Switch from methadone to buprenorphine with microinduction in outpatient setting. / Poliklinisk skifte fra metadon til buprenorfin med mikroinduksjon.

Background: Switching from methadone to buprenorphine in patients receiving opioid maintenance therapy often requires inpatient care with a gradual tapering of methadone and an opioid-free day with challenging withdrawal symptoms. This case report describes and discusses a gentle outpatient approach without the opioid-free day. Case presentation: A patient with a 15-year history of opioid maintenance therapy reduced his methadone dose from 80 mg to 50 mg due to concurrent use of other sedative substances and a significant risk of overdose. A week-long switch to buprenorphine 16 mg subcutaneous depot formulation was then undertaken using a microinduction approach in the outpatient setting. Interpretation: In line with earlier reports on microinduction, the switch from methadone to buprenorphine was carried out with no opioid withdrawal symptoms or complications. Microinduction offers a smooth and more patient-friendly approach to switching from full opioid agonists to partial agonists. Randomised controlled trials are, however, needed for a systematic evaluation of this method.

Federal opioid agonist therapy policy: interrupted time series analysis of the impact of the methadone exemption removal across eight provinces in Canada.

BACKGROUND: Federal deregulation of opioid agonist therapies are an attractive policy option to improve access to opioid use disorder care and achieve widespread beneficial impacts on growing opioid-related harms. There have been few evaluations of such policy interventions and understanding effects can help policy planning across jurisdictions. METHODS: Using health administrative data from eight of ten Canadian provinces, this study evaluated the impacts of Health Canada's decision in May 2018 to rescind the requirement for Canadian health professionals to obtain an exemption from the Canadian Drugs and Substance Act to prescribe methadone for opioid use disorder. Over the study period of June 2017 to May 2019, we used descriptive statistics to capture overall trends in the number of agonist therapy prescribers across provinces and we used interrupted time series analysis to determine the effect of this decision on the trajectories of the agonist therapy prescribing workforces. RESULTS: There were important baseline differences in the numbers of agonist therapy prescribers. The province with the highest concentration of prescribers had 7.5 more prescribers per 100,000 residents compared to the province with the lowest. All provinces showed encouraging growth in the number of prescribers through the study period, though the fastest growing province grew 4.5 times more than the slowest. Interrupted time series analyses demonstrated a range of effects of the federal policy intervention on the provinces, from clearly positive changes to possibly negative effects. CONCLUSIONS: Federal drug regulation policy change interacted in complex ways with provincial health professional regulation and healthcare delivery, kaleidoscoping the effects of federal policy intervention. For Canada and other health systems such as the US, federal policy must account for significant subnational variation in OUD epidemiology and drug regulation to maximize intended beneficial effects and mitigate the risks of negative effects.

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.

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.

Successful pain control with add-on methadone for refractory neuropathic pain due to radiation necrosis in pontine metastatic lesion: a case report.

BACKGROUND: Central pain, characterized by neuropathic pain, can manifest due to injury to the superior spinothalamic tract. The brainstem includes sensory and motor pathways as well as nuclei of the cranial nerves, and therefore cancer metastasis in the region requires early intervention. Although stereotactic radiosurgery (SRS) is commonly employed for the treatment of brain metastasis, it poses risks of late complications like radiation necrosis (RN). RN exacerbates the progression of brain lesions within the irradiated area, and in the brainstem, it can damage multiple nerves, including the superior spinothalamic tract. Central neuropathic pain is often intractable and empirically managed with a combination of conventional drugs, such as serotonin-norepinephrine reuptake inhibitors (SNRIs) and anticonvulsants. However, their efficacy is often limited, leading to a decline in performance status (PS) and quality of life (QOL). CASE PRESENTATION: We present the case of a 53-year-old man diagnosed with stage IV lung cancer, referred to our palliative care team for managing severe central pain resulting from SRS-related RN in the pons. Despite administration of opioids, including oxycodone and hydromorphone, and adjuvant analgesics, the patient continued to require frequent use of immediate-release opioids. The addition of methadone alone proved successful in achieving optimal pain control. CONCLUSIONS: Provided that RN in the brainstem can lead to intractable neuropathic pain, it is advisable to avoid SRS for brainstem metastasis when possible. Add-on methadone should be considered as a viable pain management medication for patients experiencing unresolved central pain.

