; Chinnadurai, Sathya K; Wack, Raymund F

    2015-03-01

    Information regarding analgesics in pinnipeds is limited. This study aimed to establish the pharmacokinetic parameters of a single subcutaneous dose of sustained release buprenorphine (Buprenorphine SR) in juvenile northern elephant seals (Mirounga angustirostris) with regard to its potential to provide long-lasting analgesia that requires infrequent dosing. Seals (n=26) were administered a single dose of sustained release buprenorphine at 0.12 mg/kg s.c. Blood samples were collected from the extradural intervertebral vein at 0 hr and at three or four of the following time points: 0.5, 1, 2, 6, 12, 24, 36, 48, 60, 96, 120, and 144 hr. Seals were examined daily for systemic and local adverse reactions. Plasma was analyzed by liquid chromatography tandem-mass spectrometry for buprenorphine and norbuprenorphine concentrations. A noncompartmental analysis for pharmacokinetic parameters was calculated using standard methods and equations. An average maximum concentration of 1.21 ng/ml (0.3-2.9 ng/ml) was detected 12 hr postadministration. Concentrations were quantifiable up to 144 hr postadministration but were below those expected to provide analgesia in some other species. No systemic adverse effects were noted in healthy seals receiving sustained release buprenorphine. Cellulitis or abscesses at the injection site were observed in 6/26 (23%) seals between 24 and 168 hr postadministration. Adverse local effects suggest that this drug should be used with caution in northern elephant seals. PMID:25831576

  13. UHPLC-MS/MS quantification of buprenorphine, norbuprenorphine, methadone, and glucuronide conjugates in umbilical cord plasma.

    PubMed

    Kyle, Amy Redmond; Carmical, Jennifer; Shah, Darshan; Pryor, Jason; Brown, Stacy

    2015-10-01

    Opioid use during pregnancy can result in the newborn being physically dependent on the substance, thus experiencing drug withdrawal, termed neonatal abstinence syndrome (NAS). Buprenorphine and methadone are two drugs used to treat opioid withdrawal and are approved for use in pregnancy. Quantification of these compounds in umbilical cord plasma would help assess in utero exposure of neonates in cases of buprenorphine or methadone use during pregnancy. An LC-MS/MS method using solid-phase extraction sample preparation was developed and validated for the simultaneous quantification of methadone, buprenorphine, norbuprenorphine, and glucuronide metabolites in umbilical cord plasma. The average accuracy (percentage error) and precision (relative standard deviation) were <15% for each validated concentration. Our data establishes a 2 week maximum freezer storage window in order to achieve the most accurate cord plasma concentrations of these analytes. Additionally, we found that the umbilical cord tissue analysis was less sensitive compared with analysis with umbilical cord blood plasma, indicating that this may be a more appropriate matrix for determination of buprenorphine and metabolite concentrations. This method was successfully applied to the analysis of cord blood from women with known buprenorphine or methadone use during pregnancy. PMID:25808363

  14. A Question About the Safety of Buprenorphine/Naloxone and Benzodiazepine Drugs.

    PubMed

    Howland, Robert H

    2015-12-01

    Drug overdose is the leading cause of injury death in the United States, and most deaths are related to prescription drugs. A substantial proportion of these deaths involve opioid or benzodiazepine drugs, and many overdoses include a combination of both drug classes. Buprenorphine/naloxone has an unusual pharmacology that distinguishes it from other opioid drugs. Animal and human studies have found that buprenorphine is associated with a ceiling to its cardio-respiratory depressant effect at higher doses, such that it may have a wider safety margin compared to other opioid drugs. Compared to buprenorphine alone, buprenorphine/naloxone is associated with less cardiorespiratory depression. Drug safety data from the National Poison Data System, Drug Abuse Warning Network, and other sources suggest that the safety of buprenorphine/naloxone is favorable compared to the morbidity and mortality associated with other opioid drugs and other classes of psychotropic drugs. [Journal of Psychosocial Nursing and Mental Health Services, 53(12), 11-14.]. PMID:26653090

  15. Analgesic Activity of Tramadol and Buprenorphine after Voluntary Ingestion by Rats (Rattus norvegicus).

    PubMed

    Taylor, Bryan F; Ramirez, Harvey E; Battles, August H; Andrutis, Karl A; Neubert, John K

    2016-01-01

    Effective pain management for rats and mice is crucial due to the continuing increase in the use of these species in biomedical research. Here we used a recently validated operant orofacial pain assay to determine dose-response curves for buprenorphine and tramadol when mixed in nut paste and administered to male and female rats. Statistically significant analgesic doses of tramadol in nut paste included doses of 20, 30, and 40 mg/kg for female rats but only 40 mg/kg for male rats. For male rats receiving buprenorphine mixed in nut paste, a significant analgesic response was observed at 0.5 and 0.6 mg/kg. None of the doses tested produced a significant analgesic response in female rats. Our results indicate that at the doses tested, tramadol and buprenorphine produced an analgesic response in male rats. In female rats, tramadol shows a higher analgesic effect than buprenorphine. The analgesic effects observed 60 min after administration of the statistically significant oral doses of both drugs were similar to the analgesic effects of 0.03 mg/kg subcutaneous buprenorphine 30 min after administration. The method of voluntary ingestion could be effective, is easy to use, and would minimize stress to the rats during the immediate postoperative period. PMID:26817983

  16. Clinical Efficacy of Sustained-Release Buprenorphine with Meloxicam for Postoperative Analgesia in Beagle Dogs Undergoing Ovariohysterectomy

    PubMed Central

    Nunamaker, Elizabeth A; Stolarik, DeAnne F; Ma, Junli; Wilsey, Amanda S; Jenkins, Gary J; Medina, Chris L

    2014-01-01

    The goal of the current study was to compare the efficacy, adverse effects, and plasma buprenorphine concentrations of sustained-release buprenorphine (SRB) and buprenorphine after subcutaneous administration in dogs undergoing ovariohysterectomy. In a prospective, randomized, blinded design, 20 healthy adult female Beagle dogs underwent routine ovariohysterectomy and received multimodal analgesia consisting of meloxicam and one of two buprenorphine formulations. Dogs were randomly assigned to receive either SRB (0.2 mg/kg SC, once) or buprenorphine (0.02 mg/kg SC every 12 h for 3 d). Blinded observers assessed all dogs by using sedation scores, pain scores, temperature, HR, RR, and general wellbeing. Dogs were provided rescue analgesia with 0.02 mg/kg buprenorphine SC if the postoperative pain score exceeded a predetermined threshold. Blood samples were collected, and mass spectrometry was used to determine plasma buprenorphine concentrations. Data were analyzed with a linear mixed model and Tukey–Kramer multiple comparison. Age, body weight, anesthetic duration, surgical duration, sevoflurane concentration, and cardiorespiratory variables did not differ significantly between groups. Dogs in both formulation groups had comparable postoperative sedation and pain scores. One dog from each formulation group had breakthrough pain requiring rescue analgesia. Plasma buprenorphine concentrations remained above a hypothesized therapeutic concentration of 0.6 ng/mL for 136.0 ± 11.3 and 10.67 ± 0.84 h for SRB and buprenorphine, respectively. Based on the results of this study, multimodal analgesic regimens consisting of meloxicam and either buprenorphine or SRB are equally efficacious in managing pain associated with an ovariohysterectomy and show comparable side effects. PMID:25255072

  17. Increasing Potential Access to Opioid Agonist Treatment in U.S. Treatment Shortage Areas

    PubMed Central

    Dick, Andrew W.; Pacula, Rosalie Liccardo; Gordon, Adam J.; Sorbero, Mark; Burns, Rachel M.; Leslie, Douglas L.; Stein, Bradley D.

    2015-01-01

    Opioid use disorders are a significant public health problem, affecting over 2 million individuals in the US. Although opioid agonist treatment, predominantly offered in licensed methadone clinics, is both effective and cost-effective, many individuals do not receive it. Buprenorphine, approved in 2002 for prescription by waivered physicians, could improve opioid agonist treatment access for individuals unable or unwilling to receive methadone. We examine the extent to which the geographic distribution of waivered physicians has enhanced potential opioid agonist treatment access, particularly in non-metropolitan areas with fewer methadone clinics. We found that while the approximately 90% of counties classified as methadone clinic shortage areas remained constant, buprenorphine shortage areas fell from 99% of counties in 2002 to 51% in 2011, lowering the US population percentage residing in opioid treatment shortage counties to approximately 10%. The increase in buprenorphine-waivered physicians has dramatically increased potential access to opioid agonist treatment, especially in non-metropolitan counties. PMID:26056209

  18. Voluntary ingestion of nut paste for administration of buprenorphine in rats and mice.

    PubMed

    Abelson, Klas S P; Jacobsen, Kirsten R; Sundbom, Renée; Kalliokoski, Otto; Hau, Jann

    2012-10-01

    An adequate analgesic strategy is important to improve the postoperative recovery and welfare of laboratory rats and mice. It is desirable that the method for administering the drug is non-invasive and stress-free. We have previously validated a method for administering buprenorphine in a nut paste for voluntary ingestion. This method has many advantages over parenteral administration. To use the method in a successful way, however, it is important to prepare and administer the mix correctly. The present paper describes in detail how to implement the method, by means of habituation, presentation, adequate concentrations and amounts of buprenorphine/nut paste, and dosage of buprenorphine to rats and mice. PMID:22969145

  19. Extended release naltrexone injection is performed in the majority of opioid dependent patients receiving outpatient induction: a very low dose naltrexone and buprenorphine open label trial

    PubMed Central

    Mannelli, Paolo; Wu, Li-Tzy; Peindl, Kathleen S.; Swartz, Marvin S.; Woody, George E.

    2014-01-01

    BACKGROUND The approval of extended release injectable naltrexone (XR-NTX; Vivitrol®) has introduced a new option for treating opioid addiction, but studies are needed to identify its place within the spectrum of available therapies. The absence of physiological opioid dependence is a necessary and challenging first step for starting XR-NTX. Outpatient detoxification gives poor results and inpatient detoxification is either unavailable or too brief for the physiological effects of opioids to resolve. Here we present findings from an open label study that tested whether the transition from opioid addiction to XR-NTX can be safely and effectively performed in an outpatient setting using very low dose naltrexone and buprenorphine. METHODS Twenty treatment seeking opioid addicted individuals were given increasing doses of naltrexone starting at 0.25 mg with decreasing doses of buprenorphine starting at 4 mg during a 7-day outpatient XR-NTX induction procedure. Withdrawal discomfort, craving, drug use, and adverse events were assessed daily until the XR-NTX injection, then weekly over the next month. RESULTS Fourteen of the 20 participants received XR-NTX and 13 completed weekly assessments. Withdrawal, craving, and opioid or other drug use were significantly lower during induction and after XR-NTX administration compared with baseline, and no serious adverse events were recorded. CONCLUSIONS Outpatient transition to XR-NTX combining upward titration of very low dose naltrexone with downward titration of low dose buprenorphine was safe, well tolerated, and completed by most participants. Further studies with larger numbers of subjects are needed to see if this approach is useful for naltrexone induction. PMID:24602363

  20. Co-relationship between sexual dysfunction and high-risk sexual behavior in patients receiving buprenorphine and naltrexone maintenance therapy for opioid dependence

    PubMed Central

    Ramdurg, Santosh; Ambekar, Atul; Lal, Rakesh

    2015-01-01

    Introduction: People suffering from substance dependence suffer from various sexual dysfunctions and are at risk for indulging in various high-risk sexual behaviors and thus are vulnerable to acquire various infections such as HIV/AIDS and other sexually transmitted infections. AIM: The aim of the study was to evaluate the correlation between sexual dysfunction and high-risk sexual behavior in opioid-dependent men receiving buprenorphine and naltrexone maintenance therapy. Materials and Methods: Semi-structured questionnaire, brief male sexual functioning inventory and HIV-risk taking behavior scale was administered to a sample of 60 sexually active men, receiving buprenorphine (n = 30) and naltrexone (n = 30) maintenance therapy for opioid dependence. Results: The main outcomes are correlation between severity of sexual dysfunction and HIV-risk taking behavior. The study results showed 83% of the men on buprenorphine and 90% on naltrexone reported at least one of the sexual dysfunction symptoms. There was a negative correlation between sexual dysfunction and HIV-risk taking behavior that suggest severe the dysfunction, higher the risk taking behavior. Significant correlation was present with overall sexual dysfunction and HIV-risk taking behavior (P = 0.028 and in naltrexone receiving group premature ejaculation versus HIV-risk taking behavior however, (P = 0.022, P < 0.05) there were no significant differences among both the groups except above findings. Conclusion: Conclusion was treatment is associated with sexual dysfunctions and HIV-risk taking behavior, which has clinical implication. Future research should explore this further using biochemical analyses. PMID:26257480

  1. Skin substitutes: An Indian perspective

    PubMed Central

    Singh, A. K.; Shenoy, Y. R.

    2012-01-01

    There have been numerous alternatives developed to replace skin. These can either be permanent substitutes or temporary substitutes, which need to be replaced later by autologous grafts. These have been tried in recent times as an attempt to reduce the need or in the case of permanent substitutes ,altogether replace autologous skin grafts. However till date no ideal skin substitute has been developed. Various factors have to be considered while choosing one of these substitutes. In a developing country like India awareness and availability of these skin substitutes is not adequate considering the volume of cases that require this modality of treatment. Also there are skin substitutes developed in our country that need to be highlighted. This article is an attempt to review the vast array of skin substitutes that have been developed and consider their utility and feasibility for developing countries. PMID:23162239

  2. Sublingual Buprenorphine/Naloxone for Chronic Pain in At-Risk Patients: Development and Pilot Test of a Clinical Protocol

    PubMed Central

    Rosenblum, Andrew; Cruciani, Ricardo A.; Strain, Eric C; Cleland, Charles M.; Joseph, Herman; Magura, Stephen; Marsch, Lisa A; McNicholas, Laura F; Savage, Seddon R; Sundaram, Arun; Portenoy, Russell K.

