Virtual reality-based Mindfulness-Oriented Recovery Enhancement (MORE-VR) as an adjunct to medications for opioid use disorder: a Phase 1 trial.

INTRODUCTION: Medications for opioid use disorder (MOUD) are the most effective interventions for this condition, yet many patients discontinue treatment. Though adjunct psychosocial treatments are recommended to increase retention and reduce relapse, the scarcity of trained providers hinders access to and utilization of evidence-based interventions. We conducted a Phase 1 study to assess the feasibility of a virtual reality-delivered Mindfulness-Oriented Recovery Enhancement (MORE-VR) intervention for patients receiving MOUD. PATIENTS AND METHODS: Patients receiving buprenorphine or methadone for OUD (N = 34) were scheduled for 8 weekly sessions of MORE-VR. Enrollment and retention rates were analyzed. Participants reported on the usability and acceptability of MORE-VR, opioid use, and craving and affect before and after each VR session. Heart rate was monitored during one session of MORE-VR. RESULTS: Twenty-three participants completed four or more MORE-VR sessions (minimum recommended intervention dose). Participants reported high usability and acceptability of MORE-VR, which had an excellent safety profile. Illicit opioid use decreased significantly from pre- to post-treatment (F = 4.44, p=.04). We observed a significant within-session decrease in opioid craving (F = 39.3, p<.001) and negative affect (F = 36.3, p<.001), and a significant within-session increase in positive affect (F = 23.6, p<.001). Heart rate shifted during cue-exposure and mindfulness practices (F = 6.79, p<.001). CONCLUSIONS: High retention, usability and acceptability rates and low adverse events demonstrated that MORE-VR is a feasible, engaging, and safe intervention. Our findings show that MORE-VR can be delivered as an adjunctive intervention to MOUD and suggest that MORE-VR may improve OUD treatment outcomes and modulate autonomic responses. MORE-VR's efficacy will be tested in a subsequent Phase 2 trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05034276; https://classic.clinicaltrials.gov/ct2/show/NCT05034276.

MORE-VR is a digital therapeutic that uses Virtual Reality to deliver an 8-week mindfulness-based intervention for opioid use disorder treatment.Patients with OUD reported high completion rates, usability and acceptability.In participants receiving MORE-VR as an adjunct to MOUD, reduced craving and opioid use was reported over time.

Refining pain management in mice by comparing multimodal analgesia and NSAID monotherapy for neurosurgical procedures.

While neurosurgical interventions are frequently used in laboratory mice, refinement efforts to optimize analgesic management based on multimodal approaches appear to be rather limited. Therefore, we compared the efficacy and tolerability of combinations of the non-steroidal anti-inflammatory drug carprofen, a sustained-release formulation of the opioid buprenorphine, and the local anesthetic bupivacaine with carprofen monotherapy. Female and male C57BL/6J mice were subjected to isoflurane anesthesia and an intracranial electrode implant procedure. Given the multidimensional nature of postsurgical pain and distress, various physiological, behavioral, and biochemical parameters were applied for their assessment. The analysis revealed alterations in Neuro scores, home cage locomotion, body weight, nest building, mouse grimace scales, and fecal corticosterone metabolites. A composite measure scheme allowed the allocation of individual mice to severity classes. The comparison between groups failed to indicate the superiority of multimodal regimens over high-dose NSAID monotherapy. In conclusion, our findings confirmed the informative value of various parameters for assessment of pain and distress following neurosurgical procedures in mice. While all drug regimens were well tolerated in control mice, our data suggest that the total drug load should be carefully considered for perioperative management. Future studies would be of interest to assess potential synergies of drug combinations with lower doses of carprofen.

Opioid Use and the Risk of Ventricular Arrhythmias: A Systematic Review and Meta-Analysis.

