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Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement.

Tue, 04/11/2017 - 8:05am
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Sex Differences in Regional Brain Glucose Metabolism Following Opioid Withdrawal and Replacement.

Neuropsychopharmacology. 2017 Apr 10;:

Authors: Santoro GC, Carrion J, Patel K, Vilchez C, Veith J, Brodie JD, Dewey SL

Abstract
Methadone and buprenorphine are currently the most common pharmacological treatments for opioid dependence. Interestingly, the clinical response to these drugs appears to be sex-specific. That is, females exhibit superior therapeutic efficacy, defined as extended periods of abstinence and longer time to relapse, compared to males. However, the underlying metabolic effects of opioid withdrawal and replacement have not been examined. Therefore, using (18)FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement. In both males and females, spontaneous opioid withdrawal altered glucose metabolism in regions associated with reward and drug dependence. Specifically, metabolic increases in the thalamus, as well as metabolic decreases in insular cortex and the periaqueductal grey were noted. However, compared to males, females exhibited increased metabolism in the preoptic area, primary motor cortex, and the amygdala, and decreased metabolism in the caudate/putamen and medial geniculate nucleus. Methadone and buprenorphine initially abolished these changes uniformly, but subsequently produced their own regional metabolic alterations that varied by treatment and sex. Compared to sex-matched control animals undergoing spontaneous opioid withdrawal, male animals treated with methadone exhibited increased caudate/putamen metabolism, whereas buprenorphine produced increased ventral striatum and motor cortex metabolism in females, and increased ventral striatum and somatosensory cortex metabolism in males. Notably, when treatment effects were compared between sexes, methadone-treated females showed increased cingulate cortex metabolism, while buprenorphine-treated females showed decreased metabolism in cingulate cortex and increased metabolism in the globus pallidus. Perhaps the initial similarities in males and females underlie early therapeutic efficacy, while these post-treatment sex differences contribute to clinical treatment failure more commonly experienced by the former.Neuropsychopharmacology accepted article preview online, 10 April 2017. doi:10.1038/npp.2017.69.

PMID: 28393895 [PubMed - as supplied by publisher]

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HIV And HCV infection among opiate-dependent patients and methadone doses: the PROTEUS study.

Tue, 04/11/2017 - 8:05am
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HIV And HCV infection among opiate-dependent patients and methadone doses: the PROTEUS study.

AIDS Care. 2017 Apr 09;:1-6

Authors: Roncero C, Fuster D, Palma-Álvarez RF, Rodriguez-Cintas L, Martinez-Luna N, Álvarez FJ

Abstract
Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are prevalent infections in opiate-dependent patients. Opiate replacement treatment (ORT) with methadone or buprenorphine is associated with several important outcomes among patients with opiate dependence. However, little is known about outcomes in patients with HIV and/or HCV infections that are in ORT. Also, it is not well established whether the presence of HCV or HIV infection could be associated with higher methadone doses. This paper reanalyzes the database of PROTEUS study, using two principal variables: methadone dose and presence of HIV and/or HCV infection. PROTEUS recruited 621 patients (84.1% were male, mean age: 38.9 years, SD: 7.9), information about the presence of HIV in status was available for 390 patients. Of those, 134 (34.4%) were HIV-infected. Whilst, information about HCV infection was available for 377 patients. Of those, 315 (83.6%) were HCV-infected. Information on HIV/HCV coinfection was available for 376 patients, of those, 112 (29.8%) had this coinfection. HIV-infected and HIV/HCV-coinfected patients received higher methadone doses than those without these infections. Antiretroviral therapy (ART) was used in 80% of patients with HIV infection. The proportion of patients taking antiretroviral drugs was significantly higher for patients treated with higher methadone doses (p < 0.01). Findings suggest that HIV-infected and HIV/HVC-coinfected patients in ORT require higher methadone dose.

PMID: 28393548 [PubMed - as supplied by publisher]

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A case report on the treatment of complex chronic pain and opioid dependence by a multidisciplinary transitional pain service using the ACT Matrix and buprenorphine/naloxone.

Tue, 04/11/2017 - 8:05am
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A case report on the treatment of complex chronic pain and opioid dependence by a multidisciplinary transitional pain service using the ACT Matrix and buprenorphine/naloxone.