    2013-01-01

    Objective Sublingual buprenorphine/naloxone (Bup/Nx) is approved for addiction treatment and may be useful for pain management, particularly in opioid-treated pain patients with nonadherence behaviors. The transition of opioid-treated pain patients to buprenorphine carries the risk of precipitated withdrawal and increased pain. This study convened pain and addiction specialists to develop and pilot a clinical protocol for safe transitioning to Bup/Nx. Design The protocol was revised three times based on outside expert review and pilot study observations. The pilot was conducted with a prospective cohort of 12 patients with moderate to severe chronic pain, who were receiving long-term opioid therapy with any full ?-agonist drug, and had exhibited one or more aberrant drug-related behaviors. Patients were followed up for 3 to 6 months with the expectation that they would experience few adverse events and report lower pain severity. Results The three patients on the highest baseline opioid dose (equivalent to 303–450 mg of oral morphine) and the three on the lowest doses (?20 mg) had early adverse events (AEs) when switched to Bup/Nx and did not complete the trial. Of the remaining six, one withdrew due to AEs; one responded well, then withdrew; and four completed a three-month trial. A mixed effects model controlling for dropouts found that average and worst pain significantly decreased after the switch to Bup/Nx (both p < .01). Conclusion Based on this experience, the protocol recommends Bup/Nx for pain only when baseline opioid doses are within bounds that reduce AEs at transition and incorporates dose flexibility to further reduce risks. This protocol warrants further testing. PMID:23264315

  3. Pharmacokinetics of Sustained-Release and Transdermal Buprenorphine in Göttingen Minipigs (Sus scrofa domestica)

    PubMed Central

    Thiede, Allison J; Garcia, Kelly D; Stolarik, DeAnne F; Ma, Junli; Jenkins, Gary J; Nunamaker, Elizabeth A

    2014-01-01

    The opioid buprenorphine has been shown to provide adequate postoperative analgesia in both companion and laboratory animals. However, its use is still hindered by the need for multiple parenteral injections to achieve continuous analgesia. The purpose of the current study was to conduct a pharmacokinetic analysis of 2 new long-acting formulations of buprenorphine—an injectable sustained-release buprenorphine (SRB) and a transdermal buprenorphine (TDB) patch—in healthy Göttingen minipigs by using liquid chromatography–electrospray ionization–tandem mass spectrometry. Administration of 0.18 mg/kg SC SRB and 30 μg/h TDB achieved AUC0-Tlast of 221.6 ± 26.8 and 25.2 ± 3.9 ng × h/mL, respectively, compared with 9.7 ± 1.4 ng*h/mL for 0.02 mg/kg IV buprenorphine. By using a hypothesized therapeutic plasma buprenorphine concentration threshold of 0.1 ng/mL, therapeutic concentrations were achieved at the first study time point (5 to 30 min) and lasted an average of 8.0 ± 1.3 h for intravenous buprenorphine and 264.0 ± 32.2 h for SRB. TDB achieved therapeutic concentrations in 12 to 24 h after patch application, which lasted until the patch was removed at 72 h. The results of this study suggest that SRB and TDB are long-acting alternatives for pain management, and their use could decrease animal handling and stress, thereby simplifying pain management and improving welfare in laboratory swine. PMID:25650977

  4. Post-operative Analgesia in Opioid Dependent Patients: Comparison of Intravenous Morphine and Sublingual Buprenorphine

    PubMed Central

    Alizadeh, Shaabanali; Mahmoudi, Ghafar Ali; Solhi, Hassan; Sadeghi-Sedeh, Bahman; Behzadi, Reza; Kazemifar, Amir Mohammad

    2015-01-01

    Background Acute and chronic pain is prevalent in patients with opioid dependence. Lack of knowledge concerning the complex relationship between pain, opioid use, and withdrawal syndrome can account for the barriers encountered for pain management. This study was designed to evaluate the efficacy of sublingual (SL) buprenorphine for post-operative analgesia, compared with intravenous (IV) morphine. Methods A total of 68 patients, aged 20-60 years were randomly selected from whom had been underwent laparotomy due to acute abdomen in a University Teaching Hospital in Arak, Iran, and were also opioid (opium or heroin) abuser according to their history. After end of the surgery and patients’ arousal, the patients were evaluated for abdominal pain and withdrawal syndrome by visual analog scale (VAS) and clinical opioid withdrawal score (COWS), respectively 1, 6, and 24 h after the surgery. They received either morphine 5 mg IV or buprenorphine 2 mg SL, 1 h after end of the surgery, and then every 6 h for 24 h. Findings VAS was 4.47 ± 0.73 and 2.67 ± 0.53 at h 6 and 24 in buprenorphine group, respectively. The corresponding score was 5.88 ± 0.69 and 4.59 ± 0.74 in morphine group. At the same time, patients in buprenorphine experienced less severe withdrawal syndrome. Conclusion The present study confirmed the efficacy of SL buprenorphine as a non-invasive, but effective method for management of post-operative pain in opioid dependent patients. Result of this study showed that physicians can rely on SL buprenorphine for post-operative analgesia. PMID:26322212

  5. HIV Risk Reduction With Buprenorphine-Naloxone or Methadone: Findings From A Randomized Trial

    PubMed Central

    Woody, George; Bruce, Douglas; Korthuis, P. Todd; Chhatre, Sumedha; Hillhouse, Maureen; Jacobs, Petra; Sorensen, James; Saxon, Andrew J.; Metzger, David; Ling, Walter

    2014-01-01

    Objectives Compare HIV injecting and sex risk in patients being treated with methadone (MET) or buprenorphine-naloxone (BUP). Methods Secondary analysis from a study of liver enzyme changes in patients randomized to MET or BUP who completed 24-weeks of treatment and had 4 or more blood draws. The initial 1:1 randomization was changed to 2:1 (BUP: MET) after 18 months due to higher dropout in BUP. The Risk Behavior Survey (RBS) measured past 30-day HIV risk at baseline and weeks 12 and 24. Results Among 529 patients randomized to MET, 391 (74%) were completers; among 740 randomized to BUP, 340 (46%) were completers; 700 completed the RBS. There were significant reductions in injecting risk (p< 0.0008) with no differences between groups in mean number of times reported injecting heroin, speedball, other opiates, and number of injections; or percent who shared needles, did not clean shared needles with bleach, shared cookers, or engaged in front/back loading of syringes. The percent having multiple sex partners decreased equally in both groups (p<0.03). For males on BUP the sex risk composite increased; for males on MET, the sex risk decreased resulting in significant group differences over time (p<0.03). For females, there was a significant reduction in sex risk (p<0.02) with no group differences. Conclusions Among MET and BUP patients that remained in treatment, HIV injecting risk was equally and markedly reduced, however MET retained more patients. Sex risk was equally and significantly reduced among females in both treatment conditions, but increased for males on BUP, and decreased for males on MET. PMID:24751432

  6. Skin Substitutes

    PubMed Central

    Howe, Nicole; Cohen, George

    2014-01-01

    In a relatively short timespan, a wealth of new skin substitutes made of synthetic and biologically derived materials have arisen for the purpose of wound healing of various etiologies. This review article focuses on providing an overview of skin substitutes including their indications, contraindications, benefits, and limitations. The result of this overview was an appreciation of the vast array of options available for clinicians, many of which did not exist a short time ago. Yet, despite the rapid expansion this field has undergone, no ideal skin substitute is currently available. More research in the field of skin substitutes and wound healing is required not only for the development of new products made of increasingly complex biomolecular material, but also to compare the existing skin substitutes. PMID:25371771

  7. Illicit use of methadone and buprenorphine among adolescents and young adults in Sweden

    PubMed Central

    2013-01-01

    Background Illicit use of methadone and buprenorphine has been described as a growing problem in Sweden in recent years, and has been associated with an increased drug-related mortality. Critics claim that the substances have become popular among adolescents and that they function as a gateway to heroin use. The aim of this study is to investigate, firstly, the extent to which illicit use of methadone and buprenorphine occurs among adolescents and young adults in Sweden, and secondly, at what stage in a user’s drug career these substances tend to appear. Methods The study is based on surveys and structured interviews on drug use among various populations of young people, in addition to qualitative interviews with 86 informants who, in their professional capacity, encounter adolescents or young adults who are using illicit drugs. Results Illicit use of methadone and buprenorphine is rare among young people in Sweden. According to high school surveys, less than 0.1% have tried these substances. Among young drug users in general, few have tried the substances, and there is nothing to indicate that they act as gateway drugs. Among adolescents and young adults with severe drug problems, however, the illicit use of methadone and buprenorphine is more common (54% in a compulsory care sample). These substances normally enter the drug career late, and few use them as their main drug of choice. Other prescription drugs, like benzodiazepines and tramadol, are used by adolescents to a far greater extent. Diversion and illicit use of methadone and buprenorphine is not seen as a serious problem by the professionals interviewed. A general view is that the substances are mainly used by people with a heroin or polydrug addiction, often for “self-medication” purposes. However, several informants express concern that methadone and buprenorphine may cause fatalities among young drug users without an opioid tolerance. Conclusions Illicit use of methadone and buprenorphine among young drug users is not a widespread problem in Sweden. Harm-reduction measures should target drug users with more severe problems, among whom illicit use of methadone and buprenorphine is more common and pose a medical risk. Illicit use of other prescription drugs, which are less controlled and more widely used by young people, is an important issue for further research. PMID:24139199

  8. A dose-effect study of repeated administration of buprenorphine/naloxone on performance in opioid-dependent volunteers.

    PubMed

    Mintzer, Miriam Z; Correia, Christopher J; Strain, Eric C

    2004-05-10

    Based on its unique pharmacological profile, buprenorphine may produce less impairment in psychomotor and cognitive performance than methadone. However, the few studies that have investigated the performance effects of buprenorphine in opioid-abusing volunteers examined effects of single acute doses rather than effects of repeated dosing and included a very limited range of measures. The present inpatient study evaluated dose-related effects of repeated administration of the buprenorphine/naloxone combination product (8/2, 16/4, 32/8 mg, sublingual tablets) in eight opioid-dependent volunteers on performance of a broad range of tasks, following a period of 7-10 days of dosing at each level, in a double-blind, within-subject, crossover design. The testing battery included measures of psychomotor speed, time perception, conceptual flexibility, focused attention, working memory, long-term/episodic memory, and metamemory. Supporting the hypothesis of limited impairment with buprenorphine, results revealed minimal impairment in performance as buprenorphine/naloxone dose was increased four-fold. The only significant effect of dose was an impairment in episodic/long-term memory (recognition memory) performance at the highest dose (32/8 mg) relative to the two lower doses. Future studies incorporating larger sample sizes and non-drug controls, as well as directly comparing buprenorphine to methadone and LAAM are needed to further test the hypothesis of limited impairment with buprenorphine. PMID:15099664

  9. Antinociceptive efficacy and plasma concentrations of transdermal buprenorphine in dogs.

    PubMed

    Pieper, Korbinian; Schuster, Tibor; Levionnois, Olivier; Matis, Ulrike; Bergadano, Alessandra

    2011-03-01

    To assess the antinociceptive efficacy of transdermal (TD) buprenorphine (B) in dogs, a prospective, positive-controlled experimental study was performed in 10 healthy Beagles. In an open label crossover design, the dogs initially received intravenous B (IVB, 0.02 mg kg(-1)) as a positive control, followed by TDB (52.5 ?g h(-1)) 4 months later. Blood was collected at regular intervals for determination of the plasma concentrations of B ([B]) and its metabolite norbuprenorphine. The antinociceptive efficacy was assessed using thermal and mechanical models of nociception. The peak concentration [B] was 1.54 ng mL(-1) (±1.98) 60 h after TDB application, although three dogs had no measurable [B] after TDB. Maximum thermal threshold (TT) was 52.6 °C (±0.48) at 1h after IVB administration and 51.63 °C (±1.01) 72 h after TDB application. The significant increase in TT indicated that effective antinociception was achieved beyond 36 h after the application of TDB, lasting until patch removal. There was hysteresis between [B] and the antinociceptive effect. PMID:20206560

  10. Subcutaneous Implants of Buprenorphine-Cholesterol-Triglyceride Powder in Mice

    PubMed Central

    DeTolla, L.; Sanchez, R.; Khan, E.; Tyler, B.; Guarnieri, M.