BACKGROUND: The association between opioid use and the risk of ventricular arrhythmias (VA) is poorly understood. AIMS: The objective of this study was to synthesize the evidence on the risk of VA associated with opioid use. MATERIALS & METHODS: We systematically searched the Cochrane Library, Embase, MEDLINE, and CINAHL databases in July 2022. Risk of bias was assessed using the Cochrane risk for bias tool for randomized controlled trials (RCTs) and ROBINS-I for observational studies. Certainty of evidence was assessed using GRADE. RESULTS: We included 15 studies (12 observational, 2 post hoc analyses of RCTs, 1 RCT). Most studies focused on opioid use for maintenance therapy (n = 9), comparing methadone to buprenorphine (n = 13), and reported QTc prolongation (n = 13). Six observational studies had a critical risk of bias, and one RCT was at high risk of bias. Two studies could not be included in the meta-analysis as they reported a different outcome and studied an opioid antagonist. Meta-analysis of 13 studies indicated that the use of methadone was associated with an increased risk of VA compared to the use of buprenorphine, morphine, placebo, or levacetylmethadol (risk ratio [RR], 2.39; 95% CI, 1.31-4.35; I2 = 60%). The pooled estimate varied greatly between observational studies (RR, 2.12; 95% CI, 1.15-3.91; I2 = 62%) and RCTs (RR, 14.09; 95% CI, 1.52-130.61; I2 = 0%), but both indicated an increased risk. CONCLUSION: In this systematic review and meta-analysis, we found that methadone use is associated with more than twice the risk of VA compared to comparators. However, our findings should be interpreted cautiously given the limited quality of the available evidence.

Comparison of the efficacy and safety of transdermal buprenorphine patch to conventional analgesics after operative fixation of extra capsular fracture of proximal femur.

INTRODUCTION: Proximal femur fractures are common among older individuals and pose challenges in achieving effective post-operative analgesia. Age-related co-morbidities limit the selection of analgesics in this population. This study aimed to compare the safety and effectiveness of transdermal buprenorphine (TDB) patch with traditional analgesics after fixation of an extracapsular fracture of the proximal femur. METHODOLOGY: A prospective randomized controlled study was conducted over a 2-year period, involving 60 patients who underwent surgery for extra capsular intertrochanteric fracture fixation. The patients were randomly assigned to two groups by random envelope method. Group A received an intravenous formulation of paracetamol and tramadol for the initial 48 h, followed by an oral formulation. Group B received a transdermal buprenorphine (TDB) patch delivering 5 mcg/hour immediately after surgery, which continued for 2 weeks postoperatively. During the 14-day monitoring period, patients' pain scores were assessed using the Visual Analog Scale (VAS) at rest and during movement. The primary objective was to maintain a VAS score of 4 or lower. Rescue analgesics were administered if the VAS score reached 6. The secondary objectives included evaluating the quantity of rescue analgesics required and monitoring for any adverse effects or complications. RESULTS: Pain scores at rest and during movement were significantly lower in Group B at all-time points (p-value 0.0006 - ≤ 0.0001), and the requirement for rescue analgesia was also significantly lower in this group. The administration of the TDB patch did not result in any significant adverse effects. CONCLUSION: TDB patch is secure and offers better compliance and analgesia than other analgesics in the postoperative period whilst treating proximal femur extra capsular fracture.

Extended-Release 7-Day Injectable Buprenorphine for Patients With Minimal to Mild Opioid Withdrawal.

