Extended-release Injectable Naltrexone Research Articles

Optimizing retention strategies for opioid use disorder pharmacotherapy: The retention phase of the CTN-0100 trial (RDD).

The three medications approved to address OUD are effective in decreasing opioid use and morbidity and mortality; however, their utility is limited by high rates of dropout from treatment. The CTN-0100 trial will develop an evidence base for strategies to improve retention on buprenorphine and extended-release naltrexone. The National Drug Abuse Treatment Clinical Trials Network (CTN) study CTN-0100, "Optimizing Retention, Duration and Discontinuation Strategies for Opioid Use Disorder Pharmacotherapy" (RDD), is a multicenter, randomized, non-blinded trial enrolling more than a thousand patients from 18 community-based substance use disorder treatment programs. Participants are adult volunteers seeking to initiate medication treatment for OUD (MOUD). Individuals choose between buprenorphine or extended-release injectable naltrexone. The trial randomizes participants choosing buprenorphine, in a 3 × 2 factorial design, to a medication condition (standard-dose sublingual buprenorphine, high-dose sublingual buprenorphine, or extended-release injectable buprenorphine) and to a behavioral condition (Medical Management or Medical Management plus a digital therapeutic (smartphone) app). Individuals choosing extended-release naltrexone are randomized only to a behavioral condition. Participants receive study medication for 74 weeks and are then followed for a further 24 weeks. The primary outcome is successful retention on MOUD at 26 weeks (six months), with 50- and 74-week retention among the secondary outcomes. Dropout from treatment is a major barrier to the effectiveness of MOUD. The CTN-0100 study will determine whether strategies such as high dose sublingual or extended-release buprenorphine, or an app-based behavioral intervention improve retention on MOUD. gov Identifier: NCT04464980.

Extended observation of reduced methamphetamine use with combined naltrexone plus bupropion in the ADAPT-2 trial.

A 12-week placebo-controlled, sequential parallel Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder (ADAPT-2) trial evaluated the effects of extended-release injectable naltrexone plus extended-release oral bupropion (NTX + BUPN) on methamphetamine (MA) use over two stages. This study reports on the previously unpublished stage 2 MA use in participants randomized at stage 1 to receive NTX + BUPN through both stages compared with those assigned to placebo. This is a secondary analysis of the US National Institute on Drug Abuse (NIDA) ADAPT-2 network trial. The parent ADAPT-2 trial was carried out across multiple NIDA Clinical Trials Network (CTN) sites in the United States. This analysis includes 403 people with MA use disorder who participated in the ADAPT-2 CTN trial. NTX + BUPN was compared with placebo over the course of the trial. MA use was measured by urine drug screens conducted twice weekly for 12 weeks, then once in week 13 and once in week 16 post-treatment follow-up. Participants on NTX + BUPN in stage 1 showed an additional 9.2% increase [95% confidence interval (CI),0.09%-17.9%, P = 0.038]during stage 2 in their probability of testing negative for MA, with a total increase of 27.1% (95% CI, 13.2%-41.1%, P < 0.001) over the full 12 weeks of treatment. In contrast, participants on placebo in both stages increased in probability of testing MA-negative by a total of 11.4% (95% CI, 4.1%-18.6%, P = 0.002) over all 12 weeks. The 12-week increase among participants on NTX + BUPN was significantly greater-by 15.8% (95% CI, 4.5%-27.0%, P = 0.006)-than the increase among those on placebo. For people with methamphetamine (MA) use disorder receiving treatment with extended-release injectable naltrexone plus extended-release oral bupropion (NTX + BUPN), continued treatment with NTX + BUPN after 6weeks is associated with additional reductions in MA use up to 12 weeks.