    2014-01-01

    Subcutaneous drug implants are convenient systems for the long-term delivery of drugs in animals. Lipid carriers are logical tools because they generally allow for higher doses and low toxicity. The present study used an US Food and Drug Administration Target Animal Safety test system to evaluate the safety of a subcutaneous implant of a cholesterol-triglyceride-buprenorphine powder in 120 BALB/c mice. Mice were evaluated in 4- and 12-day trials with 1- and 5-fold doses of the intended 3?mg/kg dose of drug. One male mouse treated with three 3?mg/kg doses and surgery on days 0, 4, and 8 died on day 9. The cause of death was not determined. In the surviving 119 mice there was no evidence of skin reaction at the site of the implant. Compared to control animals treated with saline, weight measurements, clinical pathology, histopathology, and clinical observations were unremarkable. These results demonstrate that the lipid carrier is substantially safe. Cholesterol-triglyceride-drug powders may provide a valuable research tool for studies of analgesic and inflammatory drug implants in veterinary medicine. PMID:26464927

  11. Antidepressant-like Effects of Buprenorphine in Rats Are Strain Dependent

    PubMed Central

    Browne, Caroline A.; van Nest, Duncan; Lucki, Irwin

    2014-01-01

    The prevalence of major depressive disorder and the limited efficacy of conventional drug treatments provide significant impetus to develop novel and more rapidly acting antidepressants for individuals with treatment resistant forms of depression. The primary goal of these studies was to ascertain whether buprenorphine (BPN), a medically available drug with mixed effects at opioid receptors, was effective in behavioral tests using the Wistar Kyoto (WKY) rat strain, a rodent model of exaggerated depressive and anxiety behaviors that demonstrates resistance to certain antidepressants. As WKY rats are maintained by different sources, we assessed the behavioral effects of BPN using the modified rat forced swim test (FST) and the emergence test in WKY rat colonies obtained from different vendors. BPN dose-dependently reduced immobility and increased swimming behavior in the FST and reduced emergence latencies in two WKY lines (Charles River (WKY/NCrl) and Harlan laboratories (WKY/NHsd)) that also showed high baseline immobility in the FST. WKY rats from Taconic (WKY/NTac) did not show high baseline immobility in the FST or anxiety as had been previously reported, suggesting drift in the phenotype of rats from this supplier. Furthermore, BPN did not reduce immobility in the FST or reduce latencies in the emergence test in WKY rats from Taconic. BPN also failed to produce antidepressant-like effects in Wistar and Sprague-Dawley rats. These results indicate a striking strain-selectivity for the effects of BPN, producing antidepressant and anxiolytic-like responses in WKY/NCrl and WKY/NHsd lines but not in the normosensitive control Wistar and Sprague-Dawley strains. PMID:25453747

  12. Blood substitutes.

    PubMed Central

    Kostrzewska, E.

    1976-01-01

    With the development of modern methods of surgery, anaesthesia, and pre- and postoperative care the requirement for blood substitutes is continuously increasing. We present a review of the different blood substitutes which are already in clinical use or in an advanced stage of experimental investigation for possible practical administration. Our own clinical experience with dextrans and experimental studies on stroma-free haemoglobin and hydroxyethyl starch solutions are described. PMID:57736

  13. Pharmacodynamic modelling of placebo and buprenorphine effects on event-related potentials in experimental pain.

    PubMed

    Juul, Rasmus V; Foster, David J R; Upton, Richard N; Andresen, Trine; Graversen, Carina; Drewes, Asbjørn M; Christrup, Lona L; Kreilgaard, Mads

    2014-10-01

    The purpose of the study was to investigate placebo and buprenorphine effects on event-related potentials (ERPs) in experimental pain and the potential benefit of population pharmacodynamic modelling in data analysis. Nineteen healthy volunteers received transdermal placebo and buprenorphine in a cross-over study. Drug plasma concentrations and ERPs after electrical stimulation at the median nerve with intensity adjusted to pain detection threshold were recorded until 144 hrs after administration. Placebo and concentration-effect models were fitted to data using non-linear mixed-effects modelling implemented in NONMEM (V7.2.0.). Pharmacodynamic models were developed to adequately describe both placebo and buprenorphine ERP data. Models predicted significant placebo effects, but did not predict significant effects related to buprenorphine concentration. Models revealed that ERPs varied both between subjects and between study occasions. ERPs were found to be reproducible within subjects and occasions as population variance was found to be eight times higher than the unexplained variances. Between-subject variance accounted for more than 75% of the population variance. In conclusion, pharmacodynamic modelling was successfully implemented to allow for placebo and variability correction in ERP of experimental pain. Improved outcome of ERP studies can be expected if variation between subjects and study occasions can be identified and described. PMID:25163749

  14. Pharmaceutical and pharmacokinetic characterization of a novel sublingual buprenorphine/naloxone tablet formulation in healthy volunteers

    PubMed Central

    Fischer, Andreas; Hjelmström, Peter

    2015-01-01

    Abstract Context Bitter taste, as well as dissolve time, presents a significant challenge for the acceptability of formulations for oral transmucosal drug delivery. Objective To characterize a novel sublingual tablet formulation of buprenorphine/naloxone with regards to pharmacokinetics, dissolve time and formulation acceptability. Methods Dry mixing techniques were employed to produce a small and fast dissolving buprenorphine/naloxone sublingual tablet formulation, OX219 (Zubsolv®), using sucralose and menthol as sweetener and flavor to mask the bitter taste of the active ingredients. Two cross-over studies were performed in healthy volunteers to evaluate pharmacokinetics, dissolve time and acceptability of OX219 5.7/1.4?mg tablets compared to the commercially available buprenorphine/naloxone formulations Suboxone® tablets and films (8/2?mg). Results Buprenorphine exposure was equivalent in OX219 and Suboxone tablets. Sublingual dissolve times were significantly shorter for OX219 than for Suboxone tablets and were similar to Suboxone films. The OX219 formulation received significantly higher subjective ratings for taste and overall acceptability than both Suboxone formulations. OX219 was preferred over Suboxone tablet and film formulations by 77.4% and 88.9% of subjects, respectively. Conclusions A sublingual tablet formulation with an improved acceptability has been successfully developed. PMID:24099551

  15. The safety of high-dose buprenorphine administered subcutaneously in cats.

    PubMed

    Sramek, M K; Haas, M C; Coleman, G D; Atterson, P R; Hamlin, R L

    2015-10-01

    The safety of a proprietary formulation of buprenorphine hydrochloride administered subcutaneously (SC) to young cats was investigated in a blinded, randomized study. Four cohorts of eight cats aged approximately 4 months were administered saline, 0.24, 0.72 or 1.20 mg/kg/day buprenorphine SC for nine consecutive days, representing 0×, 1×, 3× and 5× of the intended dose. Cats were monitored daily for evidence of clinical reactions, food and water intake and adverse events (AEs). Physical examinations, clinical pathology, vital signs and electrocardiograms (ECGs) were evaluated at protocol-specified time points. Complete necropsy and histopathologic examinations were performed following humane euthanasia. Four buprenorphine-treated cats experienced AEs during the study, two unrelated and two related to study drug administration. The two cats with AEs considered related to drug administration had clinical signs of hyperactivity, difficulty in handling, disorientation, agitation and dilated pupils in one 0.24 mg/kg/day cat and one 0.72 mg/kg/day cat. All of these clinical signs were observed simultaneously. There were no drug-related effects on survival, injection response, injection site inspections, body weight, food or water consumption, bleeding time, urinalysis, respiration rate, heart rate, ECGs, blood pressures, body temperatures, macroscopic examinations or organ weights. Once daily buprenorphine s.c. injections at doses of 0.24, 0.72 and 1.20 mg/kg/day for 9 consecutive days were well tolerated in young domestic cats. PMID:25623082

  16. Pharmacokinetics of buprenorphine following intravenous and intramuscular administration in male rhesus macaques (Macaca mulatta)

    PubMed Central

    Kelly, Kristi R.; Pypendop, Bruno H.; Christe, Kari L.

    2014-01-01

    This study reports the pharmacokinetics of buprenorphine in conscious rhesus macaques (Macaca mulatta) after intravenous (IV) and intramuscular (IM) administration. Four healthy, opioid-naïve, socially-housed, adult male macaques were used. Buprenorphine (0.03 mg/kg) was administered intravenously as a bolus or intramuscularly on separate occasions. Blood samples were collected prior to, and up to 24 h, post-administration. Serum buprenorphine concentrations were analyzed with liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic analysis was performed with commercially available software. Mean residence time in the IV study as compared to the IM study was 177 (159–189) minutes vs. 185 (174–214) minutes, respectively [median (range)]. In the IV study, concentration back extrapolated to time zero was found to be 33.0 (16.8–57.0) ng/mL [median (range)]. On the other hand, the maximum serum concentration found in the IM study was 11.8 (6.30–14.8) ng/mL [median (range)]. Rhesus macaques maintained concentrations greater than 0.10 ng/mL for over 24 h in the IV study and over 12 h in the IM study. Bioavailability was found to be 68.1 (59.3–71.2)% [median (range)]. No significant adverse effects were observed in the monkeys at the 0.03 mg/kg dose of buprenorphine during either study. PMID:24666428

  17. Parallel buprenorphine phMRI responses in conscious rodents and healthy human subjects.

    PubMed

    Becerra, Lino; Upadhyay, Jaymin; Chang, Pei-Ching; Bishop, James; Anderson, Julie; Baumgartner, Richard; Schwarz, Adam J; Coimbra, Alexandre; Wallin, Diana; Nutile, Lauren; George, Edward; Maier, Gary; Sunkaraneni, Soujanya; Iyengar, Smriti; Evelhoch, Jeffrey L; Bleakman, David; Hargreaves, Richard; Borsook, David

    2013-04-01

    Pharmacological magnetic resonance imaging (phMRI) is one method by which a drug's pharmacodynamic effects in the brain can be assessed. Although phMRI has been frequently used in preclinical and clinical settings, the extent to which a phMRI signature for a compound translates between rodents and humans has not been systematically examined. In the current investigation, we aimed to build on recent clinical work in which the functional response to 0.1 and 0.2 mg/70 kg i.v. buprenorphine (partial µ-opioid receptor agonist) was measured in healthy humans. Here, we measured the phMRI response to 0.04 and 0.1 mg/kg i.v. buprenorphine in conscious, naive rats to establish the parallelism of the phMRI signature of buprenorphine across species. PhMRI of 0.04 and 0.1 mg/kg i.v. buprenorphine yielded dose-dependent activation in a brain network composed of the somatosensory cortex, cingulate, insula, striatum, thalamus, periaqueductal gray, and cerebellum. Similar dose-dependent phMRI activation was observed in the human phMRI studies. These observations indicate an overall preservation of pharmacodynamic responses to buprenorphine between conscious, naive rodents and healthy human subjects, particularly in brain regions implicated in pain and analgesia. This investigation further demonstrates the usefulness of phMRI as a translational tool in neuroscience research that can provide mechanistic insight and guide dose selection in drug development. PMID:23370795

  18. Comparison between Transdermal Buprenorphine and Transdermal Fentanyl for Postoperative Pain Relief after Major Abdominal Surgeries

    PubMed Central

    Arshad, Zia; Gautam, Shefali; Kumar, Sanjeev

    2015-01-01

    Introduction Opioid is generally regarded as an important part of multimodal, perioperative analgesia, especially for moderate to severe pain. Amongst the various modes of delivery transdermal route has several potential benefits over oral and parentral administration. These include noninvasive dosing, better absorption and lack of first-pass metabolism. A transdermal drug delivery system provides steady and continuous drug delivery resulting in steady plasma concentration. Bolus dosing of systemic analgesic results in supra and sub therapeutic plasma resulting in toxic and sub analgesic plasma drug concentration. It also improves patient compliance. Materials and Methods Sixty patients undergoing major abdominal surgery under GA were randomly divided in two groups (n=30). Group A received buprenorphine 10 mcg/h TDS and group B received 25 mcg/h fentanyl TDS, 6 hours prior to surgery. Patients were followed for three days for postoperative pain relief and adverse effects. Results Baseline and demographic variables are comparable in both groups. The mean level of VAS was significantly lower in group B as compared to group A at Day 1, 2 and 3. The mean level of sedation score was significantly lower in Group B than Group A. Haemodynamic variables in both groups (SBP, DBP and HR), shows comparable values in both groups and no significant difference was observed. Five out of 30 (16.7%) patients in group A required single dose of rescue analgesic while 0 out of 30 patients (0.00%) in group B required rescue analgesic. This difference in rescue analgesic requirement in not quiet statistically significant (p-value 0.0522). Twenty percent patient in fentanyl group and 16.7% patients in buprenorphine group experienced some adverse effects. Nausea and vomiting were main side effects of the drugs. The incidence of nausea and vomiting were 6.7% and 10% in buprenorphine and fentanyl group respectively. Conclusion Fentanyl and buprenorphine TDS were effective and safe in controlling postoperative pain. Fentanyl is better than buprenorphine in this respect. PMID:26816973

  19. Fairness heuristics and substitutability effects: inferring the fairness of outcomes, procedures, and interpersonal treatment when employees lack clear information.

