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Background: Precipitated opioid withdrawal (POW) after opioid antagonist administration can be challenging to manage in the emergency department (ED), particularly if caused by a long-acting opioid antagonist such as naltrexone. There are no evidence-based guidelines to assist in safely and efficiently managing patients with this syndrome.Objective Of Review: To review current practice on the treatment of long-acting antagonist POW and make recommendations on the treatment of this complex disease process.Methods: A literature search of opioid withdrawal cases precipitated by naltrexone was done using PubMed. One of the authors screened all the results of this search by title and abstract, leading to a final count of 27 articles that were reviewed in full by all authors. English language cases that involved precipitated opioid withdrawal from a long-acting opioid antagonist were included. Data were extracted, including the precipitant involved and dose, severity of opioid withdrawal, treatments rendered, and response to treatment. In all cases where symptoms and signs were described, a Clinical Opiate Withdrawal Scale score was calculated based on the information available.Results: Twenty-seven papers were included. Naltrexone alone was the primary antagonist reported in 19 of the papers, extended-release naltrexone in two, naltrexone-morphine combination in two, and nalmefene in four. Treatment most commonly included fluid replacement, benzodiazepines, antiemetics, and clonidine. Full opioid agonist treatment, although often suggested, was poorly described. Buprenorphine successfully reduced the severity and duration of withdrawal in several cases. No standardized response scale was used, and response to treatment ranged from 3 to 48 h prior to resolution of clinical effects.Conclusions: Management of POW from long-acting antagonists is a complex problem with little formal evaluation of treatment options. There is not currently a sufficiently robust body of literature to support an evidence-based guideline. However, use of intravenous fluids, antiemetics, and benzodiazepines is commonly reported as successful and seems to be a reasonable approach until this process is better studied. A treatment strategy using partial agonists such as buprenorphine is emerging and may represent a safe and effective treatment pathway for these patients. [ABSTRACT FROM AUTHOR]

Telemedicine is a feasible alternative to in-person evaluations for people with opioid use disorder (OUD). The literature on medications for opioid use disorder (MOUD) telemedicine has focused on ongoing OUD treatment. Emergency department (ED) visits are an opportunity to initiate MOUD; however, little is known regarding the outcomes of patients following telemedicine referrals for MOUD from emergency settings. The current study describes rates of initial outpatient clinic appointment attendance and 30-day retention in care among patients referred by telemedicine compared to ED referrals. This paper reports a retrospective review of data for patients referred from EDs or telemedicine through the Medication for Addiction Treatment and Electronic Referrals (MATTERS) Network. The MATTERS online platform collects data on patient demographic information (e.g., age, gender, race/ethnicity, and insurance type), reason for visit, prior medical and mental health history, prior OUD treatment history, and past 30-day substance use behaviors. Analyses compared initial visit attendance and 30-day retention among the patients for whom follow-up data were received from clinics by demographic and initial treatment factors. Between October 2020 and September 2022, the MATTERS Network made 1349 referrals; 39.7 % originated from an ED and 47.8 % originated from telemedicine. For patients with available data, those referred from telemedicine were 1.64 times more likely to attend their initial clinic appointment and 2.59 times more likely be engaged in treatment at 30 days compared to those referred from an ED. More than two-thirds of patients referred from the emergency telemedicine environment followed up at their first clinic visit and more than half of these patients were still retained in treatment 30 days after referral. The rates of initial clinic visit and 30-day retention when referred following a telemedicine evaluation are encouraging. Further development of telemedicine programs that offer evaluations, access to medications, and referrals to treatment should be considered. • Telemedicine evaluations are feasible for people with opioid use disorder. • Telemedicine accounted for nearly half of all referrals made during the study period. • Telemedicine patients had higher initial clinic visit and 30-day engagement rates. • More than half of telemedicine patients were engaged in treatment at 30 days. [ABSTRACT FROM AUTHOR]

Persons receiving prescription buprenorphine for opioid use disorder experience high rates of comorbid conditions such as chronic pain and depression, which present barriers to buprenorphine care retention. This paper describes the protocol of the TOPPS (Treating Opioid Patients' Pain and Sadness) study, which compares a values-based, behavioral activation intervention with a health education contact-control condition, with the aim of decreasing chronic pain and depression, and increasing buprenorphine care retention for persons with opioid use disorder. This randomized controlled trial (RCT) enrolls and randomizes up to 250 participants currently being treated with buprenorphine to receive three months of either TOPPS, a six-session phone-based behavioral intervention, or a health education (HE) control condition. We compare the TOPPS intervention to HE on the following outcomes: 1) pain interference and pain severity over the 3-month treatment phrase; 2) depressive symptoms over the 3-month treatment phase; and 3) sustained improvements in pain interference, depressive symptoms, and buprenorphine treatment retention over the 12-month study period. We also examine mechanisms by which the intervention may reduce pain interference. This RCT explores a novel intervention to address chronic pain and depression for individuals receiving buprenorphine in office-based settings. TOPPS may lead to improved pain, depression, and substance use outcomes, and can utilize providers available within buprenorphine programs, broadening the disseminability of this intervention and heightening its public health impact. # NCT03698669 • A behavioral intervention trial for pain & depression for persons on buprenorphine. • First non-pharmacological treatment for pain & depression in buprenorphine patients. • Primary outcomes are: pain interference, severity, & depressive symptoms. [ABSTRACT FROM AUTHOR]

Background: Opioid use disorder (OUD) is highly prevalent among justice-involved individuals. While risk for overdose and other adverse consequences of opioid use are heightened among this population, most justice-involved individuals and other high-risk groups experience multiple barriers to engagement in opioid agonist treatment.Methods: This paper describes the development of Project Connections at Re-Entry (PCARE), a low-threshold buprenorphine treatment program that engages vulnerable patients in care through a mobile van parked directly outside the Baltimore City Jail. Patients are referred by jail staff or can walk in from the street. The clinical team includes an experienced primary care physician who prescribes buprenorphine, a nurse, and a peer recovery coach. The team initiates treatment for those with OUD and refers those with other needs to appropriate providers. Once stabilized, patients are transitioned to longer-term treatment programs or primary care for buprenorphine maintenance. This paper describes the process of developing this program, patient characteristics and initial outcomes for the first year of the program, and implications for public health practice.Results: From November 15, 2017 through November 30, 2018, 220 people inquired about treatment services and completed an intake interview, and 190 began treatment with a buprenorphine/naloxone prescription. Those who initiated buprenorphine were primarily male (80.1%), African American (85.1%), had a mean age of 44.1 (SD = 12.2), and a mean of 24.0 (SD = 13.6) years of opioid use. The majority of patients (94.4%) had previous criminal justice involvement, were unemployed (72.9%) and were unstably housed (70.8%). Over a third (32.1%) of patients had previously overdosed. Of those who began treatment, 67.9% returned for a second visit or more, and 31.6% percent were still involved in treatment after 30 days. Of those who initiated care, 20.5% have been transferred to continue buprenorphine treatment at a partnering site.Conclusions: The PCARE program illustrates the potential for low-threshold buprenorphine treatment to engage populations who are justice-involved and largely disconnected from care. While more work is needed to improve treatment retention among vulnerable patients and engaging persons in care directly after release from detention, offering on-demand, flexible and de-stigmatizing treatment may serve as a first point to connect high-risk populations with the healthcare system and interventions that reduce risk for overdose and related harms. [ABSTRACT FROM AUTHOR]