ADVANCES IN THE TREATMENT OF ALCOHOL, OPIOID, AND CANNABIS ADDICTION

Substance use disorders, particularly those involving alcohol, opioids, and cannabis, present significant challenges in healthcare due to their widespread impact and complex nature. Recent advances in the treatment of these addictions offer new hope and more effective strategies for addressing these pervasive issues. This presentation will explore the latest developments in pharmacological, behavioral, and integrative approaches to treating alcohol, opioid, and cannabis addiction. For alcohol use disorder, pharmacotherapies such as acamprosate and extended-release naltrexone have shown promise in reducing cravings and relapse rates. Advances in behavioral therapies, including cognitive-behavioral therapy (CBT) and mindfulness-based interventions, have also proven effective in combination with medication. In the realm of opioid addiction, the introduction of long-acting buprenorphine formulations and the growing use of extended-release injectable naltrexone have revolutionized treatment, providing patients with more convenient and less stigmatizing options. The role of harm reduction strategies, such as supervised consumption sites and the distribution of naloxone, will also be discussed. For cannabis use disorder, emerging research highlights the potential of cannabinoid receptor antagonists, such as rimonabant, NAC and the application of motivational enhancement therapy (MET) and contingency management (CM) as effective treatment modalities. This presentation will also address the importance of personalized treatment plans, integrating pharmacological and behavioral approaches tailored to individual patient needs. The discussion will include insights into the role of technology in addiction treatment, such as telemedicine and digital therapeutics, which are expanding access and improving outcomes. By examining these advances, this presentation aims to provide healthcare professionals with a comprehensive overview of current best practices and innovative strategies for treating alcohol, opioid, and cannabis addiction, ultimately contributing to more effective patient care and better long-term outcomes.

Nurse Care Management for Opioid Use Disorder Treatment

Few primary care (PC) practices treat patients with medications for opioid use disorder (OUD) despite availability of effective treatments. To assess whether implementation of the Massachusetts model of nurse care management for OUD in PC increases OUD treatment with buprenorphine or extended-release injectable naltrexone and secondarily decreases acute care utilization. The Primary Care Opioid Use Disorders Treatment (PROUD) trial was a mixed-methods, implementation-effectiveness cluster randomized clinical trial conducted in 6 diverse health systems across 5 US states (New York, Florida, Michigan, Texas, and Washington). Two PC clinics in each system were randomized to intervention or usual care (UC) stratified by system (5 systems were notified on February 28, 2018, and 1 system with delayed data use agreement on August 31, 2018). Data were obtained from electronic health records and insurance claims. An implementation monitoring team collected qualitative data. Primary care patients were included if they were 16 to 90 years old and visited a participating clinic from up to 3 years before a system's randomization date through 2 years after. The PROUD intervention included 3 components: (1) salary for a full-time OUD nurse care manager; (2) training and technical assistance for nurse care managers; and (3) 3 or more PC clinicians agreeing to prescribe buprenorphine. The primary outcome was a clinic-level measure of patient-years of OUD treatment (buprenorphine or extended-release injectable naltrexone) per 10 000 PC patients during the 2 years postrandomization (follow-up). The secondary outcome, among patients with OUD prerandomization, was a patient-level measure of the number of days of acute care utilization during follow-up. During the baseline period, a total of 130 623 patients were seen in intervention clinics (mean [SD] age, 48.6 [17.7] years; 59.7% female), and 159 459 patients were seen in UC clinics (mean [SD] age, 47.2 [17.5] years; 63.0% female). Intervention clinics provided 8.2 (95% CI, 5.4-∞) more patient-years of OUD treatment per 10 000 PC patients compared with UC clinics (P = .002). Most of the benefit accrued in 2 health systems and in patients new to clinics (5.8 [95% CI, 1.3-∞] more patient-years) or newly treated for OUD postrandomization (8.3 [95% CI, 4.3-∞] more patient-years). Qualitative data indicated that keys to successful implementation included broad commitment to treat OUD in PC from system leaders and PC teams, full financial coverage for OUD treatment, and straightforward pathways for patients to access nurse care managers. Acute care utilization did not differ between intervention and UC clinics (relative rate, 1.16; 95% CI, 0.47-2.92; P = .70). The PROUD cluster randomized clinical trial intervention meaningfully increased PC OUD treatment, albeit unevenly across health systems; however, it did not decrease acute care utilization among patients with OUD. ClinicalTrials.gov Identifier: NCT03407638.

Comorbid alcohol use disorder and posttraumatic stress disorder: A proof-of-concept randomized placebo-controlled trial of buprenorphine and naltrexone combination treatment.