J Pain Res. 2017;10:747-755

Authors: Weinrib AZ, Burns LC, Mu A, Azam MA, Ladak SS, McRae K, Katznelson R, Azargive S, Tran C, Katz J, Clarke H

Abstract
In an era of growing concern about opioid prescribing, the postsurgical period remains a critical window with the risk of significant opioid dose escalation, particularly in patients with a history of chronic pain and presurgical opioid use. The purpose of this case report is to describe the multidisciplinary care of a complex, postsurgical pain patient by an innovative transitional pain service (TPS). A 59-year-old male with complex chronic pain, as well as escalating long-term opioid use, presented with a bleeding duodenal ulcer requiring emergency surgery. After surgery, the TPS provided integrated pharmacological and behavioral treatment, including buprenorphine combined with naloxone and acceptance and commitment therapy (ACT) using the ACT Matrix. The result was dramatic pain reduction and improved functioning and quality of life after 40+ years of chronic pain, thus changing the pain trajectory of a chronic, complex, opioid-dependent patient.

PMID: 28392713 [PubMed - in process]

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Vermont Hub-and-Spoke Model of Care For Opioid Use Disorder: Development, Implementation, and Impact.

Thu, 04/06/2017 - 7:07am

Vermont Hub-and-Spoke Model of Care For Opioid Use Disorder: Development, Implementation, and Impact.

J Addict Med. 2017 Apr 04;:

Authors: Brooklyn JR, Sigmon SC

Abstract
BACKGROUND: Opioid use disorders (OUDs) are reaching epidemic proportions in the United States, and many geographic areas struggle with a persistent shortage in availability of opioid agonist treatment. Over the past 5 years, Vermont addiction medicine physicians and public health leaders have responded to these challenges by developing an integrated hub-and-spoke opioid treatment network.
METHODS: In the present report, we review the development, implementation, and impact of this novel hub-and-spoke model for expanding OUD treatment in Vermont.
RESULTS: Vermont's hub-and-spoke system has been implemented state-wide and well-received by providers and patients alike. Adoption of this model has been associated with substantial increases in the state's OUD treatment capacity, with Vermont now having the highest capacity for treating OUD in the United States with 10.56 people in treatment per 1000. There has been a 64% increase in physicians waivered to prescribe buprenorphine, a 50% increase in patients served per waivered physician, and a robust bidirectional transfer of patients between hubs and spokes based upon clinical need. Challenges to system implementation and important future directions are discussed.
CONCLUSIONS: Development and implementation of a hub-and-spoke system of care has contributed substantially to improvements in opioid agonist treatment capacity in Vermont. This system may serve as a model for other states grappling with the current opioid use epidemic.

PMID: 28379862 [PubMed - as supplied by publisher]

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Targeting multiple opioid receptors - improved analgesics with reduced side effects?

Thu, 04/06/2017 - 7:07am
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Targeting multiple opioid receptors - improved analgesics with reduced side effects?

Br J Pharmacol. 2017 Apr 05;:

Authors: Günther T, Dasgupta P, Mann A, Miess E, Kliewer A, Fritzwanker S, Steinborn R, Schulz S

Abstract
Classical opioid analgesics, including morphine, mediate all of their desired and undesired effects by specific activation of the μ-opioid receptor (μ receptor). The use of morphine for treating chronic pain, however, is limited by the development of constipation, respiratory depression, tolerance and dependence. Analgesic effects can also be mediated through other members of the opioid receptor family such as the κ-opioid receptor (κ receptor), δ-opioid receptor (δ receptor) and the nociceptin/orphanin FQ peptide receptor (NOP receptor). Currently, a new generation of opioid analgesics is being developed that can simultaneously bind with high affinity to multiple opioid receptors. With this new action profile, it is hoped that additional analgesic effects and fewer side effects can be achieved. Recent research is mainly focused on the development of bifunctional μ/NOP receptor agonists, which has already led to novel lead structures such as the spiroindole-based cebranopadol and a compound class with a piperidin-4-yl-1,3-dihydroindol-2-one backbone (SR16835/AT-202 and SR14150/AT-200). In addition, the ornivol BU08028 is an analogue of the clinically well-established buprenorphine. Moreover, the morphinan-based nalfurafine exerts its effect with a dominant κ receptor-component and is therefore utilized in the treatment of pruritus. The very potent dihydroetorphine is a true multi-receptor opioid ligand in that it binds to μ, κ and δ receptor. The main focus of this review is to assess the paradigm of opioid ligands targeting multiple receptors with a single chemical entity. We reflect on this rationale by discussing the biological actions of selected multi-opioid receptor ligands, but not on their medicinal chemistry and design.

PMID: 28378462 [PubMed - as supplied by publisher]

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Six-Year Outcome of Opioid Maintenance Treatment in Heroin-Dependent Patients: Results from a Naturalistic Study in a Nationally Representative Sample.

Wed, 04/05/2017 - 6:00am

Six-Year Outcome of Opioid Maintenance Treatment in Heroin-Dependent Patients: Results from a Naturalistic Study in a Nationally Representative Sample.