    PubMed

    Qin, Xin; Ren, Run; Zhang, Zhi-Xue; Johnson, Russell E

    2015-05-01

    Employees routinely make judgments of 3 kinds of justice (i.e., distributive, procedural, and interactional), yet they may lack clear information to do so. This research examines how justice judgments are formed when clear information about certain types of justice is unavailable or ambiguous. Drawing from fairness heuristic theory, as well as more general theories of cognitive heuristics, we predict that when information for 1 type of justice is unclear (i.e., low in justice clarity), people infer its fairness based on other types of justice with clear information (i.e., high in justice clarity). Results across 3 studies employing different designs (correlational vs. experimental), samples (employees vs. students), and measures (proxy vs. direct) provided support for the proposed substitutability effects, especially when inferences were based on clear interactional justice information. Moreover, we found that substitutability effects were more likely to occur when employees had high (vs. low) need for cognitive closure. We conclude by discussing the theoretical contributions and practical implications of our findings. PMID:25365727

  20. Effect of tramadol use on three point-of-care and one instrument-based immunoassays for urine buprenorphine.

    PubMed

    Shaikh, Salima; Hull, Mindy J; Bishop, Kenneth A; Griggs, David A; Long, William H; Nixon, Andrea L; Flood, James G

    2008-06-01

    We report that use of the popular analgesic tramadol can cause false-positive urine buprenorphine results. We examined the extent of tramadol cross-reactivity in three point-of-care urine buprenorphine immunoassays (ACON, QuikStrip, and ABMC) and an instrument-based one (Cedia). We tested 29 urine samples from patients known to be taking tramadol. Ten different samples tested positive for urine buprenorphine by at least one immunoassay. Samples with positive buprenorphine screens by immunoassay were tested for total buprenorphine and total norbuprenorphine content by liquid chromatography-tandem mass spectrometry (LC-MS-MS), which confirmed that seven of the 10 positive samples were false-positives. The remaining three positive immunoassay samples had insufficient quantity for LC-MS-MS testing. No false-positives were detected with the ACON (10 ng/mL calibration cutoff) or the Cedia assay (using a 20 ng/mL calibration cutoff). All four false-positive Cedia results (using a 5 ng/mL cutoff) in this study tested negative using the ACON device. Our data suggest that tramadol use can cause false-positive urine buprenorphine immunoassays, and this effect appears to be assay-dependent. Tramadol interference with the Cedia assay is clinically relevant, especially if the 5 ng/mL calibration cutoff is used. PMID:18544218

  1. Lack of adverse effects during a target animal safety trial of extended-release buprenorphine in Fischer 344 rats.

    PubMed

    Cowan, Alan; Sarabia-Estrada, Rachel; Wilkerson, Gina; McKnight, Patrick; Guarnieri, Michael

    2015-12-18

    Extended-release buprenorphine is an effective analgesic in laboratory animals, and its safety has been established in mice but not in rats. The authors used a target animal safety trial to evaluate the safety of extended-release buprenorphine in rats. Fischer 344 rats received post-surgical subcutaneous injections of 1.3 mg, 3.9 mg or 6.5 mg buprenorphine per kg body weight (two times, six times or ten times the intended dose, respectively), and their body weight, clinical signs and symptoms, clinical pathology and histopathology were monitored for 4 d. Body weight was not significantly different in rats that received buprenorphine compared with control rats. Signs of nausea-related behavior were observed in 25% of the rats treated with buprenorphine. Clinical pathology results for all rats were normal, and gross and microscopic histopathology examinations identified no substantial abnormalities, suggesting that this behavior was of minor consequence. Other adverse events previously reported to occur with opiate therapy, including weight loss and dermal lesions at drug injection sites, were not observed in this study. The results of this study show that post-surgical administration of an extended-release buprenorphine product is safe in Fischer 344 rats and does not necessarily cause substantial adverse effects, confirming that opiate therapy is a viable choice in laboratory animal medicine. PMID:26684956

  2. A randomized trial of one-day vs. three-day buprenorphine inpatient detoxification protocols for heroin dependence.

    PubMed

    Hopper, John A; Wu, Joanna; Martus, Wesley; Pierre, James D

    2005-01-01

    Detoxification from opioids remains an important first step in the treatment of many patients with opioid dependence. Several pharmacologic regimens have been used for opioid detoxification. In the United States, the partial mu-opioid agonist, buprenorphine (BUP) is the most recently approved pharmacotherapy for opioid detoxification and replacement. The literature in recent years has described detoxification protocols using a single high dose of BUP and a three-day BUP regimen. In many settings, such as drug-free programs, a single-dose detoxification protocol would be of significant benefit. There have been no prior studies comparing one-day and three-day BUP-assisted opioid withdrawal. In this pilot study, we conducted an open-label, randomized trial of one-day vs. three-day BUP/naloxone sublingual tablet-assisted opioid withdrawal. Twenty patients from a therapeutic community treatment program were randomly assigned to receive either 32 mg sublingual BUP over one hour (one-day group), or 32 mg sublingual BUP over three days (three-day group). Nine of 10 subjects (90 percent) in each group completed seven days in the detoxification protocol. There was no statistically significant difference between the two groups in all other outcome variables, including retention in the treatment program, intensity of withdrawal signs and symptoms, amounts of adjunct medications used, and ability to produce opiate-free urine. This study further validates the feasibility of the single high dose of BUP as a rapid detoxification method. PMID:17315409

  3. Buprenorphine 5, 10 and 20??g/h transdermal patch: a review of its use in the management of chronic non-malignant pain.

    PubMed

    Plosker, Greg L

    2011-12-24

    This article reviews the pharmacology, therapeutic efficacy and tolerability profile of the 7-day lower-dose (5, 10 and 20??g/h) buprenorphine transdermal patch (BuTrans®, Norspan®) in the management of chronic non-malignant pain, with a focus on European labelling for the drug. Buprenorphine is a semi-synthetic opioid analgesic that acts primarily as a partial agonist at the mu opioid receptor. The transdermal formulation provides continuous delivery of buprenorphine, resulting in relatively consistent plasma drug concentrations throughout the 7-day dosing interval. The analgesic efficacy of transdermal buprenorphine in patients with osteoarthritis of the hip and/or knee has been demonstrated in several randomized controlled trials, which have shown the formulation to be equivalent to sublingual buprenorphine, noninferior to prolonged-release tramadol tablets, noninferior to codeine plus paracetamol (acetaminophen) combination tablets (when transdermal buprenorphine was used together with regularly scheduled oral paracetamol) and generally superior to a matching transdermal placebo patch. Transdermal buprenorphine was significantly more effective than placebo in reducing chronic low back pain of at least moderate severity in two randomized, double-blind, crossover trials. Other clinical trials, including a randomized, double-blind, maintenance-of-analgesia study, have also demonstrated the analgesic efficacy of transdermal buprenorphine in patients with chronic non-malignant pain of various causes. In general, serious adverse events with transdermal buprenorphine are similar to those for other opioid analgesics. Transdermal buprenorphine has a ceiling effect for respiratory depression, and the main risk is when it is combined with other CNS depressants. The most frequently reported adverse events with transdermal buprenorphine are headache, dizziness, somnolence, constipation, dry mouth, nausea, vomiting, pruritus, erythema, application site pruritus and application site reactions. Transdermal buprenorphine was better tolerated than sublingual buprenorphine in a 7-week, randomized, double-blind trial in patients with osteoarthritis pain. Nevertheless, as with other opioids, persistence with transdermal buprenorphine therapy is difficult for many patients because of adverse events or other reasons. Thus, transdermal buprenorphine has generally demonstrated good efficacy and tolerability in clinical trials in chronic non-malignant pain, providing effective background analgesia as part of pain management strategies for patients with osteoarthritis, low back pain and other persistent pain syndromes of at least moderate severity. It also has favourable pharmacodynamic and pharmacokinetic properties, which have beneficial clinical implications, most notably the convenience of once-weekly administration and no need for dosage adjustments in the elderly or those with compromised renal function, making it an opioid of choice in these patients, and a useful therapeutic option overall in the management of chronic non-malignant pain. PMID:22141389

  4. Linear free energy study of ring-substituted aniline ozonation for developing treatment of aniline-based pesticide wastes.

    PubMed

    Pierpoint, A C; Hapeman, C J; Torrents, A

    2001-08-01

    The relative rate constants for the reaction of ozone were determined for several substituted anilines in aqueous solutions at pH 6.5 and 1.5. At pH 6.5, with the exception of m- and p-nitroaniline, the rate constants obey Hammett's equation: log(k(X)/k(H)) = rho sigma. The departure of m- and p-nitroaniline may be explained by direct conjugation of the reaction center. The commonly used sigma(p)(-) value of 1.27, which extends the range of applicability of the Hammett equation, was insufficient to account for the conjugation effects on ozonation of p-nitroaniline; rho = -1.48 (R = 0.973). Use of amine group atomic charge determinations significantly improved correlations: (k(X)/k(H)) = 48.7 delta - 18.2 (R = 0.996). A linear plot of Hammett constants versus relative rate data at pH 1.5 showed poor correlation: rho = 0.72 (R = 0.572). Poor correlation was similarly observed for amine group atomic charge determinations, suggesting varied reaction mechanisms. PMID:11513674

  5. Use of mineralized collagen bone graft substitutes and dorsal locking plate in treatment of elder metaphyseal comminuted distal radius fracture

    NASA Astrophysics Data System (ADS)

    Liu, Ke-Bin; Huang, Kui; Teng, Yu; Qu, Yan-Zheng; Cui, Wei; Huang, Zhen-Fei; Sun, Ting-Fang; Guo, Xiao-Dong

    2014-03-01

    Bone graft may be needed to fill bone defect in elderly patients with a metaphyseal comminuted distal radius fracture. In this retrospective, nonrandomized, single-surgeon study, we evaluated the clinical and radiologic outcomes of using both dorsal locking plates with or without augmentation with mineralized collagen (MC) bone graft for elderly patients with dorsally metaphyseal comminuted radius fractures. Patients in group 1 ( n = 12) were treated with dorsal locking plates with MC bone graft application into the metaphyseal bone defect, and those in group 2 ( n = 12) only with dorsal locking plates. Clinical and radiologic parameters were determined at three and 12 months after surgery. At final follow-up, no significant difference was noted between the 2 groups in terms of palmar tilt and radial inclination ( p = 0.80); however, ulnar variance increased significantly in the group 2 treated with dorsal locking plates without augmentation ( p < 0.05). Functionally, there was no significant difference between the groups. Our preliminary study suggests that combination of MC as bone-graft substitutes and dorsal locking plates may be a usefully alternative for elderly patients with metaphyseal comminuted distal radius fracture.

  6. 7-Substituted umbelliferone derivatives as androgen receptor antagonists for the potential treatment of prostate and breast cancer.

    PubMed

    Kandil, Sahar; Westwell, Andrew D; McGuigan, Christopher

    2016-04-15

    The clinically used androgen receptor (AR) antagonists (bicalutamide, flutamide and nilutamide) bind with low affinity to AR and can induce escape mechanisms. Furthermore, under AR gene amplification or mutation conditions they demonstrate agonist activity and fail to inhibit AR, causing relapse into castration resistant prostate cancer (CRPC). Discovery of new scaffolds distinct from the 4-cyano/nitro-3-(trifluoromethyl)phenyl group common to currently used antiandrogens is urgently needed to avoid cross-resistance with these compounds. In this study, a series of twenty-nine 7-substituted umbelliferone derivatives was prepared and their antiproliferative activities were evaluated. The most active compound 7a demonstrated submicromolar inhibitory activity in the human prostate cancer cell line (22Rv1); IC50=0.93μM which represents a 50 fold improvement over the clinical antiandrogen bicalutamide (IC50=46μM) and a more than 30 fold improvement over enzalutamide (IC50=32μM). Interestingly, this compound showed even better activity against the human breast cancer cell line (MCF-7); IC50=0.47μM. Molecular modelling studies provided a plausible theoretical explanation for our findings. PMID:26965862

  7. Evaluation of drug-drug interaction between daclatasvir and methadone or buprenorphine/naloxone

    PubMed Central

    Garimella, Tushar; Wang, Reena; Luo, Wen-Lin; Wastall, Philip; Kandoussi, Hamza; Demicco, Michael; Bruce, Douglas; Hwang, Carey; Bertz, Richard; Bifano, Marc

    2014-01-01

    Introduction Daclatasvir (DCV) is a potent hepatitis C virus (HCV) NS5A replication complex inhibitor with pangenotypic (1–6) activity in vitro. Methadone (MET) and buprenorphine (BUP) are opioid medications used to treat opioid addiction; patients on HCV therapy may require MET or BUP treatment. The effect of DCV on the pharmacokinetics (PK) of MET or BUP/naloxone (NLX) was assessed in subjects on stable MET or BUP. Materials and Methods An open-label, two-part study assessed the effect of steady-state oral administration of DCV on the PK of MET (Part 1, P1) or BUP/NAL (Part 2, P2). Safety/tolerability and pharmacodynamics (PD, opioid withdrawal scales/overdose assessment) were also assessed. Subjects (P1, N=14; P2, N=11) received daily single-dose oral MET (40–120mg) or BUP/NLX (8/2–24/6mg) based on their prescribed stable dose throughout, in addition to DCV (60mg QD) on Days 2–9. Serial PK sampling occurred predose and postdose till 24 hours on Day 1 (MET/BUP) and Day 10 (MET/BUP/DCV). Noncompartmental PK were derived. Geometric mean ratios (GMR) and 90% confidence intervals (90% CI) for MET/BUP/norBUP Cmax and AUCTAU were derived from linear mixed effects models. Results Subjects were aged 19–39 years, mostly white (P1, 93%; P2, 100%) and male (P1, 71%; P2, 91%). All subjects completed the study. No clinically meaningful effect was demonstrated as the GMR and 90% CIs fell within the prespecified interval (P1, 0.7–1.4; P2, 0.5–2.0: see Table 1). DCV coadministration was well-tolerated: overall, six (43%) subjects had adverse events (AEs) (all mild and resolved without treatment). DCV had no clinically significant effect on the PD of MET or BUP/NLX. Conclusions Steady-state administration of DCV 60mg QD had no clinically meaningful effect on the PK of MET or BUP/NLX and was generally well-tolerated, suggesting that no dose adjustments will be required. PMID:25394132

  8. New Pain Management Options for the Surgical Patient on Methadone and Buprenorphine.

    PubMed

    Sen, Sudipta; Arulkumar, Sailesh; Cornett, Elyse M; Gayle, Julie A; Flower, Ronda R; Fox, Charles J; Kaye, Alan D