Racial and Ethnic Disparities in Take-Home Methadone Use for Medicare Beneficiaries With Opioid Use Disorder.

This cross-sectional study examines racial and ethnic disparities in take-home methadone use among Medicare beneficiaries with opioid use disorder following the Substance Abuse and Mental Health Services Administration's policy change in March 2020.

The fentanyl made me feel like I needed more methadone": changes in the role and use of medication for opioid use disorder (MOUD) due to fentanyl.

BACKGROUND: Fentanyl and fentanyl analogues have disrupted the illicit drug supply through contamination of other substances (i.e., methamphetamine and cocaine) and replacement of heroin in illicit markets. Increasingly, they are contributing to opioid-overdose related deaths. The rapid and growing presence of fentanyl has led to gaps in research on the impact of this illicit market change on people who use drugs (PWUD). We sought to examine how the changing opioid market and growing fentanyl availability influences the role and use of medication for opioid use disorder (MOUD). METHODS: Semi-structured qualitative interviews were conducted with a community recruited sample of PWUD (N = 22) in Los Angeles, California between September 2021 and April 2022. Interviews examined opioid use history, current opioid use behaviors and consumption patterns, and MOUD experiences and perceptions. Thematic analysis was used to systematically code and analyze textual interview data. RESULTS: The following themes related to fentanyl use and MOUD emerged: (1) Use of deviated MOUD to address fentanyl contamination, (2) Changing perception of the effectiveness of MOUD on fentanyl, and (3) Regulatory limitations of MOUD for fentanyl use disorder. CONCLUSIONS: PWUD described several repertoires for adjusting to changes in the illicit market of opioids. Clinicians treating PWUD should ask about recent fentanyl use prior to starting MOUD to account for increased tolerance to opioids. Harm reduction strategies such as naloxone kits, safe supply, and supervised consumption facilities can all prevent overdose deaths due to fentanyl.

'I'm on the coast and I'm on methadone': A qualitative study examining access to opioid agonist treatment in rural and coastal British Columbia.

INTRODUCTION: Despite rural regions being disproportionately impacted by the toxic drug supply, little is known about the contextual factors influencing access to opioid agonist treatment (OAT) specific to rural residents. The present study examines these factors in a rural and coastal setting in British Columbia, Canada. METHODS: The qualitative methods were used to examine the barriers and facilitators to OAT access. Between July and October 2021, semi-structured interviews were conducted with people who use drugs who reside in a rural and coastal community. Thematic analysis was used to identify emergent themes and subthemes. Results were corroborated by the research team and a local community advisory board. RESULTS: Twenty-seven (n = 27) participants described both limiting and facilitating factors that influenced OAT accessibility. Access was less challenging when participants' OAT dispensing pharmacy was in close proximity, had extended hours of operation, or when pharmacies provided delivery services. Barriers to OAT access identified by participants included the high cost of transportation, residing or working in remote communities and few local OAT prescribers. A variety of treatment motivations and goals that impacted OAT satisfaction are also highlighted. CONCLUSION: This study demonstrates that patient satisfaction with OAT service access in a rural and coastal setting is multi-factorial and geographic proximity alone does not fully explain OAT accessibility issues in these settings. Accessibility to OAT may be improved through delivery services, expanded OAT prescribing authorisation beyond physician-only regulations, health authorities covering transportation costs and continual assurance that prescribing practices meet individuals' goals. INTRODUCTION: Bien que les régions rurales soient touchées de manière disproportionnée par l'approvisionnement en drogues toxiques, on sait peu de choses sur les facteurs contextuels qui influencent l'accès au traitement par agoniste opioïde (TAO) spécifique aux résidents ruraux. La présente étude examine ces facteurs dans un contexte rural et côtier en Colombie-Britannique, au Canada. MTHODES: Des méthodes qualitatives ont été utilisées pour examiner les obstacles et les facilitateurs de l'accès aux TAO. Entre juillet et octobre 2021, des entretiens semi-structurés ont été menés avec des personnes qui consomment des drogues résidant dans une communauté rurale et côtière. L'analyse thématique a été utilisée pour identifier les thèmes et sous-thèmes émergents. Les résultats ont été corroborés par l'équipe de recherche et un comité consultatif communautaire local. RSULTATS: Vingt-sept (n = 27) participants ont décrit les facteurs limitants et facilitants qui ont influé sur l'accessibilité au TAO. L'accès était moins difficile lorsque la pharmacie du TAO des participants était proche, avait des heures d'ouverture prolongées ou lorsque les pharmacies offraient des services de livraison. Parmi les obstacles à l'accès au TAO mentionnés par les participants, il y avait le coût élevé du transport, le fait de résider ou de travailler dans des collectivités éloignées et la rareté des prescripteurs locaux du TAO. Les participants ont également fait état de divers objectifs et motivations liés au traitement qui ont eu une incidence sur la satisfaction à l'égard du TAO. CONCLUSION: Cette étude démontre que la satisfaction des patients à l'égard de l'accès aux services du TAO en milieu rural et côtier est multifactorielle et que la proximité géographique n'explique pas à elle seule les problèmes d'accessibilité au TAO dans ces milieux. Cette accessibilité peut être améliorée par des services de livraison, l'élargissement de l'autorisation de prescrire un TAO au-delà des règlements réservés aux médecins, la prise en charge des coûts de transport par les autorités sanitaires et l'assurance continue que les pratiques de prescription répondent aux objectifs des individus.

