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Potential uses of naltrexone in emergency department patients with opioid use disorder.

ABSTRACT: Introduction: Despite widespread recognition of the opioid crisis, opioid overdose remains a common reason for Emergency Department (ED) utilization. Treatment for these patients after stabilization often involves the provision of information for outpatient treatment options. Ideally, an ED visit for overdose would present an opportunity to start treatment for opioid use disorder (OUD) immediately. Although widely recognized as effective, opioid agonist therapy with methadone and buprenorphine commonly referred to as "medication-assisted therapy" but more correctly as "medication for addiction treatment" (MAT), can be difficult to access even for motivated individuals due to shortages of prescribers and treatment programs. Moreover, opioid agonist therapy may not be appropriate for all patients, as many patients who present after overdose are not opioid dependent. More treatment options are required to successfully match patients with diverse needs to an optimal treatment plan in order to avoid relapse. Naltrexone, a long-acting opioid antagonist, available orally and as a monthly extended-release intramuscular injection, may represent another treatment option. Methods: We conducted a literature search of MEDLINE and PubMed. We aimed to capture references related to naltrexone and is use as MAT for OUD, as well as manuscripts that discussed naltrexone in comparison toother agents used for MAT, opioid detoxification, and naltrexone metabolism. Our initial search logic returned a total of 618 articles. Following individual evaluation for relevance, we selected 65 for in-depthreview. Manuscripts meeting criteria were examined for citations meriting further review, leading to the addition of 30 manuscripts Conclusions: Here, we review the pharmacology of naltrexone as it relates to OUD, its history of use, and highlight recent studies and new approaches for use of the drug as MAT including its potential initiation after ED visit for opioid overdose.

SUBMITTER: Bradley ES

PROVIDER: S-EPMC6908461 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Potential uses of naltrexone in emergency department patients with opioid use disorder.

Bradley Evan Stuart ES Liss David D Carreiro Stephanie Pepper SP Brush David Eric DE Babu Kavita K

Clinical toxicology (Philadelphia, Pa.) 20190304 9

<b>Introduction:</b> Despite widespread recognition of the opioid crisis, opioid overdose remains a common reason for Emergency Department (ED) utilization. Treatment for these patients after stabilization often involves the provision of information for outpatient treatment options. Ideally, an ED visit for overdose would present an opportunity to start treatment for opioid use disorder (OUD) immediately. Although widely recognized as effective, opioid agonist therapy with methadone and buprenor ...[more]

PMID: 30831039

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Project description:ImportanceAlthough substantial evidence supports buprenorphine for treatment of opioid use disorder (OUD) in controlled trials, prospective study of patient outcomes in clinical implementation of emergency department (ED) buprenorphine treatment is lacking.ObjectiveTo examine the association between buprenorphine treatment in the ED and follow-up engagement in OUD treatment 1 month later.Design, setting, and participantsThis multisite cohort study was conducted in 7 California EDs participating in a statewide implementation project to improve access to buprenorphine treatment. The study population included ED patients aged at least 18 years identified with OUD between April 1, 2021, and June 30, 2022. Data analysis was performed in October 2023.ExposureAll participants were offered buprenorphine treatment for OUD (either in ED administration, prescription, or both), the uptake of which was examined as the exposure of interest.Main outcomes and measuresThe primary outcome was engagement in OUD treatment 30 days after the ED visit, determined by patient report or clinical documentation. The association of ED buprenorphine treatment with subsequent OUD treatment engagement was estimated using hierarchical generalized linear models.ResultsThis analysis included 464 ED patients with OUD. Their median age was 36.0 (IQR, 29.0-38.7) years, and most were men (343 [73.9%]). With regard to race and ethnicity, 64 patients (13.8%) self-identified as non-Hispanic Black, 183 (39.4%) as Hispanic, and 185 as non-Hispanic White (39.9%). Most patients (396 [85.3%]) had Medicaid insurance, and more than half (262 [57.8%]) had unstable housing. Self-reported fentanyl use (242 [52.2%]) and a comorbid mental health condition (328 [71.5%]) were common. Interest in buprenorphine treatment was high: 398 patients (85.8%) received buprenorphine treatment; 269 (58.0%) were administered buprenorphine in the ED and 339 (73.1%) were prescribed buprenorphine. With regard to OUD treatment engagement at 30 days after the ED visit, 198 participants (49.7%) who received ED buprenorphine treatment remained engaged compared with 15 participants (22.7%) who did not receive ED buprenorphine treatment. An association of ED buprenorphine treatment with subsequent OUD treatment engagement at 30 days was observed (adjusted risk ratio, 1.97 [95% CI, 1.27-3.07]).Conclusions and relevanceThe findings of this cohort study suggest that among patients with OUD presenting to EDs implementing low-threshold access to medications for OUD, buprenorphine treatment was associated with a substantially higher likelihood of follow-up treatment engagement 1 month later. Future research should investigate techniques to optimize both the uptake and effectiveness of buprenorphine initiation in low-threshold settings such as the ED.