Background: To systematically review the quantitative and qualitative evidence base pertaining to the prevalence, practice of, and treatment response to the diversion of prescribed opiates in the prison setting.Methods: Medline, Embase, CINAHL, PsycINFO, Google Scholar, ASSIA and Science Direct databases were searched for papers from 1995 to the present relevant to the abuse of prescribed opiate medication. Identified journals and their reference lists were hand searched for other relevant articles. Of the abstracts identified as relevant, full text papers were retrieved and critiqued against the inclusion criteria for the review.Results: Three hundred and fifty-five abstracts were identified, leading to 42 full-text articles being retrieved. Of those, 10 papers were included in the review. Significant differences in abuse behaviours between different countries were reported. However, a key theme emerged from the data regarding a culture of nasal administration of prescribed sublingual buprenorphine within some prisons due to both reduced prevalence of injection within prison and reduced supplies of illicit drugs within prison. The buprenorphine/naloxone preparation appears to be less amenable to abuse. The review highlighted a paucity of empirical research pertaining to both prevalence of the phenomenon and treatment responses.Clinical and Research Implications: Healthcare providers within prisons need to prescribe opioids in the least abuseable preparation since the risk of abuse is significant, despite widespread processes of supervised dispensing. Prescription medication abuse is not limited to opioids and the predominant drug of abuse in an individual prison can rapidly change according to availability. [ABSTRACT FROM AUTHOR]

Introduction: Opioid abuse and overdose deaths have reached epidemic proportions in the last couple decades. In response to rational prescribing initiatives, utilization of prescription opioids has decreased; however, the number of deaths due to opioid overdoses continues to rise, largely driven by fentanyl analogues in adulterated heroin. Solutions to the opioid crisis must be multifaceted and address underlying opioid addiction. In recent years, buprenorphine has become a cornerstone in the treatment of opioid use disorder (OUD) and initiation of therapy in the emergency department (ED) has become increasingly common. There have also been calls by many organizations to remove the requirement for additional training and X-waiver to prescribe buprenorphine. In April 2021, the Biden Administration eased prescribing restrictions on the drug. These initiatives are expected to increase ED utilization of the buprenorphine. The purpose of this paper is to provide an updated overview of the role and use of buprenorphine in the ED setting so physicians may adapt to the changing practice environment.Objectives: This is a narrative review describing the role of buprenorphine in the ED. A PubMed search was conducted using the keywords "opioid epidemic" "buprenorphine," and "medication assisted therapy", and "emergency department". All the articles that contained information on the opioid epidemic, medication assisted therapy, and the biological effects of buprenorphine, that were also relevant to pain management and the ED, were included in the review.Discussion: Multiple studies have pointed to the effective use of buprenorphine as a treatment for OUDs in ED patients and are superior to standard care; however, there are various barriers to its use in the ED setting.Conclusion: Emergency physicians can influence opioid related morbidity and mortality, by familiarizing themselves with the use of buprenorphine to treat opioid withdrawal and addiction, particularly now that prescribing restrictions have been eased. Further ED research is necessary to assess the optimal use of buprenorphine in this care setting. [ABSTRACT FROM AUTHOR]

• The Taliban opium ban of 2000–2001 disrupted European heroin supplies. • Effects differed across the seven Nordic and Baltic countries in systematic ways. • Some heroin markets bounced back, although perhaps with less vibrancy. • Other markets substituted to another opioid, either more or less harmful. • Market responses to the 2000–2001 ban may be informative for the new, current ban. The 2000–2001 and the 2022–2023 Taliban opium bans were and could be two of the largest ever disruptions to a major illegal drug market. To help understand potential implications of the current ban for Europe, this paper analyzes how opioid markets in seven Baltic and Nordic countries responded to the earlier ban, using literature review, key informant interviews, and secondary data analysis. The seven nations' markets responded in diverse ways, including rebounding with the same drug (heroin in Norway), substitution to a more potent opioid (fentanyl replacing heroin in Estonia), and substitution to one with lower risk of overdose (buprenorphine replacing heroin in Finland). The responses were not instantaneous, but rather evolved, sometimes over several years. This variety suggests that it can be hard to predict how drug markets will respond to disruptions, but two extreme views can be challenged. It would be naive to imagine that drug markets will not adapt to shocks, but also unduly nihilistic to presume that they will always just bounce back with no lasting effects. Substitution to another way of meeting demand is possible, but that does not always negate fully the benefits of disrupting the original market. Nonetheless, there is historical precedent for a European country's opioid market switching to synthetic opioids when heroin supplies were disrupted. Given how much that switch has increased overdose rates in Canada and the United States, that is a serious concern for Europe at present. A period of reduced opioid supply may be a particularly propitious time to expand treatment services (as Norway did in the early 2000s). [ABSTRACT FROM AUTHOR]

Objectives: This systematic review synthesizes evidence on both the effects and perspectives of the use of novel long-acting injectable buprenorphine (LAIB) as part of medication-assisted treatment (MAT) and its impact on social determinants of health (SDH), specifically abstinence, accessibility, employment, forensic matters, and gender and social relationships via a framework approach.Methods: The study team searched three databases between January 2010 and June 2020 to identify English-language original research published in peer reviewed journals. This search yielded 9253 papers. A comprehensive search followed by 67 full text publication screenings by two independent reviewers yielded 15 papers meeting inclusion criteria. The study included three randomized control trials, one open label safety study, two case series, and six qualitative papers examining patient perspectives toward the LAIB prior to use. The team assessed the quality of studies via standardized quality assessment tools.Results: The LAIB was positively associated with improvements in abstinence, accessibility, employment, social relationships, and forensic matters. Limited evidence exists on gender equity within the current literature. The qualitative papers highlighted the importance of patients' preferences and individualization of treatment planning to ensure the success of MAT.Conclusion: The quality of evidence was rated as medium or high risk of bias, which does limit interpretation of the results. Overall, the LAIB was positively associated with SDH and should be offered as part of MAT in alignment with the recovery model. Future research should evaluate the implementation and longitudinal impacts of LAI buprenorphine compared to treatment as usual (TAU). [ABSTRACT FROM AUTHOR]

In August 2017, California launched the Hub and Spoke Program to address the growing number of opioid overdose deaths in the state. The program connects opioid treatment programs ("hubs") with office based opioid treatment settings, like primary care clinics ("spokes") to build a network of treatment expertise and referral resources. A key objective of this program is to expand access to medications for opioid use disorders (MOUD), with a particular focus on getting more buprenorphine into spokes. This article describes the preliminary results of the evaluation of the California Hub and Spoke program. Using a mixed methods approach, this portion of the evaluation measures changes in numbers of MOUD patients and providers, and barriers and facilitators to implementation. Findings reveal that, in the first 15 months of the program, 3480 new patients started buprenorphine in 118 spokes, increasing treatment initiations by 94.7% over baseline. The number of waivered spoke providers also increased 52.4% to 268. Although these data demonstrate promising growth in the network, challenges to expanding treatment access remain. Provider activity was among the most notable. Despite growth in the number of spoke providers with waivers to prescribe buprenorphine, only 68.7% (n = 184) were actively prescribing to patients. A survey of providers found that those who were not yet using their waivers lacked the confidence and mentorship they needed to prescribe. Provider knowledge and attitudes toward MOUD, fear of legal consequences, and limited patient outreach were also contributing factors. Recommendations for strengthening Hub and Spoke program implementation include facilitating mentor linkage for prescribers, expanding the support offered to spoke providers, and offering additional training and technical assistance aimed at provider stigma. Efforts to address these recommendations are described in a companion paper (Miele et al., under review). • Spokes nearly doubled their monthly buprenorphine initiation numbers. • Just over two-thirds of waivered providers were prescribing buprenorphine. • Inactive prescribers were less likely to feel they had the mentorship they needed. • Some providers expressed fear over the legal ramifications of prescribing. • Other barriers included limited patient outreach, and lack of community resources. [ABSTRACT FROM AUTHOR]

As part of the State Targeted Response to the opioid epidemic, California has adopted the Hub and Spoke model to expand access to medications for opioid use disorder, particularly buprenorphine, throughout the state. By aligning opioid treatment programs as hubs with primary care, office-based practitioners, and other health care settings as spokes, a broader treatment model can reach more people with opioid use disorder, improve access to medications for opioid use disorders, and decrease overdose deaths. Expanding access requires expanding knowledge and intensive implementation support of new practices. This paper describes the rationale, specific activities and anticipated impact of the implementation plan in California's Hub and Spoke system. Training and technical assistance are designed to: increase the number and capacity of waivered prescribers; enhance skills of prescribers and multidisciplinary teams; and create systems change. Activities include buprenorphine waiver trainings and provider support, a practice facilitator program, Project ECHO sessions, webinars, clinical skills trainings, and regional learning collaboratives. This overview highlights the steps California is taking to build treatment capacity to address the opioid epidemic. [ABSTRACT FROM AUTHOR]

