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Towards an Effective Peripheral Visceral Analgesic: Responding to the National Opioid Crisis.

12 hours 19 min ago

Towards an Effective Peripheral Visceral Analgesic: Responding to the National Opioid Crisis.

Am J Physiol Gastrointest Liver Physiol. 2018 Feb 22;:

Authors: Camilleri M

Abstract
This is an editorial summarizing recent new developments in visceral analgesics. This promising field is important as a new approach to address abdominal pain with peripheral visceral analgesics is considered a key approach to addressing the current opioid crisis. Some of the novel compounds address peripheral pain mechanisms through modulation of opioid receptors through biased ligands, nociceptin/orphanin FQ opioid peptide (NOP) receptor or dual action on NOP and μ-opioid receptor, buprenorphine and morphiceptin analogs. Other compounds target non-opioid mechanisms including cannabinoid (CBR2), N-methyl-D-aspartate, calcitonin gene-related peptide, estrogen, and adenosine A2b receptors, and transient receptor potential (TRP) channels (TRPV1, TRPV4, TRPM8). Although current evidence is based predominantly on animal models of visceral pain, there are also early human studies that support the evidence emanating from the basic and animal research. This augurs well for the development of non-addictive, visceral analgesics for treatment of chronic abdominal pain, an unmet clinical need.

PMID: 29470146 [PubMed - as supplied by publisher]

Pharmacokinetics of buprenorphine after intravenous and oral transmucosal administration in guinea pigs (Cavia porcellus).

February 22, 2018 - 8:56pm
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Pharmacokinetics of buprenorphine after intravenous and oral transmucosal administration in guinea pigs (Cavia porcellus).

Am J Vet Res. 2018 Mar;79(3):260-266

Authors: Sadar MJ, Knych HK, Drazenovich TL, Paul-Murphy JR

Abstract
OBJECTIVE To determine pharmacokinetics and sedative effects of buprenorphine after IV and oral transmucosal (OTM) administration in guinea pigs. ANIMALS 14 male guinea pigs (6 adults for preliminary experiment; eight 8 to 11-week-old animals for primary study). PROCEDURES A preliminary experiment was conducted to determine an appropriate buprenorphine dose. In the primary study, buprenorphine (0.2 mg/kg) was administered IV or OTM, and blood samples were obtained. The pH of the oral cavity was measured before OTM administration. Sedation was scored for 6 hours on a scale of 0 to 3 (0 = no sedation and 3 = heavy sedation). After a 7-day washout period, procedures were repeated in a crossover manner. Plasma buprenorphine concentration was quantified, and data were analyzed with a noncompartmental pharmacokinetic approach. RESULTS Mean peak plasma buprenorphine concentrations were 46.7 and 2.4 ng/mL after IV and OTM administration, respectively. Mean time to maximum plasma buprenorphine concentration was 1.5 and 71.2 minutes, and mean terminal half-life was 184.9 and 173.0 minutes for IV and OTM administration, respectively. There was a range of sedation effects (0 to 2) for both routes of administration, which resolved within the 6-hour time frame. CONCLUSIONS AND CLINICAL RELEVANCE On the basis of pharmacokinetic parameters for this study, buprenorphine at 0.2 mg/kg may be administered IV every 7 hours or OTM every 4 hours to maintain a target plasma concentration of 1 ng/mL. Further studies are needed to evaluate administration of multiple doses and sedative effects in guinea pigs with signs of pain.

PMID: 29466036 [PubMed - in process]

Caring for Ms. L. - Overcoming My Fear of Treating Opioid Use Disorder.

February 21, 2018 - 6:24am
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Caring for Ms. L. - Overcoming My Fear of Treating Opioid Use Disorder.

N Engl J Med. 2018 Feb 15;378(7):600-601

Authors: Provenzano AM

PMID: 29443676 [PubMed - indexed for MEDLINE]

Impact of opioid therapy on gonadal hormones: focus on buprenorphine.

February 18, 2018 - 8:54am
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Impact of opioid therapy on gonadal hormones: focus on buprenorphine.