Eur Addict Res. 2017 Apr 05;23(2):97-105

Authors: Soyka M, Strehle J, Rehm J, Bühringer G, Wittchen HU

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

PMID: 28376505 [PubMed - as supplied by publisher]

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Effectiveness and cost-effectiveness of unsupervised buprenorphine-naloxone for the treatment of heroin dependence in a randomized waitlist controlled trial.

Tue, 04/04/2017 - 7:08am

Effectiveness and cost-effectiveness of unsupervised buprenorphine-naloxone for the treatment of heroin dependence in a randomized waitlist controlled trial.

Drug Alcohol Depend. 2017 Mar 01;174:181-191

Authors: Dunlop AJ, Brown AL, Oldmeadow C, Harris A, Gill A, Sadler C, Ribbons K, Attia J, Barker D, Ghijben P, Hinman J, Jackson M, Bell J, Lintzeris N

Abstract
BACKGROUND: Access to opioid agonist treatment can be associated with extensive waiting periods with significant health and financial burdens. This study aimed to determine whether patients with heroin dependence dispensed buprenorphine-naloxone weekly have greater reductions in heroin use and related adverse health effects 12-weeks after commencing treatment, compared to waitlist controls and to examine the cost-effectiveness of this strategy.
METHODS: An open-label waitlist RCT was conducted in an opioid treatment clinic in Newcastle, Australia. Fifty patients with DSM-IV-TR heroin dependence (and no other substance dependence) were recruited. The intervention group (n=25) received take-home self-administered sublingual buprenorphine-naloxone weekly (mean dose, 22.7±5.7mg) and weekly clinical review. Waitlist controls (n=25) received no clinical intervention. The primary outcome was heroin use (self-report, urine toxicology verified) at weeks four, eight and 12. The primary cost-effectiveness outcome was incremental cost per additional heroin-free-day.
RESULTS: Outcome data were available for 80% of all randomized participants. Across the 12-weeks, treatment group heroin use was on average 19.02days less/month (95% CI -22.98, -15.06, p<0.0001). A total 12-week reduction in adjusted costs including crime of $A5,722 (95% CI 3299, 8154) in favor of treatment was observed. Excluding crime, incremental cost per heroin-free-day gained from treatment was $A18.24 (95% CI 4.50, 28.49).
CONCLUSION: When compared to remaining on a waitlist, take-home self-administered buprenorphine-naloxone treatment is associated with significant reductions in heroin use for people with DSM-IV-TR heroin dependence. This cost-effective approach may be an efficient strategy to enhance treatment capacity.

PMID: 28371689 [PubMed - as supplied by publisher]

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Efficacy and safety of buprenorphine in peripheral nerve blocks: A meta-analysis of randomised controlled trials.

Tue, 04/04/2017 - 7:08am

Efficacy and safety of buprenorphine in peripheral nerve blocks: A meta-analysis of randomised controlled trials.

Eur J Anaesthesiol. 2017 Mar 31;:

Authors: Schnabel A, Reichl SU, Zahn PK, Pogatzki-Zahn EM, Meyer-Frieem CH

Abstract
BACKGROUND: The duration of analgesia provided by nerve blocks is limited if local anaesthetics are administered alone. Therefore, a variety of additives to local anaesthetics have been investigated to prolong postoperative analgesia following single-shot nerve blocks.
OBJECTIVE(S): The aims of the current meta-analysis were to assess the efficacy and safety of the addition of perineural buprenorphine to local anaesthetic compared with local anaesthetic alone, or combined with systemic administration of buprenorphine, or other perineural opioids for peripheral nerve blocks.
DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs).
DATA SOURCES: The following data sources were systematically searched: MEDLINE, CENTRAL and EMBASE (till 03/2016).
ELIGIBILITY CRITERIA: All RCTs focusing on the efficacy and safety of perineural buprenorphine combined with local anaesthetic compared with local anaesthetic alone, or in combination with systemic buprenorphine, or other perineural opioids for peripheral nerve blocks were included.
RESULTS: We included 13 RCTs (685 patients). Participants treated with perineural buprenorphine combined with local anaesthetic showed a longer duration of analgesia compared with those receiving local anaesthetic alone [mean difference 8.64 h, 95% confidence interval (CI) (6.44 to 10.85); P < 0.01]. However, the buprenorphine group had a significantly higher relative risk (RR) for postoperative nausea and vomiting (PONV) [RR 5.0, 95% CI (1.12 to 22.27); P = 0.03]. The perineural administration of buprenorphine provided a longer duration of analgesia than an intramuscular application [mean difference 6.87 h, 95% CI (4.02 to 9.71); P < 0.01] without evidence of a difference in the incidence of PONV between the modes of administration [RR 0.76, 95% CI (0.28 to 2.03); P = 0.58].
CONCLUSION: This meta-analysis revealed that the addition of buprenorphine to a local anaesthetic peripheral nerve block prolongs postoperative analgesia for about 8 h but significantly increases the risk for PONV. Perineural administration is more effective than systemic application but is associated with a similar risk of PONV. However, these results were influenced by heterogeneity so that further trials (especially head-to-head comparisons) are needed in the future.
TRIAL REGISTRATION: PROSPERO(www.crd.york.ac.uk) identifier: CRD42016036054.