Project description:Study objectiveConcurrent use of amphetamine-type stimulants among individuals with opioid use disorder can exacerbate social and medical harms, including overdose risk. The study evaluated rates of amphetamine-type stimulant use among patients with untreated opioid use disorder presenting at emergency departments in Baltimore, MD; New York, NY; Cincinnati, OH; and Seattle, WA.MethodsEmergency department (ED) patients with untreated opioid use disorder (N=396) and enrolled between February 2017 and January 2019 in a multisite hybrid type III implementation science study were evaluated for concurrent amphetamine-type stimulant use. Individuals with urine tests positive for methamphetamine, amphetamine, or both were compared with amphetamine-type stimulant-negative patients.ResultsOverall, 38% of patients (150/396) were amphetamine-type stimulant positive; none reported receiving prescribed amphetamine or methamphetamine medications. Amphetamine-type stimulant-positive versus -negative patients were younger: mean age was 36 years (SD 10 years) versus 40 years (SD 12 years), 69% (104/150) versus 46% (114/246) were white, 65% (98/150) versus 54% (132/246) were unemployed, 67% (101/150) versus 49 (121/246) had unstable housing, 47% (71/150) versus 25% (61/245) reported an incarceration during 1 year before study admission, 60% (77/128) versus 45% (87/195) were hepatitis C positive, 79% (118/150) versus 47% (115/245) reported drug injection during 1 month before the study admission, and 42% (62/149) versus 29% (70/244) presented to the ED for an injury. Lower proportions of amphetamine-type stimulant-positive patients had cocaine-positive urine test results (33% [50/150] versus 52% [129/246]) and reported seeking treatment for substance use problems as a reason for their ED visit (10% [14/148] versus 19% [46/246]). All comparisons were statistically significant at P<.05 with the false discovery rate correction.ConclusionAmphetamine-type stimulant use among ED patients with untreated opioid use disorder was associated with distinct sociodemographic, social, and health factors. Improved ED-based screening, intervention, and referral protocols for patients with opioid use disorder and amphetamine-type stimulant use are needed.

