Bup Feeds

Where do we stand in the field of anti-abuse drug discovery?

Buprenorphine Research (PubMed) - 15 hours 11 min ago

Where do we stand in the field of anti-abuse drug discovery?

Expert Opin Drug Discov. 2014 Aug 27;:1-4

Authors: Tzschentke TM

Abstract
Drug abuse and addiction to licit and illicit drugs constitute an almost worldwide health and socioeconomic problem. This problem can be addressed in a number of ways. As far as pharmaceutical development and drug therapy is concerned, abuse-deterrent formulations (ADF), substitution therapies, antagonist therapies, aversion therapies, and diverse novel approaches can be considered. ADF (or tamper-resistant formulations) are an important step towards preventing the abuse of medically used drugs, such as strong opioid analgesics, and some drug treatments are well established, such as substitution therapy in opioid dependence with methadone and buprenorphine. Nevertheless, a large medical need remains, and drugs that effectively curb opioid or psychostimulant addiction by promoting abstinence and preventing relapse have yet to be developed. Many different targets and mechanisms are currently being considered in preclinical research, but apart from repurposing or reformulating already known drugs, very little clinical development is currently ongoing. It is hoped that at least a few of the investigated approaches (e.g., various glutamate and GABA receptor modulators, nociceptin/orphanin FQ peptide receptor agonists, or histamine H3 receptor antagonists) reach the stage of clinical development and eventually reach regulatory approval.

PMID: 25162980 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Buprenorphine in the workers' compensation setting.

Buprenorphine Research (PubMed) - 15 hours 11 min ago

Buprenorphine in the workers' compensation setting.

J Opioid Manag. 2014 July-August;10(4):277-283

Authors: Colameco S, Pohl M

Abstract
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 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Buprenorphine-naloxone buccal soluble film for the treatment of opioid dependence: current update.

Buprenorphine Research (PubMed) - Wed, 08/27/2014 - 8:30am
Related Articles

Buprenorphine-naloxone buccal soluble film for the treatment of opioid dependence: current update.

Expert Opin Drug Deliv. 2014 Aug 25;:1-9

Authors: Soyka M

Abstract
Introduction: Opioid dependence is a severe medical disorder with a high psychiatric and somatic comorbidity and mortality rate. The opioid agonist methadone, mixed agonist-antagonist buprenorphine and the combination of buprenorphine with the opioid antagonist naloxone are the first-line maintenance treatments for opioid dependence. Risk of diversion and accidental intoxications, especially in children, are of great concern. To lower these risks, a novel buprenorphine-naloxone film has been developed and introduced in the USA and Australia. Areas covered: This review evaluates the available preclinical and clinical data on the novel buprenorphine-naloxone film for treatment of opioid dependence. Literature was identified through a comprehensive PubMed search. Data sources also included official FDA information and material made public by the manufacturer. Expert opinion: Few preclinical and clinical data on safety and efficacy have been published. The pharmacological differences between the novel film and the conventional buprenorphine/naloxone are small. In an experimental study, the new formulation suppressed symptoms of opioid withdrawal. The spectrum of adverse events seems to be similar to that of the conventional sublingual tablet. Recent data show that patients prefer the novel film over the conventional sublingual tablet. Emerging surveillance data indicate a lower risk of accidental poisoning in children compared with the conventional formulation. Further clinical and preclinical data are needed to explore additional possible advantages of the new formulation.

PMID: 25156759 [PubMed - as supplied by publisher]

Categories: Bup Feeds

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

Buprenorphine Research (PubMed) - Tue, 08/26/2014 - 6:30am

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

PLoS One. 2014;9(8):e106013

Authors: Le AH, Bonachea LA, Cargill SL

Abstract
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 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Prenatal Buprenorphine Versus Methadone Exposure and Neonatal Outcomes: Systematic Review and Meta-Analysis.

Buprenorphine Research (PubMed) - Tue, 08/26/2014 - 6:30am
Related Articles

Prenatal Buprenorphine Versus Methadone Exposure and Neonatal Outcomes: Systematic Review and Meta-Analysis.