Ketamine-assisted buprenorphine initiation: a pilot case series.

BACKGROUND: Many people with opioid use disorder who stand to benefit from buprenorphine treatment are unwilling to initiate it due to experience with or fear of both spontaneous and buprenorphine-precipitated opioid withdrawal (BPOW). An effective means of minimizing withdrawal symptoms would reduce patient apprehensiveness, lowering the barrier to buprenorphine initiation. Ketamine, approved by the FDA as a dissociative anesthetic, completely resolved BPOW in case reports when infused at a sub-anesthetic dose range in which dissociative symptoms are common. However, most patients attempt buprenorphine initiation in the outpatient setting where altered mental status is undesirable. We explored the potential of short-term use of ketamine, self-administered sublingually at a lower, sub-dissociative dose to assist ambulatory patients undergoing transition to buprenorphine from fentanyl and methadone. METHODS: Patients prescribed ketamine were either (1) seeking transition to buprenorphine from illicit fentanyl and highly apprehensive of BPOW or (2) undergoing transition to buprenorphine from illicit fentanyl or methadone and experiencing BPOW. We prescribed 4-8 doses of sublingual ketamine 16 mg (each dose bioequivalent to 3-6% of an anesthetic dose), monitored patients daily or near-daily, and adjusted buprenorphine and ketamine dosing based on patient response and prescriber experience. RESULTS: Over a period of 14 months, 37 patients were prescribed ketamine. Buprenorphine initiation was completed by 16 patients, representing 43% of the 37 patients prescribed ketamine, and 67% of the 24 who reported trying it. Of the last 12 patients who completed buprenorphine initiation, 11 (92%) achieved 30-day retention in treatment. Most of the patients who tried ketamine reported reduction or elimination of spontaneous opioid withdrawal symptoms. Some patients reported avoidance of severe BPOW when used prophylactically or as treatment of established BPOW. We developed a ketamine protocol that allowed four of the last patients to complete buprenorphine initiation over four days reporting only mild withdrawal symptoms. Two patients described cognitive changes from ketamine at a dose that exceeded the effective dose range for the other patients. CONCLUSIONS: Ketamine at a sub-dissociative dose allowed completion of buprenorphine initiation in the outpatient setting in the majority of patients who reported trying it. Further research is warranted to confirm these results and develop reliable protocols for a range of treatment settings.