    2016-03-01

    Perioperative management of patients receiving opioid addiction therapy presents a unique challenge for the anesthesiologist. The goal of pain management in this patient population is to effectively manage postoperative pain, to improve patient satisfaction and outcomes, and to reduce the cost of health care. Multimodal analgesics, including nonsteroid anti-inflammatory drugs, intravenous acetaminophen, gabapentanoid agents, and low-dose ketamine infusions, have been used to improve postoperative pain and to reduce postoperative opioid use. Patients on long-term opioid management therapy with methadone and buprenorphine require special considerations. Recommendations and options for treating postoperative pain in patients on methadone and buprenorphine are outlined below. Other postoperative pain management options include patient-controlled analgesia, intravenous, and transdermal, in addition to neuraxial and regional anesthesia techniques. Special patient populations include the parturient on long-term opioid therapy. Recommendations for use of opioids in these patients during labor and delivery and in the postpartum period are discussed. PMID:26879874

  9. Buprenorphine and Norbuprenorphine Determination in Mice Plasma and Brain by Gas Chromatography–Mass Spectrometry

    PubMed Central

    Chiadmi, Fouad; Schlatter, Joël

    2014-01-01

    A gas chromatography tandem mass spectrometry method for quantification of buprenorphine (BUP) and norbuprenorphine (NBUP) in brain and plasma samples from mice was developed and validated. Analytes were extracted from the brain or plasma by solid phase extraction and quantified within 20 minutes. Calibration was achieved by linear regression with a 1/x weighting factor and d4-buprenorphine internal standard. All products were linear from 1 to 2000 ng/mL with a correlation of determination >0.99. Assay accuracy and precision of back-calculated standards were within ±10%. The lower limit of quantification for both BUP and NBUP from the brain and plasma was 1 ng/mL. This sensitive and specific method can be used for the investigation of BUP mechanism of action and clinical profile. PMID:24653644

  10. Effects of buprenorphine on responses to social stimuli in healthy adults.

    PubMed

    Bershad, Anya K; Seiden, Jacob A; de Wit, Harriet

    2016-01-01

    In addition to its classical role in mediating responses to pain, the opioid system is strongly implicated in the regulation of social behavior. In young laboratory animals, low doses of opioid analgesic drugs reduce responses to isolation distress and increase play behavior. However, little is known about how opioid drugs affect responses to social stimuli in humans. Here we examined the effects of buprenorphine, a mu-opioid partial agonist and kappa-antagonist, on three dimensions of social processing: (i) responses to simulated social rejection, (ii) attention to emotional facial expressions, and (iii) emotional responses to images with and without social content. Healthy adults (N=36) attended two sessions during which they received either placebo or 0.2mg sublingual buprenorphine in randomized order, under double-blind conditions. Ninety minutes after drug administration, they completed three behavioral tasks: (i) a virtual ball-toss game in which they were first included and then excluded by the other players; (ii) an attention task in which they were shown pairs of faces (one emotional and one neutral), while the direction of their gazes was recorded using electrooculography, and (iii) a picture-viewing task, in which they rated standardized images with and without social content. During the ball-toss game, buprenorphine decreased perceived social rejection. During the attention task, the drug reduced initial attention to fearful facial expressions, without influencing attention to angry, happy, or sad faces. Finally, during the picture-viewing task, buprenorphine increased ratings of positivity of images with social content without affecting ratings of nonsocial images. These results suggest that even at low doses, opioid analgesic drugs reduce responses to some types of negative social stimuli while enhancing positive responses to social stimuli. This provides further support for the role of the opioid system in mediating responses to social rejection and social reward. PMID:26409030

  11. Relative efficacy of cash versus vouchers in engaging opioid substitution treatment clients in survey-based research.

    PubMed

    Topp, Libby; Islam, M Mofizul; Day, Carolyn Ann

    2013-04-01

    Concerns that cash payments to people who inject drugs (PWID) to reimburse research participation will facilitate illicit drug purchases have led some ethical authorities to mandate department store/supermarket vouchers as research reimbursement. To examine the relative efficacy of the two forms of reimbursement in engaging PWID in research, clients of two public opioid substitution therapy clinics were invited to participate in a 20-30 min, anonymous and confidential interview about alcohol consumption on two separate occasions, 4 months apart. Under the crossover design, at Time 1, clients of Clinic 1 were offered $A20 cash as reimbursement, while clients of Clinic 2 were offered an $A20 voucher; at Time 2, the form of reimbursement was reversed. Using clinic records to determine the denominator (number of clients dosed), we found that compared with clients offered a voucher, a significantly higher proportion of clients who were offered cash participated in the survey (58% (139/241) vs 74% (186/252); χ(2)=14.27; p=0.0002). At first participation, respondents most commonly reported planning to purchase food/drinks/groceries (68%), cigarettes (21%) and transport/fuel (11%) with their payments, with those reimbursed in cash more likely to report planning to fund transport/fuel (19% vs 1%; p<.01) and less likely to report planning to purchase food/drinks/groceries (62% vs 76%; p=0.02). Just three out of 155 cash participants reported planning to purchase illicit drugs with their payment. Results demonstrate that modest cash payments enhanced recruitment of this group, an important consideration given the challenges of delineating the parameters of a population defined by illegal activity, seemingly without promoting excessive additional drug use. PMID:23236087

  12. An international perspective on using opioid substitution treatment to improve hepatitis C prevention and care for people who inject drugs: Structural barriers and public health potential.

    PubMed

    Perlman, David C; Jordan, Ashly E; Uuskula, Anneli; Huong, Duong Thi; Masson, Carmen L; Schackman, Bruce R; Des Jarlais, Don C

    2015-11-01

    People who inject drugs (PWID) are central to the hepatitis C virus (HCV) epidemic. Opioid substitution treatment (OST) of opioid dependence has the potential to play a significant role in the public health response to HCV by serving as an HCV prevention intervention, by treating non-injection opioid dependent people who might otherwise transition to non-sterile drug injection, and by serving as a platform to engage HCV infected PWID in the HCV care continuum and link them to HCV treatment. This paper examines programmatic, structural and policy considerations for using OST as a platform to improve the HCV prevention and care continuum in 3 countries-the United States, Estonia and Viet Nam. In each country a range of interconnected factors affects the use OST as a component of HCV control. These factors include (1) that OST is not yet provided on the scale needed to adequately address illicit opioid dependence, (2) inconsistent use of OST as a platform for HCV services, (3) high costs of HCV treatment and health insurance policies that affect access to both OST and HCV treatment, and (4) the stigmatization of drug use. We see the following as important for controlling HCV transmission among PWID: (1) maintaining current HIV prevention efforts, (2) expanding efforts to reduce the stigmatization of drug use, (3) expanding use of OST as part of a coordinated public health approach to opioid dependence, HIV prevention, and HCV control efforts, (4) reductions in HCV treatment costs and expanded health system coverage to allow population level HCV treatment as prevention and OST as needed. The global expansion of OST and use of OST as a platform for HCV services should be feasible next steps in the public health response to the HCV epidemic, and is likely to be critical to efforts to eliminate or eradicate HCV. PMID:26050614

  13. Effect of plasma proteins on Buprenorphine transfer across dually perfused placental lobule

    PubMed Central

    Nanovskaya, TN; Bowen, RS; Patrikeeva, SL; Hankins, GDV; Ahmed, MS

    2015-01-01

    Objective The aim of this investigation is to determine the effect of human serum albumin (HSA) and α-acid glycoprotein (AAG) on buprenorphine (BUP) transplacental transfer and distribution. Methods The technique of dual perfusion of placental lobule (DPPL) was utilized. Buprenorphine was co-perfused with the marker compound antipyrine (AP). In each experiment, the radiolabeled isotopes [3H]-buprenorphine and [14C]-AP were added to enhance their detection limits. Human plasma proteins, HSA and AAG, were added to both the maternal and fetal circuits separately and in combination at their physiological concentrations in maternal and fetal circulations close to term. Results Transplacental transfer of BUP, in absence of plasma proteins, is a 2-step process: the first is its uptake by the syncytiotrophoblast from the maternal circuit, and the second is its transfer/release from the tissue to the fetal circuit. The addition of HSA to the perfusion medium affected only the second step of BUP transfer, but AAG affected both steps. The combined effect of HSA and AAG was not different from that observed in presence of the latter alone. Conclusions Binding of BUP to circulating AAG could have an important role in the transfer of the drug from the maternal to fetal circulation. PMID:19544152

  14. Buprenorphine 5, 10 and 20??g/h transdermal patch: a guide to its use in chronic non-malignant pain.

    PubMed

    Plosker, Greg L; Lyseng-Williamson, Katherine A

    2012-04-01

    Buprenorphine lower-dose (5, 10 and 20??g/h) transdermal patches, which are administered once every 7 days, are indicated in the management of chronic non-malignant pain. This review focuses on the labelling of this formulation (BuTrans®) in the EU. The analgesic efficacy of transdermal buprenorphine in patients with osteoarthritis of the hip and/or knee has been demonstrated to be equivalent to sublingual buprenorphine, noninferior to prolonged-release tramadol and generally superior to a matching transdermal placebo patch. When used together with regularly scheduled oral paracetamol (acetaminophen), transdermal buprenorphine was noninferior to codeine plus paracetamol. Transdermal buprenorphine has also shown analgesic efficacy in patients with chronic non-malignant pain of various causes. PMID:22369187

  15. Antinociceptive effects of intravenous administration of hydromorphone hydrochloride alone or followed by buprenorphine hydrochloride or butorphanol tartrate to healthy conscious cats.

    PubMed

    Simon, Bradley T; Steagall, Paulo V; Monteiro, Beatriz P; Troncy, Eric; Lizarraga, Ignacio

    2016-03-01

    OBJECTIVE To evaluate antinociceptive effects of IV administration of hydromorphone alone or followed by buprenorphine or butorphanol to cats. ANIMALS 6 healthy adult cats. PROCEDURES In a randomized, blinded crossover design, cats received each of 4 treatments in which 2 IV injections were given 30 minutes apart: 2 of saline (0.9% NaCl) solution (Sal-Sal) or 1 each of hydromorphone HCl and saline solution (H-Sal), hydromorphone and buprenorphine HCl (H-Bupre), or hydromorphone and butorphanol tartrate (H-Butor). Skin temperature and thermal threshold were recorded before (baseline) and for 12 hours after the first injection. Percentage of maximum possible effect (%MPE) and thermal excursion (TE) were compared among treatments and measurement points. RESULTS Compared with baseline values, skin temperature was higher from 0.75 to 2 hours after the first injection for H-Sal; at 0.5, 1, 3, and 4 hours for H-Bupre; from 0.5 to 3 hours for H-Butor; and from 0.5 to 1 hours for Sal-Sal. Thermal excursion was higher than at baseline from 0.25 to 2 hours for H-Sal and H-Bupre and 0.25 to 0.75 hours for H-Butor; %MPE increased from 0.25 to 2 hours for H-Sal, 0.25 to 3 hours for H-Bupre, and 0.25 to 0.75 hours for H-Butor. Results were similar for comparisons with Sal-Sal, except TE was greater for H-Sal versus Sal-Sal and TE and %MPE were greater for H-Bupre versus Sal-Sal from 0.25 to 1 hours after the first injection. CONCLUSIONS AND CLINICAL RELEVANCE Butorphanol administration decreased the duration of antinociception achieved with hydromorphone administration in cats. This opioid interaction and its impact on pain management require additional investigation. PMID:26919594

  16. The analgesic drug buprenorphine inhibits osteoclastic bone resorption in vitro, but is proinflammatory in rat adjuvant arthritis.

    PubMed

    Hall, T J; Jagher, B; Schaeublin, M; Wiesenberg, I

    1996-06-01

    We have examined the effect of the micro-opioid analgesic buprenorphine on osteoclastic bone resorption in vitro and in the rat adjuvant arthritis model. In the bone slice assay buprenorphine inhibited osteoclastic bone resorption with an IC50 of 1 microM. This effect was not mimicked by the micro-opioid agonist ([D-Ala, N-Me-Phe, Gly-ol]-enkephalin and was not prevented by the micro-opioid antagonist naloxone. Since other agents that inhibit osteoclastic bone resorption, such as bisphosphonates and calcitonin prevent bone erosion in the rat adjuvant arthritis model, we also examined the effect of buprenorphine in this model. Surprisingly, buprenorphine exacerbated inflammation measured by paw volume and increased joint destruction assessed by X-ray scores, in the injected paws and particularly in the non-injected paws. These studies also show that attempts to ameliorate animal suffering in this chronic model by using centrally acting analgesics such as buprenorphine may lead to complications in interpreting screening results obtained with novel, potential anti-arthritic compounds. PMID:8814462

  17. Modulation of CNS pain circuitry by intravenous and sublingual doses of buprenorphine.

    PubMed

    Upadhyay, Jaymin; Anderson, Julie; Baumgartner, Richard; Coimbra, Alexandre; Schwarz, Adam J; Pendse, Gautam; Wallin, Diana; Nutile, Lauren; Bishop, James; George, Edward; Elman, Igor; Sunkaraneni, Soujanya; Maier, Gary; Iyengar, Smriti; Evelhoch, Jeffrey L; Bleakman, David; Hargreaves, Richard; Becerra, Lino; Borsook, David

    2012-02-15

    Buprenorphine (BUP) is a partial agonist at μ-, δ- and ORL1 (opioid receptor-like)/nociceptin receptors and antagonist at the κ-opioid receptor site. BUP is known to have both analgesic as well as antihyperalgesic effects via its central activity, and is used in the treatment of moderate to severe chronic pain conditions. Recently, it was shown that intravenous (IV) administration of 0.2mg/70 kg BUP modulates the blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) response to acute noxious stimuli in healthy human subjects. The present study extends these observations by investigating the effects of BUP dose and route of administration on central nervous system (CNS) pain circuitry. Specifically, the modulation of evoked pain BOLD responses and resting state functional connectivity was measured following IV (0.1 and 0.2mg/70 kg) and sublingual (SL) (2mg) BUP administration in healthy human subjects. While 0.1mg/70 kg IV BUP is sub-analgesic, both 0.2mg/70 kg IV BUP and 2.0mg SL BUP are analgesic doses of the drug. Evoked BOLD responses were clearly modulated in a dose-dependent manner. The analgesic doses of BUP by both routes of administration yielded a potentiation in limbic/mesolimbic circuitry and attenuation in sensorimotor/sensory-discriminative circuitry. In addition, robust decreases in functional connectivity between the putamen and the sensorimotor/sensory-discriminative structures were observed at the two analgesic doses subsequent to measuring the maximum plasma BUP concentrations (C(max)). The decreases in functional connectivity within the sensorimotor/sensory-discriminative circuitry were also observed to be dose-dependent in the IV administration cohorts. These reproducible and consistent functional CNS measures at clinically effective doses of BUP demonstrate the potential of evoked pain fMRI and resting-state functional connectivity as objective tools that can inform the process of dose selection. Such methods may be useful during early clinical phase evaluation of potential analgesics in drug development. PMID:22119647

  18. The 'Expanded HIV care in opioid substitution treatment' (EHOST) cluster-randomized, stepped-wedge trial: A study protocol.