Importance: Buprenorphine is an effective yet underused treatment for opioid use disorder (OUD). Objective: To evaluate the feasibility (acceptability, tolerability, and safety) of 7-day injectable extended-release buprenorphine in patients with minimal to mild opioid withdrawal. Design, Setting, and Participants: This nonrandomized trial comprising 4 emergency departments in the Northeast, mid-Atlantic, and Pacific geographic areas of the US included adults aged 18 years or older with moderate to severe OUD and Clinical Opiate Withdrawal Scale (COWS) scores less than 8 (minimal to mild), in which scores range from 0 to 7, with higher scores indicating increasing withdrawal. Exclusion criteria included methadone-positive urine, pregnancy, overdose, or required admission. Outcomes were assessed at baseline, daily for 7 days by telephone surveys, and in person at 7 days. Patient recruitment occurred between July 13, 2020, and May 25, 2023. Intervention: Injection of a 24-mg dose of a weekly extended-release formulation of buprenorphine (CAM2038) and referral for ongoing OUD care. Main Outcomes and Measures: Primary feasibility outcomes included the number of patients who (1) experienced a 5-point or greater increase in the COWS score or (2) transitioned to moderate or greater withdrawal (COWS score ≥13) within 4 hours of extended-release buprenorphine or (3) experienced precipitated withdrawal within 1 hour of extended-release buprenorphine. Secondary outcomes included injection pain, satisfaction, craving, use of nonprescribed opioids, adverse events, and engagement in OUD treatment. Results: A total of 100 adult patients were enrolled (mean [SD] age, 36.5 [8.7] years; 72% male). Among the patients, 10 (10.0% [95% CI, 4.9%-17.6%]) experienced a 5-point or greater increase in COWS and 7 (7.0% [95% CI, 2.9%-13.9%]) transitioned to moderate or greater withdrawal within 4 hours, and 2 (2.0% [95% CI, 0.2%-7.0%]) experienced precipitated withdrawal within 1 hour of extended-release buprenorphine. A total of 7 patients (7.0% [95% CI, 2.9%-13.9%]) experienced precipitated withdrawal within 4 hours of extended-release buprenorphine, which included 2 of 63 (3.2%) with a COWS score of 4 to 7 and 5 of 37 (13.5%) with a COWS score of 0 to 3. Site pain scores (based on a total pain score of 10, in which 0 indicated no pain and 10 was the worst possible pain) after injection were low immediately (median, 2.0; range, 0-10.0) and after 4 hours (median, 0; range, 0-10.0). On any given day among those who responded, between 29 (33%) and 31 (43%) patients reported no cravings and between 59 (78%) and 75 (85%) reported no use of opioids; 57 patients (60%) reported no days of opioid use. Improving privacy (62%) and not requiring daily medication (67%) were deemed extremely important. Seventy-three patients (73%) were engaged in OUD treatment on day 7. Five serious adverse events occurred that required hospitalization, of which 2 were associated with medication. Conclusions and Relevance: This nonrandomized trial of the feasibility of a 7-day buprenorphine injectable in patients with minimal to mild opioid withdrawal (COWS scores, 0-7) found the formulation to be acceptable, well tolerated, and safe in those with COWS scores of 4 to 7. This new medication formulation could substantially increase the number of patients with OUD receiving buprenorphine. Trial Registration: ClinicalTrials.gov Identifier: NCT04225598.

Post-operative pain control in patients on buprenorphine or methadone for opioid use disorder.

OBJECTIVE: This study aimed to determine whether there is a difference in pain scores and opioid consumption after elective surgery in patients maintained on methadone or buprenorphine for opioid use disorder (OUD). Additionally, we investigated the impact of continuing or discontinuing methadone or buprenorphine on post-operative pain outcomes. DESIGN: A single-center retrospective cohort study. SETTING: Tertiary care medical center. PATIENTS AND PARTICIPANTS: Adults aged 18 years or older with OUD maintained on buprenorphine or methadone who underwent elective surgery between January 1, 2017, and January 1, 2021. INTERVENTIONS: Patients were identified through electronic medical records, and demographic and clinical data were collected. MAIN OUTCOME MEASURES: The primary outcome was opioid consumption at 24 hours post-operatively, measured in milligram morphine equivalents. The secondary outcome was opioid consumption and pain scores up to 72 hours post-operatively, assessed using a numeric rating scale. RESULTS: This study included 366 patients (64 percent on buprenorphine and 36 percent on methadone). Opioid utilization significantly increased when buprenorphine was not administered post-operatively. Both groups exhibited comparable total opioid consumption during the post-operative period. In the buprenorphine cohort, pain scores differed significantly based on the receipt of medications for OUD post-operatively. CONCLUSIONS: This study reinforces existing evidence supporting the continuation of medications for opioid use disorder, specifically buprenorphine and methadone, during the perioperative period. Dissemination of guideline recommendations is essential to ensure optimal post-operative pain management for this patient population.