Project description:ImportanceEmergency department (ED)-initiated buprenorphine for the treatment of opioid use disorder (OUD) is underused.ObjectiveTo evaluate whether provision of ED-initiated buprenorphine with referral for OUD increased after implementation facilitation (IF), an educational and implementation strategy.Design, setting, and participantsThis multisite hybrid type 3 effectiveness-implementation nonrandomized trial compared grand rounds with IF, with pre-post 12-month baseline and IF evaluation periods, at 4 academic EDs. The study was conducted from April 1, 2017, to November 30, 2020. Participants were ED and community clinicians treating patients with OUD and observational cohorts of ED patients with untreated OUD. Data were analyzed from July 16, 2021, to July 14, 2022.ExposureA 60-minute in-person grand rounds was compared with IF, a multicomponent facilitation strategy that engaged local champions, developed protocols, and provided learning collaboratives and performance feedback.Main outcomes and measuresThe primary outcomes were the rate of patients in the observational cohorts who received ED-initiated buprenorphine with referral for OUD treatment (primary implementation outcome) and the rate of patients engaged in OUD treatment at 30 days after enrollment (effectiveness outcome). Additional implementation outcomes included the numbers of ED clinicians with an X-waiver to prescribe buprenorphine and ED visits with buprenorphine administered or prescribed and naloxone dispensed or prescribed.ResultsA total of 394 patients were enrolled during the baseline evaluation period and 362 patients were enrolled during the IF evaluation period across all sites, for a total of 756 patients (540 [71.4%] male; mean [SD] age, 39.3 [11.7] years), with 223 Black patients (29.5%) and 394 White patients (52.1%). The cohort included 420 patients (55.6%) who were unemployed, and 431 patients (57.0%) reported unstable housing. Two patients (0.5%) received ED-initiated buprenorphine during the baseline period, compared with 53 patients (14.6%) during the IF evaluation period (P < .001). Forty patients (10.2%) were engaged with OUD treatment during the baseline period, compared with 59 patients (16.3%) during the IF evaluation period (P = .01). Patients in the IF evaluation period who received ED-initiated buprenorphine were more likely to be in treatment at 30 days (19 of 53 patients [35.8%]) than those who did not 40 of 309 patients (12.9%; P < .001). Additionally, there were increases in the numbers of ED clinicians with an X-waiver (from 11 to 196 clinicians) and ED visits with provision of buprenorphine (from 259 to 1256 visits) and naloxone (from 535 to 1091 visits).Conclusions and relevanceIn this multicenter effectiveness-implementation nonrandomized trial, rates of ED-initiated buprenorphine and engagement in OUD treatment were higher in the IF period, especially among patients who received ED-initiated buprenorphine.Trial registrationClinicalTrials.gov Identifier: NCT03023930.

Project description:ImportanceEmergency departments (EDs) sporadically use a high-dose buprenorphine induction strategy for the treatment of opioid use disorder (OUD) in response to the increasing potency of the illicit opioid drug supply and commonly encountered delays in access to follow-up care.ObjectiveTo examine the safety and tolerability of high-dose (>12 mg) buprenorphine induction for patients with OUD presenting to an ED.Design, setting, and participantsIn this case series of ED encounters, data were manually abstracted from electronic health records for all ED patients with OUD treated with buprenorphine at a single, urban, safety-net hospital in Oakland, California, for the calendar year 2018. Data analysis was performed from April 2020 to March 2021.InterventionsED physicians and advanced practice practitioners were trained on a high-dose sublingual buprenorphine induction protocol, which was then clinically implemented.Main outcomes and measuresVital signs; use of supplemental oxygen; the presence of precipitated withdrawal, sedation, and respiratory depression; adverse events; length of stay; and hospitalization during and 24 hours after the ED visit were reported according to total sublingual buprenorphine dose (range, 2 to >28 mg).ResultsAmong a total of 391 unique patients (median [interquartile range] age, 36 [29-48] years), representing 579 encounters, 267 (68.3%) were male and 170 were (43.5%) Black. Homelessness (88 patients [22.5%]) and psychiatric disorders (161 patients [41.2%]) were common. A high dose of sublingual buprenorphine (>12 mg) was administered by 54 unique clinicians during 366 (63.2%) encounters, including 138 doses (23.8%) greater than or equal to 28 mg. No cases of respiratory depression or sedation were reported. All 5 (0.8%) cases of precipitated withdrawal had no association with dose; 4 cases occurred after doses of 8 mg of buprenorphine. Three serious adverse events unrelated to buprenorphine were identified. Nausea or vomiting was rare (2%-6% of cases). The median (interquartile range) length of stay was 2.4 (1.6-3.75) hours.Conclusions and relevanceThese findings suggest that high-dose buprenorphine induction, adopted by multiple clinicians in a single-site urban ED, was safe and well tolerated in patients with untreated OUD. Further prospective investigations conducted in multiple sites would enhance these findings.

