Long-Acting Injectable Buprenorphine for Opioid Use Disorder: A Qualitative Analysis of Patients' Interpersonal Relationships during the First Year of Treatment.

Introduction: Long-acting injectable buprenorphine (LAIB) is a new treatment for opioid use disorder. Drawing upon new materialism and the concept of social capital, this article provides a focused analysis of how LAIB affects, and is affected by, patients' relationships with other people. Methods: Data derive from a longitudinal qualitative study. Twenty-six people (18 males; 8 females) initiating LAIB were recruited from England and Wales (2020/2021) and interviewed up to six times each over a year (125 interviews in total). Interviews were audio-recorded, transcribed, and coded. Coded relationship data were summarized in Excel and analyzed via Iterative Categorization. Results: Core significant others who did not use substances offered participants important support with LAIB. Children and grandchildren provided motivation for LAIB, whilst other family relationships could be supportive and unsupportive. Participants wanted to avoid friends, peers and associates who might offer them substances, but valued sharing experiences with others in similar circumstances. Whilst some participants were unconcerned when treatment staff did not contact them, others were angry and upset. Those who did not continue LAIB or were lost from the study were more isolated at recruitment. Meanwhile, participants who remained on LAIB described increased sociability over time. Conclusions: Findings are consistent with ideas relating to new materialism (LAIB is part of an interacting network of material and non-material factors) and social capital (those with supportive relationships benefited more from LAIB). Interpersonal relationships need to be considered as part of routine care and should be reviewed with patients throughout the treatment journey.

Direct induction onto high-dose long-acting injectable buprenorphine: A case series.

INTRODUCTION: This case series reports on five patients with opioid use disorder (OUD) who were commenced directly onto high-dose long-acting injectable buprenorphine (LAIB). METHOD: A retrospective audit and manual review of the electronic medical record at cohealth Innerspace was conducted for patients who had been directly inducted onto high-dose LAIB. RESULTS: Five cases were identified on retrospective manual file review. All patients identified were males aged between 33 and 60 years old and were treated with either high-dose Buvidal Weekly and Monthly preparations. No immediate significant adverse effects were noticed and 4 out of 5 remain engaged with treatment. CONCLUSION: This case series shows it is possible to directly induct patients with OUD onto high-dose LAIB preparations without significant side effects or harm to the patient and could be considered a viable option in the treatment of patients with OUD.

Inpatient initiation of long-acting injectable buprenorphine at a community hospital: A retrospective case series.

OBJECTIVES: Determine if long-acting injectable buprenorphine (LAIB) can be successfully and safely administered in the hospital with minimal sublingual buprenorphine lead-in and potentially improve follow-up engagement in care. METHODS: We performed a retrospective case series of 46 patients who received LAIB while hospitalized at a safety-net community hospital. We abstracted demographic information, details about substance use disorder treatment history, in-hospital buprenorphine initiation methods and follow-up data from inpatient and outpatient electronic medical records. RESULTS: In total, 46 hospitalized patients received LAIB during the study period. The majority of our patients were older Black adults with Medicaid who self-reported intranasal heroin use. A low-dose buprenorphine initiation protocol was used most commonly, either in sublingual or intravenous form, with only two cases of precipitated withdrawal occurring during the buprenorphine initiation process and no cases of precipitated withdrawal after the administration of LAIB. 87% (40) of the patients received LAIB after receiving either sublingual or IV buprenorphine for fewer than the recommended seven days. Of the 46 hospitalized patients who received LAIB, 23 (50%) attended a follow-up addiction medicine appointment within 30 days of discharge. CONCLUSIONS: Hospital administration of LAIB could play an important role in retention in care after hospital discharge.

The FASTER-BUP Study, Extended-Release Injectable Buprenorphine for the Treatment of Opioid Use Disorder Among Individuals at High Risk of Overdose: Protocol for an Observational Prospective Study.