Direct rotation from a fentanyl patch to a buprenorphine patch in a patient with chronic pain.

Transitioning a patient with chronic pain from a fentanyl patch to a buprenorphine patch has not been well described in the literature. Even after a patient removes their fentanyl patch, the residual fentanyl in the skin continues to be absorbed for hours. Due to the risk of precipitated withdrawal when initiating buprenorphine, this transition is a more challenging opioid rotation to plan safely. We report a case of a patient who had been using a fentanyl patch for over 10 years and was successfully rotated directly to a buprenorphine patch.

NIR-Remote Selectively Triggered Buprenorphine Hydrochloride Release from Microneedle Patches for the Treatment of Neuropathic Pain.

Neuropathic pain is a prevalent form of intermittent chronic pain, affecting approximately 7-10% of the global population. However, the current clinical administration methods, such as injection and oral administration, are mostly one-time administration, which cannot achieve accurate control of pain degree and drug dose. Herein, we developed near-infrared (NIR) light-responsive microneedle patches (MNPs) to spatiotemporally control the drug dose released to treat neuropathic pain according to the onset state. The mechanism of action utilizes upconversion nanoparticles to convert NIR light into visible and ultraviolet light. This conversion triggers the rapid rotation of the azobenzene molecular motor in the mesoporous material, enabling the on-demand controlled release of a drug dose. Additionally, MNs are used to overcome the barrier of the stratum corneum in a minimally invasive and painless manner, effectively promoting the transdermal penetration of drug molecules. The effectiveness of these patches has been demonstrated through significant results. Upon exposure to NIR light for five consecutive cycles, with each cycle lasting 30 s, the patches achieved a precise release of 318 µg of medication. In a mouse model, maximum pain relief was observed within 1 h of one cycle of NIR light exposure, with the effects lasting up to 6 h. The same level of precise treatment efficacy was maintained for subsequent pain episodes with similar light exposure. The NIR-controlled drugs precision-released MNPs provide a novel paradigm for the treatment of intermittent neuropathic pain.

Considerations when prescribing opioid agonist therapies for people living with HIV.

INTRODUCTION: Medications for opioid use disorder (MOUD) include opioid agonist therapies (OAT) (buprenorphine and methadone), and opioid antagonists (extended-release naltrexone). All forms of MOUD improve opioid use disorder (OUD) and HIV outcomes. However, the integration of services for HIV and OUD remains inadequate. Persistent barriers to accessing MOUD underscore the immediate necessity of addressing pharmacoequity in the treatment of OUD in persons with HIV (PWH). AREAS COVERED: In this review article, we specifically focus on OAT among PWH, as it is the most commonly utilized form of MOUD. Specifically, we delineate the intersection of HIV and OUD services, emphasizing their integration into the United States Ending the HIV Epidemic (EHE) plan by offering comprehensive screening, testing, and treatment for both HIV and OUD. We identify potential drug interactions of OAT with antiretroviral therapy (ART), address disparities in OAT access, and present the practical benefits of long-acting formulations of buprenorphine, ART, and pre-exposure prophylaxis for improving HIV prevention and treatment and OUD management. EXPERT OPINION: Optimizing OUD outcomes in PWH necessitates careful attention to diagnosing OUD, initiating OUD treatment, and ensuring medication retention. Innovative approaches to healthcare delivery, such as mobile pharmacies, can integrate both OUD and HIV and reach underserved populations.