Effective pharmacologic treatments for comorbid alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) are lacking. Kappa (κ) opioid receptor antagonists may address this unmet need. Buprenorphine is a κ-opioid antagonist and a partial agonist of mu (μ) opioid receptors. Whereas naltrexone blocks all μ-mediated effects combining it with buprenorphine yields a pharmacologic net effect of opioid receptor antagonism. Because no κ-opioid receptor antagonist it available for clinical use, we tested this combination in a proof-of-concept study. Consenting participants were enrolled in a Phase II, multisite, double-blind, randomized, placebo-controlled trial evaluating the effectiveness of sublingual (SL) buprenorphine combined with extended-release (XR) injectable naltrexone for the treatment of comorbid AUD and PTSD. Eligible participants (n = 75) were randomized (1:1:1) to receive either buprenorphine 2 mg/day plus naltrexone-XR (n = 35), buprenorphine 8 mg/day plus naltrexone-XR (n = 6) or SL plus injectable placebo (n = 34) for 12 weeks. The buprenorphine 8 mg/day plus naltrexone-XR arm was dropped early in the trial due to the negative impact of COVID-19 on enrollment. A binary primary outcome of response at week 8 was defined as a decrease from baseline of ≥10 points on the past week Clinician-Administered PTSD Scale (CAPS-5) and a reduction of ≥1 of past month alcohol risk level, as defined by the World Health Organization (WHO) and measured by the Timeline Follow-Back. Based on the results of a futility analysis, enrollment was stopped prior to reaching the initial goal of 90 participants. At the week eight primary timepoint, there were no statistically significant differences between buprenorphine plus naltrexone-XR and placebo group for the primary composite outcome (OR = 0.63; p-value = 0.52), or the subcomponents of the PTSD outcome (OR = 0.76; p-value = 0.69) and AUD outcome (OR = 0.17; p-value = 0.08). The placebo arm had a significantly higher proportion of participants with ≥1 WHO risk level reduction than the buprenorphine plus naltrexone-XR arm (OR = 0.18, p value = 0.02). This is the first study to evaluate the potential of κ-opioid receptor antagonism for the treatment of comorbid AUD and PTSD. The combination of buprenorphine and naltrexone-XR showed no significant improvement over placebo for the composite, PTSD, or alcohol measures.

Medication treatment for alcohol use disorder in special populations.

Alcohol use disorder (AUD) is a significant public health concern, with underutilized effective treatments, particularly in special populations. This article summarizes the current evidence and guidelines for treating AUD in special populations. This article is a literature review that synthesizes the latest research on AUD treatment for special populations. We screened 242 articles and included 57 in our final review. There are four food and Drug Administration-approved medications for AUD (MAUD): disulfiram, oral naltrexone, extended-release injectable naltrexone (XR-NTX), and acamprosate. Naltrexone and disulfiram have the potential to cause liver toxicity, and acamprosate should be avoided in patients with severe kidney disease. Psychosocial treatments should be considered first-line for pregnant and nursing patients. Naltrexone is contraindicated in patients on opioids, as it may precipitate acute withdrawal. For patients experiencing homelessness, nonabstinent treatment goals may be more practical, and XR-NTX should be considered to improve adherence. Limited evidence suggests medication can improve AUD treatment outcomes in adolescents and young adults. For patients with poor treatment response despite adequate medication adherence, switching to a different medication and augmentation with psychosocial treatments should be considered. Understanding the unique considerations for special populations with AUD is crucial, and addressing their special needs may improve their treatment outcomes. Our study significantly contributes to the existing literature by summarizing crucial information for the treatment of AUD in special populations, highlighting distinct challenges, and emphasizing tailored approaches to improve overall health and well-being.

Sexual orientation differences among men in a randomized clinical trial of extended-release naltrexone and bupropion for methamphetamine use disorder

BackgroundMethamphetamine use disorder (MethUD) disproportionately affects men who have sex exclusively with men or with men and women (collectively MSM/W), compared to men who have sex with women (MSW). This study is the first MethUD medication trial to compare treatment effect for these groups, hypothesizing that extended-release injectable naltrexone 380mg every 3 weeks plus oral extended-release bupropion 450mg daily would be less effective for MSM/W than MSW. MethodsData come from men (N = 246) in a multi-site, double-blind, randomized, placebo-controlled trial with sequential parallel comparison design. In Stage 1 (6-weeks), participants were randomized to active treatment or placebo. In Stage 2 (6-weeks), Stage 1 placebo non-responders were rerandomized. Treatment response was ≥3 methamphetamine-negative urine samples, out of four obtained at the end of Stages 1 and 2. Treatment effect was the active-versus-placebo between-group difference in the weighted average Stages 1 and 2 responses. ResultsMSM/W (n = 151) were more likely than MSW (n = 95) to be Hispanic, college-educated, and living with HIV. Adjusting for demographics, among MSM/W, response rates were 13.95 % (active treatment) and 2.78 % (placebo) in Stage 1; 23.26 % (active treatment) and 4.26 % (placebo) in Stage 2. Among MSW, response rates were 7.69 % (active treatment) and 5.80 % (placebo) in Stage 1; 3.57 % (active treatment) and 0 % (placebo) in Stage 2. Treatment effect was significantly larger for MSM/W (h = 0.1479) than MSW (h = 0.0227) (p = 0.04). ConclusionsFindings suggest efficacy of extended-release naltrexone plus bupropion for MSM/W, a population heavily burdened by MethUD. While a secondary outcome, this intriguing finding merits testing in prospective trials.