Am J Epidemiol. 2014 Aug 22;

Authors: Brogly SB, Saia KA, Walley AY, Du HM, Sebastiani P

Abstract
Increasing rates of maternal opioid use during pregnancy and neonatal withdrawal, termed neonatal abstinence syndrome (NAS), are public health concerns. Prenatal buprenorphine maintenance treatment (BMT) versus methadone maintenance treatment (MMT) may improve neonatal outcomes, but associations vary. To summarize evidence, we used a random-effects meta-analysis model and estimated summary measures of BMT versus MMT on several outcomes. Sensitivity analyses evaluated confounding, publication bias, and heterogeneity. Subjects were 515 neonates whose mothers received BMT and 855 neonates whose mothers received MMT and who were born from 1996 to 2012 and who were included in 12 studies. The unadjusted NAS treatment risk was lower (risk ratio = 0.90, 95% confidence interval (CI): 0.81, 0.98) and mean length of hospital stay shorter (-7.23 days, 95% CI: -10.64, -3.83) in BMT-exposed versus MMT-exposed neonates. In treated neonates, NAS treatment duration was shorter (-8.46 days, 95% CI: -14.48, -2.44) and morphine dose lower (-3.60 mg, 95% CI: -7.26, 0.07) in those exposed to BMT. BMT-exposed neonates had higher mean gestational age and greater weight, length, and head circumference at birth. Fewer women treated with BMT used illicit opioids near delivery (risk ratio = 0.44, 95% CI: 0.28, 0.70). Simulations suggested that confounding by indication could account for some of the observed differences. Prenatal BMT versus MMT may improve neonatal outcomes, but bias may contribute to this protective association. Further evidence is needed to guide treatment choices.

PMID: 25150272 [PubMed - as supplied by publisher]

Categories: Bup Feeds

The role of nurses in comprehensive care management of pregnant women with drug addiction.

Buprenorphine Research (PubMed) - Tue, 08/26/2014 - 6:30am
Related Articles

The role of nurses in comprehensive care management of pregnant women with drug addiction.

Nurs Womens Health. 2014 Aug;18(4):284-93

Authors: McKeever AE, Spaeth-Brayton S, Sheerin S

Abstract
Drug addiction during pregnancy is a complex health and social issue that requires an interdisciplinary health care team providing nonjudgmental, comprehensive care. Critical challenges include onset of and attendance at prenatal care, potential obstetric complications, transition to extrauterine life and potential neonatal abstinence syndrome for the neonate, newborn feeding issues, postpartum depression and risk of relapse for women.

PMID: 25145717 [PubMed - in process]

Categories: Bup Feeds

The Opioid System and Brain Development: Effects of Methadone on the Oligodendrocyte Lineage and the Early Stages of Myelination.

Buprenorphine Research (PubMed) - Thu, 08/21/2014 - 9:00am
Related Articles

The Opioid System and Brain Development: Effects of Methadone on the Oligodendrocyte Lineage and the Early Stages of Myelination.

Dev Neurosci. 2014 Aug 19;

Authors: Vestal-Laborde AA, Eschenroeder AC, Bigbee JW, Robinson SE, Sato-Bigbee C

Abstract
Oligodendrocytes express opioid receptors throughout development, but the role of the opioid system in myelination remains poorly understood. This is a significant problem as opioid use and abuse continue to increase in two particular populations: pregnant addicts (in whom drug effects could target early myelination in the fetus and newborn) and adolescents and young adults (in whom late myelination of 'higher-order' regions takes place). Maintenance treatments for opioid addicts include the long-lasting opioids methadone and buprenorphine. Similar to our previous findings on the effects of buprenorphine, we have now found that early myelination in the developing rat brain is also altered by perinatal exposure to therapeutic doses of methadone. Pups exposed to this drug exhibited elevated brain levels of the 4 major splicing variants of myelin basic protein, myelin proteolipid protein, and myelin-oligodendrocyte glycoprotein. Consistent with the enrichment and function of these proteins in mature myelin, analysis of the corpus callosum in these young animals also indicated an elevated number of axons with already highly compacted myelin sheaths. Moreover, studies in cultured cells showed that methadone exerts direct effects at specific stages of the oligodendrocyte lineage, stimulating the proliferation of progenitor cells while on the other hand accelerating the maturation of the more differentiated but still immature preoligodendrocytes. While the long-term effects of these observations remain unknown, accelerated or increased oligodendrocyte maturation and myelination could both disrupt the complex sequence of synchronized events leading to normal connectivity in the developing brain. Together with our previous observations on the effects of buprenorphine, the present findings further underscore a crucial function of the endogenous opioid system in the control of oligodendrocyte development and the timing of myelination. Interference with these regulatory systems by opioid use or maintenance treatments could disrupt the normal process of brain maturation at critical stages of myelin formation. © 2014 S. Karger AG, Basel.

