Treatment Of Opioid Use Disorder Research Articles

Pharmacist-prescriber collaborative models of care for opioid use disorder: an overview of recent research.

Collaborative models of care where pharmacists work alongside physicians have been developed for a range of physical health conditions, with benefits including improved patient outcomes and increased access to ongoing care. Opioid agonist treatment (methadone and buprenorphine) is a clinically effective and cost-effective treatment for opioid use disorder that is under-utilized in many countries due to a shortage of prescribers. In recent years, there has been increased interest in the development of collaborative models that utilize pharmacists to overcome barriers to treatment. In this article, we present a narrative review to synthesise recent work in this rapidly developing area. Two key aspects of opioid agonist treatment were identified: Collaborative models have utilized pharmacists to facilitate buprenorphine induction, and collaborative models provide increased capacity for delivering ongoing care in a variety of settings and patient groups where prescriber access is limited. Pharmacists have undertaken direct patient care responsibilities with varying degrees of autonomy, with benefits including a reduction in prescriber workload, and improvements in treatment retention and continuity of care. Collaborative models in which pharmacists are responsible for buprenorphine induction and ongoing management with methadone and buprenorphine have been shown to reduce demands on prescribers while improving or maintaining patient outcomes, and appear feasible and acceptable in a wide range of outpatient settings.

The Role of Medicinal Cannabis as an Emerging Therapy for Opioid Use Disorder.

This narrative review explores current insights into the potential use of medicinal cannabis-related products as an emerging therapy for opioid use disorder in the landscape of increasing knowledge about medicinal cannabis-based products, commercialisation and global legalisation. Preclinical studies have provided preliminary insight into the putative neurobiological mechanisms that underpin the potential for medicinal cannabis to be considered a therapeutic in opioid use disorder and addiction. With the progressive legalisation of cannabis in many jurisdictions worldwide, contemporary research has highlighted further evidence that medicinal cannabis may have efficacy in reducing cravings and withdrawal effects, and therefore may be considered as an adjunct or standalone to current medications for opioid use disorder. Despite this potential, the landscape of research in this space draws from a large number of observational studies, with a paucity of rigorous randomised controlled trials to ascertain a true understanding of effect size and safety profile. With current challenges in implementation that arise from political and legal qualms about adopting medicinal cannabis on the background of associated social stigma, significant hurdles remain to be addressed by government, policy-makers, healthcare providers and researchers before medical cannabis can be introduced globally for the treatment of opioid use disorder.

Prevalence and predictors of medication for opioid use disorder among reproductive-aged women

BackgroundWomen of reproductive age would benefit from treatment of opioid use disorder (OUD) prior to pregnancy to improve maternal and infant outcomes. In this study, we aimed to identify the prevalence of medication for OUD (MOUD) and characterize correlates of MOUD receipt among 12–49-year-old women with OUD seeking treatment in publicly funded substance use disorder treatment programs at the time of their first treatment episode. MethodsThis cross-sectional study explores the demographic and clinical characteristics of women of reproductive age with OUD receiving publicly funded substance use treatment services. We used data from the concatenated 2015–2021 Treatment Episode Data Set–Admissions (TEDS-A), which documents demographic and clinical characteristics of patient admissions to publicly funded substance use treatment services in the United States. ResultsIn the sample of females aged 12–49 with no prior treatment admissions and primary OUD (n=325,512), 40.53% received MOUD (n=131,930), including 39.40% of non-pregnant women (n=115,315) and 52.79% of pregnant women (n=8423). Pregnant women had significantly higher odds of receiving MOUD (aOR = 2.42, 95%CI: 2.30, 2.54) compared to non-pregnant women. Non-white race, treatment setting, and treatment self-referral were also associated with higher levels of MOUD. ConclusionsWe identified a significant unmet need among both pregnant and non-pregnant women with OUD seeking care in publicly funded treatment clinics. While women who are pregnant are significantly more likely to receive evidence-based treatment with MOUD, still 47.21% of pregnant women did not receive MOUD. All reproductive-aged women with OUD should be offered evidence-based treatment options, including MOUD.