Abstract: Background: The dominant biomedical discourse stresses the physiological risks to the foetus or newborn posed by the prenatal use of illicit drugs. There is also a strong moral incentive for pregnant women to abstain from drugs. Yet few researchers have explored how pregnant, drug-using women themselves perceive the risks involved. The present paper investigates the reasoning by women about risks involved in prenatal drug use. Theoretically, a socio-cultural approach to risk is taken. Methods: The paper is based on fourteen ethnographic interviews with women who had used illicit drugs during pregnancy (mainly buprenorphine), had recently given birth and had regularly used prenatal services during pregnancy. The interviews were informal, semi-structured and focused on the women''s experiences of pregnancy and service use. Each interview lasted about an hour. The interviews were transcribed and inductively analysed using thematic coding. Risk perceptions were identified in the interviewees’ expressions and understanding of fears, dangers, threats and worries. Results: The women were not primarily concerned about health risks: their greatest fears in connection with the prenatal use of illicit drugs were giving birth to a child with withdrawal symptoms, child protection interventions and child removal, encountering negative attitudes in seeking professional help as well as terminating drug use. The interviewees did not see abstaining from drugs as a risk-free option. On the contrary, the prospect of a drug-free life was filled with fears linked to physical and mental pain and disruptions in significant social bonds. The women made use of biomedical and nonprofessional understandings of risks. The women''s friends and acquaintances played a central role as providers of knowledge about risks. Conclusion: When providing health education to pregnant women with drug problems, professionals should take women''s perceptions of risk seriously, treat the women respectfully and engage them in dialogue about the risks involved. Further studies on pregnant women''s perceptions of risk in using illicit drugs would be highly valuable. [Copyright &y& Elsevier]

Background: Buprenorphine maintenance therapy (BMT) has been widely recognized as one of the most effective treatments for opioid use disorders (OUD). In the midst of the U.S. opioid overdose crisis, local, state, and federal authorities have attempted to increase the availability of BMT, yet few individuals meeting the criteria for OUD utilize BMT. Moreover, recent research suggests that a significant proportion of individuals who use opioids seek out buprenorphine on the illicit market to self-govern and manage withdrawal sickness.Methods: This paper presents data from a geographic sub-sample within a multi-site study of buprenorphine diversion in Pennsylvania. We endeavor to bolster a slim qualitative literature on the use of non-prescribed buprenorphine through in-depth interviews with 20 individuals who reported buying or receiving buprenorphine outside of medically-sanctioned contexts. Interviews characterized participants' reasons for both using non-prescribed buprenorphine and eschewing formal treatment, in a state (Pennsylvania) afflicted with high rates of heroin use and overdose deaths. Transcripts were initially coded for broad interview topics, while latent themes relating to buprenorphine diversion and extra-medical use also emerged.Results: Analyses revealed complex motivations underlying participants' extra-medical use of buprenorphine. Where some expressed a desire for treatment autonomy and treatment medications that could not be achieved or obtained within BMT, individuals also indicated a persistent lack of treatment availability and access due to diverse barriers.Conclusion: This study shows how issues related to availability, accessibility, and acceptability many explain low rates of BMT utilization, even within a place and time defined by medication-assisted treatment expansion. Beyond offering broad rhetorical and financial support for MAT, our findings suggest that governmental actors should continue to pursue policies that expand the spatial distribution of BMT. It also underscores the need to look beyond current models of buprenorphine maintenance and to consider modes of buprenorphine delivery beyond long-term maintenance. [ABSTRACT FROM AUTHOR]

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Authors. The authors have provided a clarification stating that the article does not clearly or fully disclose that it better represents a subset of a previously published manuscript in the British Journal of Anaesthesia (White LD, Hodge A, Vlok R, Hurtado G, Eastern K, Melhuish TM. Efficacy and adverse effects of buprenorphine in acute pain management: systematic review and meta-analysis of randomized controlled trials. (Br J Anaesth. 2018;120:668-678). The papers presented in their meta-analysis are a subset of those in their previous review in the British Journal of Anaesthesia, and do not present additional information beyond their previously published work. [ABSTRACT FROM AUTHOR]

Abstract: The use of medications to treat substance use disorders (SUDs) has emerged as a potentially central part of the treatment armamentarium. In this paper we present data from several recent US national surveys showing that despite the clinical promise of these medications, there has been limited adoption of pharmacotherapies in the treatment of SUDs. The data reveal variable patterns of use of disulfiram, buprenorphine, tablet naltrexone, acamprosate and injectable naltrexone. After examining the environmental and institutional context for the adoption of pharmacotherapies, the specific organizational facilitators and barriers of medication adoption are considered. The paper concludes with a discussion of the minimal clinical and administrative guidance available to enhance adoption, the lack of client and consumer knowledge of medications that puts a brake on their adoption and availability, and the difficulties that must be surmounted in bringing new medications to market. [Copyright &y& Elsevier]

The United States (US) is in the midst of an epidemic of opioid use; however, overdose mortality disproportionately affects certain subgroups. For example, more than half of state prisoners and approximately two-thirds of county jail detainees report issues with substance use. Overdose is one of the leading causes of mortality among individuals released from correctional settings. Even though the criminal justice (CJ) system interacts with a disproportionately high number of individuals at risk of opioid use and overdose, few CJ agencies screen for opioid use disorder (OUD). Even less provide access to medication assisted treatment (e.g. methadone, buprenorphine, and depot naltrexone), which is one of the most effective tools to combat addiction and lower overdose risk. However, there is an opportunity to implement programs across the CJ continuum in collaboration with law enforcement, courts, correctional facilities, community service providers, and probation and parole. In the current paper, we introduce the concept of a "CJ Continuum of Care for Opioid Users at Risk of Overdose", grounded by the Sequential Intercept Model. We present each step on the CJ Continuum and include a general overview and highlight opportunities for: 1) screening for OUD and overdose risk, 2) treatment and/or diversion, and 3) overdose prevention and naloxone provision. [ABSTRACT FROM AUTHOR]

Abstract: The adoption of pharmacotherapies for the treatment of alcohol and drug use disorders has progressed slowly despite the approval of new and effective medications. This paper begins with overviews of the prevalence of alcohol and drug abuse and dependence, the costs of addiction to the nation, and the value of treatment services. The role of pharmacotherapy in the treatment of addictive diseases is examined, and factors that affect the adoption and use of medications for alcohol and drug treatment are identified and discussed. Investigations that tested the effectiveness of buprenorphine for treatment of opioid dependence in new settings illustrate physician and counselor training and mentorship strategies that may promote the adoption of medications in the treatment of alcohol and drug use disorders. The paper concludes with a discussion of barriers and ways to surmount the barriers and to foster greater use of medications in alcohol and drug treatment. [Copyright &y& Elsevier]

Objective: The Opiate Dosage Adequacy Scale (ODAS) is a clinical tool to individually measure the "adequacy" of opioid doses in patients on maintenance treatment. The aim of this paper is to provide evidence for the validity and reliability of the ODAS in a sample of patients in buprenorphine/naloxone (B/N) maintenance treatment.Method: Cross-sectional study of a convenience sample of B/N-treated patients (n = 316) from four Autonomous Communities in Spain. Participants completed a battery of instruments to assess the following: buprenorphine dose adequacy; heroin dependence severity; psychological adjustment; and patient-desired adjustment of buprenorphine dose.Results: Exploratory Factor Analysis identified four factors from the ODAS that together account for 85.4% of the total variance: "Heroin craving and use"; "Overmedication"; "Objective opiate withdrawal symptoms (OWS)" and 'Subjective OWS'. Compared to patients with an "inadequate" B/N dose (ODAS), patients with "adequate" doses had less heroin use in the last week (0.01 vs. 0.40; t = -2.73; p < 0.01, 95% CI: -0.67, -0.10), less severe heroin dependence (2.20 vs. 5.26, t = -5.14, p < 0.001; 95% CI: -4.23, -1.88), less psychological distress (3.00 vs. 6.31, t = -4.37, p < 0.001; 95% CI: -4.80, -1.81), and greater satisfaction with their doses (42.1% vs. 13.6%, χ2 = 14.44, p < 0.01). Cronbach's alpha coefficient was 0.76 (0.81, 0.92, 0.94, and 0.93, respectively, for the four factor dimensions).Conclusion: These findings support the validity and reliability of the ODAS as a tool to measure and assess buprenorphine dose adequacy in the context of an opioid dependency treatment program. [ABSTRACT FROM AUTHOR]