PMID: 25138998 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Parenting and Concerns of Pregnant Women in Buprenorphine Treatment.

Buprenorphine Research (PubMed) - Wed, 08/20/2014 - 9:00am

Parenting and Concerns of Pregnant Women in Buprenorphine Treatment.

MCN Am J Matern Child Nurs. 2014 September/October;39(5):319-324

Authors: Rizzo RA, Neumann AM, King SO, Hoey RF, Finnell DS, Blondell RD

Abstract
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 a 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 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Addiction Disorders.

Buprenorphine Research (PubMed) - Wed, 08/20/2014 - 9:00am

Addiction Disorders.

Med Clin North Am. 2014 Sep;98(5):1097-1122

Authors: Merrill JO, Duncan MH

Abstract
Substance use disorders are common in primary care settings, but detection, assessment, and management are seldom undertaken. Substantial evidence supports alcohol screening and brief intervention for risky drinking, and pharmacotherapy is effective for alcohol use disorders. Substance use disorders can complicate the management of chronic noncancer pain, making routine monitoring and assessment for substance use disorders an important aspect of long-term opioid prescribing. Patients with opioid use disorders can be effectively treated with methadone in opioid treatment programs or with buprenorphine in the primary care setting.

PMID: 25134875 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Buprenorphine in the workers' compensation setting.

Buprenorphine Research (PubMed) - Tue, 08/19/2014 - 8:30am
Related Articles

Buprenorphine in the workers' compensation setting.

J Opioid Manag. 2014 July-August;10(4):271-277

Authors: Colameco S, Pohl M

Abstract
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: 25133913 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Health Outcomes and Retention in Care Following Release from Prison for Patients of an Urban Post-incarceration Transitions Clinic.

Buprenorphine Research (PubMed) - Tue, 08/19/2014 - 8:30am
Related Articles

Health Outcomes and Retention in Care Following Release from Prison for Patients of an Urban Post-incarceration Transitions Clinic.

J Health Care Poor Underserved. 2014;25(3):1139-52

Authors: Fox AD, Anderson MR, Bartlett G, Valverde J, Starrels JL, Cunningham CO

Abstract
Chronic health conditions are overrepresented among prisoners who often face barriers to medical care following release. Transitions clinics seek to provide timely access to medical care following release. This retrospective cohort study investigated care delivery and health outcomes for recently released prisoners receiving care at the Bronx Transitions Clinic. Among 135 recently released prisoners, median time from release to initial medical visit was 10 days (IQ Range: 5-31). Six-month retention in care was high for HIV-infection (86%), but lower for opioid dependence (33%), hypertension (45%) and diabetes (43%). At six months, 54% of HIV-patients had a suppressed viral load, but fewer buprenorphine-treated patients reduced opioid use (19%), and fewer hypertensive and diabetic patients reached respective blood pressure (35%) and hemoglobin A1c (14%) goals. Access to medical care is necessary but not sufficient to control chronic health conditions. Additional interventions are necessary for formerly incarcerated people to achieve optimal health outcomes.

PMID: 25130230 [PubMed - in process]

Categories: Bup Feeds

Ethnic- and gender-specific differences in the prevalence of HIV among patients in opioid maintenance treatment--a case register analysis.

Buprenorphine Research (PubMed) - Tue, 08/19/2014 - 8:30am
Related Articles

Ethnic- and gender-specific differences in the prevalence of HIV among patients in opioid maintenance treatment--a case register analysis.