Protocol for the development of a consensus practice guideline To address clinical and regulatory barriers to buprenorphine dispensing in community pharmacy

BackgroundLess than half of community pharmacies in the United States stock buprenorphine products indicated for the treatment of opioid use disorder. This lack of access to buprenorphine in community pharmacies is a significant barrier to care. To address this issue, this protocol outlines a comprehensive approach to develop a practice guideline aimed at improving access to safe and effective opioid use disorder treatment in community pharmacies.MethodsThe guideline development process will proceed in three phases, following a technique closely aligned with the Institute of Medicine’s guidance on guideline development. The first phase will involve conducting qualitative interviews with pharmacists in three states to identify their beliefs toward buprenorphine dispensing. As limitations on buprenorphine supply are related to constraints at all levels of the drug supply and regulatory system, the second phase, we will recruit representatives from regulatory agencies, pharmacy organizations, the Drug Enforcement Administration, pharmaceutical wholesalers as well as addiction medicine physicians and psychiatric pharmacists to develop consensus recommendations through a modified Delphi design. This will be followed by a public comment period and external expert review of the recommendations led by the National Association of Boards of Pharmacy. Finally, in the third phase, a national, mixed media dissemination campaign will be led by the National Community Pharmacists Association (NCPA) to convey recommendations to practicing pharmacists.DiscussionThe guideline development process aims to incorporate the perspectives of multiple stakeholders and emphasize the importance of addressing the regulatory and pharmacy-specific aspects of care in addition to clinical evidence and guidance. The development of this guideline will provide targeted, multidisciplinary guidance for pharmacists, improving access to safe and effective opioid use disorder treatment in the community setting.PreregistrationThis protocol was registered with the Open Science Framework in March of 2023. Registration may be found at: https://doi.org/10.17605/OSF.IO/6S9DY.

Evaluating preferences for medication formulation and treatment model among people who use opioids non-medically: A web-based cross-sectional study

IntroductionOver the past decade, treatment for opioid use disorder has expanded to include long-acting injectable and implantable formulations of medication for opioid use disorder (MOUD), and integrated treatment models systematically addressing both behavioral and physical health. Patient preference for these treatment options has been underexplored. Gathering data on OUD treatment preferences is critical to guide the development of patient-centered treatment for OUD. This cross-sectional study assessed preferences for long-acting MOUD and integrated treatment using an online survey. MethodsAn online Qualtrics survey assessed preferences for MOUD formulation and integrated treatment models. The study recruited participants (n = 851) in October and November 2019 through advertisements or posts on Facebook, Google AdWords, Reddit, and Amazon Mechanical Turk (mTurk). Eligible participants scored a two or higher on the opioid pain reliever or heroin scales of the Tobacco, Alcohol Prescription Medication and other Substance Use (TAPS) Tool. Structured survey items obtained patient preference for MOUD formulation and treatment model. Using stated preference methods, the study assessed preference via comparison of preferred options for MOUD and treatment model. ResultsIn the past year, 824 (96.8 %) participants reported non-prescribed use of opioid pain relievers (mean TAPS score = 2.72, SD = 0.46) and 552 (64.9 %) reported heroin or fentanyl use (mean TAPS score = 2.73, SD = 0.51). Seventy-four percent of participants (n = 631) reported currently or previously receiving OUD treatment, with 407 (48.4 %) receiving MOUD. When asked about preferences for type of MOUD formulation, 452 (53.1 %) preferred a daily oral formulation, 115 (13.5 %) preferred an implant, 114 (13.4 %) preferred a monthly injection and 95 (11.2 %) preferred a weekly injection. Approximately 8.8 % (n = 75) would not consider MOUD regardless of formulation. The majority of participants (65.2 %, n = 555) preferred receiving treatment in a specialized substance use treatment program distinct from their medical care, compared with receiving care in an integrated model (n = 296, 34.8 %). ConclusionsThough most participants expressed willingness to try long-acting MOUD formulations, the majority preferred short-acting formulations. Likewise, the majority preferred non-integrated treatment in specialty substance use settings. Reasons for these preferences provide insight on developing effective educational tools for patients and suggesting targets for intervention to develop a more acceptable treatment system.