Lost in transition: A protocol for a retrospective, longitudinal cohort study for addressing challenges in opioid treatment for transition-age adults.

BACKGROUND: In the United States, there has been a concerning rise in the prevalence of opioid use disorders (OUD) among transition-age (TA) adults, 18 to 25-years old, with a disproportionate impact on individuals and families covered by Medicaid. Of equal concern, the treatment system continues to underperform for many young people, emphasizing the need to address the treatment challenges faced by this vulnerable population at a pivotal juncture in their life course. Pharmacotherapy is the most effective treatment for OUD, yet notably, observational studies reveal gaps in the receipt of and retention in medications for opioid use disorder (MOUD), resulting in poor outcomes for many TA adults in treatment. Few current studies on OUD treatment quality explicitly consider the influence of individual, organizational, and contextual factors, especially for young people whose social roles and institutional ties remain in flux. METHODS: We introduce a retrospective, longitudinal cohort design to study treatment quality practices and outcomes among approximately 65,000 TA adults entering treatment for OUD between 2012 and 2025 in New York. We propose to combine data from multiple sources, including Medicaid claims and encounter data and a state registry of substance use disorder (SUD) treatment episodes, to examine three aspects of OUD treatment quality: 1) MOUD use, including MOUD option (e.g., buprenorphine, methadone, or extended-release [XR] naltrexone); 2) adherence to pharmacotherapy and retention in treatment; and 3) adverse events (e.g., overdoses). Using rigorous analytical methods, we will provide insights into how variation in treatment practices and outcomes are structured more broadly by multilevel processes related to communities, treatment programs, and characteristics of the patient, as well as their complex interplay. DISCUSSION: Our findings will inform clinical decision making by patients and providers as well as public health responses to the rising number of young adults seeking treatment for OUD amidst the opioid and polysubstance overdose crisis in the U.S.

Opioid Dosing Deviation and Dose Banding Development in Young Hospitalized Children.

BACKGROUND AND OBJECTIVES: Individualized, weight-based opioid dosing poses safety risks and contributes to inefficient medication delivery processes. Dose banding is a patient safety strategy to reduce dosing errors through standardized doses based on weight ranges. Study objectives were (1) determine the frequency of dosing deviation from reference ranges of common intravenous (IV) and oral opioid medications, (2) evaluate the differences in dosing deviations by age, and (3) determine the potential reduction in dose variation that could be achieved by dose banding. METHODS: We conducted a cross-sectional analysis of hospitalized children ≥2 months to ≤24 months old who received IV morphine, oral methadone, or oral oxycodone at a single center. Dosing was categorized as no dosing deviation (within ±5% of the reference range), negative dosing deviation (>5% below the reference range), or positive dosing deviation (>5% above the reference range). Descriptive and bivariate analyses were conducted. RESULTS: A total of 3361 opioid doses met the inclusion criteria. A total of 2663 (79.2%) had no dosing deviation, 214 (6.3%) demonstrated negative deviations, and 484 (14.4%) demonstrated positive deviations. Dosing deviations were more frequent among subjects ≥2 months to ≤6 months old for oral methadone and oxycodone (P < .0001) and more frequent among older age group for IV morphine (P < .0001). Dose banding has the potential to reduce the number of unique doses prescribed for all medications by 75% while eliminating unintended dosing deviations. CONCLUSIONS: A total of 20% of opioid doses prescribed to children ≤24 months of age are outside the recommended ranges. Dose banding represents a promising method for simplifying opioid prescribing in the pediatric inpatient setting.

Direct effects of heroin and methadone on T cell function.