Introduction: Despite evidence for the efficacy of buprenorphine treatment in primary care, few studies have identified factors associated with treatment success, nor have such factors been evaluated in community settings. Identifying correlates of treatment success can facilitate the development of treatment models tailored for distinct populations, including low-income communities of color. The current study examined client-level socio-demographic factors associated with treatment success in community-based buprenorphine programs serving vulnerable populations.Methods: Data were abstracted from client records for participants (N=445) who met DSM-IV criteria for opioid dependence and sought treatment at one of Behavioral Health Leadership Institute's two community-based recovery programs in Baltimore City from 2010 to 2015. Logistic regression estimated the odds ratios of treatment success (defined as retention in treatment for ≥90days) by sociodemographic predictors including age, race, gender, housing, legal issues and incarceration.Results: The odds of being retained in treatment ≥90days increased with age (5% increase with each year of age; p<0.001), adjusting for other sociodemographic factors. Clients who reported unstable housing had a 41% decreased odds of remaining in treatment for 90 or more days compared to clients who lived independently at intake. Treatment success did not significantly differ by several other client-level characteristics including gender, race, employment, legal issues and incarceration.Conclusions: In vulnerable populations, the age factor appears sufficiently significant to justify creating models formulated for younger populations. The data also support attention to housing needs for people in treatment. Findings from this paper can inform future research and program development. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C Virus (HCV) risk is elevated for individuals with an opioid use disorder (OUD). Routine HCV testing is recommended for high-risk individuals, including those with an injection drug use history. HCV antibody testing addresses the first step in the HCV treatment care cascade, with uptake and completion of HCV treatment among individuals with chronic HCV as the optimal care cascade endpoint. The aim of this study was to characterize self-reported HCV treatment cascade outcomes among individuals with an OUD in outpatient medication assisted treatment (MAT).Methods: Individuals receiving methadone or buprenorphine treatment (N=202, 67.8% female, M age=35.0, SD=8.4) completed a brief, anonymous paper-and-pencil survey examining self-reported history of HCV testing, diagnosis, and treatment. Descriptive statistics characterized HCV treatment cascade outcomes.Results: A majority (79.3%) endorsed a lifetime HCV testing history; 34.9% were tested for HCV during the past year. Of those with a lifetime HCV testing history, 42.7% indicated they have been told they have HCV (n=67/157), with 21% (n=14/67) of those individuals reporting that they have been told they have chronic HCV, and 71.4% (n=10/14) of those with chronic HCV reporting receipt of HCV treatment.Discussion: Results underscore gaps in the HCV care continuum among individuals with OUD in MAT. Interventions to increase uptake of HCV testing, communication of HCV diagnostic and treatment information by medical providers, linkage to HCV medical care, and uptake and adherence to HCV treatment are urgently needed, particularly among individuals with an OUD in MAT. [ABSTRACT FROM AUTHOR]

Opioid-related deaths continue to rise in the U.S. A shared decision-making (SDM) system to help primary care clinicians (PCCs) identify and treat patients with opioid use disorder (OUD) could help address this crisis. In this cluster-randomized trial, primary care clinics in three healthcare systems were randomized to receive or not receive access to an OUD-SDM system. The OUD-SDM system alerts PCCs and patients to elevated risk of OUD and supports OUD screening and treatment. It includes guidance on OUD screening and diagnosis, treatment selection, starting and maintaining patients on buprenorphine for waivered clinicians, and screening for common comorbid conditions. The primary study outcome is, of patients at high risk for OUD, the percentage receiving an OUD diagnosis within 30 days of index visit. Additional outcomes are, of patients at high risk for or with a diagnosis of OUD, (a) the percentage receiving a naloxone prescription, or (b) the percentage receiving a medication for OUD (MOUD) prescription or referral to specialty care within 30 days of an index visit, and (c) total days covered by a MOUD prescription within 90 days of an index visit. The intervention started in April 2021 and continues through December 2023. PCCs and patients in 90 clinics are included; study results are expected in 2024. This protocol paper describes the design of a multi-site trial to help PCCs recognize and treat OUD. If effective, this OUD-SDM intervention could improve screening of at-risk patients and rates of OUD treatment for people with OUD. [ABSTRACT FROM AUTHOR]

Opioid Substitution Treatment (OST) is a firmly established method of treating and managing dependence to opioids in Europe, the US and rest of the developed world. It has a solid evidence base and a positive safety track record. Dissemination of its practice, in parallel to the acceptance of harm reduction as an effective approach, is still timid in low and middle Income countries. After years of advocacy on the parts of clinicians and the voluntary sector, the government of Lebanon launched a national opioid substitution program in 2011 using buprenorphine as the substance of substitution. Lebanon is one of the first countries in the MENA region to establish such a program despite a difficult socio-political context. This paper provides the background of harm reduction efforts in the region and presents the outline of the program from inception to present date. Challenges and recommendations for the future are also discussed. The Lebanese experience with opioid substitution is encouraging so far and can be used as a template for others in the region who might be contemplating broadening the range of services available to tackle addiction to heroin and related substances. [ABSTRACT FROM AUTHOR]

Background: Opioid substitution therapy (OST) has been established as the gold standard in treating opioid use disorders. Nevertheless, there is still a debate regarding the qualitative characteristics that define the optimal OST intervention, namely the treatment threshold. The aim of this review is twofold: first, to provide a summary and definition of "treatment thresholds", and second, to outline these thresholds and describe how they related to low and high threshold treatment characteristics and outcomes.Method: We searched the main databases of Medline, PubMed, PsycInfo, EMBASE, CINAHL and the Cochrane Library. Original published research papers, reviews, and meta-analyses, containing the eligible keywords: "opioid substitution", "OST", "low threshold", "high threshold" were searched alone and in combination, up to June, 2015.Results: Treatment thresholds were defined as barriers a patient may face prior to and during treatment. The variables of these barriers were classified into treatment accessibility barriers and treatment design barriers. There are increasing numbers of studies implementing low threshold designs with an increasing body of evidence suggesting better treatment outcomes compared to high threshold designs.Conclusion: Clinical characteristics of low threshold treatments that were identified to increase the effectiveness of OST intervention include increasing accessibility so as to avoid waiting lists, using personalized treatment options regarding medication choice and dose titration, flexible treatment duration, a treatment design that focuses on maintenance and harm reduction with emphasis on the retention of low adherence patients. [ABSTRACT FROM AUTHOR]

People who inject drugs (PWID) are central to the hepatitis C virus (HCV) epidemic. Opioid substitution treatment (OST) of opioid dependence has the potential to play a significant role in the public health response to HCV by serving as an HCV prevention intervention, by treating non-injection opioid dependent people who might otherwise transition to non-sterile drug injection, and by serving as a platform to engage HCV infected PWID in the HCV care continuum and link them to HCV treatment. This paper examines programmatic, structural and policy considerations for using OST as a platform to improve the HCV prevention and care continuum in 3 countries-the United States, Estonia and Viet Nam. In each country a range of interconnected factors affects the use OST as a component of HCV control. These factors include (1) that OST is not yet provided on the scale needed to adequately address illicit opioid dependence, (2) inconsistent use of OST as a platform for HCV services, (3) high costs of HCV treatment and health insurance policies that affect access to both OST and HCV treatment, and (4) the stigmatization of drug use. We see the following as important for controlling HCV transmission among PWID: (1) maintaining current HIV prevention efforts, (2) expanding efforts to reduce the stigmatization of drug use, (3) expanding use of OST as part of a coordinated public health approach to opioid dependence, HIV prevention, and HCV control efforts, (4) reductions in HCV treatment costs and expanded health system coverage to allow population level HCV treatment as prevention and OST as needed. The global expansion of OST and use of OST as a platform for HCV services should be feasible next steps in the public health response to the HCV epidemic, and is likely to be critical to efforts to eliminate or eradicate HCV. [ABSTRACT FROM AUTHOR]