Social ecological factors and medication treatment for opioid use disorder among justice-involved rural and urban persons: the Geographic variation in Addiction Treatment Experiences (GATE) longitudinal cohort study protocol

IntroductionThree medications are Food and Drug Administration approved for the treatment of opioid use disorder (OUD); however, these medications are underused within prisons, which elevates the risk of relapse and...

Time-lagged association between counseling and/or 12-Step attendance with subsequent opioid use in a secondary analysis from a randomized, clinical trial of medications for opioid use disorder

IntroductionPsychosocial support is recommended in conjunction with medication for opioid use disorder (MOUD), although optimal “dose,” modality, and timing of participation is not established. This study comprised a secondary analysis of counseling and 12-Step attendance and subsequent opioid use in a MOUD randomized clinical trial. Methods: The parent study randomly assigned 570 participants to receive buprenorphine-naloxone (BUP-NX, n=287) or extended-release injectable naltrexone (XR-NTX, n=283). Mixed-effects logistic regression models were fit with opioid use as the response variable, and a counseling/12-Step attendance predictor. Differences by treatment assignment were examined. Results: Any counseling or 12-Step attendance was associated with reduced odds of opioid use at the subsequent visit, whether considered individually or aggregated across type. A continuous relationship was observed for 12-Step attendance (F(1,5083)=5.01, p=.025); with each additional hour associated with 13% (95% CI: 0.83, 0.90) reduction in odds of opioid use. The strength of this association grew over time. In the BUP-NX arm, group counseling was associated with a greater reduction in odds of opioid use than for XR-NTX, (OR=0.32 (95% CI: .22, 0.48) vs. OR=0.69 (95% CI: 0.43, 1.08)). For XR-NTX, 12-Step was associated with a greater reduction in odds of opioid use (OR=0.35 (95% CI: 0.22, 0.54) vs. OR=0.65 (95% CI: 0.47, 0.89) for BUP-NX)). Conclusions: Psychosocial engagement has a proximal association with opioid use, the strength of that association may grow with dose and time. Alternatively, more motivated individuals may both attend more counseling/12-Step and have better treatment outcomes, or the relationship may be reciprocal.

Rutgers Grad Students RIOT for Opioid Education

Rutgers Grad Students RIOT for Opioid Education

Cost-effectiveness of extended-release injectable naltrexone among incarcerated persons with opioid use disorder before release from prison versus after release

IntroductionOpioid use disorder (OUD) is highly prevalent among incarcerated populations, and the risk of fatal overdose following release from prison is substantial. Despite efficacy, few correctional facilities provide evidence-based addiction treatment. Extended-release injectable naltrexone (XR-NTX) administered prior to release from incarceration may improve health and economic outcomes. MethodsWe conducted an economic evaluation alongside a randomized controlled trial testing the effectiveness of XR-NTX before release from prison (n = 38) vs. XR-NTX referral after release (n = 48) of incarcerated participants with OUD, both groups continuing treatment at a community addiction treatment center. The incremental cost-effectiveness ratio (ICER) assessed the cost-effectiveness of XR-NTX before release compared to referral after release for three stakeholder perspectives at 12- and 24-week periods: state policymaker, health care sector, and societal. Effectiveness measures included quality-adjusted life-years (QALYs) and abstinent years from opioids. In addition, we categorized resources as OUD-related and non-OUD-related medical care, state transfer payments, and other societal costs (productivity, criminal justice resources, etc.). ResultsResults showed an association between XR-NTX and greater OUD-related costs and total costs from the state policymaker perspective. QALYs gained were positive but statistically insignificant between arms; however, results showed XR-NTX had an estimated 15.5 more days of opioid abstinence over 24 weeks and statistically significant at a 95 % confidence level based on the distribution of bootstrapped samples. We found that estimated ICERs to be > $500,000 per QALY for all stakeholder perspectives. For the abstinent-year effectiveness measure, we found XR-NTX before release to be cost-effective at a 95 % confidence level for willingness-to-pay values >$49,000 per abstinent-year, across all perspectives. ConclusionsXR-NTX administered to persons who are incarcerated with OUD before release may provide value for stakeholders and bridge a well-known treatment gap for this vulnerable population. Lower than expected participant engagement and missing data limit our results, and study outcomes may be sensitive to methods that address missing data if replicated.