Opioid addiction presents a relevant health challenge, with chronic heroin use linked to detrimental effects on various aspects of physical, mental, and sociological health. Opioid maintenance therapy (OMT), particularly using methadone, is the primary treatment option for heroin addiction. Previous studies using blood samples from current heroin addicts and OMT patients have shown immunomodulatory effects of heroin and methadone on T cell function. However, various additional factors beyond heroin and methadone affect these results, including the consumption of other substances, a stressful lifestyle, comorbid psychological and somatic disorders, as well as additional medications. Therefore, we here investigated the direct effects of heroin and methadone on purified human T cells in vitro. Our results reveal that both, heroin and methadone directly suppress Tcell activation and proliferation. Strikingly, this inhibitory effect was markedly stronger in the presence of methadone, correlating with a decrease in secretion of pro-inflammatory cytokines. While heroin did not interfere with the in vitro differentiation and expansion of regulatory Tcells (Tregs), methadone significantly impaired the proliferation of Tregs. Overall, our findings suggest a direct inhibitory impact of both opioids on effector T cell function in vitro, with methadone additionally interfering with Treg induction and expansion in contrast to heroin.

The cascade of care for commercially-insured persons with opioid use disorder and comorbid HIV and HCV infections.

BACKGROUND: Opioid use disorder (OUD) significantly impacts individual and public health and exacerbated further by concurrent infectious diseases. A syndemic approach is needed to address the intertwined OUD, HIV, and HCV epidemics, including the expanded use of medications for opioid use disorder (MOUD). METHODS: To identify MOUD scale-up opportunities, we conducted a retrospective cohort study, representing commercially insured persons, and created the OUD care continuum, including HIV and HCV influences in adults (18-64 years) newly diagnosed with OUD in 2019 using Merative MarketSan data. RESULTS: Among 124,467,633 individuals, the prevalence of OUD was 0.4 % (95 % CI: 0.36 %-0.46 %; N = 497,871), with 327,277 (65.7 %, 95 % CI: 65.60 %-65.87 %) newly diagnosed in 2019. Among these newly diagnosed individuals (54 % men, mean age 44±0.01), 53,568 (27.0 %, 95 % CI: 26.4 %-27.5 %) were prescribed MOUD, with retention rates at 1, 3, and 6 months being 89.0 % (95 % CI: 88.2 %-89.8 %), 66.0 % (95 % CI: 64.8 %-67.2 %), and 50.3 % (95 % CI: 48.3 %-51.6 %), respectively. Buprenorphine was the most prescribed MOUD (79.6 %, 95 % CI: 78.6 %-80.7 %), followed by XR-NTX (14.9 %, 95 % CI:14.0 %-15.8 %) and methadone (5.5 %, 95 % CI: 4.9 %-6.1 %). Six-month retention was highest for methadone (73.4 %, 95 % CI: 73.0 %-73.8 %), however, followed by buprenorphine (55.7 %, 95 % CI: 55.3 %-57.1 %) and substantially lower for XR-NTX (12.6 %, 95 % CI: 10.6 %-14.6 %). Screening for HIV and HCV was low among OUD enrollees (11.1 %, 14.4 %), slightly higher for MOUD initiators (18.0 %, 21.6 %). Being prescribed MOUD was correlated with HCV infection (AOR: 2.54; 95 % CI: 2.41-2.68), HCV/HIV coinfection (AOR: 1.89; 95 % CI: 1.41-2.53), and hospitalization for OUD-related services (AOR: 1.14; 95 % CI: 1.11-1.17), yet hospitalization for OUD-related services was positively correlated with XR-NTX (AOR: 2.72; 95 % CI: 2.56-2.85) prescription and negatively with methadone (AOR: 0.19; 95 % CI: 0.16-0.23) prescription. Having HIV was negatively correlated with being prescribed methadone (AOR: 0.33; 95 % CI: 0.13-0.86). CONCLUSIONS: Substantial gaps in the OUD cascade persist, underscoring better implementation opportunities for MOUD prescription in hospital-based settings and expanding access to methadone beyond highly regulated sites given its low coverage yet high treatment retention.

Intraoperative methadone administration for total mastectomy: A single center retrospective study.