The effect of a pilot brief educational intervention on preferences regarding treatments for opioid use disorder

PurposeNegative perceptions around medications for opioid use disorder (MOUD) amongst the public could deter patients with opioid use disorder (OUD) from engaging with MOUD. Thus, we evaluated whether a brief intervention could improve preferences for MOUD in people who may or may not use opioids. MethodsWe employed a pre-post design to assess the effect of a brief educational intervention on preferences for methadone, buprenorphine, naltrexone, and non-medication treatment in an online sample of US adults stratified by race, who may or may not use opioids. Respondents ranked their preferences in OUD treatment before and after watching four one-minute educational videos about treatment options. Changes in treatment preferences were analyzed using Bhapkar’s test and post hoc McNemar’s tests. A binary logistic generalized estimating equation (GEE) assessed factors associated with preference between treatments. ResultsThe sample had 530 responses. 194 identified as White, 173 Black, 163 Latinx. Treatment preferences changed significantly towards MOUD (p<.001). This effect was driven by changes toward buprenorphine (OR=2.38; p<.001) and away from non-medication treatment (OR=0.20; p<.001). There was no significant difference in effect by race/ethnicity. People with lower opioid familiarity were significantly more likely to change their preferences towards MOUD following the intervention. ConclusionRespondent preferences for MOUD increased following the intervention suggesting that brief educational interventions can change treatment preferences towards MOUD. These findings offer insights into perceptions of OUD treatment in a racially stratified sample and serve as a foundation for future educational materials that target MOUD preferences in the general public.

Discontinuation of medication treatment for opioid use disorder after a successful course: The discontinuation phase of the CTN-0100 (RDD) trial

Introduction and backgroundBuprenorphine, and extended-release naltrexone, are effective in decreasing opioid use, morbidity and mortality. The available evidence suggests that these medications should be used for long term treatment; however, patients often ask how long they need to be on medication, and whether it would be safe to discontinue. There are sparse data to guide us. The CTN-0100 trial will address this gap in our knowledge by studying participants who have decided to discontinue buprenorphine and extended-release naltrexone for OUD. Research design and methodsThe trial is a multicenter, randomized, non-blinded study. Participants are stable adult volunteers, on sublingual buprenorphine, extended-release buprenorphine, or extended-release naltrexone, expressing an interest in discontinuing medication. Participants on buprenorphine must be stable for at least 1 year and participants on extended-release naltrexone must be stable for at least 6 months. Participants are engaged in the study for up to 96 weeks, including a flexible taper period, and are then transitioned to follow-up within the trial. All participants are randomly assigned to the study Medical Management (MM) or to MM plus Connections (CHESS health) digital smartphone application aimed at recovery and abstinence (MMD). Sublingual Buprenorphine participants are also randomized (2 × 2 design) to a taper using either sublingual or extended-release buprenorphine. Discussion/conclusionIt is hoped that this trial will provide a rich source of data on management of patients discontinuing medication for opioid use disorder (MOUD) to inform future research and practice. The trial will shed light on which strategies are most likely to lead to long-term success (absence of relapse), and what participant characteristics distinguish those who can safely discontinue MOUD from those who remain at risk of relapse should they discontinue.ClinicalTrials.gov Identifier: NCT04464980

Emergency Department Management of Precipitated Opioid Withdrawal after Intravenous Buprenorphine/Naloxone Use: A Case Report

The opioid epidemic in the United States continues to grow at staggering rates. More than 760,000 people have died of drug overdose since 1999, with the annual death toll increasing exponentially. In response, the use of medication assisted treatment (MAT) for opioid use disorder has grown considerably. Abuse of MAT is common, with studies showing rates as high as 28% of patients on MAT abusing the medications. There are case reports detailing precipitated withdrawal following intravenous buprenorphine/naloxone (Suboxone) misuse, but little literature exists regarding management of these cases. The current recommendation per other case reports is to treat with additional doses of Suboxone. We present the case of a 44-year-old male presenting to the emergency department in precipitated withdrawal after injecting Suboxone intravenously. In this case, the patient had eloped from inpatient rehabilitation about 36 hours after his last dose of Fentanyl. He then injected Suboxone to combat symptoms of opioid withdrawal. He felt markedly worse following the injection, prompting him to seek treatment. On arrival he was visibly uncomfortable and irritable during the exam. He was treated with additional Suboxone at the suggestion of other case reports, but this significantly worsened his symptoms. He was additionally treated with diazepam, resulting in improvement. He was discharged with resources for opioid use disorder and was successfully contacted six months after his initial presentation, at which time he reported continued opioid use as well as suboxone misuse.