Serious treatment-emergent adverse events in chronic low back pain patients treated with buprenorphine or oral opioids: a retrospective commercial claims analysis.

Aim: Explore the safety of Belbuca® (buprenorphine buccal film), buprenorphine transdermal patches and oral opioids for chronic low back pain (cLBP) treatment. Methods: The retrospective analysis of the MarketScan Commercial database (2018-2021) included treatment-naive cLBP adults. The first date of buprenorphine (Belbuca and transdermal patch) or opioid prescription was index date. Cohorts were defined based on the index medication. Observation included a 6-month pre-index period, while post-index lasted until the end of continuous insurance coverage. There were 44 relevant treatment-emergent adverse events (TEAEs) identified in the literature. Incidence rate ratio (IRR) and incidence rate difference (IRD) were used to compare serious TEAE rates (in 1000 person-years) between cohorts. Propensity-score matching minimized the selection bias. Results: Buprenorphine had lower rates of 15 serious TEAEs than oral opioids (all p ≤ 0.037), while higher rates only for serious dizziness (IRR 2.44, p = 0.011; driven by Belbuca), opioid abuse/dependence (IRR 3.13, p = 0.004; driven by patches) and cholecystitis (IRD 20.25, p = 0.044; an outlier). Additionally, a comparison between Belbuca and oral opioids showed lower rates of 13 serious TEAEs (all p ≤ 0.024) and a higher serious dizziness rate (IRR 3.17, p = 0.024). Although the rates of serious opioid abuse/dependence were similar (24.60 vs 26.93, p = 0.921), all Belbuca patients and none of the opioid patients had a positive history of these events. Belbuca also had lower rates of five serious TEAEs than transdermal patches (all p ≤ 0.018), including a serious opioid abuse/dependence (IRR 0.04, p < 0.001), but higher rates of serious cholecystitis (IRD 52.17, p = 0.035; an outlier) and suicidal ideation (IRD 156.50, p < 0.001; an outlier). Conclusion: Buprenorphine had a better safety profile than oral opioids in cLBP treatment. Belbuca showed a more favorable TEAE profile than buprenorphine transdermal patches and oral opioids.

A case of severe opioid and methamphetamine use disorder in a 14 year old.

We present the case of a 14-year-old who established care at our primary care clinic after hospitalization for unintentional fentanyl overdose. They were diagnosed with severe opioid use disorder (OUD) and stimulant use disorder (StUD) and initiated buprenorphine while inpatient. They were then transitioned to the only known outpatient primary care clinic in her county who was actively providing medications for opioid use disorder (MOUD) in adolescents.At the first visit, they reported a history of 20 overdoses, struggling with adherence to buprenorphine and continued opioid cravings. An overdose safety plan was reviewed with them and their parent including providing them naloxone kits, fentanyl test strips, and education handout sheets. Due to their significant overdose history and adherence challenges with sublingual buprenorphine, they were started on long-acting injectable buprenorphine (LAIB) with weekly provider visits and urine toxicology screening. In collaboration with the treatment team, they initiated behavioral treatment with contingency management (CM), with incentives for appointment completion, expected urine results, and successful medication administration. Over the next 19 months, and to date, they have increasingly engaged with care and have remained abstinent. LAIB may be an appealing alternative for adolescents with OUD to improve adherence and reduce risk of recurrent use and overdose. Adjunctive treatment with CM may improve retention in MOUD and have the benefit of treating StUD. There is a need for further research to explore innovative, community-based treatment for youth with OUD.

Low-dose overlap initiation with split tablets of buprenorphine in intubated intensive care unit patients with opioid use disorder.