North America is facing an unprecedented public health emergency of opioid-related morbidity and mortality. The mortality benefits of oral medication treatment for opioid use disorder (MOUD), such as methadone or buprenorphine, are well documented. However, barriers to access and long-term engagement have prevented maximizing their benefits. Long-acting injectable buprenorphine formulations were developed to address some of the challenges associated with oral MOUD. The "Pilot study to assess the feasibility, efficacy, and safety of extended-release injectable buprenorphine for the treatment of opioid use disorder among individuals at high risk of overdose" (FASTER-BUP) was developed to explore this treatment option in populations at high risk of overdose in a real-world Canadian setting. FASTER-BUP is a 24-week observational prospective study evaluating the feasibility and clinical utility of extended-release injectable buprenorphine (XR-BUP) for the treatment of opioid use disorder (OUD) among 40 adults at high risk of overdose (ie, lifetime history of overdose or a positive urine drug test (UDT) for fentanyl within 30 days prior to screening) in Vancouver, BC. The primary outcome is retention in treatment and secondary outcomes include: use of unregulated opioids, safety, overdose events, treatment satisfaction, changes in drug-related problems, changes in quality of life, opioid cravings, health service utilization, and criminal activity. FASTER-BUP is the first study to explore XR-BUP among individuals at high risk of overdose in a real-world Canadian setting. This commentary provides a brief narrative about the study thus far and presents insights on key adaptations to the study protocol, including those adopted to mitigate recruitment challenges.

Long-acting injectable buprenorphine in the real world: case report on dual disorders.

OBJECTIVES: Long-acting injectable buprenorphine (LAIB) has demonstrated a good profile for opioid use disorder (OUD) management. However, there is scarce information on LAIB in OUD patients with comorbid mental disorders (dual disorder patients). METHODS: We present a case report on OUD patients with a comorbid mental disorder who have received LAIB for at least 3 months. RESULTS: Two women and one man with OUD and another comorbid mental disorder were prescribed with LAIB ranging from three to twelve months. Good adherence and opioid abstinence were observed during the follow-up. Psychopathological issues related to comorbid mental disorders were stabilized. A deep discussion on LAIB in this profile of patients is conducted. CONCLUSIONS: LAIB in OUD patients with comorbid mental disorders may be a safe and well tolerated option, similar to OUD patients without comorbid mental disorders. LAIB's impact on psychopathological issues requires further high-quality research to understand the real impact of LAIB on OUD and comorbid mental disorders.

Reduced emergency department use among insured individuals receiving extended-release buprenorphine in a health system setting.

Introduction: Extended-release buprenorphine (XR-Bup) is associated with reduced opioid use and opioid negative urine drug screens. Little is known about its use in outpatient addiction care provided within health systems. Methods: Individuals prescribed XR-Bup were identified from electronic health records; chart abstraction was conducted. Primary outcome was all-cause emergency department (ED) use. Secondary outcomes included ED use or inpatient stays for mental health or substance use, ED use for any other cause, discontinuation reasons, and drug substitution. Statistical comparisons used nonparametric tests from related samples (McNemar's test and Wilcoxon matched pair tests) to test outcomes six months prior and 6 months following XR-Bup initiation. Results: 152 individuals had an XR-Bup order, 126 received >1 injection. Among those consistently insured 6 months prior to and following XR-Bup initiation (n=99), the mean number of injections following initiation was 3.95; one-third received 6 doses in the 6 months. The proportion of individuals using ED services for all causes declined (41% prior vs. 28% following XR-Bup initiation, p<.05); similar results were found for secondary ED use outcomes. The proportion of individuals requiring inpatient treatment for mental health or substance use also declined (46% vs. 16%, p<.01). Common reasons for discontinuing XR-Bup included losing insurance (21%) or cost (11%). The most common non-prescribed substances used during treatment were opioids (n=31) and THC (n=20). Conclusions: In this non-randomized retrospective observational study, use of XR-Bup was associated with reduced ED use 6 months following initiation. XR-Bup may help health systems reduce use of costly ED services.