Horm Mol Biol Clin Investig. 2018 Feb 17;:

Authors: Varma A, Sapra M, Iranmanesh A

Abstract
Objective The USA is in the midst of an opioid crisis. Understanding the impact of opioids and commonly used treatments for opioid dependence is essential for clinicians and researchers in order to educate and treat the nation's growing population with opioid use disorders. As a relatively new treatment for opioid dependence, buprenorphine is gaining popularity to the extent of becoming not only a preferred approach to the maintenance of opiate addiction, but also an option for chronic pain management. The purpose of this report is to review the available evidence on the endocrine effects of buprenorphine, particularly as it relates to the hypothalamic-pituitary-gonadal (HPG) axis, which is controversial and not fully defined. Method We conducted a Pubmed search (2000-2017) for human studies in the English language for articles that were available as full length regarding buprenorphine, endocrinopathy, hypogonadism, bone density, opioids. Case reports were also reviewed, although prospective studies and randomized controlled trials received more weight. Results Opioid induced hypogonadism is well established. Most studies report that buprenorphine being a partial agonist/antagonist may not be impacting the pituitary trophic hormones as much. There are reports of sexual dysfunction in subjects maintained on buprenorphine, some without hormonal correlation. Thus with the understanding that pertinent clinical studies are limited in number, varied in methodology, mostly cross sectional, predominantly in men and small number of participants, more research in this area is warranted. Conclusion Based on a comprehensive review of the available literature, we conclude that despite its increasing popularity, buprenorphine has not been adequately studied in respect to its long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis. There is a great need for longitudinal systematic trials to define the potential buprenorphine-induced endocrine consequences.

PMID: 29453925 [PubMed - as supplied by publisher]

Illicit and prescription drug misuse as reported to the Maine Diversion Alert Program.

February 18, 2018 - 8:54am
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Illicit and prescription drug misuse as reported to the Maine Diversion Alert Program.

Forensic Sci Int. 2018 Feb 06;285:65-71

Authors: Piper BJ, Suarez MJ, Piserchio JP, Shah DT, Simoyan OM, McCall KL, Desrosiers CE, Nichols SD

Abstract
BACKGROUND: The opioid epidemic is rapidly evolving and new tools are needed to combat drug abuse. The Maine Diversion Alert Program (DAP) is an informational resource that facilitates communication about drug arrests between the criminal justice and healthcare fields. The objectives of this report were to: (1) describe the illegal and prescription pharmaceuticals reported to the DAP; (2) determine if the drugs implicated in arrests changed from the first to latter half of 2016; (3) identify the demographic and other characteristics of arrestees; and (4) outline the strengths and limitations of the DAP for other areas considering implementing similar programs.
METHODS: The arrests (N=2,368, 31.4% female, mean age=33.7, SD=9.9, Min=18, Max=71.5) reported to the DAP were examined. Drugs were classified by Drug Enforcement Administration Schedule (I-V, non-controlled prescription) and into families (opioids, stimulants, sedatives, hallucinogens, and other). A comparison between the first and second half of 2016 and arrest by county was completed.
RESULTS: Arrests involved 2,957 substances (drugs and paraphernalia). Most arrests (80.6%) involved a single drug. One-third (33.2%) of arrests involved illicit drugs (i.e. Schedule I) and three-fifths (59.8%) were for controlled prescription medical drugs (i.e. Schedule II-V), and a minority (6.8%) involved non-controlled prescription drugs (e.g. gabapentin, bupropion). Opioids (e.g. heroin, buprenorphine, and oxycodone) accounted for over-half (51.3%) of arrests followed by stimulants (29.0%, e.g. cocaine), and sedatives (7.6%). Arrests for oxycodone significantly decreased (51.9%) and alprazolam increased (89.3%) during 2016. Arrestees for non-controlled prescription drugs were older than arrestees for illegal drugs. Arrests, correcting for population, were most common in more urban (e.g. Androscoggin and Cumberland) counties.
CONCLUSIONS: Opioids (illicit and prescription) account for over half of all arrests. However, arrests for oxycodone decreased while arrests for benzodiazepines, and especially alprazolam, increased in 2016. The DAP is a novel source of information for healthcare decisions and can empirically inform law enforcement about drug misuse and addiction.

PMID: 29453006 [PubMed - as supplied by publisher]

Patients Maintained on Buprenorphine for Opioid Use Disorder Should Continue Buprenorphine Through the Perioperative Period.

February 17, 2018 - 8:26am

Patients Maintained on Buprenorphine for Opioid Use Disorder Should Continue Buprenorphine Through the Perioperative Period.

Pain Med. 2018 Feb 14;:

Authors: Lembke A, Ottestad E, Schmiesing C

PMID: 29452378 [PubMed - as supplied by publisher]

Pharmacogenomics-guided policy in opioid use disorder (OUD) management: An ethnically-diverse case-based approach.

February 17, 2018 - 8:26am
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Pharmacogenomics-guided policy in opioid use disorder (OUD) management: An ethnically-diverse case-based approach.