BACKGROUND: As the opioid public health crisis evolves to include fentanyl and other potent synthetic opioids, more patients are admitted to the hospital with serious complications of drug use and frequently require higher levels of care, including intensive care unit (ICU) admission, for acute and chronic conditions related to opioid use disorder (OUD). This patient population poses a unique challenge when managing sedation and ensuring adequate ventilation while intubated given their high opioid requirements. Starting a patient on medications such as buprenorphine may be difficult for inpatient providers unfamiliar with its use, which may lead to undertreatment of patients with OUD, prolonged mechanical ventilation and length of stay. METHODS: We developed a 7-day buprenorphine low dose overlap initiation (LDOI) schedule for patients with OUD admitted to the ICU (Table 1). Buprenorphine tablets were split by pharmacists and placed into pre-made blister packs as a kit to be loaded into the automated medication dispensing machine for nursing to administer daily. An internal quality review validated the appropriate dosing of split-dose tablets. To simplify order entry and increase prescriber comfort with this new protocol, we generated an order set within our electronic health record software with prebuilt buprenorphine titration orders. This protocol was implemented alongside patient and healthcare team education and counseling on the LDOI process, with follow-up offered to all patients upon discharge. RESULTS: Here we report a series of 6 ICU patients started on buprenorphine using the LDOI schedule with split buprenorphine tablets. None of the 6 patients experienced precipitated withdrawal upon buprenorphine initiation using the LDOI schedule, and 5/6 patients were successfully extubated during the buprenorphine initiation. Four of six patients had a decrease in daily morphine milligram equivalents, with 3 patients transitioning to buprenorphine alone. CONCLUSION: Initiating buprenorphine via LDOI was found to be successful in the development of a protocol for critically ill patients with OUD. We examined LDOI of buprenorphine in intubated ICU patients and found no events of acute precipitated withdrawal. This protocol can be used as a guide for other institutions seeking to start critically ill patients on medication treatment for OUD during ICU admission.

The role of recovery peer navigators in retention in outpatient buprenorphine treatment: a retrospective cohort study.

BACKGROUND: Racial and ethnic disparities are evident in the accessibility of treatment for opioid use disorder (OUD). Even when medications for OUD (MOUD) are accessible, racially and ethnically minoritized groups have higher attrition rates from treatment. Existing literature has primarily identified the specific racial and ethnic groups affected by these disparities, but has not thoroughly examined interventions to address this gap. Recovery peer navigators (RPNs) have been shown to improve access and overall retention on MOUD. PATIENTS AND METHODS: In this retrospective cohort study, we evaluate the role of RPNs on patient retention in clinical care at an outpatient program in a racially and ethnically diverse urban community. Charts were reviewed of new patients seen from January 1, 2019 through December 31, 2019. Sociodemographic and clinical visit data, including which providers and services were utilized, were collected, and the primary outcome of interest was continuous retention in care. Bivariate analysis was done to test for statistically significant associations between variables by racial/ethnic group and continuous retention in care using Student's t-test or Pearson's chi-square test. Variables with p value ≤0.10 were included in a multivariable regression model. RESULTS: A total of 131 new patients were included in the study. RPNs improved continuous retention in all-group analysis (27.6% pre-RPN compared to 80.2% post-RPN). Improvements in continuous retention were observed in all racial/ethnic subgroups but were statistically significant in the non-Hispanic Black (NHB) group (p < 0.001). Among NHB, increases in continuous retention were observed post-RPN in patients with male sex (p < 0.001), public health insurance (p < 0.001), additional substance use (p < 0.001), medical comorbidities (p < 0.001), psychiatric comorbidities (p = 0.001), and unstable housing (p = 0.005). Multivariate logistic regression demonstrated that patients who lacked insurance had lower odds of continuous retention compared to patients with public insurance (aOR = 0.17, 95% CI 0.039-0.70, p = 0.015). CONCLUSIONS: RPNs can improve clinical retention for patients with OUD, particularly for individuals experiencing several sociodemographic and clinical factors that are typically correlated with discontinuation of care.

Recovery peer navigators improve continuous clinical retention following initiation of outpatient treatment for opioid use disorder.Recovery peer navigators may be especially beneficial for patients with factors and identifiers commonly associated with discontinuation of care.