Background: In a previously reported randomized controlled trial, formerly opioid-dependent prisoners were more likely to enter community drug abuse treatment when they were inducted in prison onto buprenorphine/naloxone (hereafter called buprenorphine) than when they received counseling without buprenorphine in prison (47.5% vs. 33.7%, p=0.012) (Gordon et al., 2014). In this communication we report on the results of the induction schedule and the adverse event profile seen in pre-release prisoners inducted onto buprenorphine.Method: This paper examines the dose induction procedure, a comparison of the proposed versus actual doses given per week, and side effects reported for 104 adult participants who were randomized to buprenorphine treatment in prison. Self-reported side effects were analyzed using generalized estimated equations to determine changes over time in side effects.Results: Study participants were inducted onto buprenorphine at a rate faster than the induction schedule. Of the 104 (72 males, 32 females) buprenorphine recipients, 64 (37 males, 27 females) remained on medication at release from prison. Nine participants (8.6%) discontinued buprenorphine because of unpleasant opioid side effects. There were no serious adverse events reported during the in-prison phase of the study. Constipation was the most frequent symptom reported (69 percent).Conclusion: Our findings suggest that buprenorphine administered to non-opioid-tolerant adults should be started at a lower, individualized dose than customarily used for adults actively using opioids, and that non-opioid-tolerant pre-release prisoners can be successfully inducted onto therapeutic doses prior to release. [ABSTRACT FROM AUTHOR]

Background: Side effects of medications for opioid use disorder (MOUD) such as weight gain contribute to their stigma. Substantial evidence suggests that women have a more severe side effect profile to MOUD than men, and concerns about weight gain during treatment are prevalent. However, the few studies reporting sex differences in weight gain during treatment show conflicting results and are restricted to methadone. In addition, little is known about possible sex differences in weight gain to buprenorphine, which is the most commonly prescribed MOUD in the United States.Methods: To address these issues, we performed a systematic review and meta-analysis on the few studies reporting longitudinal data on sex differences in body mass index (BMI) gain during methadone treatment (Study 1). In a separate study, we also re-analyzed data from trial CTN-0030 of the National Institute on Drug Abuse Clinical Trial Network (NIDA CTN), which involved a 12-week buprenorphine treatment regimen (Study 2; n = 360; 209 Male, 151 Female).Results: For Study 1, across all papers reporting longitudinal data (k = 4, n = 362 OUD patients), there were BMI increases that ranged from 2.2 to 5.4 BMI after at least one year of methadone treatment, but there were no significant sex differences in BMI increases (Standardized Mean Difference, Female > Male = 0.352, SE =0.270; 95 % CI = [-0.18 0.88]; p = .193). Study 2 showed no significant differences in weight before and after 12 weeks of buprenorphine treatment nor did it show sex differences in weight change with treatment (β = 2.34, p = .511).Conclusion: These analyses corroborate evidence of weight gain with methadone treatment but did not observe a sex-based disparity in weight gain with methadone or buprenorphine treatment for OUD. [ABSTRACT FROM AUTHOR]

Opioid use disorder is a significant global issue and the rate of opioid use in women of childbearing age and pregnant women is on the rise. Whilst the adverse general health, cognitive, and neurodevelopmental outcomes of in utero exposure to opioids have been explored, there is a lack of prospective, controlled, longitudinal research into the ophthalmic outcomes. Existing research suggests that there is an association between prenatal exposure and future risk of abnormalities in visual functioning. This systematic review and meta-analysis analysed studies that measured eye abnormalities in infants or children exposed to opioid maintenance therapy in utero and compared them to non-opioid exposed controls. After considering the clinical findings, limitations of the studies, confounding factors, and quantitative analysis, a causal relationship between in utero opioid exposure and future eye abnormalities could not be confirmed. The implications of the findings and their clinical relevance, in addition to identified gaps for future research are also discussed in this paper. • The association between prenatal opioid maintenance therapy exposure and ophthalmic outcomes isunclear. • Some evidence suggests the presence of visual abnormalities in children prenatally exposed to OMT compared tocontrols. • Current data is not enough to conclude a causalrelationship. • Longitudinal research is needed to investigate the link between opioid maintenance therapy in utero and ophthalmicoutcomes. [ABSTRACT FROM AUTHOR]

Rationale In recent years, the U.S. has experienced a significant increase in the prevalence of pregnant opioid-dependent women and of neonatal abstinence syndrome (NAS), which is caused by withdrawal from in-utero drug exposure. While methadone-maintenance currently is the standard of care for opioid dependence during pregnancy, research suggests that buprenorphine-maintenance may be associated with shorter infant hospital lengths of stay (LOS) relative to methadone-maintenance. There is no “gold standard” treatment for NAS but there is evidence that buprenorphine, relative to morphine or methadone, treatment may reduce LOS and length of treatment. Design Point-of-care clinical trial (POCCT) designs, maximizing external validity while reducing cost and complexity associated with classic randomized clinical trials, were selected for two planned trials to compare methadone to buprenorphine treatment for opioid dependence during pregnancy and for NAS. This paper describes design considerations for the M edication-assisted treatment for O pioid-dependent expecting M others (MOMs; estimated N = 370) and I nvestigation of N arcotics for A meliorating N eonatal abstinence syndrome on T ime in hospital (INFANTs; estimated N = 284) POCCTs, both of which are randomized, intent-to-treat, two-group trials. Outcomes would be obtained from participants' electronic health record at three participating hospitals. Additionally, a subset of infants in the INFANTs POCCT would be from mothers in the MOMs POCCT and, thus, potential interaction between medication treatment of mother and infant could be evaluated. Conclusion This pair of planned POCCTs would evaluate the comparative effectiveness of treatments for opioid dependence during pregnancy and for NAS. The results could have a significant impact on practice. [ABSTRACT FROM AUTHOR]

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

Abstract: Opioid maintenance treatment (OMT) is the most widely used treatment for opioid dependence. Maintenance programmes differ in various aspects and may also change over time. This paper investigates the changes in treatment practices within a national OMT programme during a 10year period (2002–2011), especially with regard to the prescribing of methadone and buprenorphine. Data (n =34,001) were collected by annual assessments questionnaires. In 2002, only 16% of the OMT patients received buprenorphine as their maintenance medication. By 2011 this percentage had increased significantly (p <.001) to 50.3%. In the same period the number of patients more than tripled (from 1,984 to 6,640, p <.001), and programme attrition rates decreased (p =.020). This relatively rapid shift is a part of the increasing reliance of addiction medicine upon a range of medications administered by different routes which has not been previously charted within a national treatment programme. [Copyright &y& Elsevier]