    PubMed

    Nosyk, B; Krebs, E; Min, J E; Ahamad, K; Buxton, J; Goldsmith, C; Hull, M; Joe, R; Krajden, M; Lima, V D; Olding, M; Wood, E; Montaner, J S G

    2015-11-01

    The public health response to HIV/AIDS has turned its focus onto optimizing health care system delivery to maximize case identification, access and sustained engagement in antiretroviral treatment (ART). Opioid Agonist Treatment (OAT) provides a critical opportunity for HIV testing and linkage to ART. The EHOST study is a cluster-randomized, stepped-wedge trial to evaluate a prescriber-focused intervention to increase HIV testing rates, and optimize ART engagement and retention outcomes among individuals engaged in OAT. The study will encompass all drug treatment clinics currently admitting patients for the treatment of opioid use disorder across the province of British Columbia, encompassing an estimated 90% of the OAT caseload. The trial will be executed over a 24-month period, with groups of clinics receiving the intervention in 6-month intervals. Evaluation of the proposed intervention's effectiveness will focus on three primary outcomes: (i) the HIV testing rate among those not known to be HIV positive; (ii) the rate of ART initiation among those not on ART; and (iii) the rate of ART continuation among those on ART. A difference-in-differences analytical framework will be applied to estimate the intervention's effect. This approach will assess site-specific changes in primary outcomes across clusters while adjusting for potential residual heterogeneity in patient case mix, volume, and quality of care across clinics. Statistical analysis of outcomes will be conducted entirely with linked population-level administrative health datasets. Facilitated by established collaborations between key stakeholders across the province, the EHOST intervention promises to optimize HIV testing and care within a marginalized and hard-to-reach population. PMID:26342295

  19. Effect of partial substitution of invert sugar for sucrose in combination with Duraphat treatment on caries development in preschool children: the Malmö Study.

    PubMed

    Frostell, G; Birkhed, D; Edwardsson, S; Goldberg, P; Petersson, L G; Priwe, C; Winholt, A S

    1991-01-01

    The aim was to study the effect of substitution of invert sugar for sucrose, in combination with fluoride varnish (Duraphat) treatment twice a year, on caries development in preschool children. One hundred and eighty-seven 4-years-olds were divided randomly into four sugar groups: (1) sucrose (S), (2) sucrose-Duraphat (SD), (3) invert sugar (I), and (4) invert sugar-Duraphat (ID). All families were asked to buy beverages, biscuits, breakfast cereals, marmalade, ice cream, jam, ketchup, sweets and table sugar, totally 32 different food items, sweetened with invert sugar or sucrose. The substitution was, thus, restricted to a number of sugar-rich between-meal products. The study was carried out double-blind for 2 years. The children of those parents who did not want to participate in the sugar groups were divided randomly into one of the following two groups: (5) Duraphat (D), and control (C). Because of lack of cooperation, only 114 of the 187 children (61%) were considered to have completed the study. The mean caries increment, including initial lesions, was 3.86 dmfs in the combined groups S and SD (n = 63) and 3.10 dmfs in the combined groups I and ID (n = 51) during the 2 years (p = 0.34). The corresponding values for the 2nd year only were 1.84 and 0.67 dmfs, respectively (p = 0.09). The mean caries increment was 2.86 dmfs in group D (n = 113) and 4.10 dmfs (p = 0.08) in group C (n = 93). If initial caries lesions were excluded from the index, the difference between groups D and C was significant (p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1913770

  20. The SAR development of substituted purine derivatives as selective CB2 agonists for the treatment of chronic pain.

    PubMed

    Guidetti, Rossella; Astles, Peter C; Sanderson, Adam J; Hollinshead, Sean P; Johnson, Michael P; Chambers, Mark G

    2014-12-15

    Osteoarthritis (OA) and the associated joint pain are highly prevalent and a leading cause of disability. We have previously reported the identification of a series of purines as selective CB2 agonists and the identification of compound 1 as a clinical candidate for the treatment of joint pain. In this article we describe the further SAR development of the purine scaffold leading to the discovery of compound 6 as a potent, CNS penetrating CB2 agonist with high selectivity for CB2 over CB1 and oral efficacy in animal models of chronic OA pain. PMID:25466177

  1. Blood substitutes.

    PubMed

    Palmer, Andre F; Intaglietta, Marcos

    2014-07-11

    The toxic side effects of early generations of red blood cell substitutes have stimulated development of more safe and efficacious high-molecular-weight polymerized hemoglobins, poly(ethylene glycol)-conjugated hemoglobins, and vesicle-encapsulated hemoglobins. Unfortunately, the high colloid osmotic pressure and blood plasma viscosity of these new-generation materials limit their application to blood concentrations that, in general, are not sufficient for full restoration of oxygen-carrying and -delivery capacity. However, these materials may serve as oxygen therapeutics for treating tissues affected by ischemia and trauma, particularly when the therapeutics are coformulated with antioxidants. These new oxygen therapeutics also possess additional beneficial effects owing to their optimal plasma expansion properties, which induce systemic supraperfusion that increases endothelial nitric oxide production and improves tissue washout of metabolic wastes, further contributing to their therapeutic role. PMID:24819476

  2. Concluding statement - neuropharmacological basis and clinical rationale for control of transdermal buprenorphine as a step II analgesic.

    PubMed

    Henningfield, Jack E; Sun, Wei-Zen

    2015-06-01

    In this commentary on the medical use and regulation of transdermal buprenorphine we bring together our complimentary perspectives on the neuropharmacology of analgesics (Dr. Henningfield) and clinical medicine to address the needs of people with pain (Dr. Sun). Together, the neuropharmacology of buprenorphine, the clinical and abuse deterring benefits of the 7-day transdermal formulation, the low rates of harmful use and abuse detected in post-marketing surveillance studies, and the desirable clinical benefits in the elderly, in persons with compromised kidney function, and other populations support the regulation of buprenorphine comparable to tramadol-like analgesics. We support this approach and believe that it strikes the right balance of control to provide appropriate access to people with pain and their health providers, while still providing the basis for deterring harmful use and abuse. PMID:26068437

  3. Italy’s Electronic Health Record System for Opioid Agonist Treatment

    PubMed Central

    Serpelloni, Giovanni; Gomma, Maurizio; Genetti, Bruno; Zermiani, Monica; Rimondo, Claudia; Mollica, Roberto; Gryczynski, Jan; O’Grady, Kevin E.; Schwartz, Robert P.

    2013-01-01

    Electronic health record systems (EHRs) play an increasingly important role in opioid agonist treatment. In Italy, an EHR called the Multi Functional Platform (MFP) is in use in 150 opioid-agonist treatment facilities in 8 of Italy’s 23 regions. This report describes MFP and presents 2010 data from 65 sites that treated 8,145 patients, of whom 72.3% were treated with methadone and 27.7% with buprenorphine. Patients treated with buprenorphine compared to methadone were more likely to be male (p < 0.01) and younger (p < 0.001). Methadone compared to buprenorphine patients had a higher percentage of opioid-positive urine tests (p < 0.001) and longer mean length of stay (p = 0.004). MFP has been implemented widely in Italy and has been able to track patient outcomes across treatment facilities. In the future, this EHR system can be used for performance improvement initiatives. PMID:23518287

  4. Magnesium substitution in brushite cements: Efficacy of a new biomaterial loaded with vancomycin for the treatment of Staphylococcus aureus infections.

    PubMed

    Cabrejos-Azama, Jatsue; Alkhraisat, Mohammad Hamdan; Rueda, Carmen; Torres, Jesús; Pintado, Concepción; Blanco, Luis; López-Cabarcos, Enrique

    2016-04-01

    Staphylococcus aureus is the most relevant pathogen associated with bone infection that sometimes appears after implant surgery, thus compromising a successful treatment. The aim of this work was to assess the effectiveness of brushite cements, doped with magnesium, as a new vancomycin carrier system against S.aureus infections. We performed an "in vitro" study to evaluate vancomycin release from the cements by measuring its antimicrobial activity against a strain of S.aureus. We have used two methods to load the cements with vancomycin: i) adsorption from a solution and ii) incorporation of the antibiotic into the solid phase during the cement synthesis. Furthermore, the compression strength of the loaded samples was measured to detect changes in the mechanical properties of the system. The "in vitro" study showed that the sustained release of vancomycin depends on the concentration of magnesium in the cement matrix. In addition, the standardized antibacterial assay revealed that the release of vancomycin from the cements may be helpful to prevent infections in bone regeneration procedures. PMID:26838826

  5. Extensive Self-Harm Scarring: Successful Treatment With Simultaneous Use of a Single Layer Skin Substitute and Split-Thickness Skin Graft

    PubMed Central

    Todd, Jodi; Ud-Din, Sara; Bayat, Ardeshir

    2012-01-01

    Objective: Deliberate self-harm resulting in extensive skin scarring is a difficult clinical problem and is commonly associated with physical and sexual abuse or a known history of mental illness. Immediate hospital attendance often addresses the acute wound and current psychological state of patients; however, ongoing regret of these resulting scars present a problem to the patient and clinician. Deliberate self-harm to the skin leaves permanent and socially unacceptable scars in anatomically conspicuous areas and recognizable to others. Therefore, the aim was to offer a treatment to change these scars to that of an unknown entity. Methods: Six patients with extensive linear scars covering most of the forearm received surgical reconstruction. Patients were female aged between 18 and 47 years. Each patient had a history of psychosocial problems, and each had undergone psychiatric treatment. After an in-depth consultation and a further clinical psychological assessment, each individual was deemed suitable for reconstructive surgery. Scars were excised from the forearm en block, removing the majority of the affected area. Simultaneous use of a single layer skin substitute was used, covered by an autologous split-thickness skin graft. Negative pressure wound therapy was then applied immediately for 2 weeks after surgery. Results: The original scars were successfully converted to a socially and cosmetically acceptable appearance. Postoperative infection due to negative pressure wound therapy failure in one patient was the only complication reported. Conclusions: This case series highlights the utility of an innovative treatment for patients with DSH scarring resulting in aesthetic, psychological, and functional benefits. PMID:22662281

  6. Mechanism-based PK/PD modeling of the respiratory depressant effect of buprenorphine and fentanyl in healthy volunteers.

    PubMed

    Yassen, A; Olofsen, E; Romberg, R; Sarton, E; Teppema, L; Danhof, M; Dahan, A

    2007-01-01

    The objective of this study was to characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship of buprenorphine and fentanyl for the respiratory depressant effect in healthy volunteers. Data on the time course of the ventilatory response at a fixed P(ET)CO(2) of 50 mm Hg and P(ET)O(2) of 110 mm Hg following intravenous administration of buprenorphine and fentanyl were obtained from two phase I studies (50 volunteers received buprenorphine: 0.05-0.6 mg/70 kg and 24 volunteers received fentanyl: 0.075-0.5 mg/70 kg). The PK/PD correlations were analyzed using nonlinear mixed effects modeling. A two- and three-compartment pharmacokinetic model characterized the time course of fentanyl and buprenorphine concentration, respectively. Three structurally different PK/PD models were evaluated for their appropriateness to describe the time course of respiratory depression: (1) a biophase distribution model with a fractional sigmoid E(max) pharmacodynamic model, (2) a receptor association/dissociation model with a linear transduction function, and (3) a combined biophase distribution-receptor association/dissociation model with a linear transduction function. The results show that for fentanyl hysteresis is entirely determined by the biophase distribution kinetics, whereas for buprenorphine hysteresis is caused by a combination of biophase distribution kinetics and receptor association/dissociation kinetics. The half-time values of biophase equilibration (t(1/2, k(eo))) were 16.4 and 75.3 min for fentanyl and buprenorphine, respectively. In addition, for buprenorphine, the value of k(on) was 0.246 ml/ng/min and the value of k(off) was 0.0102 min(-1). The concentration-effect relationship of buprenorphine was characterized by a ceiling effect at higher concentrations (intrinsic activity alpha=0.56, 95% confidence interval (CI): 0.50-0.62), whereas fentanyl displayed full respiratory depressant effect (alpha=0.91, 95% CI: 0.19-1.62). PMID:17185999

  7. PLASMA SUBSTITUTES

    PubMed Central

    Robscheit-Robbins, F. S.; Miller, L. L.; Alling, E. L.; Whipple, G. H.