Prolonged diacetylmorphine take-home during the COVID-19 pandemic-Results of a retrospective cohort study.

Legal regulations for dispensing in Swiss heroin-assisted treatment were relaxed during the COVID-19 pandemic, allowing prolonged take-home of up to 7 days instead of two to reduce patient contact and the risk of infection. Our study aimed to measure the consequences of this new practice. This was a retrospective cohort study set in Switzerland's largest outpatient centre for opioid agonist therapy. One hundred and thirty-four (72.4%) of the 185 patients receiving oral diacetylmorphine (DAM) participated in the study. Through the utilization of electronic medication prescription and dispensing software, as well as the electronic medical record, the following data were extracted to explore the potential consequences: dose of DAM, the number of antibiotic therapies, emergency hospitalizations and incarcerations. Age, gender, prescriptions for psychotrophic drugs and additional prescription for injectable DAM were tested to assess an increased risk of losing prolonged take-home privileges. Data in the year since prolonged take-home (period 2) were compared with data from the equivalent prior year (period 1). DAM take-home was not associated with a change in DAM dose (P = 0.548), the number of emergency hospitalizations (P = 0.186) or the number of incarcerations (P = 0.215); 79.1% of all patients were able to maintain their extended take-home privileges. However, patients who had injectable DAM experienced significant reductions in their prolonged take-home privileges. Allowing patients to take home oral diacetylmorphine for up to 7days as treatment for opioid use disorder does not appear to pose any demonstrable health risk. It is generally manageable for the large majority of patients. However, careful consideration of prolonged take-home for patients with additional injectable diacetylmorphine is recommended, as these patients are more likely to lose take-home privileges.

Inpatient opioid withdrawal: a qualitative study of the patient perspective.

Opioid withdrawal is common among hospitalized patients. Those with substance use disorders exhibit higher rates of patient-directed discharge. The literature lacks information regarding the patient perspective on opioid withdrawal in the hospital setting. In this study, we aimed to capture the patient-reported experience of opioid withdrawal during hospitalization and its impact on the desire to continue treatment for opioid use disorder after discharge. We performed a single-center qualitative study involving semi-structured interviews of hospitalized patients with opioid use disorder (OUD) experiencing opioid withdrawal. Investigators conducted in-person interviews utilizing a combination of open-ended and dichotomous questions. Interview transcripts were then analyzed with open coding for emergent themes. Nineteen interviews were performed. All participants were linked to either buprenorphine (79%) or methadone (21%) at discharge. Eight of nineteen patients (42%)reported a patient-directed discharge during prior hospitalizations.Themes identified from the interviews included: (1) opioid withdrawal was well-managed in the hospital; (2) patients appreciated receiving medication for opioid use disorder (MOUD) for withdrawal symptoms; (3) patients valued and felt cared for by healthcare providers; and (4) most patients had plans to follow-up for opioid use disorder treatment after hospitalization. In this population with historically high rates of patient-directed discharge, patients reported having a positive experience with opioid withdrawal management during hospitalization. Amongst our hospitalized patients, we observed several different individualized MOUD induction strategies. All participants were offered MOUD at discharge and most planned to follow-up for further treatment.

Association of Receipt of Opioid Prescription for Acute Post-Delivery Pain Management with Buprenorphine Discontinuation among Postpartum People with Opioid Use Disorder