Background: Opioid use disorder (OUD) is a global public health concern. The standard of care for OUD involves treatment using medications such as buprenorphine, methadone, or naltrexone. No known review exists to assess the contextual factors associated with medication for opioid use disorder (MOUD) in the Arab World. This systematic review serves as an implementation science study to address this research gap and improve the uptake of MOUD in the Arab World.Methods: Systematic searches of Medline, PsycINFO, and EMBASE, and a citation analysis, were used to identify peer-reviewed articles with original data on MOUD in the Arab World. Quality assessment was conducted using the CASP appraisal tools, and main findings were extracted and coded according to the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework.Results: 652 research articles were identified, and 10 met inclusion criteria for final review. Four studies considered health-systems aspects of MOUD administration, such as cost-effectiveness, the motivations for and impact of national MOUD policies, the types of social, political, and scientific advocacy that led to the adoption of MOUD in Arab countries, and the challenges limiting its wide-scale adoption in the Arab World. Six papers considered MOUD at individual and group patient levels by evaluating patient quality of life, addiction severity, patient satisfaction, and patient perspectives on opioid agonist therapy.Conclusion: Despite financial and geographic barriers that limit access to MOUD in the Arab World, this review found MOUD to be cost-effective and associated with positive health outcomes for OUD patients in the Arab World. MOUD can be successfully established and scaled to the national level in the Arab context, and strong coalitions of health practitioners can lobby to establish MOUD programs in Arab countries. Still, the relative novelty of MOUD in this context precludes an abundance of research to address its long-term delivery in the Arab World. [ABSTRACT FROM AUTHOR]

Abstract: Background: Effective medications to treat cocaine dependence have not been identified. Recent pharmacotherapy trials demonstrate the potential efficacy of buprenorphine (BUP) (alone or with naltrexone) for reducing cocaine use. The National Institute on Drug Abuse Clinical Trials Network (CTN) launched the Cocaine Use Reduction with Buprenorphine (CURB) investigation to examine the safety and efficacy of sublingual BUP (as Suboxone®) in the presence of extended-release injectable naltrexone (XR-NTX, as Vivitrol®) for the treatment of cocaine dependence. This paper describes the design and rationale for this study. Methods: This multi-site, double-blind, placebo-controlled study will randomize 300 participants across 11 sites. Participants must meet the DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. Participants are inducted onto XR-NTX after self-reporting at least 7days of abstinence from opioids and tolerating a naloxone challenge followed by oral naltrexone and are then randomly assigned to one of three medication conditions (4mg BUP, 16mg BUP, or placebo) for 8weeks. Participants receive a second injection of XR-NTX 4weeks after the initial injection, and follow-up visits are scheduled at 1 and 3months post-treatment. Participants receive weekly cognitive behavioral therapy (CBT). Recruitment commenced in September, 2011. Enrollment, active medication, and follow-up phases are ongoing, and recruitment is exceeding targeted enrollment rates. Conclusions: This research using 2 medications will demonstrate whether BUP, administered in the presence of XR-NTX, reduces cocaine use in adults with cocaine dependence and opioid use disorders and will demonstrate if XR-NTX prevents development of physiologic dependence on BUP. [Copyright &y& Elsevier]

Abstract: A number of studies point to methadone exposure in utero as a possible risk factor in the developing mother–infant relationship in the first year of life. This study is part of a larger, national follow-up of 38 infants prenatally exposed to methadone or buprenorphine and 36 comparison, low-risk infants. The aim of the present paper is to assess the quality of mother–infant relationship when the infants are 6 months old. Videotaped mother–infant interactions were rated in a global scale (NICHD). Maternal and infant contributions collapsed into the variables “infant style” and “maternal style” showed that the only factor making significant contribution to the outcome measure “dyadic mutuality” was maternal style. The importance of group membership (exposed versus non-exposed), was reduced when controlling for maternal drug use prior to opioid maintenance treatment (OMT), maternal depression and parenting stress as well as infants’ developmental status and sensory-integrative functions. This suggests that prediction of dyadic mutuality should be based on individual characteristics rather than group characteristics. These results support previous research findings that methadone and buprenorphine use per se does not have direct influence on the quality of early mother–infant relationship, but tailored follow-up procedures targeting drug-free pregnancies and parenting support are beneficial for women in OMT and their children. [Copyright &y& Elsevier]

Abstract: Background: Buprenorphine maintenance is efficacious for treating opioid dependence, but problems with diversion and misuse of buprenorphine (BUP) may limit its acceptability and dissemination. The buprenorphine/naloxone combination tablet (BNX) was developed to reduce potential problems with diversion and abuse. This paper provides data regarding the characteristics of BUP injection drug users in Malaysia and preliminary data regarding the impact of withdrawing BUP and introducing BNX. BUP was introduced in 2002 and subsequently withdrawn from the Malaysian market in 2006. BNX was introduced in 2007. Methods: A two wave survey of BUP IDUs was conducted shortly prior to BUP withdrawal from the Malaysian market (n =276) and six months after BNX was introduced (n =204). Six focus groups with BUP and/or BNX IDUs were also conducted shortly before the second wave. Results: In addition to current BUP or BNX IDU, 96% of first wave participants and 97% second wave participants reported lifetime heroin IDU preceding the onset of their BUP/BNX IDU. Additionally, 58% of first and 64% of second wave survey participants reported current heroin IDU. Benzodiazepine abuse, often injected with BUP, was reported in both the surveys. Focus group participants reported that BNX was not as desirable as BUP, nonetheless, the results of the second wave survey suggest a continuing widespread BNX IDU, at least in Kuala Lumpur. Conclusions: In Malaysia, BUP and BNX IDU occur among heroin IDUs. The introduction of BNX and withdrawal of BUP may have helped to reduce, but did not eliminate the problems with diversion and abuse. [ABSTRACT FROM AUTHOR]

Abstract: The National Institute on Drug Abuse Clinical Trials Network launched the Prescription Opioid Addiction Treatment Study (POATS) in response to rising rates of prescription opioid dependence and gaps in understanding the optimal course of treatment for this population. POATS employed a multi-site, two-phase adaptive, sequential treatment design to approximate clinical practice. The study took place at 10 community treatment programs around the United States. Participants included men and women age ≥18 who met Diagnostic and Statistical Manual, 4th Edition criteria for dependence upon prescription opioids, with physiologic features; those with a prominent history of heroin use (according to pre-specified criteria) were excluded. All participants received buprenorphine/naloxone (bup/nx). Phase 1 consisted of 4weeks of bup/nx treatment, including a 14-day dose taper, with 8weeks of follow-up. Phase 1 participants were monitored for treatment response during these 12weeks. Those who relapsed to opioid use, as defined by pre-specified criteria, were invited to enter Phase 2; Phase 2 consisted of 12weeks of bup/nx stabilization treatment, followed by a 4-week taper and 8weeks of post-treatment follow-up. Participants were randomized at the beginning of Phase 1 to receive bup/nx, paired with either Standard Medical Management (SMM) or Enhanced Medical Management (EMM; defined as SMM plus individual drug counseling). Eligible participants entering Phase 2 were re-randomized to either EMM or SMM. POATS was developed to determine what benefit, if any, EMM offers over SMM in short-term and longer-term treatment paradigm. This paper describes the rationale and design of the study. [Copyright &y& Elsevier]

Abstract: Objective: This study was first conducted to compare the consequences of the use of methadone and high-dose buprenorphine in pregnancy in France and secondly to describe the heterogeneity of women under high-dose buprenorphine. This paper focuses on the second point only. Study design: From October 1998 to September 1999, data on pregnancy, delivery outcomes and neonatal parameters were collected for 251 addicted women on methadone or high-dose buprenorphine (HDB) substitution followed in 35 hospitals and clinics in continental France. Then the data of 159 women who had been taking HDB during pregnancy and had delivered 160 live infants were analyzed. Results: Most of these women were treated as outpatients by general practitioners. 43% of them belong to what we considered a “hidden population” of drug users: most of them were native French citizens, who lived with the future fathers in their own homes, had at least some secondary education, and were usually not followed in specialized centers for drug addicts. Almost all the women smoked every day during their pregnancies; 20% used heroin during the last 4 weeks preceding delivery; 16% admitted having injected HDB at least once. Notably, neither the severity nor the duration of the neonatal abstinence syndrome (NAS) seemed to be related to the daily doses of the substitution agent. Half of the newborns were treated for NAS, mainly with morphine hydrochloride. Conclusion: Although two different populations of women were clearly identified, 64 with no social disadvantage and 95 socially disadvantaged, there was no difference between the groups as for the severity of NAS which was only related to the mothers’ compliance with a programme of treatment against addiction. [Copyright &y& Elsevier]