Addict Behav Rep. 2017 Dec;6:8-14

Authors: Ettienne EB, Chapman E, Maneno M, Ofoegbu A, Wilson B, Settles-Reaves B, Clarke M, Dunston G, Rosenblatt K

Abstract
Introduction: Opioid use disorder (OUD) is characterized by a problematic pattern of opioid use leading to clinically-significant impairment or distress. Opioid agonist treatment is an integral component of OUD management, and buprenorphine is often utilized in OUD management due to strong clinical evidence for efficacy. However, interindividual genetic differences in buprenorphine metabolism may result in variable treatment response, leaving some patients undertreated and at increased risk for relapse. Clinical pharmacogenomics studies the effect that inherited genetic variations have on drug response. Our objective is to demonstrate the impact of pharmacogenetic testing on OUD management outcomes.
Methods: We analyzed a patient who reported discomfort at daily buprenorphine dose of 24 mg, which was a mandated daily maximum by the pharmacy benefits manager. Regular urine screenings were conducted to detect the presence of unauthorized substances, and pharmacogenetic testing was used to determine the appropriate dose of buprenorphine for OUD management.
Results: At the 24 mg buprenorphine daily dose, the patient had multiple relapses with unauthorized substances. Pharmacogenetic testing revealed that the patient exhibited a cytochrome P450 3A4 ultrarapid metabolizer phenotype, which necessitated a higher than recommended daily dose of buprenorphine (32 mg) for adequate OUD management. The patient exhibited a reduction in the number of relapses on the pharmacogenetic-based dose recommendation compared to standard dosing.
Conclusion: Pharmacogenomic testing as clinical decision support helped to individualize OUD management. Collaboration by key stakeholders is essential to establishing pharmacogenetic testing as standard of care in OUD management.

PMID: 29450233 [PubMed]

Sofosbuvir-Based Direct-Acting Antiviral Therapies for HCV in People Receiving Opioid Substitution Therapy: An Analysis of Phase 3 Studies.

February 17, 2018 - 8:26am
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Sofosbuvir-Based Direct-Acting Antiviral Therapies for HCV in People Receiving Opioid Substitution Therapy: An Analysis of Phase 3 Studies.

Open Forum Infect Dis. 2018 Feb;5(2):ofy001

Authors: Grebely J, Feld JJ, Wyles D, Sulkowski M, Ni L, Llewellyn J, Mir HM, Sajed N, Stamm LM, Hyland RH, McNally J, Brainard DM, Jacobson I, Zeuzem S, Bourlière M, Foster G, Afdhal N, Dore GJ

Abstract
Background: Hepatitis C virus (HCV) direct-acting antiviral therapy is effective among people receiving opioid substitution therapy (OST), but studies are limited by small numbers of nongenotype 1 (GT1) patients. The aim of this study was to evaluate the treatment completion, adherence, SVR12, and safety of sofosbuvir-based therapies in HCV patients receiving and not receiving OST.
Methods: Ten phase 3 studies of sofosbuvir-based regimens included ION (ledipasvir/sofosbuvir ± ribavirin for 8, 12, or 24 weeks in GT1), ASTRAL (sofosbuvir/velpatasvir for 12 weeks in GT1-6), and POLARIS (sofosbuvir/velpatasvir and sofosbuvir/velpatasvir/voxilaprevir in GT1-6). Patients with clinically significant drug use (last 12 months) or noncannabinoids detected at screening were ineligible.
Results: Among 4743 patients, 4% (n = 194) were receiving OST (methadone; n = 113; buprenorphine, n = 75; other, n = 6). Compared with those not receiving OST (n = 4549), those receiving OST (n = 194) were younger (mean age, 48 vs 54), more often male (73% vs 61%), GT3 (38% vs 17%), treatment-naïve (78% vs 65%), and cirrhotic (36% vs 23%). Among those receiving and not receiving OST, there was no significant difference in treatment completion (97% vs 99%, P = .06), SVR12 (94% vs 97%, P = .06), relapse (0.5% vs 2.1%, P = .19), adverse events (78% vs 77%, P = .79), or serious adverse events (3.6% vs 2.4%, P = .24). There was no difference in SVR12 in patients with cirrhosis (99% vs 95%, P = .25) or those with G3 (95% vs 95%, P = .77) in those receiving OST. Among patients receiving OST, SVR12 was high among those receiving methadone (95%) and buprenorphine (96%).
Conclusion: Sofosbuvir-based therapies are effective and safe in patients receiving OST.

PMID: 29450210 [PubMed]

Why It's Inappropriate Not to Treat Incarcerated Patients with Opioid Agonist Therapy.

February 17, 2018 - 8:26am
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Why It's Inappropriate Not to Treat Incarcerated Patients with Opioid Agonist Therapy.