Feasibility of Web-Based Single-Session Empowered Relief in Patients With Chronic Pain Taking Methadone or Buprenorphine: Protocol for a Single-Arm Trial.

BACKGROUND: Chronic pain affects tens of millions of US adults and continues to rise in prevalence. Nonpharmacologic behavioral pain treatments are greatly needed and yet are often inaccessible, particularly in settings where medication prescribing is prioritized. OBJECTIVE: This study aims to test the feasibility of a live-instructor, web-based 1-session pain relief skills class in an underserved and potentially at-risk population: people with chronic pain prescribed methadone or buprenorphine either solely for pain or for comorbid opioid use disorder (OUD). METHODS: This is a national, prospective, single-arm, uncontrolled feasibility trial. The trial is untethered from medical care; to enhance participants' willingness to join the study, no medical records or drug-monitoring records are accessed. At least 45 participants will be recruited from outpatient pain clinics and from an existing research database of individuals who have chronic pain and are taking methadone or buprenorphine. Patient-reported measures will be collected at 6 time points (baseline, immediately post treatment, 2 weeks, and months 1-3) via a web-based platform, paper, or phone formats to include individuals with limited internet or computer access and low literacy skills. At baseline, participants complete demographic questions and 13 study measures (Treatment Expectations, Body Pain Map, Medication Use, Pain Catastrophizing Scale [PCS], Patient-Reported Outcomes Measurement Information System [PROMIS] Measures, and Opioid Craving Scale). Immediately post treatment, a treatment satisfaction and acceptability measure is administered on a 0 (very dissatisfied) to 10 (completely satisfied) scale, with 3 of these items being the primary outcome (perceived usefulness, participant satisfaction, and likelihood of using the skills). At each remaining time point, the participants complete all study measures minus treatment expectations and satisfaction. Participants who do not have current OUD will be assessed for historical OUD, with presence of OUD (yes or no), and history of OUD (yes or no) reported separately. Feasibility threshold is set as an overall group treatment satisfaction rating of 8 of 10. In-depth qualitative interviews will be conducted with about 10 participants to obtain additional data on patient perceptions, satisfactions, needs, and wants. To assess preliminary efficacy, we will examine changes in pain catastrophizing, pain intensity, pain bothersomeness, sleep disturbance, pain interference, depression, anxiety, physical function, global impression of change, and opioid craving at 1 month post treatment. RESULTS: This project opened to enrollment in September 2021 and completed the recruitment in October 2023. The data collection was completed in February 2024. Results are expected to be published in late 2024. CONCLUSIONS: Results from this trial will inform the feasibility and preliminary efficacy of Empowered Relief in this population and will inform the design of a future randomized controlled trial testing web-based Empowered Relief in chronic pain and comorbid OUD. TRIAL REGISTRATION: ClinicalTrials.gov NCT05057988; https://clinicaltrials.gov/study/NCT05057988. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53784.

Compared implementation of the long-acting buprenorphine treatment buvidal in four European countries.

BACKGROUND: Buvidal is the only depot buprenorphine currently available in Europe. Buvidal offers a new treatment paradigm, which may require some adjustment in the national regulatory frameworks for opioid agonist treatments (OATs), as well as the national care systems. RESEARCH DESIGN AND METHODS: Data on the national dissemination of Buvidal, types of populations treated, and the national regulatory framework and care organization system through which Buvidal has been implemented were compared between the UK, Finland, Spain, and France, using a qualitative survey. RESULTS: In 2022, the proportion of people on OAT who received Buvidal was 2.1% in the UK, 60-65% in Finland, 1% in Spain, and 0.3% in France. In both Finland and the UK, the cost of the medication is covered by the national health system, whereas, in Spain and France, Buvidal is accessible only in specialized centers, which must carry its cost. Other national features may explain the gaps in Buvidal use, including the baseline level of OAT coverage, which was high in both France and Spain. CONCLUSIONS: Important national discrepancies are found regarding Buvidal dissemination among people on OAT.