Introduction: Methadone and buprenorphine/naloxone medications are among the most effective treatment options for opioid use disorders, yet many people remain misinformed about their benefits and hold negative perceptions about the use of medications to treat opioid use disorders. Such perceptions, especially negative perceptions based on misinformation, may be especially harmful or stigmatizing within the context of disclosure (i.e., telling another about one's opioid use disorder history or treatment), inhibiting important recovery outcomes and sources of social support.Methods: Therefore, using the Disclosure Process Model as a framework, the current study seeks to characterize and compare participants' perceptions of stigmatizing reactions to their disclosures of MOUD use that stem from misinformation about methadone or buprenorphine/naloxone. Participants included people who are actively receiving MOUD as treatment.Results: Results suggest that participants (N = 52) receiving both types of medications experienced similar stigmatizing reactions to disclosures. Participants also reported treatment consequences of misinformed reactions to their disclosure, such as dropping out of support groups (e.g., Narcotics Anonymous) or prematurely ending their medication use. Further, the paper provides participants' recommendations for avoiding or managing misinformed disclosure reactions.Conclusions: Short-term intervention efforts may promote strategies to manage misinformation, equipping individuals to respond to misinformation surrounding their medication use. Long-term interventions may target misinformation about methadone and buprenorphine/naloxone medications to increase health literacy, reduce stigma, and combat cultural ambivalence within communities, as well as promote recovery among people receiving medications for opioid use disorder. [ABSTRACT FROM AUTHOR]

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

Abstract: Cognitive dysfunction is a major feature of drug addiction. In the present paper, we compared the decision-making ability using the Iowa gambling task of methadone- and buprenorphine-maintained individuals to non opiate-dependent drug-free controls. Buprenorphine-maintained individuals performed better than methadone-maintained individuals, and not differently than non opiate-dependent controls. In addition, methadone-maintained individuals had more perseverative errors on the Wisconsin card sorting task (WCST) as compared with non opiate-dependent drug-free controls whereas buprenorphine-maintained individuals had intermediate scores. Scores on Weschler adult intelligence scale (WAIS-R) were similar for methadone- and buprenorphine-maintained individuals whereas drug-free controls had significantly higher scores. In addition, both opiate-dependent groups performed more poorly than drug-free controls on the Benton visual retention test (BVRT). The results suggest that buprenorphine in contrast to methadone improves decision-making, and thus may be more effective in rehabilitation programs of opiate-dependent subjects and this improvement may be related to its distinct pharmacological action as a k antagonist. [Copyright &y& Elsevier]

Buprenorphine has become of increasing interest to be an alternative to methadone in the treatment of heroin addicts. The aim of the paper is to review, from a clinical perspective, the current status of what is known about the pharmacology of buprenorphine, with a particular emphasis on the issues of maintenance therapy in heroin addiction. A systematic review of published follow-up data, from observational and experimental studies was done. Electronic databases Medline and PSYNDEXplus were searched from their earliest entries. Buprenorphine appears to be a well-tolerated drug, with a benign overall side effect. Buprenorphine is an additional treatment option for heroin dependent patients, especially for those who do not wish to start or continue with methadone or for those who do not seem to benefit from adequate dosages of methadone. [Copyright &y& Elsevier]

This paper aims to provide an overview on the delivery and coverage of opiate substitution treatment (hereafter, ‘substitution treatment’) in the European Union (EU) and Norway by the year 2000. It sketches which substitution substances are being used and when they were introduced in which countries, to what extent they are used, and how the delivery of substitution substances is organised in the EU Member States and Norway. Substitution treatments were introduced at different stages in the EU countries and although such measures now exist in all Member States there are considerable differences in coverage. Methadone remains predominant although other substitution substances such as buprenorphine, dihydrocodeine, slow-release morphine and heroin have been launched or are on trial in some Member States. The organisation of the delivery of substitution treatment varies considerably but may tentatively be categorised into four overall ‘organisation modes’: firstly, countries offering this treatment through general practitioners; secondly, those offering it through specialised centres; thirdly, those who provide it through specialised centres but with a limited number of treatment slots; and lastly, ‘mixed modes’ in which both general practitioners and specialised centres deliver substitution treatment services. [Copyright &y& Elsevier]

Objectives: Buprenorphine at high dosage became available in France in 1996, as a substitution treatment for heroin addicts. Since this date, numerous deaths were attributed to this drug. This paper reports a new series of 13 fatalities involving buprenorphine observed at the Institute of Legal Medicine of Strasbourg, between August 2000 to October 2001.Design and methods: During the mentioned period, about 800 forensic cases were screened at the laboratory. Buprenorphine and its primary metabolite norbuprenophine were assayed in postmortem specimens by HPLC/MS. From these 13 subjects, 11 were male. Blood levels ranged from 0.3 to 7.7 ng/mL (mean 3.5 ng/mL) and 0.3 to 16.2 ng/mL (mean 2.9 ng/mL) for buprenorphine and norbuprenorphine, respectively. The mean values appear to be within the therapeutic range.Conclusions: IV injection of crushed tablets, a concomitant intake of psychotropics (especially benzodiazepines and neuroleptics) and the high dosage of the buprenorphine formulation available in France appear as the major risk factors for such fatalities. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Background: Medication for opioid use disorder (MOUD) using buprenorphine in primary or specialty care settings is accessed primarily by persons with private health insurance, stable housing, and no polysubstance use. This paper applies Social Cognitive Theory to frame links between social factors and treatment outcomes among patients with social and economic disadvantages who are seeking MOUD at California Bridge Program (CA Bridge) hospitals.Methods: Electronic medical records for patients identified with OUD between January-April, 2020 receiving care at CA Bridge hospitals defined outcomes: hospital-administered buprenorphine; provision of buprenorphine prescription at discharge. Multi-level models assessed whether social factors-housing status, insurance type, and co-methamphetamine use-predicted outcomes while accounting for group-level effects of treating hospital and controlling for age, race/ethnicity, and gender.Results: 15 CA Bridge hospitals yielded 845 patient records. Most patients received hospital-administered buprenorphine (58 %) and/or a buprenorphine prescription (55 %); 26 % received neither treatment. Patients with unstable housing had greater odds of hospital-administered buprenorphine compared to patients with stable housing. Patients with Medicaid had greater odds of receiving a buprenorphine prescription compared to patients with other insurance. Co-methamphetamine use was not associated with outcomes.Conclusions: Patients with OUD are successful in accessing same-day MOUD in CA Bridge hospital settings over a significant period. Importantly, access to MOUD in these settings was facilitated for patients traditionally not treated using buprenorphine, i.e., those with housing instability, Medicaid insurance, and co-methamphetamine use. Findings suggest barriers to MOUD for patients with social and economic disadvantages can be lowered by changing treatment delivery. [ABSTRACT FROM AUTHOR]

Background: There has been much research on the efficacy and effectiveness of opioid agonist treatment (OAT), but less on its implementation and sustainability. A challenge internationally has been recruiting and retaining prescribers. This paper aims to characterise the prescribers in terms of OAT prescribing behaviours.Methods: Retrospective cohort study in New South Wales, Australia. Participants were 2199 OAT prescribers between 1 st August 2001-19th September 2018.We examined trends in initiation and cessation of OAT prescribers. Adjusted hazard ratios were calculated to estimate prescriber retention, adjusting for year of initiation, practice type, client load and treatment prescribed.Results: The rate of prescribers ceasing OAT prescribing has been increasing over time: a prescriber who initiated between 2016-2017 had over four times the risk of cessation compared with one who initiated before 2001, AHR: 4.77; [3.67-6.21]. The highest prescriber cessation rate was in prescribers who had prescribed for shorter time periods. The annual percentage of prescribers who ceased prescribing among those who prescribed for ≤5 years increased from 3% in 2001 to 20 % in 2017. By 2017 more prescribers were discontinuing prescribing than new prescribers were starting. Approximately 87 % (n = 25,167) of OAT clients were under the care of 20 % of OAT prescribers (n = 202); half had been prescribing OAT for 17+ years.Conclusions: OAT prescribing is increasingly concentrated in a small group of mature prescribers, and new prescribers are not being retained. There is a need to identify and respond to the reasons that contribute to newer prescribers to cease prescribing and put in place strategies to increase retention and broaden the base of doctors involved in such prescribing. [ABSTRACT FROM AUTHOR]