AMA J Ethics. 2017 Sep 01;19(9):922-930

Authors: Wakeman SE

Abstract
Due to the criminalization of drug use and addiction, opioid use disorder is overrepresented in incarcerated populations. Decades of evidence supports opioid agonist therapy as a highly effective treatment that improves clinical outcomes and reduces illicit opioid use, overdose death, and cost. Opioid agonist therapy has been both studied within correctional facilities and initiated prerelease. It has been found to be beneficial, yet few incarcerated persons receive this evidence-based treatment. In addition to not offering treatment initiation for those who need it, most correctional facilities forcibly withdraw stable patients from opioid agonist therapy upon their entry into the criminal justice system. This approach limits their access to evidence-based health care and results in negative outcomes for individuals, communities, and society.

PMID: 28905733 [PubMed - indexed for MEDLINE]

Physician prescribing of opioid agonist treatments in provincial correctional facilities in Ontario, Canada: A survey.

February 16, 2018 - 6:39am

Physician prescribing of opioid agonist treatments in provincial correctional facilities in Ontario, Canada: A survey.

PLoS One. 2018;13(2):e0192431

Authors: Kouyoumdjian FG, Patel A, To MJ, Kiefer L, Regenstreif L

Abstract
BACKGROUND: Substance use and substance use disorders are common in people who experience detention or incarceration in Canada, and opioid agonist treatment (OAT) may reduce the harms associated with substance use disorders. We aimed to define current physician practice in provincial correctional facilities in Ontario with respect to prescribing OAT and to identify potential barriers and facilitators to prescribing OAT.
METHODS: We invited all physicians practicing in the 26 provincial correctional facilities for adults in Ontario to participate in an online survey.
RESULTS: Twenty-seven physicians participated, with representation from most correctional facilities in Ontario. Of participating physicians, 52% reported prescribing methadone and 48% reported prescribing buprenorphine/naloxone to patients in provincial correctional facilities. Nineteen percent of participants reported initiating methadone treatment and 11% reported initiating buprenorphine/naloxone for patients in custody. Participants identified multiple barriers to initiating OAT in provincial correctional facilities including concerns about medication diversion and safety, concerns about initiating treatment in patients who are not currently using opioids, lack of linkage with community-based providers and the Ministry of Community Safety and Correctional Services policy. Identified facilitators to initiating OAT were support from institutional health care staff and administrative staff, adequate resources for program delivery and access to linkage with community-based OAT providers.
CONCLUSIONS: This study identifies opportunities to improve OAT programs and to improve access to OAT for persons in provincial correctional facilities in Ontario.

PMID: 29447177 [PubMed - in process]

Neonatal Outcomes after Fetal Exposure to Methadone and Buprenorphine: National Registry Studies from the Czech Republic and Norway.

February 15, 2018 - 6:39am

Neonatal Outcomes after Fetal Exposure to Methadone and Buprenorphine: National Registry Studies from the Czech Republic and Norway.

Addiction. 2018 Feb 14;:

Authors: Nechanská B, Mravčík V, Skurtveit S, Lund IO, Gabrhelík R, Engeland A, Handal M

Abstract
BACKGROUND AND AIMS: Opioid maintenance treatment (OMT) is recommended to opioid dependent females during pregnancy. However, it is not clear which medication should be preferred. We aimed to compare neonatal outcomes after prenatal exposure to methadone (M) and buprenorphine (B) in two European countries.
DESIGN: Nationwide register-based cohort study using personalized IDs assigned to all citizens for data linkage.
SETTING: The Czech Republic (2000-2014) and Norway (2004-2013).
PARTICIPANTS: Opioid dependent pregnant Czech (N = 333) and Norwegian (N = 235) women in OMT who received either B or M during pregnancy and their new-borns.
MEASUREMENTS: We linked data from health registries to identify the neonatal outcomes: gestational age, preterm birth, birth weight, length and head circumference, small for gestational age, miscarriages and stillbirth, neonatal abstinence syndrome (NAS) and Apgar score. We performed multivariate linear regression and binary logistic regression to explore the associations between M and B exposure and outcomes. Regression coefficient (b) and Odds ratio (OR) were computed.
FINDINGS: Most neonatal outcomes were more favourable after exposure to B as compared with M, but none of the differences was statistically significant. For instance, in the multivariate analysis birth weight was b = 111.6 g (95% confidence interval (CI) = -10.5 - 233.6) and b = 83.1 g (95% CI = -100.8 - 267.0) higher after B exposure in the Czech Republic and Norway, respectively. Adjusted OR of NAS for B compared with M was 0.94 (95% CI = 0.46 - 1.92) in the Norwegian cohort.
CONCLUSIONS: Two national cohorts of women receiving opioid maintenance treatment during pregnancy, showed small but not statistically significant differences in neonatal outcomes in favour of buprenorphine compared with methadone.