BACKGROUND: Breast cancer is the most frequent type of cancer and the second leading cause of cancer-related mortality in women. Mastectomies remain a key component of the treatment of non-metastatic breast cancer, and strategies to treat acute postoperative pain, a complication affecting nearly all patients undergoing surgery, continues to be an important clinical challenge. This study aimed to determine the impact of intraoperative methadone administration compared to conventional short-acting opioids on pain-related perioperative outcomes in women undergoing a mastectomy. METHODS: This single-center retrospective study included adult women undergoing total mastectomy. The primary outcome of this study was postoperative pain intensity on day 1 after surgery. Secondary outcomes included perioperative opioid consumption, perioperative non-opioid analgesics use, duration of surgery and anesthesia, time to extubation, pain intensity in the postanesthesia care unit (PACU), anti-emetic use in PACU, and length of stay in hospital. We used the propensity score-based nearest matching with a 1:3 ratio to balance the patient baseline characteristics. RESULTS: 133 patients received methadone, and 2192 patients were treated with short-acting opioids. The analysis demonstrated that methadone was associated with significantly lower intraoperative and postoperative opioid consumption as measured by oral morphine equivalents and lower average pain intensity scores in the postanesthesia care unit. Moreover, methadone was also shown to reduce the use of non-opioid analgesia during surgery. CONCLUSION: Our study suggests that the unique pharmacological properties of methadone, including a short onset of action when given intravenously, long-acting pharmacokinetics, and multimodal effects, are associated with better acute pain management after a total mastectomy.

Pharmacokinetics, Tolerability, and Safety of Esmethadone in Subjects with Chronic Kidney Disease or Hepatic Impairment.

BACKGROUND AND OBJECTIVES: Esmethadone (dextromethadone; d-methadone; S-methadone (+)-methadone; REL-1017) is a low potency N-methyl-D-aspartate (NMDA) receptor channel blocker that showed a rapid and sustained adjunctive antidepressant effects in patients with major depressive disorder with inadequate response to ongoing serotonergic antidepressant treatment. Previous studies indicated that esmethadone is partially excreted by the kidney (53.9% of the dose) and by the liver (39.1% of the dose). METHODS: Here we studied the pharmacokinetics and safety of esmethadone after a single oral dose of 25 mg in subjects with different stages of kidney and liver impairment. RESULTS: In subjects with a mild and moderate decrease in glomerular fraction rate (GFR), esmethadone Cmax and AUC0-inf values did not differ compared with healthy subjects. In patients with severe renal impairment, the ratios of Cmax and AUC0-inf values compared with healthy subjects were above 100% (138.22-176.85%) and, while modest, these increases reached statistical significance. In subjects with end stage renal disease (ESRD) undergoing intermittent hemodialysis (IHD), Cmax and AUC0-inf values were not statistically different compared with healthy subjects. IHD did not modified plasma total esmethadone concentrations in blood exiting versus entering the dialyzer. Dose adjustment is not warranted in subjects with mild-to-moderate impaired renal function. Dose reduction may be considered for select patients with severe renal disfunction. In subjects with mild-or-moderate hepatic impairment, Cmax and AUC0-inf were approximately 20-30% lower compared with healthy controls. The drug free fraction increased with the severity of hepatic impairment, from 5.4% in healthy controls to 8.3% in subjects with moderate hepatic impairment. CONCLUSION: Mild and moderate hepatic impairment has a minimal to modest impact on exposure to total or unbound esmethadone and dose adjustments are not warranted in subjects with mild and moderate hepatic impairment. Administration of esmethadone was well tolerated in healthy adult subjects, in subjects with mild or moderate hepatic impairment, and in subjects with mild moderate or severe renal impairment, including patients with ESRF undergoing dialysis.

A Novel Use of the "3-Day Rule": Post-discharge Methadone Dosing in the Emergency Department.