Buprenorphine is a safe and effective medication to treat opioid use disorder (OUD) in pregnant patients and is intended to be continued throughout pregnancy, delivery, and at least the one-year postpartum period. However, delivery often involves the need for acute pain management with opioid medications, such as after a cesarean section. For patients receiving buprenorphine, the provision of prescription opioids may negatively impact OUD treatment outcomes; however, not optimally managing acute pain may also impede OUD treatment benefit. Evidence is needed to disentangle the impacts of opioid prescription provision and methods of pain management in the immediate postpartum period on OUD treatment trajectories, ultimately to inform clinical guidelines tailored to the unique needs of pregnant and postpartum people receiving buprenorphine. Accordingly, this study took an initial step towards this goal to conduct a secondary analysis of a retrospective cohort of pregnant patients taking buprenorphine for OUD at the time of delivery (n = 142) to determine whether receipt of an opioid prescription at birth hospitalization discharge was associated with the time of buprenorphine discontinuation within the 12 months following delivery. Among the sample, 26% (n = 37) were prescribed an opioid at the time of birth hospitalization discharge. The number of weeks post-delivery until buprenorphine discontinuation occurred was shorter amongst patients who were prescribed an opioid (median 11 weeks) compared to patients who were not prescribed an opioid (median 39 weeks; p &lt; 0.001 by Mann–Whitney U test). However, a Cox regression model reported that receipt of an opioid prescription following delivery did not significantly increase the hazard ratio for buprenorphine discontinuation. In other words, OUD patients not prescribed an opioid at birth hospitalization discharge continued their buprenorphine for a longer median duration after delivery compared to their counterparts who received prescription opioids; yet, this finding did not reach statistical significance when taking into account additional clinical variables. The findings indicate how further research is warranted to inform evidence-based post-delivery pain practices for postpartum OUD treatment patients.

The development and internal validation of a multivariable model predicting 6-month mortality for people with opioid use disorder presenting to community drug services in England: a protocol

BackgroundPeople with opioid use disorder have substantially higher standardised mortality rates compared to the general population; however, lack of clear individual prognostic information presents challenges to prioritise or target interventions within drug treatment services. Previous prognostic models have been developed to estimate the risk of developing opioid use disorder and opioid-related overdose in people routinely prescribed opioids but, to our knowledge, none have been developed to estimate mortality risk in people accessing drug services with opioid use disorder. Initial presentation to drug services is a pragmatic time to evaluate mortality risk given the contemporaneous routine collection of prognostic indicators and as a decision point for appropriate service prioritisation and targeted intervention delivery. This study aims to develop and internally validate a model to estimate 6-month mortality risk for people with opioid use disorder from prognostic indicators recorded at initial assessment in drug services in England.MethodsAn English national dataset containing records from individuals presenting to drug services between 1 April 2013 and 1 April 2023 (n > 800,000) (the National Drug Treatment Monitoring System (NDTMS)) linked to their lifetime hospitalisation and death records (Hospital Episode Statistics-Office of National Statistics (HES-ONS)). Twelve candidate prognostic indicator variables were identified based on literature review of demographic and clinical features associated with increased mortality for people in treatment for opioid use disorder. Variables will be extracted at initial presentation to drug services with mortality measured at 6 months. Two multivariable Cox regression models will be developed one for 6-month all-cause mortality and one for 6-month drug-related mortality using backward elimination with a fractional polynomial approach for continuous variables. Internal validation will be undertaken using bootstrapping methods. Discrimination of both models will be reported using Harrel’s c and d-statistics. Calibration curves and slopes will be presented comparing expected and observed event rates.DiscussionThe models developed and internally validated in this study aim to improve clinical assessment of mortality risk for people with opioid use disorder presenting to drug services in England. External validation in different populations will be required to develop the model into a tool to assist future clinical decision-making.

Frontiers in Operations: Equitable Data-Driven Facility Location and Resource Allocation to Fight the Opioid Epidemic

Problem definition: The opioid epidemic is a crisis that has plagued the United States for decades. One central issue of the epidemic is inequitable access to treatment for opioid use disorder (OUD), which puts certain populations at a higher risk of opioid overdose. Methodology/results: We integrate a predictive dynamical model and a prescriptive optimization problem to compute high-quality opioid treatment facility and treatment budget allocations for each U.S. state. Our predictive model is a differential equation-based epidemiological model that captures the dynamics of the opioid epidemic. We use a process inspired by neural ordinary differential equations to fit this model to opioid epidemic data for each state and obtain estimates for unknown parameters in the model. We then incorporate this epidemiological model into a corresponding mixed-integer optimization problem (MIP) that aims to minimize the number of opioid overdose deaths and the number of people with OUD. We develop strong relaxations based on McCormick envelopes to efficiently compute approximate solutions to our MIPs that have a mean optimality gap of 3.99%. Our method provides socioeconomically equitable solutions, as it incentivizes investments in areas with higher social vulnerability (from the U.S. Centers for Disease Control’s Social Vulnerability Index) and opioid prescribing rates. On average, when allowing for overbudget solutions, our approach decreases the number of people with OUD by [Formula: see text], increases the number of people in treatment by [Formula: see text], and decreases the number of opioid-related deaths by [Formula: see text] after 2 years compared with the baseline epidemiological model’s predictions. Managerial implications: Our solutions show that policymakers should target adding treatment facilities to counties that have significantly fewer facilities than their population share and are more socially vulnerable. Furthermore, we demonstrate that our optimization approach, guided by epidemiological and socioeconomic factors, should help inform these strategic decisions, as it yields population health benefits in comparison with benchmarks based solely on population and social vulnerability. History: This paper has been accepted in the Manufacturing &amp; Service Operations Management Frontiers in Operations Initiative. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2023.0042 .