Harm Reduct J. 2014 Aug 18;11(1):23

Authors: Liebrenz M, Stohler R, Nordt C

Abstract
BACKGROUND: We have sought to identify ethnic- and gender-specific differences in HIV prevalence among heroin users receiving opioid maintenance treatment in the canton of Zurich, Switzerland.
METHODS: We used a generalized linear model (GEE) to analyze data from the anonymized case register for all opioid maintenance treatments in the canton of Zurich. Patients who received either methadone or buprenorphine between 1991 and 2012 (n = 11,422) were evaluated for gender (male vs. female), ethnic background (Swiss vs. non-Swiss), and lifetime method of drug use (ever injector vs. non-injector). We addressed missing data by multiple imputation.
RESULTS: The overall prevalence of HIV among patients declined substantially from 33.7% in 1991 to 10.6% in 2012 in the complete dataset. In the imputed datasets, the respective prevalence dropped from 32.8% in 1991 to 9.7% in 2012. Non-injectors had a four to five times lower risk ratio (RR) compared to the reference group, 'Swiss males who ever injected'. In addition, we found a significantly higher risk ratio of HIV prevalence among females who had ever injected; this was true both for the complete dataset and the imputed dataset (Swiss RR 1.18 CI 95% 1.04-1.34, non-Swiss RR 1.58 CI 95% 1.18-2.12).
CONCLUSION: In this population, gender, ethnic background, and lifetime method of drug use influenced the risk of being HIV positive. Different access to treatment and different characteristics of risk exposure among certain subgroups might explain these findings. In particular, the higher risk for women who inject drugs--especially for those with an immigrant background--warrants additional research. Further exploration should identify what factors deter women from using available HIV-prevention measures and whether and how these measures can be better adapted to high-risk groups.

PMID: 25130184 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Integration of health services improves multiple healthcare outcomes among HIV-infected people who inject drugs in Ukraine.

Buprenorphine Research (PubMed) - Sun, 08/17/2014 - 9:00am
Related Articles

Integration of health services improves multiple healthcare outcomes among HIV-infected people who inject drugs in Ukraine.

Drug Alcohol Depend. 2014 Jan 1;134:106-14

Authors: Bachireddy C, Soule MC, Izenberg JM, Dvoryak S, Dumchev K, Altice FL

Abstract
BACKGROUND: People who inject drugs (PWID) experience poor outcomes and fuel HIV epidemics in middle-income countries in Eastern Europe and Central Asia. We assess integrated/co-located (ICL) healthcare for HIV-infected PWID, which despite international recommendations, is neither widely available nor empirically examined.
METHODS: A 2010 cross-sectional study randomly sampled 296 HIV-infected opioid-dependent PWID from two representative HIV-endemic regions in Ukraine where ICL, non-co-located (NCL) and harm reduction/outreach (HRO) settings are available. ICL settings provide onsite HIV, addiction, and tuberculosis services, NCLs only treat addiction, and HROs provide counseling, needles/syringes, and referrals, but no opioid substitution therapy (OST). The primary outcome was receipt of quality healthcare, measured using a quality healthcare indicator (QHI) composite score representing percentage of eight guidelines-based recommended indicators met for HIV, addiction and tuberculosis treatment. The secondary outcomes were individual QHIs and health-related quality-of-life (HRQoL).
RESULTS: On average, ICL-participants had significantly higher QHI composite scores compared to NCL- and HRO-participants (71.9% versus 54.8% versus 37.0%, p<0.001) even after controlling for potential confounders. Compared to NCL-participants, ICL-participants were significantly more likely to receive antiretroviral therapy (49.5% versus 19.2%, p<0.001), especially if CD4 ≤ 200 (93.8% versus 62.5% p<0.05); guideline-recommended OST dosage (57.3% versus 41.4%, p<0.05); and isoniazid preventive therapy (42.3% versus 11.2%, p<0.001). Subjects receiving OST had significantly higher HRQoL than those not receiving it (p<0.001); however, HRQoL did not differ significantly between ICL- and NCL-participants.
CONCLUSIONS: These findings suggest that OST alone improves quality-of-life, while receiving care in integrated settings collectively and individually improves healthcare quality indicators for PWID.

PMID: 24128379 [PubMed - indexed for MEDLINE]

Categories: Bup Feeds

Costs of care for persons with opioid dependence in commercial integrated health systems.

Buprenorphine Research (PubMed) - Sat, 08/16/2014 - 6:00am

Costs of care for persons with opioid dependence in commercial integrated health systems.

Addict Sci Clin Pract. 2014 Aug 14;9(1):16

Authors: Lynch FL, McCarty D, Mertens J, Perrin NA, Green CA, Parthasarathy S, Dickerson JF, Anderson BM, Pating D