    1946-01-01

    Hemoglobin and globin alone, supplemented, or modified in various ways are seriously considered as plasma substitutes. Human globin given to doubly depleted (anemic and hypoproteinemic) dogs by vein contributes to the production of new hemoglobin and plasma protein, but there is some toxicity and weight loss. Dog hemoglobin given intraperitoneally is better tolerated and somewhat more completely utilized with more blood proteins formed and less weight loss. Dog globin (tryptic digest) given by vein in anemic dogs is associated with a moderate production of new hemoglobin. Horse globin by mouth contributes to the formation of new hemoglobin in the standard anemic dog. Dog hemoglobin given intraperitoneally in protein fasting, non-anemic dogs is well utilized to maintain nitrogen and weight balance. A dl-isoleucine supplement fails to improve this utilization of hemoglobin for maintenance in the dog. A small supplement of dl-methionine greatly improves the utilization of dog hemoglobin for maintenance in the dog and further addition of isoleucine is without effect. The intermediary metabolism of dog hemoglobin is not yet worked out. Electrophoretic analyses (Table 6) suggest that globin appears in the peripheral circulation after intraperitoneal injections of hemoglobin. PMID:19871535

  8. Simultaneous Quantification of Buprenorphine, Norbuprenorphine, Buprenorphine-Glucuronide and Norbuprenorphine-Glucuronide in Human Umbilical Cord by Liquid Chromatography Tandem Mass Spectrometry

    PubMed Central

    Concheiro, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.

    2009-01-01

    A LCMS method was developed and validated for the simultaneous determination of buprenorphine (BUP), norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-Gluc) and norbuprenorphine glucuronide (NBUP-Gluc) in human umbilical cord. Quantification was achieved by selected ion monitoring of precursor ions m/z 468.4 for BUP; 414.3 for NBUP; 644.4 for BUP-Gluc and 590 for NBUP-Gluc. BUP and NBUP were identified by MS2, with m/z 396, 414 and 426 for BUP, and m/z 340, 364 and 382 for NBUP. Glucuronide conjugates were identified by MS3 with m/z 396 and 414 for BUP-Gluc and m/z 340 and 382 for NBUP-Gluc. The assay was linear 1–50 ng/g. Intra, inter-day and total assay imprecision (%RSD) were <14.5%, and analytical recovery ranged from 94.1% to 112.3% for all analytes. Extraction efficiencies were >66.3%, and process efficiency >73.4%. Matrix effect ranged, in absolute value, from 3.7% to 27.4% (CV<21.8%, n=8). The method was selective with no endogenous or exogenous interferences from 41 compounds evaluated. Sensitivity was high with limits of detection of 0.8 ng/g. In order to prove method applicability, an authentic umbilical cord obtained from an opioid-dependent pregnant woman receiving BUP pharmacotherapy was analyzed. Interestingly, BUP was not detected but concentrations of the other metabolites were NBUP-Gluc 13.4 ng/g, BUP-Gluc 3.5 ng/g and NBUP 1.2 ng/g. PMID:19406593

  9. Allergic contact dermatitis from buprenorphine and oral tolerance to other opioid derivatives in three patients.

    PubMed

    Huilaja, Laura; Riekki, Riitta; Immonen, Aila; Tasanen, Kaisa

    2014-01-01

    Transdermal buprenorphine (TDB) is a widely used analgesic for moderate pain. TDB is generally well tolerated, but both irritant and allergic contact dermatitis occur at patch application sites. Oral opioid tolerance in patients with allergic contact dermatitis to TDB remains controversial. Here, we describe 3 patients with allergic contact dermatitis to TDB who subsequently used oral opioid derivatives without adverse reactions. Thus, oral intolerance to opioid derivatives is not a rule in patients with allergic contact dermatitis to TDB, but the possibility should be taken into consideration. PMID:24280659

  10. Buprenorphine-elicited alteration of adenylate cyclase activity in human embryonic kidney 293 cells coexpressing ?-, ?-opioid and nociceptin receptors.

    PubMed

    Wang, Pei-Chen; Ho, Ing-Kang; Lee, Cynthia Wei-Sheng

    2015-11-01

    Buprenorphine, a maintenance drug for heroin addicts, exerts its pharmacological function via ?- (KOP), ?-opioid (MOP) and nociceptin/opioid receptor-like 1 (NOP) receptors. Previously, we investigated its effects in an in vitro model expressing human MOP and NOP receptors individually or simultaneously (MOP, NOP, and MOP+NOP) in human embryonic kidney 293 cells. Here, we expanded this cell model by expressing human KOP, MOP and NOP receptors individually or simultaneously (KOP, KOP+MOP, KOP+NOP and KOP+MOP+NOP). Radioligand binding with tritium-labelled diprenorphine confirmed the expression of KOP receptors. Immunoblotting and immunocytochemistry indicated that the expressed KOP, MOP and NOP receptors are N-linked glycoproteins and colocalized in cytoplasmic compartments. Acute application of the opioid receptor agonists- U-69593, DAMGO and nociceptin- inhibited adenylate cyclase (AC) activity in cells expressing KOP, MOP and NOP receptors respectively. Buprenorphine, when applied acutely, inhibited AC activity to ~90% in cells expressing KOP+MOP+NOP receptors. Chronic exposure to buprenorphine induced concentration-dependent AC superactivation in cells expressing KOP+NOP receptors, and the level of this superactivation was even higher in KOP+MOP+NOP-expressing cells. Our study demonstrated that MOP receptor could enhance AC regulation in the presence of coexpressed KOP and NOP receptors, and NOP receptor is essential for concentration-dependent AC superactivation elicited by chronic buprenorphine exposure. PMID:26153065

  11. Hemodynamic and Behavioral Differences after Administration of Meloxicam, Buprenorphine, or Tramadol as Analgesics for Telemeter Implantation in Mice

    PubMed Central

    Rätsep, Matthew T; Barrette, Valerie F; Winterborn, Andrew; Adams, Michael A; Croy, B Anne

    2013-01-01

    Cannulation of the common carotid artery for chronic, continuous radiotelemetric recording of aortic hemodynamic properties in mice is a highly invasive recovery surgery. Radiotelemetric recording, by its continuous nature, gives the most accurate measurements of hemodynamic variables in experimental animals, and is widely used in the study of cardiovascular diseases including hypertension. The American Heart Association has recommended data acquisition by radiotelemetric recording but did not provide guidelines regarding postoperative analgesic support. We assessed hemodynamic parameters, locomotor activity, food intake, and weight loss in radiotransmitter-implanted CD1 female mice receiving analgesic support during the first 48 h after surgery. The efficacy of analgesic support from the NSAID meloxicam was compared with that of the widely used opioid agonist buprenorphine and the related compound, tramadol. Meloxicam-treated mice recovered lost body weight more rapidly than did tramadol- or buprenorphine-treated mice. Furthermore, meloxicam-treated mice maintained circadian rhythm after surgery and had tighter regulation of mean arterial pressure than did tramadol- or buprenorphine-treated mice. Meloxicam was also superior with regard to food intake, locomotor activity, and limiting variance in hemodynamic parameters. This study indicates that when compared with buprenorphine and tramadol, meloxicam should be the postoperative analgesic of choice for radiotelemeter implantation in mice. PMID:24041211

  12. Evaluation of the One-Step ELISA kit for the detection of buprenorphine in urine, blood, and hair specimens.

    PubMed

    Cirimele, V; Etienne, S; Villain, M; Ludes, B; Kintz, P

    2004-07-16

    A solid-phase enzyme immunoassay involving microtiter plates was recently proposed by International Diagnostic Systems corporation (IDS) to screen for buprenorphine in human serum. The performance of the kit led us to investigate its applicability in other biological matrices such as urine or blood, and also hair specimens. Low concentrations of buprenorphine were detected with the ELISA test and confirmed by HPLC/MS (buprenorphine concentrations measured by HPLC/MS: 0.3 ng/mL in urine, 0.2 ng/mL in blood, and 40 pg/mg in hair). The intra-assay precision values were 8.7% at 1 ng/mL of urine (n = 8), 11.5% at 2 ng/mL in serum (n = 8), and 11.5% at 250 pg/mg of hair (n = 8), respectively. The immunoassay had no cross-reactivity with dihydrocodeine, ethylmorphine, 6-monoacetylmorphine, pholcodine, propoxyphene, dextromoramide, dextrometorphan at 1 and 10 mg/L, or codeine, morphine, methadone, and its metabolite EDDP. A 1% cross-reactivity was measured for a norbuprenorphine concentration of 50 ng/mL. Finally, the immunoassay was validated by comparing authentic specimens results with those of a validated HPLC/MS method. From the 136 urine samples tested, 93 were positive (68.4%) after the ELISA screening test (cutoff: 0.5 ng/mL) and confirmed by HPLC/MS (buprenorphine concentrations: 0.3-2036 ng/mL). From the 108 blood or serum samples screened, 27 were positive (25%) after the ELISA test with a cutoff value of 0.5 ng/mL (buprenorphine concentrations: 0.2-13.3 ng/mL). Eighteen hair specimens were positive (72%) after the screening (cutoff: 10 pg/mg) and confirmed by LC/MS (buprenorphine concentrations: 40-360 pg/mg). The ELISA method produced false positive results in less than 21% of the cases, but no false negative results were observed with the immunological test. Four potential adulterants (hypochloride 50 mL/L, sodium nitrite 50 g/L, liquid soap 50 mL/L, and sodium chloride 50 g/L) that were added to 10 positive urine specimens (buprenorphine concentrations in the range 5.3-15.6 ng/mL), did not cause a false negative response by the immunoassay. PMID:15240036

  13. In vivo efficacy of oral and intralesional administration of 2-substituted quinolines in experimental treatment of new world cutaneous leishmaniasis caused by Leishmania amazonensis.

    PubMed Central

    Fournet, A; Ferreira, M E; Rojas De Arias, A; Torres De Ortiz, S; Fuentes, S; Nakayama, H; Schinini, A; Hocquemiller, R

    1996-01-01

    The antileishmanial efficacies of 2-n-propylquinoline, chimanines B and D, 2-n-pentylquinoline, 2-phenylquinoline, 2-(3,4-methylenedioxyphenylethyl) quinoline, and two total alkaloidal extracts of Galipea longiflora were evaluated in BALB/c mice infected with Leishmania amazonensis or Leishmania venezuelensis. Animals were treated for 4 to 6 weeks postinfection with a quinoline by the oral route at 50 mg/kg of body weight twice daily for 15 days or by five intralesional injections at intervals of 4 days with a quinoline at 50 mg/kg of body weight. The reference drug, N-methylglucamine antimonate (Glucantime), was administered by subcutaneous or intralesional injection (regimens of 14, 28, or 56 mg of pentavalent antimony [Sbv] per kg of body weight daily). Twice-daily oral treatment with chimanine B at 50 mg/kg resulted in a decrease in lesion weight by 70% (P < 0.001) and a decrease in the parasite loads by 95% (P < 0.001). Five injections of chimanine B at intervals of 4 days reduced the lesion weight by 74% and the parasite loads in the lesion by 90% compared with the values for the group of untreated mice. Subcutaneous administration of N-methylglucamine antimonate at 28 mg of Sbv kg per day for 15 days reduced the parasite burden by 95% (P < 0.001), and five intralesional injections at the same concentration reduced the parasite burden by 96% (P < 0.001). Other 2-substituted quinolines, 2-n-propylquinoline administered by the oral and intralesional routes, 2-phenylquinoline administered by the oral route, 2-n-pentylquinoline administered by intralesional injection, and two total alkaloidal extracts of G. longiflora administered by the oral route, had intermediate effects. These findings suggest that chimanine B may be chosen as a lead molecule in the development of oral therapy against leishmaniasis. PMID:8913444

  14. Treating tobacco use disorder in pregnant women in medication-assisted treatment for an opioid use disorder: a systematic review.