PMID: 29443414 [PubMed - as supplied by publisher]

Buprenorphine Treatment for Adolescents and Young Adults With Opioid Use Disorders: A Narrative Review.

February 13, 2018 - 2:54pm

Buprenorphine Treatment for Adolescents and Young Adults With Opioid Use Disorders: A Narrative Review.

J Addict Med. 2018 Feb 09;:

Authors: Borodovsky JT, Levy S, Fishman M, Marsch LA

Abstract
: In the past decade, a new cohort of adolescents and young adults with opioid use disorders (OUD) has emerged. While medications and psychosocial treatments are available, few adolescents and young adults with OUD can access and remain in treatment. Effective, practical, and scalable treatment paradigms for this young population are needed. Buprenorphine is a medication with unique pharmacological and regulatory characteristics that make it a promising component of adolescent and young adult OUD treatment models. Three randomized controlled trials and multiple observational studies have evaluated the use of buprenorphine to treat this population. However, data from these studies have not been consolidated into an up-to-date summary that may be useful to clinicians. The objective of this narrative review is to inform clinical practice by summarizing results of primary and secondary analyses from randomized controlled clinical trials and observational studies that have evaluated the use of buprenorphine to treat adolescents and young adults with OUD. Based on results from these studies, we encourage the conceptualization of OUD among youth as a chronic medical condition requiring a long-term management strategy. This includes treatment with buprenorphine in conjunction with medication-prescribing protocols that do not necessarily require daily clinic attendance for observed medication adherence. However, more study of treatment delivery models, addressing such issues as medication adherence and intensity requirements, is needed to determine practices that optimize outcomes for youth.

PMID: 29432333 [PubMed - as supplied by publisher]

Overcoming medication stigma in peer recovery: a new paradigm.

February 13, 2018 - 2:54pm

Overcoming medication stigma in peer recovery: a new paradigm.

Subst Abus. 2018 Feb 12;:0

Authors: Krawczyk N, Negron T, Nieto M, Agus D, Fingerhood MI

Abstract
BACKGROUND: Treatment for opioid use disorder involving opioid-based pharmacotherapies is considered most effective when accompanied by psychosocial interventions. Peer-led support groups are widely available and have been described by many as fundamental to the recovery process. However, some individuals using medications face stigma in these settings, which can be contradictory and counterproductive to their recovery.
METHODS: This article describes the development of the Ability, Inspiration and Motivation or "AIM" group, an alternative peer support group that aims to remove medication stigma from peer-recovery. Qualitative interviews with staff, peers, and clients of a community-based buprenorphine treatment program were used to establish the core components of the curriculum to support client needs.
RESULTS: Staff, peers and clients of the buprenorphine program indicated a need and desire to establish a peer recovery group that recognizes persons on medication as being in recovery and de-stigmatizes use of medication to treat opioid addiction. A respectful environment, holistic perspective on health, spirituality, sharing and celebration were all established as necessary pillars of the AIM group curriculum.
CONCLUSIONS: The community-based effort to establish and develop the AIM group demonstrates that combining the strengths of a peer support with evidence-based medication treatment is both possible and desirable. Shifting the culture of peer-recovery groups to support the use of medications may have implications for improving treatment retention and should be considered as a potential strategy to reduce the burden of the opioid epidemic.

PMID: 29432086 [PubMed - as supplied by publisher]

Rationale, design, and methodology of a trial evaluating three models of care for HCV treatment among injection drug users on opioid agonist therapy.

February 11, 2018 - 6:26am

Rationale, design, and methodology of a trial evaluating three models of care for HCV treatment among injection drug users on opioid agonist therapy.

BMC Infect Dis. 2018 Feb 09;18(1):74

Authors: Akiyama MJ, Agyemang L, Arnsten JH, Heo M, Norton BL, Schackman BR, Linas BP, Litwin AH