Abstract
BACKGROUND: When used in general medical practices, buprenorphine is an effective treatment for opioid dependence, yet little is known about how use of buprenorphine affects the utilization and cost of health care in commercial health systems.Objectives: To examine how buprenorphine affects patterns of medical care, addiction medicine services, and costs from the health system perspective.Research design: Retrospective cohort study.Subjects: Individuals with two or more opioid-dependence diagnoses per year, in two large health systems (System A: n = 1836; System B: n = 4204), over the time span 2007-2008.Measures: Health system utilization, cost, propensity scores.
RESULTS: Patients receiving buprenorphine plus addiction counseling had significantly lower total health care costs than patients with little or no addiction treatment (mean health care costs with buprenorphine treatment = $13,578; vs. mean health care costs with no addiction treatment = $31,055; p < .0001), while those receiving buprenorphine plus addiction counseling and those with addiction counseling only did not differ significantly in total health care costs (mean costs with counseling only: $17,017; p = .5897). In comparison to patients receiving buprenorphine plus counseling, those with little or no addiction treatment had significantly greater use of primary care (p < .001), other medical visits (p = .001), and emergency services (p = .020). Patients with counseling only (compared to patients with buprenorphine plus counseling) used less inpatient detoxification (p < .001), and had significantly more PC visits (p = .001), other medical visits (p = .005), and mental health visits (p = .002).
CONCLUSIONS: Buprenorphine is a viable alternative to other treatment approaches for opioid dependence in commercial integrated health systems, with total costs of health care similar to abstinence-based counseling. Patients with buprenorphine plus counseling had reduced use of general medical services compared to the alternatives.

PMID: 25123823 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Methadone maintenance treatment may improve completion rates and delay opioid relapse for opioid dependent individuals under community corrections supervision.

Buprenorphine Research (PubMed) - Fri, 08/15/2014 - 6:30am

Methadone maintenance treatment may improve completion rates and delay opioid relapse for opioid dependent individuals under community corrections supervision.

Addict Behav. 2014 Jul 10;39(12):1736-1740

Authors: Clark CB, Hendricks PS, Lane PS, Trent L, Cropsey KL

Abstract
AIMS: Several studies have demonstrated the importance of agonist therapies such as methadone and buprenorphine for preventing relapse for individuals being released from jail or prison to the community. No studies have examined the impact of methadone for increasing the completion of community supervision requirements and preventing opioid relapse for individuals under community corrections supervision. This observational study compared the community corrections completion rate and opioid relapse rate of individuals receiving methadone maintenance therapy (MMT) to individuals who did not.
METHODS: Of the 2931 individuals enrolled under criminal justice supervision in the community, Treatment Accountability for Safer Communities (TASC), and who met criteria for opioid dependence, 329 (11%) individuals reported receiving MMT in the community.
RESULTS: The majority of participants were White (79.8%) and male (63.5%), with a mean age of 31.33years (SD=9.18), and were under supervision for 10.4months (SD=9.1). MMT participants were less likely to fail out of supervision compared to individuals not in MMT (39.0% vs. 52.9%, p<0.001), and had a lower rate of relapse (32.9%) and longer time to relapse (average days=89.7, SD=158.9) compared to the relapse rate (55.9%) and time to relapse (average days=60.5, SD=117.9) of those not on MMT.
CONCLUSIONS: While the observational nature of this study prevents causal inferences, these results suggest that utilization of MMT in community corrections may increase the likelihood of completing supervision requirements and delay time to opioid relapse. Providing agonist therapies to opioid dependent individuals under supervision appears to be a critical strategy in this important population.

PMID: 25117851 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Opioid Selective Antinociception Following Microinjection into the Periaqueductal Gray of the Rat.

Buprenorphine Research (PubMed) - Tue, 08/12/2014 - 9:00am
Related Articles

Opioid Selective Antinociception Following Microinjection into the Periaqueductal Gray of the Rat.

J Pain. 2014 Aug 5;