Opioid use disorder (OUD) in pregnant women has increased significantly in recent years. Maintaining these women on sublingual (SL) buprenorphine (BUP) is an evidence-based practice but BUP-SL is associated with several disadvantages that an extended-release (XR) BUP formulation could eliminate. The National Drug Abuse Treatment Clinical Trials Network (CTN) is conducting an intent-to-treat, two-arm, open-label, pragmatic randomized controlled trial, Medication treatment for Opioid-dependent expectant Mothers (MOMs), to compare mother and infant outcomes of pregnant women with OUD treated with BUP-XR, relative to BUP-SL. A second aim is to determine the relative economic value of utilizing BUP-XR. Approximately 300 pregnant women with an estimated gestational age (EGA) of 6–30 weeks, recruited from 12 sites, will be randomized in a 1:1 ratio to BUP-XR or BUP-SL, balancing on site, EGA, and BUP-SL status (taking/not taking) at the time of randomization. Participants will be provided with study medication and attend weekly medication visits through 12 months postpartum. Participants will be invited to participate in two sub-studies to evaluate the: 1) mechanisms by which BUP-XR may improve mother and infant outcomes; and 2) effects of prenatal exposure to BUP-XR versus BUP-SL on infant neurodevelopment. This paper describes the key design decisions for the main trial made during protocol development. This Investigational New Drug (IND) trial uniquely uses pragmatic features where feasible in order to maximize external validity, hence increasing the potential to inform clinical practice guidelines and address multiple knowledge gaps for treatment of this patient population. [ABSTRACT FROM AUTHOR]

The United States continues to experience an opioid epidemic of unprecedented proportions despite FDA approval of life saving medications, such as buprenorphine. This paper describes a novel group-based buprenorphine treatment model and summarizes patient characteristics and treatment retention. This model, known as the Comprehensive Opioid Addiction Treatment (COAT) program, was developed in West Virginia, the epicenter of the opioid epidemic. Data on 454 patients actively enrolled in the COAT program were extracted from an administrative clinical data set and electronic medical records and analyzed using descriptive and quantitative analysis to determine long-term retention in treatment using frequencies and means. The characteristics of the 454 patients are as follows: average age of 39, 53% female, predominantly white (94%) and Medicaid was the primary insurance provider (68%). Analysis of retention showed 37.8% of patents were retained less than one year and 14.7% were retained 10 or more years. Initiating treatment at a younger age was associated with long-term retention. Opioid use disorder is a chronic relapsing disease and treatment models that retain patients long-term have the greatest benefit. The COAT model has been successful in retaining patients long-term in a rural setting where barriers to treatment are many. • Group-based medication for opioid use disorder (MOUD) provides a model that improves access and may improve retention in long-term treatment. • In this group-based model, 62.7% of patients were retained in MOUD treatment at least1 year, 23.7% for five or more years and 14.7% for ten or more years. • Initiating treatment at a younger age was associated with long-term retention. • Buprenorphine dose was not associated with longer retention in treatment. [ABSTRACT FROM AUTHOR]

In August 2017, California launched the Hub and Spoke Program to address the growing number of opioid overdose deaths in the state. The program connects opioid treatment programs ("hubs") with office based opioid treatment settings, like primary care clinics ("spokes") to build a network of treatment expertise and referral resources. A key objective of this program is to expand access to medications for opioid use disorders (MOUD), with a particular focus on getting more buprenorphine into spokes. This article describes the preliminary results of the evaluation of the California Hub and Spoke program. Using a mixed methods approach, this portion of the evaluation measures changes in numbers of MOUD patients and providers, and barriers and facilitators to implementation. Findings reveal that, in the first 15 months of the program, 3480 new patients started buprenorphine in 118 spokes, increasing treatment initiations by 94.7% over baseline. The number of waivered spoke providers also increased 52.4% to 268. Although these data demonstrate promising growth in the network, challenges to expanding treatment access remain. Provider activity was among the most notable. Despite growth in the number of spoke providers with waivers to prescribe buprenorphine, only 68.7% (n = 184) were actively prescribing to patients. A survey of providers found that those who were not yet using their waivers lacked the confidence and mentorship they needed to prescribe. Provider knowledge and attitudes toward MOUD, fear of legal consequences, and limited patient outreach were also contributing factors. Recommendations for strengthening Hub and Spoke program implementation include facilitating mentor linkage for prescribers, expanding the support offered to spoke providers, and offering additional training and technical assistance aimed at provider stigma. Efforts to address these recommendations are described in a companion paper (Miele et al., under review). [ABSTRACT FROM AUTHOR]

Abstract: The development and implementation of programs in the U.S. to minimize risks and assess unintended consequences of new medications has been increasingly required by the Food and Drug Administration (FDA) since the mid 1990s. This paper provides four case histories of risk management and post-marketing surveillance programs utilized recently to address problems associated with possible abuse, dependence and diversion. The pharmaceutical sponsors of each of these drugs were invited to present their programs and followed a similar template for their summaries that are included in this article. The drugs and presenting companies were OxyContin®, an analgesic marketed by Purdue Pharma L.P., Daytrana® and Vyvanse®, ADHD medications marketed by Shire Pharmaceuticals, Xyrem® for narcolepsy marketed by Jazz Pharmaceuticals, and Subutex® and Suboxone® for opioid dependence marketed by Reckitt Benckiser Pharmaceuticals Inc. These case histories and subsequent discussions provide invaluable real-world examples and illustrate both the promise of risk management programs in providing a path to market and/or for keeping on the market drugs with serious potential risks. They also illustrate the limitations of such programs in actually controlling unintended consequences, as well as the challenge of finding the right balance of reducing risks without posing undue barriers to patient access. These experiences are highly relevant as the FDA increasingly requires pharmaceutical sponsors to develop and implement the more formalized and enforceable versions of the risk management term Risk Evaluation and Mitigation Strategies (REMS). [Copyright &y& Elsevier]

This paper will review clinical pharmacology studies on buprenorphine, a mixed opioid agonist–antagonist currently approved as a treatment for opioid dependence. The focus is on studies characterizing buprenorphine''s pharmacodynamic actions, including its safety, abuse liability, withdrawal suppression and withdrawal precipitation capacity, physical dependence potential, cross-tolerance and duration of action as well as a review of the pharmacological profile of buprenorphine/naloxone combinations. The findings from these clinical pharmacology studies are synthesized and presented in a framework designed to (1) inform clinicians about the advantages and disadvantages of buprenorphine as an opioid maintenance agent, and (2) provide information about dosing procedures that may optimize the use of buprenorphine in the clinic. [Copyright &y& Elsevier]

Opiate dependence remains a fundamental challenge confronting health delivery systems and is often characterized as a social and moral issue. The impact of this disorder on healthcare policy is changing with the increased incidence of HIV, hepatitis C, and tuberculosis infections in opiate-dependent patients. These medical illnesses have substantial effect on escalating healthcare costs, and, therefore, also affect healthcare policy priorities, which are responsive to these costs. Pharmacological treatments for opiate dependence have had limited success; often the consequence of limited access to care. Hence, there is a need to develop new pharmacotherapies for opiate dependence that extend the range of clinical options, including new first-line treatment approaches. This paper will focus on the safety and health policy considerations related to the use of buprenorphine and buprenorphine/naloxone based on data derived from clinical trials and post-marketing surveillance that provide evidence for the use of the medications as first-line treatments in an office-based environment. The evaluation of this evidence formed the basis by the National Institute on Drug Abuse to support and pursue the evaluation and registration of buprenorphine/naloxone and buprenorphine in a public/private sector cooperative effort to become an office-based, first-line treatment for opiate dependence. [Copyright &y& Elsevier]