Sex Differences in Comorbid Mental and Substance Use Disorders Among Primary Care Patients With Opioid Use Disorder.

The authors sought to characterize the 3-year prevalence of mental disorders and nonnicotine substance use disorders among male and female primary care patients with documented opioid use disorder across large U.S. health systems. This retrospective study used 2014-2016 data from patients ages ≥16 years in six health systems. Diagnoses were obtained from electronic health records or claims data; opioid use disorder treatment with buprenorphine or injectable extended-release naltrexone was determined through prescription and procedure data. Adjusted prevalence of comorbid conditions among patients with opioid use disorder (with or without treatment), stratified by sex, was estimated by fitting logistic regression models for each condition and applying marginal standardization. Females (53.2%, N=7,431) and males (46.8%, N=6,548) had a similar prevalence of opioid use disorder. Comorbid mental disorders among those with opioid use disorder were more prevalent among females (86.4% vs. 74.3%, respectively), whereas comorbid other substance use disorders (excluding nicotine) were more common among males (51.9% vs. 60.9%, respectively). These differences held for those receiving medication treatment for opioid use disorder, with mental disorders being more common among treated females (83% vs. 71%) and other substance use disorders more common among treated males (68% vs. 63%). Among patients with a single mental health condition comorbid with opioid use disorder, females were less likely than males to receive medication treatment for opioid use disorder (15% vs. 20%, respectively). The high rate of comorbid conditions among patients with opioid use disorder indicates a strong need to supply primary care providers with adequate resources for integrated opioid use disorder treatment.

Cost-Effectiveness of Extended-Release Injectable Naltrexone Among Incarcerated Persons with Opioid Use Disorder Before Release from Prison Versus after Release

Cost-Effectiveness of Extended-Release Injectable Naltrexone Among Incarcerated Persons with Opioid Use Disorder Before Release from Prison Versus after Release