Abstract
BACKGROUND: People who inject drugs (PWID) constitute 60% of the approximately 5 million people in the U.S. infected with hepatitis C virus (HCV). Treatment of PWID is complex due to addiction, mental illness, poverty, homelessness, lack of positive social support, poor adherence-related skills, low motivation and knowledge, and poor access to and trust in the health care system. New direct-acting antiviral medications are available for HCV with high cure rates and few side effects. The life expectancy and economic benefits of new HCV treatments will not be realized unless we determine optimal models of care for the majority of HCV-infected patients. The purpose of this study is to evaluate the effectiveness of directly observed therapy and group treatment compared with self-administered individual treatment in a large, urban opioid agonist therapy clinic setting in the Bronx, New York.
METHODS/DESIGN: In this randomized controlled trial 150 PWID with chronic HCV were recruited from opioid agonist treatment (OAT) clinics and randomized to one of three models of onsite HCV treatment in OAT: 1) modified directly observed therapy; 2) group treatment; or 3) control - self-administered individual treatment. Participants were age 18 or older, HCV genotype 1, English or Spanish speaking, treatment naïve (or treatment experienced after 12/3/14), willing to receive HCV treatment onsite, receiving methadone or buprenorphine at the medication window at least once per week, and able to provide informed consent. Outcomes of interest include adherence (as measured by self-report and electronic blister packs), HCV treatment completion, sustained virologic response, drug resistance, and cost-effectiveness.
DISCUSSION: This paper describes the design and rationale of a randomized controlled trial comparing three models of care for HCV therapy delivered in an opioid agonist treatment program. Our trial will be critical to rigorously identify models of care that result in high adherence and cure rates. Use of blister pack technology will help us determine the role of adherence in successful cure of HCV. Moreover, the trial methodology outlined here can serve as a template for the development of future programs and studies among HCV-infected drug users receiving opioid agonist therapy, as well as the cost-effectiveness of such programs.
TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov ( NCT01857245 ). Trial registration was obtained prospectively on May 20th, 2013.

PMID: 29426304 [PubMed - in process]

The Comprehensive Addiction and Recovery Act: Opioid Use Disorder and Midwifery Practice.

February 9, 2018 - 6:09am

The Comprehensive Addiction and Recovery Act: Opioid Use Disorder and Midwifery Practice.

Obstet Gynecol. 2018 Feb 05;:

Authors: Murphy J, Goodman D, Johnson MC, Terplan M

Abstract
The federal response to the opioid use disorder crisis has included a mobilization of resources to encourage office-based pharmacotherapy with buprenorphine, an effort culminating in the 2016 Comprehensive Addiction and Recovery Act, signed into law as Public Law 114-198. The Comprehensive Addiction and Recovery Act was designed to increase access to treatment with special emphasis on services for pregnant women and follow-up for infants affected by prenatal substance exposure. In this effort, the Comprehensive Addiction and Recovery Act laudably expands eligibility for obtaining a waiver to prescribe buprenorphine to nurse practitioners and physician assistants. However, certified nurse-midwives and certified midwives, who care for a significant proportion of pregnant and postpartum women and attend a significant proportion of births in the United States, were not included in the Comprehensive Addiction and Recovery Act legislation. In this commentary, we argue that an "all-hands" approach to providing office-based medication-assisted treatment for opioid use disorder is essential to improving access to treatment. Introduced in the House of Representatives in September 2017, the Addiction Treatment Access Improvement Act (H.R. 3692) would allow midwives to apply for the federal waiver to prescribe buprenorphine and is supported by the American College of Obstetricians and Gynecologists and the American College of Nurse-Midwives. We support this change and encourage the U.S. Congress to act quickly to allow midwives to prescribe medication-assisted treatment for pregnant women with opioid use disorder.

PMID: 29420414 [PubMed - as supplied by publisher]

A qualitative assessment of attitudes about and preferences for extended-release naltrexone, a new pharmacotherapy to treat opioid use disorders in Ukraine.

February 9, 2018 - 6:09am

A qualitative assessment of attitudes about and preferences for extended-release naltrexone, a new pharmacotherapy to treat opioid use disorders in Ukraine.

J Subst Abuse Treat. 2018 Mar;86:86-93

Authors: Marcus R, Bojko MJ, Mazhnaya A, Makarenko I, Filippovych S, Dvoriak S, Altice FL, Springer SA

Abstract
Numerous individual barriers, including negative attitudes toward opioid agonist therapies (OAT), have undermined HIV prevention efforts in Ukraine where the epidemic is concentrated in people who inject drugs (PWID). The recent availability of extended-release naltrexone (XR-NTX), an opioid antagonist, provides new opportunities for treatment and prevention, but little is known about patient preferences. We conducted qualitative analysis using focus groups (FG) of PWID recruited based on OAT experience: currently, previously, and never on OAT in five Ukrainian cities. FG included 199 PWID in 25 focus groups. Focus group transcripts were coded and analyzed using a modified grounded theory approach to identify common themes and domains related to attitudes about and preferences for XR-NTX, relative to other treatments. Interest in XR-NTX was supported if supervised opioid withdrawal and psychological support were assured. Other factors supporting XR-NTX included a focus on younger PWID early in their injection career and motivated for recovery. Perceptions of recovery included not receiving psychoactive medications like methadone or buprenorphine. With more information, XR-NTX could be a viable option for PWID in Ukraine, especially if concerns regarding withdrawal and psychological support are adequately addressed.