    PubMed

    Akerman, Sarah C; Brunette, Mary F; Green, Alan I; Goodman, Daisy J; Blunt, Heather B; Heil, Sarah H

    2015-05-01

    Smoking is associated with adverse effects on pregnancy and fetal development, yet 88-95% of pregnant women in medication-assisted treatment for an opioid use disorder smoke cigarettes. This review summarizes existing knowledge about smoking cessation treatments for pregnant women on buprenorphine or methadone, the two forms of medication-assisted treatment for opioid use disorder indicated for prenatal use. We performed a systematic review of the literature using indexed terms and key words to capture the concepts of smoking, pregnancy, and opioid substitution and found that only three studies met search criteria. Contingency management, an incentive based treatment, was the most promising intervention: 31% of participants achieved abstinence within the 12-week study period, compared to 0% in a non-contingent behavior incentive group and a group receiving usual care. Two studies of brief behavioral interventions resulted in reductions in smoking but not cessation. Given the growing number of pregnant women in medication-assisted treatment for an opioid use disorder and the negative consequences of smoking on pregnancy, further research is needed to develop and test effective cessation strategies for this group. PMID:25592332

  15. Buprenorphine signalling is compromised at the N40D polymorphism of the human ? opioid receptor in vitro

    PubMed Central

    Knapman, Alisa; Santiago, Marina; Connor, Mark

    2014-01-01

    Background and Purpose There is significant variation in individual response to opioid drugs, which may result in inappropriate opioid therapy. Polymorphisms of the ? opioid receptor (MOP receptor) may contribute to individual variation in opioid response by affecting receptor function, and the effect may be ligand-specific. We sought to determine functional differences in MOP receptor signalling at several signalling pathways using a range of structurally distinct opioid ligands in cells expressing wild-type MOP receptors (MOPr-WT) and the commonly occurring MOP receptor variant, N40D. Experimental Approach MOPr-WT and MOPr-N40D were stably expressed in CHO cells and in AtT-20 cells. Assays of AC inhibition and ERK1/2 phosphorylation were performed on CHO cells, and assays of K activation were performed on AtT-20 cells. Signalling profiles for each ligand were compared between variants. Key Results Buprenorphine efficacy was reduced by over 50% at MOPr-N40D for AC inhibition and ERK1/2 phosphorylation. Buprenorphine potency was reduced threefold at MOPr-N40D for K channel activation. Pentazocine efficacy was reduced by 50% for G-protein-gated inwardly rectifying K channel activation at MOPr-N40D. No other differences were observed for any other ligands tested. Conclusions and Implications The N40D variant is present in 10–50% of the population. Buprenorphine is a commonly prescribed opioid analgesic, and many individuals do not respond to buprenorphine therapy. This study demonstrates that buprenorphine signalling to several effectors via the N40D variant of MOP receptors is impaired, and this may have important consequences in a clinical setting for individuals carrying the N40D allele. PMID:24846673

  16. Buprenorphine detection in urine using liquid chromatography-high-resolution mass spectrometry: comparison with cloned enzyme donor immunoassay (ThermoFisher) and homogeneous enzyme immunoassay (immunalysis).

    PubMed

    Belsey, Sarah L; Couchman, Lewis; Flanagan, Robert J

    2014-09-01

    A sensitive liquid chromatographic-high-resolution mass spectrometric (LC-HR-MS) assay for buprenorphine and its urinary metabolites has been developed that requires minimal sample preparation. The results obtained have been compared with those given by (i) cloned enzyme donor immunoassay (CEDIA) and (ii) homogeneous enzyme immunoassay (HEIA) in the analysis of patient urines submitted for buprenorphine analysis. Centrifuged urine (100 µL) was diluted with internal standard solution (25 µL) + LC eluent (875 µL), and 50 µL of the prepared sample were analyzed (Accucore Phenyl-Hexyl column). MS detection was in alternating positive and negative mode using heated electrospray ionization (ThermoFisher Q Exactive). Intra- and inter-assay accuracy and precision were 104-128 and <11%, respectively, at 5 µg/L. Limits of detection were 1.3 µg/L (buprenorphine, norbuprenorphine and buprenorphine glucuronide) and 2.5 µg/L (norbuprenorphine glucuronide). Immunoassay sensitivity and selectivity were 97 and 100% (HEIA) and 99 and 84% (CEDIA), respectively, compared with LC-HR-MS. In 120 patient urines, norbuprenorphine glucuronide was easily the most abundant analyte except when adulteration with buprenorphine had occurred. The median immunoreactive buprenorphine species present (unhydrolysed urine) were 7.5 and 13% for HEIA and CEDIA, respectively. However, codeine, dihydrocodeine, morphine and morphine-3-glucuronide did not interfere in the HEIA assay. PMID:24925983

  17. Heat treatment effects on structural and dielectric properties of Mn substituted CuFe2O4 and ZnFe2O4 nanoparticles

    NASA Astrophysics Data System (ADS)

    Ranjith Kumar, E.; Arunkumar, T.; Prakash, T.

    2015-09-01

    Manganese substituted copper and zinc ferrite nanoparticles were synthesized by an auto-combustion technique using metal nitrates and urea. The nanoparticles were characterized by XRD, SEM, EDX, and TEM techniques. The effect of annealing temperature on structural and dielectric properties of Mn substituted spinel ferrite nanoparticles was analyzed. The presenting elements in the prepared samples are recorded by EDX. TEM analysis clearly showed the particles are in the nanometer range. The dielectric loss and dielectric constant have been measured in the frequency range of 100 kHz-5 MHz. The variation in structural and dielectric properties of the prepared and annealed samples are discussed.

  18. Pharmacokinetic Comparison of Sustained-Release and Standard Buprenorphine in Mice

    PubMed Central

    Clark, Tannia S; Clark, David D; Jr, Robert F Hoyt

    2014-01-01

    Effective pain medication is important for animal stewardship and valid research results. We compared the pharmacokinetic assessments of standard, immediate-release buprenorphine (Bup IR) and a sustained-release buprenorphine formulation (Bup SR Lab) in male C57BL/6J mice, a mouse strain commonly used in biomedical research. We postulated that the administration of Bup SR Lab would achieve a more persistent blood drug concentration (>1 ng/mL) compared with single-dose Bup IR. The study assumed a blood buprenorphine concentration of 1 ng/mL as the minimum that may result in adequate analgesia, as previously reported. The 7 experimental groups included Bup IR (0.03, 0.05, 0.1, and 2 mg/kg), Bup SR Lab (0.3 and 1.2 mg/kg), and saline placebo (0.7 mL/100 g). Blood sampling occurred at 0.5, 1, 3, 6, 12, 24, 48, and 72 h for evaluation by using a forensic ELISA. Bup IR at 0.03 and 0.05 mg/kg and Bup SR Lab at 0.3 mg/kg failed to obtain maximal blood concentrations (Cmax) above 1 ng/mL. All other doses (0.1 and 2 mg/kg Bup IR and 1.2 mg/kg Bup SR Lab) reached a Cmax above 1 ng/mL within 3 h after injection. In addition, 1.2 mg/kg Bup SR Lab and 2 mg/kg Bup IR provided blood concentrations above 1 ng/mL for up to 12 h, and 0.1 mg/kg Bup IR achieved this criterion for as long as 3 h. In conclusion, Bup SR Lab at 1.2 mg/kg and Bup IR at 0.1 or 2.0 mg/kg achieve or surpass the published threshold for adequate analgesia in mice. PMID:25199095

  19. Biologic and synthetic skin substitutes: An overview

    PubMed Central

    Halim, Ahmad Sukari; Khoo, Teng Lye; Mohd. Yussof, Shah Jumaat

    2010-01-01

    The current trend of burn wound care has shifted to more holistic approach of improvement in the long-term form and function of the healed burn wounds and quality of life. This has demanded the emergence of various skin substitutes in the management of acute burn injury as well as post burn reconstructions. Skin substitutes have important roles in the treatment of deep dermal and full thickness wounds of various aetiologies. At present, there is no ideal substitute in the market. Skin substitutes can be divided into two main classes, namely, biological and synthetic substitutes. The biological skin substitutes have a more intact extracellular matrix structure, while the synthetic skin substitutes can be synthesised on demand and can be modulated for specific purposes. Each class has its advantages and disadvantages. The biological skin substitutes may allow the construction of a more natural new dermis and allow excellent re-epithelialisation characteristics due to the presence of a basement membrane. Synthetic skin substitutes demonstrate the advantages of increase control over scaffold composition. The ultimate goal is to achieve an ideal skin substitute that provides an effective and scar-free wound healing. PMID:21321652

  20. Cross-reactivity of the CEDIA buprenorphine assay in drugs-of-abuse screening: influence of dose and metabolites of opioids

    PubMed Central

    Berg, Jon Andsnes; Schjøtt, Jan; Fossan, Kjell O; Riedel, Bettina

    2015-01-01

    Purpose The cloned enzyme donor immunoassay (CEDIA) for buprenorphine is applied for both urine drugs-of-abuse screening and compliance monitoring. Sensitivity, specificity, and optimal cutoff of this assay have differed between studies. This may indicate that cross-reactivity has to be taken into account during assay evaluation. We therefore investigated the performance of the CEDIA buprenorphine assay for use in our patient population and explored the impact of cross-reactivity on assay accuracy. Methods The CEDIA buprenorphine assay and high-performance liquid chromatography–tandem mass spectrometry were employed to analyze drugs-of-abuse in urine samples from a healthy drug-naïve male volunteer after intake of two tablets of a prescription drug containing 400 mg paracetamol +30 mg codeine phosphate, and in urine samples (n=2,272) from drug-addicted patients. Receiver operating characteristic analyses were performed to express the diagnostic accuracy of the CEDIA buprenorphine assay. Results CEDIA buprenorphine was positive in one urine sample from the drug-naïve person after intake of the prescription drug. Twenty-five (1.1%) of the patient urine samples were positive for buprenorphine by CEDIA, but negative by high-performance liquid chromatography–tandem mass spectrometry. Codeine, morphine, and their respective metabolites were prevalent in samples that were false positive for buprenorphine. The specificity of the CEDIA buprenorphine assay increased to 99.7% when the cutoff was increased from 5 ng/mL to 10 ng/mL. Conclusion Intake of a therapeutic dose of codeine can yield a false-positive CEDIA buprenorphine result. Additive effects from metabolites of codeine contribute to cross-reactivity in concentrations much lower than listed in the manufacturer’s cross-reactivity guide. Raising the cutoff from 5 ng/mL to 10 ng/mL increased the diagnostic accuracy. Clinicians should be informed about the risk of false-positive results with the CEDIA buprenorphine assay. PMID:26604854

  1. Bone Graft Substitution and Augmentation.

    PubMed

    Nauth, Aaron; Lane, Joseph; Watson, J Tracy; Giannoudis, Peter

    2015-12-01

    Selection of appropriate bone graft or bone graft substitute requires careful recognition of the bone healing needs of the patient's specific clinical problem and a thorough understanding of the different properties possessed by the available bone grafts and substitutes. Although autogenous iliac crest bone graft remains the gold standard of treatment for delayed unions, nonunions, and bone defects, there are a number of promising alternatives available, and emerging evidence suggests that they can be very effective when used in the proper setting. Among these, reamer-irrigator-aspirator bone graft, bone marrow concentrate, bone morphogenetic proteins, and calcium phosphate cements have received a great deal of attention in the literature. This review describes these grafts in detail along with the evidence for their use. In addition, a framework is provided for selecting the appropriate graft or substitute based on their provided properties. PMID:26584264

  2. Adding an Internet-delivered Treatment to an Efficacious Treatment Package for Opioid Dependence

    PubMed Central

    Christensen, Darren R.; Landes, Reid D.; Jackson, Lisa; Marsch, Lisa A.; Mancino, Michael; Chopra, Mohit P.; Bickel, Warren K.

    2014-01-01

    Objective To examine the benefit of adding an internet-delivered behavior therapy to a buprenorphine medication program and voucher-based motivational incentives. Method A block-randomized, unblinded, parallel, 12-week treatment trial was conducted with 170 opioid-dependent adult patients (mean age 34.3 years; 54.1% male; 95.3% white). Participants received an internet-based community reinforcement approach intervention plus contingency management (CRA+) and buprenorphine, or contingency management alone (CM-alone) plus buprenorphine. The primary outcomes, measured over the course of treatment, were longest continuous abstinence, total abstinence, and days retained in treatment. Results Compared to those receiving CM-alone, CRA+ recipients exhibited on average 9.7 total days more of abstinence, 95% CI: (2.3, 17.2), and had a reduced hazard of dropping out of treatment, Hazard Ratio (HR)=0.47; 95% CI: (0.26, 0.85). Prior treatment for opioid dependence significantly moderated the additional improvement of CRA+ for longest continuous days of abstinence. Conclusions These results provide further evidence that an internet-based CRA+ treatment is efficacious and adds clinical benefits to a contingency management/medication based program for opioid dependence. PMID:25090043

  3. Rifampin reduces oral morphine absorption: a case of transdermal buprenorphine selection based on morphine pharmacokinetics.

    PubMed

    Fudin, Jeffrey; Fontenelle, Dania Vanesta; Payne, Annette

    2012-12-01

    A 51-year-old male was referred to the Stratton Veterans Affairs Medical Center Pain Service after hospital admission for endocarditis with a history of heroin use and chronic low back pain. During his hospital stay he experienced a reduction in his serum morphine level ostensibly as a result of concomitant rifampin administration. We hypothesize that diminished absorption was from rifampin-mediated intestinal P-glycoprotein induction, ultimately decreasing serum free morphine and metabolites. The case became more complex in an attempt to balance managed pain, history of substance abuse, completion of antibiotic therapy, and a reasonable pain regimen upon discharge. Ultimately, the patient was titrated onto a buprenorphine transdermal patch, the initiation of which was based on serum free morphine and an extrapolated oral morphine dose by calculation. PMID:23216174

  4. Quinine substitutes in the confederate army.

    PubMed

    Hasegawa, Guy R

    2007-06-01

    During the Civil War, the unreliable supply and high cost of quinine forced the Confederate Army to use alternative treatments for malaria. Many quinine substitutes were mentioned in the literature of the time, but relatively few were advocated by Confederate officials and even fewer are described in surviving records. Medical supply officers often issued substitute remedies when quinine was requisitioned. Most alternative treatments were made from indigenous plants such as dogwood, willow (a constituent of which gave rise to aspirin), and tulip tree. High hopes were held for Georgia bark, which was thought to be closely related to cinchona, from which quinine was derived. Documentation of the effectiveness of quinine substitutes is scanty but is most plentiful for the external application of turpentine. The quinine substitutes were generally considered useful but not as effective as quinine. The Confederate Surgeon General's Office was active in seeking out and supplying troops with quinine substitutes. PMID:17615851

  5. Efficacy of Sustained-Release Buprenorphine in an Experimental Laparotomy Model in Female Mice.