Utilization of long-acting injectable monthly depot buprenorphine for opioid use disorder (OUD) in Kentucky, before and after COVID-19 related buprenorphine access policy changes.

INTRODUCTION: Long-acting injectable buprenorphine (LAI-bup) formulations have advantages over transmucosal buprenorphine (TM-bup), but barriers may limit their utilization. Several policies shifted during the COVID-19 pandemic to promote buprenorphine access. The federal government expanded telemedicine treatment for opioid use disorder and Kentucky (KY) Medicaid lifted prior authorization requirements (PAs) for LAI-bup (i.e., Sublocade®). This retrospective cohort study evaluated changes in LAI-bup access, utilization, and retention before and after these policy changes in KY. METHODS: Individual-level TM-bup and LAI-bup dispensing record data from KY's prescription drug monitoring program examined LAI-bup utilization and retention, without a >30-day gap in coverage, for patients starting a new episode of LAI-bup treatment. Two key time periods were examined: pre-policy changes (Apr 1, 2019 - Dec 31, 2019) and post-policy changes (Apr 1, 2020 - Dec 31, 2020). Data on PA requests among Medicaid managed care organizations and availability of LAI-bup Risk Evaluation and Mitigation Strategy (REMS)-certified pharmacies were also obtained. A multivariable Cox proportional hazard regression model analysis compared pre- versus post-policy period treatment discontinuation. RESULTS: The number of patients initiating LAI-bup increased from 211 to 481 over the two periods. By the end of the post-policy period, 24.3 % of eligible patients were retained on LAI-bup, versus 12.5 % in the pre-policy change period. The adjusted hazard ratio, comparing discontinuation during the post- versus pre-policy change periods, was 0.70 (95 % confidence interval: 0.55-0.89). There were also more REMS-certified pharmacies and providers in the post-policy change period. CONCLUSIONS: LAI-bup access, utilization, and retention increased after several policy changes.

Evaluation of an injectable monthly extended-release buprenorphine program in a low-barrier specialty addiction medicine clinic.

INTRODUCTION: Monthly injectable extended-release buprenorphine (XR-BUP) can address several systemic and individual barriers to consistent sublingual buprenorphine treatment for patients with opioid use disorder (OUD). Real-world evaluations of XR-BUP in the outpatient addiction treatment setting are limited. The purpose of this study was to compare 6-month treatment retention and urine drug tests between patients who initiated XR-BUP compared to those who were prescribed but did not initiate XR-BUP in a low-barrier addiction medicine specialty clinic. METHODS: We conducted a retrospective cohort study of adults with OUD prescribed XR-BUP between 12/1/2018 and 12/31/2020 in a low-barrier addiction medicine specialty clinic to compare 6-month treatment retention between patients who initiated XR-BUP and those who were prescribed but did not initiate XR-BUP (comparison group). Secondary outcomes included percent of urine toxicology tests negative for non-prescribed opioids. Multivariable logistic regression models evaluated factors associated with 6-month treatment retention and XR-BUP initiation. RESULTS: Of the 233 patients prescribed XR-BUP, 148 (63.8 %) identified as non-Hispanic white, 218 (93.6 %) were insured by public insurance (Medicare/Medicaid), and nearly two-thirds were prescribed XR-BUP due to unstable OUD. Approximately 50 % of patients initiated XR-BUP treatment (mean number of injections = 3.7). About 60 % of XR-BUP-treated patients received supplemental sublingual buprenorphine and nearly two-thirds received a 300 mg maintenance dose. Six-month treatment retention was greater in the XR-BUP treatment versus comparison group (70.3 % vs. 36.5 %, p < 0.001). The XR-BUP treatment group had a higher percentage of opioid-negative urine toxicology tests versus the comparison group (67.2 % vs. 36.3 %, p < 0.001). Receipt of XR-BUP was an independent predictor of 6-month treatment retention (OR 5.40, 95 % CI 2.18-13.38). Those prescribed XR-BUP due to unstable OUD had lower odds of treatment retention (OR 0.41, 95 % CI 0.24-0.98) after controlling for receipt of XR-BUP and other variables known to impact retention. CONCLUSIONS: XR-BUP improved 6-month treatment retention and resulted in a greater proportion of opioid-negative urine toxicology tests compared to a comparison group of patients who were prescribed but did not initiate XR-BUP. Patients with unstable OUD had lower odds of XR-BUP initiation, suggesting the need for targeted interventions to increase XR-BUP uptake in this high-risk population.