PMID: 29415856 [PubMed - in process]

Predictors of treatment retention in postpartum women prescribed buprenorphine during pregnancy.

February 9, 2018 - 6:09am

Predictors of treatment retention in postpartum women prescribed buprenorphine during pregnancy.

J Subst Abuse Treat. 2018 Mar;86:26-29

Authors: O'Connor AB, Uhler B, O'Brien LM, Knuppel K

Abstract
AIM: To determine variables related to treatment retention in women six and twelve months postpartum that were in medication treatment using buprenorphine during pregnancy.
METHODS: This retrospective cohort study of 190 maternal-infant dyads exposed to buprenorphine during pregnancy examines rates of treatment retention at six and twelve months postpartum and also analyzes a variety of potential predictors of treatment retention including illicit drug use in the third trimester, delayed entry into medication treatment and co-occurring mental health diagnoses requiring prescription medication.
RESULTS: At 12months postpartum, women appeared more likely to remain in medication treatment if they entered treatment early in pregnancy (defined as either being in treatment at the time of conception, p=0.001, or entering medication treatment prior to 13weeks gestation, p=0.037). Being prescribed an antidepressant medication during the third trimester was also associated with enhanced treatment retention at six months postpartum (p=0.005). At both six and twelve months postpartum, the use of illicit drugs (including opioids, cocaine and benzodiazepines) during the third trimester was negatively correlated with treatment retention (p=0.012 and p<0.001, respectively).
CONCLUSIONS: Early access to medication treatment is associated with treatment retention in women prescribed buprenorphine during pregnancy. This has important public health implications as access to treatment is limited in many parts of the country and many women are only able to obtain treatment after becoming pregnant. Being prescribed an antidepressant medication during pregnancy may enhance treatment retention, supporting the work of previous authors.

PMID: 29415847 [PubMed - in process]

Associations between pharmacotherapy for opioid dependence and clinical and criminal justice outcomes among adults with co-occurring serious mental illness.

February 9, 2018 - 6:09am

Associations between pharmacotherapy for opioid dependence and clinical and criminal justice outcomes among adults with co-occurring serious mental illness.

J Subst Abuse Treat. 2018 Mar;86:17-25

Authors: Robertson AG, Easter MM, Lin HJ, Frisman LK, Swanson JW, Swartz MS

Abstract
Adults suffering from a serious mental illness (SMI) and a substance use disorder are at especially high risk for poor clinical outcomes and also arrest and incarceration. Pharmacotherapies for treating opioid dependence could be a particularly important mode of treatment for opioid-dependent adults with SMI to lower their risk for overdose, high-cost hospitalizations, repeated emergency department visits, and incarceration, given relapse rates are very high following detoxification in the absence of one of the three FDA-approved pharmacotherapies. This study estimates the effects of methadone, buprenorphine, and oral naltrexone on clinical and justice-related outcomes in a sample of justice-involved adults with SMI, opioid dependence, and criminal justice involvement. Administrative data were merged from several public agencies in Connecticut for 8736 adults 18years of age or older with schizophrenia spectrum disorder, bipolar disorder, or major depression; co-occurring moderate to severe opioid dependence; and who also had at least one night in jail during 2002-2009. Longitudinal multivariable regression models estimated the effect of opioid-dependence pharmacotherapy as compared to outpatient substance abuse treatment without opioid-dependence pharmacotherapy on inpatient substance abuse or mental health treatment, emergency department visits, criminal convictions, and incarcerations, analyzing instances of each outcome 12months before and after an index treatment episode. Several baseline differences between the study groups (opioid-dependence pharmacotherapy group versus outpatient treatment without opioid-dependence pharmacotherapy) were adjusted for in the regression models. All three opioid-dependence pharmacotherapies were associated with reductions in inpatient substance abuse treatment, and among the oral naltrexone subgroup, also reductions in inpatient mental health treatment, as well as improved adherence to SMI medications. Overall, the opioid-dependence pharmacotherapy group had higher rates of arrest and incarceration in the follow-up period than the comparison group; but those using oral naltrexone had lower rates of arrest (including felonies). The analysis of observational administrative data provides useful population-level estimates but also has important limitations that preclude conclusive causal inferences. Large reductions in crisis-driven service utilization associated with opioid-dependence pharmacotherapy in this study suggest that evidence-based medications for treating opioid dependence can be used successfully in adults with SMI and should be considered more systematically during assessments of treatment needs for this population.