Growing importance of high-volume buprenorphine prescribers in OUD treatment: 2009–2018

BackgroundWe examined the number and characteristics of high-volume buprenorphine prescribers and the nature of their buprenorphine prescribing from 2009 to 2018. MethodsIn this observational cohort study, IQVIA Real World retail pharmacy claims data were used to characterize trends in high-volume buprenorphine prescribers (clinicians with a mean of 30 or more active patients in every month that they were an active prescriber) during 2009–2018. Very high-volume prescribing (mean of 100+ patients per month) was also examined. ResultsOverall, 94,491 clinicians prescribed buprenorphine dispensed during 2009–2018. The proportion of active prescribers meeting high-volume criteria increased from 7.4 % in 2009 to 16.7 % in 2018. High-volume prescribers accounted for 80 % of dispensed buprenorphine prescriptions during 2009–2018; very high-volume prescribers accounted for 26 %. Adult primary care physicians consistently comprised the majority of high-volume prescribers. Addiction specialists were much more likely to be high-volume prescribers compared to other specialties, including psychiatrists and pain specialists. By 2018, the proportion of prescriptions from high-volume prescribers paid by Medicaid had doubled to 40 %, accompanied by a decline in both self-pay and commercial insurance. High-volume prescribers were overwhelmingly concentrated in urban counties with the highest fatal overdose rates. In 2018, the highest density of high-volume prescribers was in New England and the mid-Atlantic region. ConclusionsGrowth in high-volume prescribers outpaced the overall growth in buprenorphine prescribers across 2009–2018. High-volume prescribers play an increasingly central role in providing medication for OUD in the U.S., yet results indicate key regional variation in the availability of high-volume buprenorphine prescribers.

Cognitive processing therapy (CPT) versus individual drug counseling (IDC) for PTSD for veterans with opioid use disorder maintained on buprenorphine.

There are high rates of comorbidity between posttraumatic stress disorder (PTSD) and opioid use disorder (OUD). Evidence-based trauma-focused psychotherapies such as Cognitive Processing Therapy (CPT) are a first-line treatment for PTSD. Veterans with OUD are treated primarily in substance use disorder (SUD) clinics where the standard of care is drug counseling; they often do not have access to first-line PTSD treatments. This study tested whether CPT can be conducted safely and effectively in veterans with comorbid OUD treated with buprenorphine. This 12-week, 2-site, randomized clinical trial (RCT) included open-label randomization to two groups: (a) CPT versus (b) Individual Drug Counselling (IDC) in veterans with PTSD and comorbid OUD who were maintained on buprenorphine (N = 38). Veterans randomized to either IDC (n = 18) or CPT (n = 20) showed a significant reduction in self-reported PTSD symptoms over time as measured by the PTSD checklist (PCL-5) but there were no treatment group differences; there was some indication that reduction in PTSD symptoms in the CPT group were sustained in contrast to the IDC group. Recruitment was significantly impacted by COVID-19 pandemic, so this study serves as a proof-of-concept pilot study. Veterans with OUD and PTSD can safely and effectively participate in evidence-based therapy for PTSD; further work should confirm that trauma-focused treatment may be more effective in leading to sustained remission of PTSD symptoms than drug counseling. This is the first study to evaluate CPT for PTSD in the context of buprenorphine treatment for OUD.