Introduction: Methadone is a medically necessary and lifesaving medication for many patients with opioid use disorder. To adequately address these patients' needs, methadone should be offered in the hospital, but barriers exist that limit its continuation upon discharge. The code of federal regulations allows for methadone dosing as an inpatient as well as outpatient dispensing for up to three days to facilitate linkage to treatment. As a quality initiative, we created a new workflow for discharging patients on methadone to return to the emergency department (ED) for uninterrupted dosing. Methods: Our addiction medicine team changed hospital methadone policy to better allow hospitalization as a window of opportunity to start methadone. This necessitated the creation of a warm-handoff process to link patients to methadone clinics if that linkage could not happen immediately on discharge. Thus, our team created the "ED Bridge" process, which uses the "3-day rule" to dispense methadone from the ED post hospital discharge. We then followed every patient we directed through this workflow as an observational cohort for outcomes and trends. Results: Of the patients for whom ED bridge dosing was planned, 40.4% completed all bridge dosing and an additional 17.3% received at least one but not all bridge doses. Established methadone patients made up 38.1% of successful linkages, and 61.9% were patients who were newly started on methadone in the hospital. Conclusion: Improving methadone as a treatment option remains an ongoing issue for policymakers and advocates. Our ED bridge workflow allows us to expand access and continuation of methadone now using existing laws and regulations, and to better use hospitals as a point of entry into methadone treatment.

Medicare Payment for Opioid Treatment Programs.

Importance: Medicare began paying for medications for opioid use disorder (MOUD) at opioid treatment programs (OTPs) that dispense methadone and other MOUD in January 2020. There has been little research describing the response to this payment change and whether it resulted in more patients receiving MOUD or just a shift in who pays for this care. Objective: To describe how many and which Medicare beneficiaries receive care from OTPs and how this compares to those receiving MOUD in other settings. Design, Setting, and Participants: This cross-sectional study included all patients receiving MOUD care identified in 2019-2022 100% US Medicare Parts B and D claims. Patients receiving care in an OTP who were dually insured with Medicare and Medicaid in the 2019-2020 Transformed Medicaid Statistical Information System were also included. Exposure: Receiving MOUD care in an OTP. Main Outcomes and Measures: Comparisons of 2022 beneficiaries treated in OTPs vs other non-OTP settings in 2022. Results: The share of Medicare beneficiaries treated by OTPs rose steadily from 4 per 10 000 (14 160 beneficiaries) in January 2020 to 7 per 10 000 (25 596 beneficiaries) in August 2020, then plateaued through December 2022; of 38 870 patients (23% ≥66 years; 35% female) treated at an OTP in 2022, 96% received methadone. Patients in OTPs, compared to those receiving MOUD in other settings, were more likely be 65 years and younger (65% vs 62%; P < .001), less likely to be White (72% vs 82%; P < .001), and more likely to be an urban resident (86% vs 74%; P < .001). When Medicare OTP coverage began, there was no associated drop in the number of dually insured patients with Medicaid with an OTP claim. Of the 1854 OTPs, 1115 (60%) billed Medicare in 2022, with the share billing Medicare ranging from 13% to 100% across states. Conclusions and Relevance: This study showed that since the initiation of Medicare OTP coverage in 2020, there has been a rapid increase in the number of Medicare beneficiaries with claims for OTP services for MOUD, and most OTPs have begun billing Medicare. Patients in OTPs were more likely to be urban residents and members of racial or ethnic minority groups than the patients receiving other forms of MOUD.

Accessing opioid agonist treatment in prison in England and Scotland remains problematic - the views of people with lived experience.