PMID: 29415846 [PubMed - in process]

Prenatal exposure to methadone or buprenorphine: Early childhood developmental outcomes.

February 8, 2018 - 8:41am

Prenatal exposure to methadone or buprenorphine: Early childhood developmental outcomes.

Drug Alcohol Depend. 2018 Feb 01;185:40-49

Authors: Kaltenbach K, O'Grady KE, Heil SH, Salisbury AL, Coyle MG, Fischer G, Martin PR, Stine S, Jones HE

Abstract
BACKGROUND: Methadone and buprenorphine are recommended to treat opioid use disorders during pregnancy. However, the literature on the relationship between longer-term effects of prenatal exposure to these medications and childhood development is both spare and inconsistent.
METHODS: Participants were 96 children and their mothers who participated in MOTHER, a randomized controlled trial of opioid-agonist pharmacotherapy during pregnancy. The present study examined child growth parameters, cognition, language abilities, sensory processing, and temperament from 0 to 36 months of the child's life. Maternal perceptions of parenting stress, home environment, and addiction severity were also examined.
RESULTS: Tests of mean differences between children prenatally exposed to methadone vs. buprenorphine over the three-year period yielded 2/37 significant findings for children. Similarly, tests of mean differences between children treated for NAS relative to those not treated for NAS yielded 1/37 significant finding. Changes over time occurred for 27/37 child outcomes including expected child increases in weight, head and height, and overall gains in cognitive development, language abilities, sensory processing, and temperament. For mothers, significant changes over time in parenting stress (9/17 scales) suggested increasing difficulties with their children, notably seen in increasing parenting stress, but also an increasingly enriched home environment (4/7 scales) CONCLUSIONS: Findings strongly suggest no deleterious effects of buprenorphine relative to methadone or of treatment for NAS severity relative to not-treated for NAS on growth, cognitive development, language abilities, sensory processing, and temperament. Moreover, findings suggest that prenatal opioid agonist exposure is not deleterious to normal physical and mental development.

PMID: 29413437 [PubMed - as supplied by publisher]

Extended-release injectable naltrexone for opioid use disorder: A systematic review.

February 6, 2018 - 6:39am
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Extended-release injectable naltrexone for opioid use disorder: A systematic review.

Addiction. 2018 Feb 03;:

Authors: Jarvis BP, Holtyn AF, Subramaniam S, Tompkins DA, Oga EA, Bigelow GE, Silverman K

Abstract
AIMS: To review systematically the published literature on extended-release naltrexone (XR-NTX, Vivitrol®), marketed as a once-per-month injection product to treat opioid use disorder. We addressed the following questions: (1) How successful is induction on XR-NTX?; (2) What are adherence rates to XR-NTX?; and (3) Does XR-NTX decrease opioid use? Factors associated with these outcomes as well as overdose rates were examined.
METHODS: We searched PubMed and used Google Scholar for forward citation searches of peer-reviewed articles from January 2006 to June 2017. Studies that included individuals seeking treatment for opioid use disorder who were offered XR-NTX were included.
RESULTS: We identified and included 34 studies. Pooled estimates showed that XR-NTX induction success was lower in studies that included individuals that required opioid detoxification (62.6% [95% CI: 54.5% - 70.0%]) compared with studies that included individuals already detoxified from opioids (85.0% [95% CI: 78.0% - 90.1%]). 44.2% (95% CI: 33.1% - 55.9%) of individuals took all scheduled injections of XR-NTX, which were usually 6 or less. Adherence was higher in prospective investigational studies (i.e., studies conducted in a research context according to a study protocol) compared to retrospective studies of medical records taken from routine care (6-month rates: 46.7% [95% CI: 34.5% - 59.2%] vs. 10.5% [95% CI: 4.6%-22.4%], respectively). Compared with referral to treatment, XR-NTX reduced opioid use in adults under criminal justice supervision and when administered to inmates before release. XR-NTX reduced opioid use compared with placebo in Russian adults, but this effect was confounded by differential retention between study groups. XR-NTX showed similar efficacy to buprenorphine when randomization occurred after detoxification but was inferior to buprenorphine when randomization occurred prior to detoxification.
CONCLUSIONS: Many individuals intending to start extended-release naltrexone (XR-NTX) do not and most who do start XR-NTX discontinue treatment prematurely, two factors that limit its clinical utility significantly. XR-NTX appears to decrease opioid use but there are few experimental demonstrations of this effect.

PMID: 29396985 [PubMed - as supplied by publisher]

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