Authors: Morgan MM, Reid RA, Stormann TM, Lautermilch NJ

Abstract
Morphine and fentanyl produce antinociception in part by binding to mu-opioid receptors (MOPr) in the periaqueductal gray (PAG). The present study tested the hypothesis that the PAG also contributes to the antinociceptive effects of other commonly used opioids (oxycodone, methadone, & buprenorphine). Microinjection of high doses of oxycodone (32 - 188 μg/0.4 μl) into the ventrolateral PAG of the rat produced a dose dependent increase in hot plate latency. This antinociception was evident within 5 min and nearly gone by 30 min. In contrast, no antinociception was evident following microinjection of methadone or buprenorphine into the ventrolateral PAG despite use of a wide range of doses and test times. Antinociception was evident following subsequent microinjection of morphine into the same injection sites or following systemic administration of buprenorphine demonstrating that the injections sites and drugs could support antinociception. Antinociception to systemic, but not PAG administration of buprenorphine occurred in both male and female rats. These and previous data demonstrate that the MOPr signaling pathway for antinociception in the PAG is selectively activated by some commonly used opioids (e.g., morphine, fentanyl and oxycodone), but not others (e.g., methadone or buprenorphine). The fact that methadone and buprenorphine produce antinociception following systemic administration demonstrates that MOPr signaling varies depending on location in the nervous system.
PERSPECTIVE: This study demonstrates that the periaqueductal gray contributes to the antinociceptive effects of some commonly used opioids (morphine, fentanyl and oxycodone), but not others (methadone or buprenorphine). Such functional selectivity in periaqueductal gray mediated opioid antinociception helps explain why the analgesic profile of opioids is so variable.

PMID: 25106089 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Faster, better, stronger: Towards new antidepressant therapeutic strategies.

Buprenorphine Research (PubMed) - Wed, 08/06/2014 - 7:30am

Faster, better, stronger: Towards new antidepressant therapeutic strategies.

Eur J Pharmacol. 2014 Aug 1;

Authors: O'Leary OF, Dinan TG, Cryan JF

Abstract
Major depression is a highly prevalent disorder and is predicted to be the second leading cause of disease burden by 2020. Although many antidepressant drugs are currently available, they are far from optimal. Approximately 50% of patients do not respond to initial first line antidepressant treatment, while approximately one third fail to achieve remission following several pharmacological interventions. Furthermore, several weeks or months of treatment are often required before clinical improvement, if any, is reported. Moreover, most of the commonly used antidepressants have been primarily designed to increase synaptic availability of serotonin and/or noradrenaline and although they are of therapeutic benefit to many patients, it is clear that other therapeutic targets are required if we are going to improve the response and remission rates. It is clear that more effective, rapid-acting antidepressants with novel mechanisms of action are required. The purpose of this review is to outline the current strategies that are being taken in both preclinical and clinical settings for identifying superior antidepressant drugs. The realisation that ketamine has rapid antidepressant-like effects in treatment resistant patients has reenergised the field. Further, developing an understanding of the mechanisms underlying the rapid antidepressant effects in treatment-resistant patients by drugs such as ketamine may uncover novel therapeutic targets that can be exploited to meet the Olympian challenge of developing faster, better and stronger antidepressant drugs.

PMID: 25092200 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Buprenorphine Treatment for Hospitalized, Opioid-Dependent Patients: A Randomized Clinical Trial.

Buprenorphine Research (PubMed) - Tue, 08/05/2014 - 9:00am
Related Articles

Buprenorphine Treatment for Hospitalized, Opioid-Dependent Patients: A Randomized Clinical Trial.

JAMA Intern Med. 2014 Aug 1;174(8):1369-1376

Authors: Liebschutz JM, Crooks D, Herman D, Anderson B, Tsui J, Meshesha LZ, Dossabhoy S, Stein M

Abstract
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.
Trial Registration: clinicaltrials.gov Identifier: NCT00987961.

PMID: 25090173 [PubMed - as supplied by publisher]

Categories: Bup Feeds

Adding an Internet-Delivered Treatment to an Efficacious Treatment Package for Opioid Dependence.

Buprenorphine Research (PubMed) - Tue, 08/05/2014 - 9:00am
Related Articles

Adding an Internet-Delivered Treatment to an Efficacious Treatment Package for Opioid Dependence.

J Consult Clin Psychol. 2014 Aug 4;

Authors: Christensen DR, Landes RD, Jackson L, Marsch LA, Mancino MJ, Chopra MP, Bickel WK

Abstract
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% confidence interval [CI = 2.3, 17.2]) and had a reduced hazard of dropping out of treatment (hazard ratio = 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. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

PMID: 25090043 [PubMed - as supplied by publisher]

Categories: Bup Feeds

The Anti-Suicidal Potential of Buprenorphine: A Case Report.

Buprenorphine Research (PubMed) - Sun, 08/03/2014 - 6:30am

The Anti-Suicidal Potential of Buprenorphine: A Case Report.

Int J Psychiatry Med. 2014 Jan 1;47(2):169-174

Authors: Striebel JM, Kalapatapu RK

Abstract
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 [PubMed - as supplied by publisher]

Categories: Bup Feeds
Subscribe to BupPractice aggregator - Bup Feeds