Early emergency department experience with 7-day extended-release injectable buprenorphine for opioid use disorder.

As the opioid overdose epidemic escalates, there is an urgent need for treatment innovations to address both patient and clinician barriers when initiating buprenorphine in the emergency department (ED). These include insurance status, logistical challenges such as the ability to fill a prescription and transportation, concerns regarding diversion, and availability of urgent referral sites. Extended-release buprenorphine (XR-BUP) preparations such as a new 7-day injectable could potentially solve some of these issues. We describe the pharmacokinetics of a new 7-day XR-BUP formulation and the feasibility of its use in the ED setting. We report our early experiences with this medication (investigational drug CAM2038), in the context of an ongoing clinical trial entitled Emergency Department-Initiated BUP VAlidaTION (ED INNOVATION), to inform emergency clinicians as they consider incorporating this medication into their practice. The medication was approved by the European Medicines Agency in 2018 and the U.S. Food and Drug Administration in 2023 for those 18 years or older for the treatment of moderate to severe opioid use disorder (OUD). We report our experience with approximately 800 ED patients with OUD who received the 7-day XR-BUP preparation in the ED between June 2020 and July 2023.

Patients' goals when initiating long-acting injectable buprenorphine treatment for opioid use disorder: findings from a longitudinal qualitative study.

BACKGROUND: Long-acting injectable buprenorphine (LAIB) is a new treatment for opioid use disorder that has been introduced against an international policy backdrop of recovery and person-centred care. This paper explores the goals that people want to achieve from LAIB to identify potential implications for policy and practice. METHODS: Data derive from longitudinal qualitative interviews conducted with 26 people (18 male; 8 female) initiating LAIB in England and Wales, UK (June 2021-March 2022). Participants were interviewed up to five times by telephone over six months (107 interviews in total). Transcribed interview data relating to each participant's treatment goals were coded, summarised in Excel, and then analysed via a process of Iterative Categorization. RESULTS: Participants often articulated a desire to be abstinent without defining exactly what they meant by this. Most intended to reduce their dosage of LAIB but did not want to rush. Although participants seldom used the term 'recovery', almost all identified objectives consistent with current definitions of this concept. Participants articulated broadly consistent goals over time, although some extended the timeframes for achieving treatment-related goals at later interviews. At their last interview, most participants remained on LAIB, and there were reports that the medication was enabling positive outcomes. Despite this, participants were aware of the complex personal, service-level, and situational factors that hindered their treatment progress, understood the additional support they needed to achieve their goals, and voiced frustrations when services failed them. CONCLUSIONS: There is a need for wider debate regarding the goals people initiating LAIB are seeking and the diverse range of positive treatment outcomes LAIB could potentially generate. Those providing LAIB should offer regular on-going contact and other forms of non-medical support so that patients have the best opportunity to succeed. Policies relating to recovery and person-centred care have previously been criticised for responsibilising patients and service users to take better care of themselves and to change their own lives. In contrast, our findings suggest that these policies may, in fact, be empowering people to expect a greater range of support as part of the package of care they receive from service providers.

How do patients feel during the first 72 h after initiating long-acting injectable buprenorphine? An embodied qualitative analysis.