A pilot randomized controlled trial of medication adherence therapy: Psychosocial leverage using a significant other (MAT-PLUS) for individuals on extended-release naltrexone

BackgroundExtended-release naltrexone (XR-NTX) is an important treatment option for individuals with opioid use disorder (OUD) and/or alcohol use disorder (AUD). However, problems with retention are a major barrier to its overall effectiveness, and interventions to improve adherence are underdeveloped. The purpose of this study was to pilot test the MAT-PLUS intervention, which combines assertive outreach and involvement of a treatment significant other (TSO) to improve adherence to XR-NTX. MethodsAdults (N = 41) seeking treatment for OUD and/or AUD with XR-NTX were recruited from an inpatient addiction treatment center and randomized to the MAT-PLUS intervention or treatment as usual (TAU) for 16-weeks. TSOs (N = 19) of individuals in the MAT-PLUS condition were also enrolled. The primary outcome was the number of XR-NTX doses received and relapse to regular heavy use (opioid or alcohol) was a secondary outcome. ResultsParticipants in the MAT-PLUS group received 3.4 doses compared to 2.5 in TAU, which was significant after controlling for SUD diagnosis (p < 0.05). Rates of receipts of all prescribed doses were 61.1 % in MAT-PLUS compared to 30.4 % in TAU, giving an NNT of 3.3. Relapse rates and days of heavy use did not vary by treatment group. ConclusionsThis study demonstrates preliminary efficacy of the MAT-PLUS intervention for XR-NTX adherence. This study was limited by its small sample size and future research should broaden the intervention to apply across medications for SUD in larger samples. Family support with an emphasis on medication adherence has strong potential for improving addiction treatment outcomes.

Empirically contrasting urine drug screening-based opioid use disorder treatment outcome definitions.

A lack of consensus on the optimal outcome measures to assess opioid use disorder (OUD) treatment efficacy and their precise definition and computation has hampered the pooling of research data for evidence synthesis and meta-analyses. This study aimed to empirically contrast multiple clinical trial definitions of treatment success by applying them to the same dataset. Data analysis used a suite of functions, developed as a software package for the R language, to operationalize 61 treatment outcome definitions based on urine drug screening (UDS) results. Outcome definitions were derived from clinical trials that are among the most influential in the OUD treatment field. Outcome functions were applied to a harmonized dataset from three large-scale National Drug Abuse Treatment Clinical Trials Network (CTN) studies, which tested various medication for OUD (MOUD) options (n = 2492). Hierarchical clustering was employed to empirically contrast outcome definitions. The optimal number of clusters identified was three. Cluster 1, comprising eight definitions focused on detecting opioid-positive UDS, did not include missing UDS in outcome calculations, potentially resulting in inflated rates of treatment success. Cluster 2, with the highest variability, included 10 definitions characterized by strict criteria for treatment success, relying heavily on UDS results from either a brief period or a single study visit. The 43 definitions in Cluster 3 represented a diverse range of outcomes, conceptualized as measuring abstinence, use reduction and relapse. These definitions potentially offer more balanced measures of treatment success or failure, as they avoid the extreme methodologies characteristic of Clusters 1 and 2. Clinical trials using urine drug screening (UDS) for objective substance use assessment in outcome definitions should consider (1) incorporating missing UDS data in outcome computation and (2) avoiding over-reliance on UDS data confined to a short time frame or the occurrence of a single positive urine test following a period of abstinence.

Catharanthine Modulates Mesolimbic Dopamine Transmission and Nicotine Psychomotor Effects via Inhibition of α6-Nicotinic Receptors and Dopamine Transporters.