Economic burden and dosing trends of buprenorphine buccal film and transdermal patch in chronic low back pain.

Aim: Exploring prescribing trends and economic burden of chronic low back pain (cLBP) patients prescribed buprenorphine buccal film (Belbuca®) or transdermal patches. Methods: In the MarketScan® commercial insurance claims (employees and their spouses/dependents, 2018-2021), the first film or patch prescription date was an index event. The observation covered 6-month pre-index and 12-month post-index periods. Results: Patients were propensity-score matched (708 per cohort). Buprenorphine initiation had stable cost trends in buccal film and increasing trends in transdermal patch cohort. Between-cohort comparisons of healthcare expenditures, cost trends and resource utilization showed significant differences, mostly in favor of buccal film. Buccal film also had higher daily doses and wider dosing range. Conclusion: Buprenorphine film is more cost-effective cLBP treatment with more flexible dosing.

What is this article about? This retrospective study included patients with chronic low back pain (cLBP) and commercial insurance in the USA. Only patients treated with Belbuca®, a buprenorphine buccal film, or a buprenorphine transdermal patch were included. Patients were observed 6 months prior to and 12 months after the first buprenorphine prescription. Healthcare costs, cost trends, resource use and buprenorphine treatment characteristics were explored.What were the results? Patients with cLBP on buccal film had lower costs, stable cost trends and less healthcare resources used. Also, they had higher buprenorphine daily doses.What do the results mean? The results imply that buccal film is less costly for cLBP patients than patches. The buccal film had more flexible dosing with higher daily doses, which might be associated with better pain control.

Rapid induction of transdermal buprenorphine to subcutaneous extended-release buprenorphine for the treatment of opioid use disorder.

BACKGROUND: Buprenorphine is an effective and safe treatment for opioid use disorder, but the requirement for moderate opioid withdrawal symptoms to emerge prior to initiation is a significant treatment barrier. CASE PRESENTATION: We report on two cases of hospitalized patients with severe, active opioid use disorder, in which we initiated treatment with transdermal buprenorphine over 48 h, followed by the administration of a single dose of sublingual buprenorphine/naloxone and then extended-release subcutaneous buprenorphine. The patients did not experience precipitated withdrawal and only had mild withdrawal symptoms. CONCLUSIONS: This provides preliminary evidence for a rapid induction strategy that may improve tolerability, caregiver burden, and treatment retention as compared to previous induction strategies.

Availability and Opportunities for Expansion of Buprenorphine for the Treatment of Opioid Use Disorder.

There is an urgent need to expand access to treatment for persons with opioid use disorder (OUD). As neurologists may frequently encounter patients with chronic pain who have developed OUD, they are in a position to serve as advocates for treatment. Buprenorphine is the most scalable medication for OUD in the United States, yet expansion has plateaued in recent years despite growing treatment needs. Reluctance of providers to establish treatment with new patients, challenges with rural expansion, stigma related to buprenorphine-based care, and pharmacy pressures that incentivize low dispensing and inventories may have stalled expansion. This review introduces these challenges before outlining actionable and evidenced-based strategies that warrant investigation, including methods to improve patient access to care (remotely delivered care, mobile delivery programs, Bridge programs) and provider retention and confidence in prescribing (expert consults, Extension for Community Healthcare Outcomes, a telementoring model, hub-and-spoke services), as well as novel innovations (virtual reality, artificial intelligence, wearable technologies). Overall, fortifying existing delivery systems while developing new transformative models may be necessary to achieve more optimal levels of buprenorphine treatment expansion.

Study protocol for the Treating Opioid Patients' Pain and Sadness (TOPPS) study - A randomized control trial to lower depression and chronic pain interference, and increase care retention among persons receiving buprenorphine.

BACKGROUND: 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. METHODS: 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. DISCUSSION: 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. CLINICAL TRIAL: #NCT03698669.