BACKGROUND AND AIMS: Long-acting injectable buprenorphine (LAIB) is a new treatment for opioid use disorder that is generating positive outcomes. Negative effects are typically mild and transient, but can occasionally be serious, resulting in treatment discontinuation/non-adherence. This paper aims to analyse patients' accounts of how they felt during the first 72 h after initiating LAIB. METHODS: Semi-structured interviews were conducted (June 2021-March 2022) with 26 people (18 males and 8 females) who had started LAIB within the previous 72 h. Participants were recruited from treatment services in England and Wales and were interviewed by telephone using a topic guide. Interviews were audio-recorded, transcribed and coded. The concepts of embodiment and embodied cognition framed the analyses. Data on participants' substance use, initiation onto LAIB and feelings were tabulated. Next, participants' accounts of how they felt were analysed following the stages of Iterative Categorization. RESULTS: Participants reported complex combinations of changing negative and positive feelings. Bodily experiences included withdrawal symptoms, poor sleep, injection-site pain/soreness, lethargy and heightened senses inducing nausea ('distressed bodies'), but also enhanced somatic wellbeing, improved sleep, better skin, increased appetite, reduced constipation and heightened senses inducing pleasure ('returning body functions'). Cognitive responses included anxiety, uncertainties and low mood/depression ('the mind in crisis') and improved mood, greater positivity and reduced craving ('feeling psychologically better'). Whereas most negative effects reported are widely recognized, the early benefits of treatment described are less well-documented and may be an overlooked distinctive feature of LAIB. CONCLUSIONS: During the first 72 h after initiating long-acting injectable buprenorphine, new patients report experiencing a range of interconnected positive and negative short-term effects. Providing new patients with information about the range and nature of these effects can prepare them for what to expect and help them manage feelings and reduce anxiety. In turn, this may increase medication adherence.

Rapid induction onto extended-release injectable buprenorphine following opioid overdose: A case series.

Background: Buprenorphine treatment has been associated with reduced non-prescribed opioid use and opioid related overdose (OD). We evaluated initial outcomes of rapid induction onto extended-release injectable buprenorphine (BUP-XR) within 7 days of emergency department presentation for unintentional OD. Methods: Between February 2019-February 2021, N = 19 patients with opioid use disorder received buprenorphine/naloxone (4/1 mg), followed by BUP-XR (300 mg) at induction and continued BUP-XR outpatient for 6 months. Primary outcomes included adverse events, repeat OD, and death. Results: For patients who received at least one dose of BUP-XR, there were no treatment related serious adverse events or symptoms of precipitated withdrawal. In addition, there were no repeat visits for ODs or deaths within 6 months of the initial OD. Discussion: These preliminary findings support the need for larger controlled clinical trials to examine the safety and efficacy of rapid induction of BUP-XR in patients with opioid use disorder at high risk of opioid OD. Rapid induction onto long-lasting injectable buprenorphine may be a promising and protective treatment approach in the future.

Extended-release pharmacotherapy for opioid use disorder (EXPO): protocol for an open-label randomised controlled trial of the effectiveness and cost-effectiveness of injectable buprenorphine versus sublingual tablet buprenorphine and oral liquid methadone.

BACKGROUND: Sublingual tablet buprenorphine (BUP-SL) and oral liquid methadone (MET) are the daily, standard-of-care (SOC) opioid agonist treatment medications for opioid use disorder (OUD). A sizable proportion of the OUD treatment population is not exposed to sufficient treatment to attain the desired clinical benefit. Two promising therapeutic technologies address this deficit: long-acting injectable buprenorphine and personalised psychosocial interventions (PSI). This study will determine (A) the effectiveness and cost-effectiveness - monthly injectable, extended-release (BUP-XR) in a head-to-head comparison with BUP-SL and MET, and (B) the effectiveness of BUP-XR with adjunctive PSI versus BUP-SL and MET with PSI. Safety, retention, craving, substance use, quality-adjusted life years, social functioning, and subjective recovery from OUD will be also evaluated. METHODS: This is a pragmatic, multi-centre, open-label, parallel-group, superiority RCT, with a qualitative (mixed-methods) evaluation. The study population is adults. The setting is five National Health Service community treatment centres in England and Scotland. At each centre, participants will be randomly allocated (1:1) to BUP-XR or SOC. At the London study co-ordinating centre, there will also be allocation of participants to BUP-XR with PSI or SOC with PSI. With 24 weeks of study treatment, the primary outcome is days of abstinence from non-medical opioids during study weeks 2-24 combined with up to 12 urine drug screen tests for opioids. For 90% power (alpha, 5%; 15% inflation for attrition), 304 participants are needed for the BUP-XR versus SOC comparison. With the same planning parameters, 300 participants are needed for the BUP-XR and PSI versus SOC and PSI comparison. Statistical and health economic analysis plans will be published before data-lock on the Open Science Framework. Findings will be reported in accordance with the Consolidated Standards of Reporting Trials and Consolidated Health Economic Evaluation Reporting Standards. DISCUSSION: This pragmatic randomised controlled trial is the first evaluation of injectable BUP-XR versus the SOC medications BUP-SL and MET, with personalised PSI. If there is evidence for the superiority of BUP-XR over SOC medication, study findings will have substantial implications for OUD clinical practice and treatment policy in the UK and elsewhere. TRIAL REGISTRATION: EU Clinical Trials register 2018-004460-63.