Iboga alkaloids, also known as coronaridine congeners, have shown promise in the treatment of alcohol and opioid use disorders. The objective of this study was to evaluate the effects of catharanthine and 18-methoxycoronaridine (18-MC) on dopamine (DA) transmission and cholinergic interneurons in the mesolimbic DA system, nicotine-induced locomotor activity, and nicotine-taking behavior. Utilizing ex vivo fast-scan cyclic voltammetry (FSCV) in the nucleus accumbens core of male mice, we found that catharanthine or 18-MC differentially inhibited evoked DA release. Catharanthine inhibition of evoked DA release was significantly reduced by both α4 and α6 nicotinic acetylcholine receptors (nAChRs) antagonists. Additionally, catharanthine substantially increased DA release more than vehicle during high-frequency stimulation, although less potently than an α4 nAChR antagonist, which confirms previous work with nAChR antagonists. Interestingly, while catharanthine slowed DA reuptake measured via FSCV ex vivo, it also increased extracellular DA in striatal dialysate from anesthetized mice in vivo in a dose-dependent manner. Superfusion of catharanthine or 18-MC inhibited the firing rate of striatal cholinergic interneurons in a concentration dependent manner, which are known to potently modulate presynaptic DA release. Catharanthine or 18-MC suppressed acetylcholine currents in oocytes expressing recombinant rat α6/α3β2β3 or α6/α3β4 nAChRs. In behavioral experiments using male Sprague-Dawley rats, systemic administration of catharanthine or 18-MC blocked nicotine enhancement of locomotor activity. Importantly, catharanthine attenuated nicotine self-administration in a dose-dependent manner while having no effect on food reinforcement. Lastly, administration of catharanthine and nicotine together greatly increased head twitch responses, indicating a potential synergistic hallucinogenic effect. These findings demonstrate that catharanthine and 18-MC have similar, but not identical effects on striatal DA dynamics, striatal cholinergic interneuron activity and nicotine psychomotor effects.

Stepped Care for Patients to Optimize Whole Recovery (SC-POWR): An Effectiveness Trial Evaluating a Stepped Care Model for Individuals With Opioid Use Disorder and Chronic Pain.

Many patients who receive treatment for opioid use disorder (OUD) report experiencing chronic pain (CP), which is associated with high levels of ongoing nonmedical opioid use and low retention in OUD treatment. In pilot studies of patients with OUD receiving buprenorphine or methadone who had CP, cognitive behavioral therapy (CBT) attenuated nonmedical opioid use compared with treatment-as-usual (TAU), but patients in both treatment arms exhibited similar pain improvements. Adding exercise and stress reduction to this model may augment pain-related outcomes. With funding from National Institutes of Health, we plan to conduct a randomized clinical trial of 316 patients with OUD and CP to test the effectiveness of TAU compared with Stepped Care for Patients to Optimize Whole Recovery (SC-POWR) to reduce nonmedical opioid use and pain (primary outcomes) (Aim 1) and decrease pain intensity and interference, alcohol use, anxiety, depression and stress, and improve sleep (secondary outcomes) (Aim 2). Eligible participants will be randomized to receive TAU (buprenorphine or methadone and at least once a month individual or group counseling) or SC-POWR (ie, TAU and up to 12 CBT sessions) for 24 weeks. Based on prespecified nonresponse criteria, SC-POWR may be stepped up at week 6 to receive onsite weekly group sessions of exercise (Wii Fit, Tai Chi) and "stepped up" again at week 15 to receive weekly group sessions of stress reduction (relaxation training, auricular acupuncture). They will be followed for another 24 weeks to evaluate durability of treatment response for illicit opioid use, alcohol use, pain, anxiety, depression, stress, sleep, and retention in medications for OUD (Aim 3).

Building Capacity for Injectable Diacetylmorphine and Hydromorphone for the Treatment of Opioid Use Disorder: Identifying Typical Doses

ABSTRACT Identifying typical doses of existing opioid use disorder medications, such as injectable opioid agonist treatment (iOAT), can support client and program needs, and potentially increase iOAT expansion. Longitudinal data from participants in a cohort study (n = 131), along with clinic dispensation records from August 2014 to April 2020, were used to examine physician prescribed as well as used doses of injectable diacetylmorphine and hydromorphone. Dosage groups, by medication and prescribed dose per session, were created for both hydromorphone and diacetylmorphine. A total of 534, 522 injections were registered during the study period among 129 participants. Mean received diacetylmorphine doses ranged from 106 to 989 mg per day, with most clients using 125–262 mg per session (mean 192.99 mg) and attending 2.40 sessions per day. Mean received hydromorphone doses ranged from 51.09 to 696.06 mg per day, with the majority using 88–154 mg per session (mean 121.32 mg; 2.43 sessions). Average daily doses remained stable overtime and, while mid-range doses were most typical, participants used the whole spectrum of allowable dose prescriptions. Evidence supporting typical doses of iOAT can be integrated into program planning to better allow providers and prescribers to anticipate program needs and engage in individualized care.