PMID: 28368971 [PubMed - as supplied by publisher]

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Caring for patients with opioid use disorder in the hospital.

Tue, 04/04/2017 - 7:08am
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Caring for patients with opioid use disorder in the hospital.

CMAJ. 2016 Dec 06;188(17-18):1232-1239

Authors: Donroe JH, Holt SR, Tetrault JM

PMID: 27647616 [PubMed - indexed for MEDLINE]

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Buprenorphine physician supply: Relationship with state-level prescription opioid mortality.

Sun, 04/02/2017 - 7:56am
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Buprenorphine physician supply: Relationship with state-level prescription opioid mortality.

Drug Alcohol Depend. 2017 Apr 01;173 Suppl 1:S55-S64

Authors: Knudsen HK, Havens JR, Lofwall MR, Studts JL, Walsh SL

Abstract
BACKGROUND: Buprenorphine is an effective treatment for opioid use disorder but the supply of buprenorphine physicians is currently inadequate to address the nation's prescription opioid crisis. Perception of need due to rising opioid overdose rates is one possible reason for physicians to adopt buprenorphine. This study examined associations between rates of growth in buprenorphine physicians and prescription opioid overdose mortality rates in US states.
METHODS: The total buprenorphine physician supply and number of physicians approved to treat 100 patients (per 100,000 population) were measured from June 2013 to January 2016. States were divided into two groups: those with rates of prescription opioid overdose mortality in 2013 at or above the median (>5.5 deaths per 100,000 population) and those with rates below the median. State-level growth curves were estimated using mixed-effects regression to compare rates of growth between high and low overdose states.
RESULTS: The total supply and the supply of 100-patient buprenorphine physicians grew significantly (total supply from 7.7 to 9.9 per 100,000 population, p<0.001; 100-patient supply from 2.2 to 3.4 per 100,000 population, p<0.001). Rates of growth were significantly greater in high overdose states when compared to low overdose states (total supply b=0.033, p<0.01; 100-patient b=0.022, p<0.01).
CONCLUSIONS: The magnitude of the US prescription opioid crisis, as measured by the rate of prescription opioid overdose mortality, is associated with growth in the number of buprenorphine physicians. Because this observational design cannot establish causality, further research is needed to elucidate the factors influencing physicians' decisions to begin prescribing buprenorphine.

PMID: 28363321 [PubMed - in process]

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The Prescription Opioid Addiction Treatment Study: What have we learned.

Sun, 04/02/2017 - 7:56am
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The Prescription Opioid Addiction Treatment Study: What have we learned.

Drug Alcohol Depend. 2017 Apr 01;173 Suppl 1:S48-S54

Authors: Weiss RD, Rao V

Abstract
BACKGROUND: The multi-site Prescription Opioid Addiction Treatment Study (POATS), conducted by the National Drug Abuse Treatment Clinical Trials Network, was the largest clinical trial yet conducted with patients dependent upon prescription opioids (N=653). In addition to main trial results, the study yielded numerous secondary analyses, and included a 3.5-year follow-up study, the first of its kind with this population. This paper reviews key findings from POATS and its follow-up study.
METHODS: The paper summarizes the POATS design, main outcomes, predictors of outcome, subgroup analyses, the predictive power of early treatment response, and the long-term follow-up study.
RESULTS: POATS examined combinations of buprenorphine-naloxone of varying duration and counseling of varying intensity. The primary outcome analysis showed no overall benefit to adding drug counseling to buprenorphine-naloxone and weekly medical management. Only 7% of patients achieved a successful outcome (abstinence or near-abstinence from opioids) during a 4-week taper and 8-week follow-up; by comparison, 49% of patients achieved success while subsequently stabilized on buprenorphine-naloxone. Long-term follow-up results were more encouraging, with higher abstinence rates than in the main trial. Patients receiving opioid agonist treatment at the time of follow-up were more likely to have better outcomes, though a sizeable number of patients succeeded without agonist treatment. Some patients initiated risky use patterns, including heroin use and drug injection. A limitation of the long-term follow-up study was the low follow-up rate.
CONCLUSIONS: POATS was the first large-scale study of the treatment of prescription opioid dependence; its findings can influence both treatment guidelines and future studies.

PMID: 28363320 [PubMed - in process]

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