Can a new formulation of opiate agonist treatment alter stigma?: Place, time and things in the experience of extended-release buprenorphine depot.

INTRODUCTION: Stigma has corrosive effects on all aspects of care and can undermine individual and population health outcomes. Addiction-related stigma has implications for opiate agonist treatment (OAT) and the people who receive, provide and fund it. It is important to understand how stigma is made in OAT and the political purposes that it serves, in order to change the relations of stigma and avoid the reproduction of stigma in the delivery of new treatment formulations, such as extended release buprenorphine (BUP-XR). METHODS: Semi-structured qualitative interviews were conducted at two time points with participants in a prospective single-arm, multicentre, open-label trial of monthly BUP-XR. Thirty-six participants (25 men, 11 women) were interviewed, and of these 32 participated in a second interview to explore their experience of transition from other treatment to BUP-XR. RESULTS: Participants were highly aware of the of the social and material effects of stigma through the negative stereotypes attached to OAT and those who receive it. Participants narrated examples of how stigma governed as a biopower in the relations and practices of OAT provision at numerous levels: structural (such as in public discourse about OAT and the people who receive it, in media, in perceptions about the decisions of investment in medical technologies); organisational (policies about legitimate access to OAT); interpersonal (with health workers) and individual (self-identities). BUP-XR allowed greater freedom and normalcy for clients. The experience of BUP-XR drew attention to the stigmatising potential of time, place and things associated with other OAT requiring daily (or frequent) dosing, accentuating how stigma comes to be materialised as a relational effect of everyday practices. CONCLUSIONS: Receiving BUP-XR allowed participants to avoid some of the everyday biopolitical powers of other forms of OAT and to reshape self-identities. The altering of relations between time, place and things associated with other forms of OAT allowed participants to feel as though they "pass as normal" . However, the negative public discourse and stigma of OAT is a potential threat to BUP-XR to realise its potential for individual and population benefits.

Depot Buprenorphine Injection In The Management Of Opioid Use Disorder: From Development To Implementation.

Buprenorphine has pharmacologic advantages over methadone, especially buprenorphine's better safety profile. The true significance of buprenorphine's introduction lies in returning the care of those suffering from opioid use disorder (OUD) to the hands of the physician. The clinical success of buprenorphine has been meager, in part because most physicians have not been exposed to treating these patients. For physicians inclined to treat OUD, the barriers to buprenorphine's implementation have been onerous and largely counter to the norms of medical practice. Some notable concerns pertain to buprenorphine's clinical pharmacology like street diversion, unintended use and accidental poisoning. Recently, injectable buprenorphine preparations have been introduced to mitigate these latter shortcomings. Yet, the injectable preparations' clinical and commercial success has fallen far short of expectation. Here, we review the clinical pharmacology of these products and their expected clinical advantages for the manufacturers, clinicians, policy makers and patients, and offer our perspective, as clinicians and researchers, on how things can improve. Questions remain whether clinicians are willing to overcome barriers to treat OUD using these medications.