PURPOSE: The purpose of this paper is to examine lived experiences of opioid agonist treatment (OAT) during and immediately following release from detention in prisons in England and Scotland. DESIGN/METHODOLOGY/APPROACH: Surveys were completed by serving prisoners in both countries and by those recently released from prison (England only). The survey findings were discussed in focus groups of people with lived experience. The combined findings from the surveys and focus groups were shared with an expert group of prison OAT providers and people with lived experience with the purpose of making recommendations for more accessible and effective OAT in custodial environments and continuity of OAT on release. FINDINGS: The quality and accessibility of OAT varied considerably between establishments. It was reported to be harder to access OAT in Scottish prisons. It was often hard for people in prison to get the dosage of OAT they felt they needed and it was generally harder to access buprenorphine than methadone in English prisons. Only Scottish people in prison were aware of long-lasting forms of buprenorphine. People in English prisons had mixed experiences of the help available in prison, with no improvement recorded since a 2016 study. People in Scottish prisons were more likely to rate the help available as poor. RESEARCH LIMITATIONS/IMPLICATIONS: The number of people accessed while actually in prison (73) was reduced by the impact of the pandemic, making it more difficult to access people in prison and because some were resistant to participating on the basis that they had already been consulted for a wide variety of research projects focused on the impact of COVID. The Scottish cohort (a total of 19 individuals comprising 14 survey respondents and five focus group members) is clearly too small a number on which to base robust claims about differences in OAT provision between the English and Scottish prison systems.. PRACTICAL IMPLICATIONS: The study identifies key barriers to accessing OAT in prisons and suggests key components of more user-friendly approaches. SOCIAL IMPLICATIONS: This study provides an overview of the recent lived experiences of people accessing OAT in prison and on release and offers valuable recommendations on how to make service provision more effective and consistent. ORIGINALITY/VALUE: This study provides an overview of the recent lived experiences of people accessing OAT in prison and on release in England and Scotland and offers valuable recommendations on how to make service provision more effective and consistent.

Medication for Opioid Use Disorder After Serious Injection-Related Infections in Massachusetts.

Importance: Serious injection-related infections (SIRIs) cause significant morbidity and mortality. Medication for opioid use disorder (MOUD) improves outcomes but is underused. Understanding MOUD treatment after SIRIs could inform interventions to close this gap. Objectives: To examine rehospitalization, death rates, and MOUD receipt for individuals with SIRIs and to assess characteristics associated with MOUD receipt. Design, Setting, and Participants: This retrospective cohort study used the Massachusetts Public Health Data Warehouse, which included all individuals with a claim in the All-Payer Claims Database and is linked to individual-level data from multiple government agencies, to assess individuals aged 18 to 64 years with opioid use disorder and hospitalization for endocarditis, osteomyelitis, epidural abscess, septic arthritis, or bloodstream infection (ie, SIRI) between July 1, 2014, and December 31, 2019. Data analysis was performed from November 2021 to May 2023. Exposure: Demographic and clinical factors potentially associated with posthospitalization MOUD receipt. Main Outcomes and Measures: The main outcome was MOUD receipt measured weekly in the 12 months after hospitalization. We used zero-inflated negative binomial regression to examine characteristics associated with any MOUD receipt and rates of treatment in the 12 months after hospitalization. Secondary outcomes were receipt of any buprenorphine formulation, methadone, and extended-release naltrexone examined individually. Results: Among 8769 individuals (mean [SD] age, 43.2 [12.0] years; 5066 [57.8%] male) who survived a SIRI hospitalization, 4305 (49.1%) received MOUD, 5919 (67.5%) were rehospitalized, and 973 (11.1%) died within 12 months. Of those treated with MOUD in the 12 months after hospitalization, the mean (SD) number of MOUD initiations during follow-up was 3.0 (1.7), with 956 of 4305 individuals (22.2%) receiving treatment at least 80% of the time. MOUD treatment after SIRI hospitalization was significantly associated with MOUD in the prior 6 months (buprenorphine: adjusted odds ratio [AOR], 16.51; 95% CI, 13.81-19.74; methadone: AOR, 28.46; 95% CI, 22.41-36.14; or naltrexone: AOR, 2.05; 95% CI, 1.56-2.69). Prior buprenorphine (incident rate ratio [IRR], 1.17; 95% CI, 1.11-1.24) or methadone (IRR, 1.89; 95% CI, 1.79-2.01) use was associated with higher treatment rates after hospitalization, and prior naltrexone use (IRR, 0.86; 95% CI, 0.77-0.95) was associated with lower rates. Conclusions and Relevance: This study found that in the year after a SIRI hospitalization in Massachusetts, mortality and rehospitalization were common, and only half of patients received MOUD. Treatment with MOUD before a SIRI was associated with posthospitalization MOUD initiation and time receiving MOUD. Efforts are needed to initiate MOUD treatment during SIRI hospitalizations and subsequently retain patients in treatment.