Project description:ImportanceEmergency department (ED) initiation of buprenorphine is safe and effective but underutilized in practice. Understanding the factors affecting adoption of this practice could inform more effective interventions.ObjectiveTo quantify the factors, including social contagion, associated with the adoption of the practice of ED initiation of buprenorphine for patients with opioid use disorder.Design, setting, and participantsThis is a secondary analysis of the EMBED (Emergency Department-Initiated Buprenorphine For Opioid Use Disorder) trial, a multicentered, cluster randomized trial of a clinical decision support intervention targeting ED initiation of buprenorphine. The trial occurred from November 2019 to May 2021. The study was conducted at ED clusters across health care systems from the northeast, southeast, and western regions of the US and included attending physicians, resident physicians, and advanced practice practitioners. Data analysis was performed from August 2022 to June 2023.ExposuresThis analysis included both the intervention and nonintervention groups of the EMBED trial. Graph methods were used to construct the network of clinicians who shared in the care of patients for whom buprenorphine was initiated during the trial before initiating the practice themselves, termed exposure.Main outcomes and measuresCox proportional hazard modeling with time-dependent covariates was performed to assess the association of the number of these exposures with self-adoption of the practice of ED initiation of buprenorphine while adjusting for clinician role, health care system, and intervention site status.ResultsA total of 1026 unique clinicians in 18 ED clusters across 5 health care systems were included. Analysis showed associations of the cumulative number of exposures to others initiating buprenorphine with the self-practice of buprenorphine initiation. This increased in a dose-dependent manner (1 exposure: hazard ratio [HR], 1.31; 95% CI, 1.16-1.48; 5 exposures: HR, 2.85; 95% CI, 1.66-4.89; 10 exposures: HR, 3.55; 95% CI, 1.47-8.58). Intervention site status was associated with practice adoption (HR, 1.50; 95% CI, 1.04-2.18). Health care system and clinician role were also associated with practice adoption.Conclusions and relevanceIn this secondary analysis of a multicenter, cluster randomized trial of a clinical decision support tool for buprenorphine initiation, the number of exposures to ED initiation of buprenorphine and the trial intervention were associated with uptake of ED initiation of buprenorphine. Although systems-level approaches are necessary to increase the rate of buprenorphine initiation, individual clinicians may change practice of those around them.Trial registrationClinicalTrials.gov Identifier: NCT03658642.

Project description:AIMS:To review systematically the published literature on extended-release naltrexone (XR-NTX, Vivitrol® ), marketed as a once-per-month injection product to treat opioid use disorder. We addressed the following questions: (1) how successful is induction on XR-NTX; (2) what are adherence rates to XR-NTX; and (3) does XR-NTX decrease opioid use? Factors associated with these outcomes as well as overdose rates were examined. METHODS:We searched PubMed and used Google Scholar for forward citation searches of peer-reviewed papers from January 2006 to June 2017. Studies that included individuals seeking treatment for opioid use disorder who were offered XR-NTX were included. RESULTS:We identified and included 34 studies. Pooled estimates showed that XR-NTX induction success was lower in studies that included individuals that required opioid detoxification [62.6%, 95% confidence interval (CI) = 54.5-70.0%] compared with studies that included individuals already detoxified from opioids (85.0%, 95% CI = 78.0-90.1%); 44.2% (95% CI = 33.1-55.9%) of individuals took all scheduled injections of XR-NTX, which were usually six or fewer. Adherence was higher in prospective investigational studies (i.e. studies conducted in a research context according to a study protocol) compared to retrospective studies of medical records taken from routine care (6-month rates: 46.7%, 95% CI = 34.5-59.2% versus 10.5%, 95% CI = 4.6-22.4%, respectively). Compared with referral to treatment, XR-NTX reduced opioid use in adults under criminal justice supervision and when administered to inmates before release. XR-NTX reduced opioid use compared with placebo in Russian adults, but this effect was confounded by differential retention between study groups. XR-NTX showed similar efficacy to buprenorphine when randomization occurred after detoxification, but was inferior to buprenorphine when randomization occurred prior to detoxification. CONCLUSIONS:Many individuals intending to start extended-release naltrexone (XR-NTX) do not and most who do start XR-NTX discontinue treatment prematurely, two factors that limit its clinical utility significantly. XR-NTX appears to decrease opioid use but there are few experimental demonstrations of this effect.

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Potential uses of naltrexone in emergency department patients with opioid use disorder.

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Potential uses of naltrexone in emergency department patients with opioid use disorder.

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