EOSINOPHILIC PNEUMONIA AND EXTENDED-RELEASE INJECTABLE NALTREXONE

TOPIC: Lung Pathology TYPE: Medical Student/Resident Case Reports INTRODUCTION: Extended-release injectable naltrexone is an opioid antagonist approved for the treatment of alcohol and opioid dependence. Since the release of the drug in 2006, a literature review reveals five reported cases of drug-induced eosinophilic pneumonia. Our case highlights the clinical presentation of drug-induced eosinophilic pneumonia in the setting of extended-release injectable naltrexone. CASE PRESENTATION: A 35-year-old female with a past medical history lifelong tobacco use and alcohol dependence on extended-release injectable naltrexone presented to the ED with subjective fevers, myalgias, cough, and pleuritic chest pain. She was evaluated at urgent care two days prior and sent home on a course of Levofloxacin for bronchitis. Upon ED arrival, she was noted to be hypoxic and placed on supplemental oxygen. She was afebrile and tachycardic. Exam was pertinent for tachypnea and bilateral crackles. Initial laboratory data revealed WBC 19,500 (neutrophil predominate) and lactic acid 1.4. Chest x-ray and chest CT demonstrated extensive bilateral infiltrates. Empiric antibiotics were initiated while awaiting microbiology data. Due to escalating oxygen requirements and hemodynamic instability over the next 24 hours, the patient was intubated and bedside bronchoscopy was completed. BAL studies revealed lymphocyte predominance (46%) followed by eosinophils (27%) and neutrophils (21%). Given concern for acute eosinophilic pneumonia in the setting of extended-release injectable naltrexone, corticosteroids were started. Antibiotics were discontinued given negative culture data and our patient showed marked clinical improvement with continuation of steroid therapy. DISCUSSION: Extended-release injectable naltrexone is a long-acting opioid antagonist approved for the treatment of alcohol dependence. Clinical trials showed one diagnosed case & one suspected case of naltrexone-induced eosinophilic pneumonia. A current medical literature review reveals a paucity of cases associated with naltrexone and drug-induced AEP. While the etiology & pathogenesis remain largely unknown, it is thought to be related to an acute hypersensitivity reaction to an antigen in a genetically susceptible person. Progression from mild dyspnea to overt respiratory failure is rapid. Initial diagnostics are often nonspecific, however pleural fluid analysis demonstrates striking eosinophilia (10%-50%) and BAL fluid classically shows marked eosinophilia (25%-55%). Treatment includes supportive care, withdrawal of any eliciting medications, and glucocorticoid therapy. Most patients rapidly improve within 12-48 hours of initiation of corticosteroids. The prognosis for acute eosinophilic pneumonia is excellent with the vast majority of patients enjoying complete recovery. CONCLUSIONS: This case highlights the rare but important association between drug-induced eosinophilic pneumonia and extended-release injectable naltrexone. REFERENCE #1: Korpole PR, Al-Bacha S, Hamadeh S. A Case for Biopsy: Injectable Naltrexone-Induced Acute Eosinophilic Pneumonia. Cureus. 2020;12(9):e10221. Published 2020 Sep 3. doi:10.7759/cureus.10221 REFERENCE #2: Eosinophilic pneumonia induced by injectable naltrexone. Kim H, Ali M, Buch K. http://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2014.189.1_MeetingAbstracts.A2283 Am J Respir Crit Care Med. 2014;189:2283. REFERENCE #3: Saved by the BAL: a case of acute eosinophilic pneumonia after methyl-naltrexone injection. Esposito A, Lau B. Chest. 2019;156:2210. DISCLOSURES: No relevant relationships by Kari McCoy, source=Web Response No relevant relationships by Caroline Mears, source=Web Response No relevant relationships by Xian Qiao, source=Web Response

Buprenorphine Naloxone and Extended Release Injectable Naltrexone for the Treatment of Opioid Use Disorder Among a Veteran Patient Sample: A Retrospective Chart Review

Objective Previous research has demonstrated the effectiveness of both extended-release injectable naltrexone (XR-NTX) and buprenorphine/naloxone (BUP-NX) in the treatment of opioid use disorder (OUD). However, studies using real-world samples with multiple medical and psychiatric comorbidities are lacking. The study’s primary aims were to: (1) compare clinical presentations in an inclusive sample of OUD-diagnosed US military veterans receiving XR-NTX and BUP-NX, and (2) investigate differences in 90-day treatment outcomes between these two groups. Methods: The medical records of 79 patients receiving medications to treat OUD in a VA hospital’s addiction outpatient treatment program were reviewed retrospectively. The analysis included all veterans who initiated medication treatment during the study period. Differences between medication groups on co-occurring diagnoses, treatment retention, and related outcomes were examined. Results: The two groups were similar in medical and psychiatric comorbidity, although the BUP-NX group were more likely to have a pain diagnosis. No statistically significant differences in retention or toxicology results were found between the two groups over the 90-day study period. The rate of positive urine screens for the BUP-NX group was 19.2% for opiates and 13.5% for other illicit substances, and 3.7% and 11.1% respectively for the XR- NTX group. Conclusion: There was no evidence that 90-days outcomes differed for veterans based on medication received, and there were more similarities than differences in clinical characteristics. Additional research is needed, including larger sample size and prospective randomized control trial to evaluate VA patients’ treatment outcomes receiving BUP-NX or XR-NTX for OUD.

Economic Evaluations of Pharmacologic Treatment for Opioid Use Disorder: A Systematic Literature Review

ObjectiveThe crisis of opioid use puts a strain on resources in the United States and worldwide. There are 3 US Food and Drug Administration–approved medications for treatment of opioid use disorder: methadone, buprenorphine, and injectable extended-release naltrexone (XR-NTX). The comparative effectiveness and cost vary considerably among these 3 medications. Economic evaluations provide evidence that help stakeholders efficiently allocate scarce resources. Our objective was to summarize recent health economic evidence of pharmacologic treatment of opioid use disorder interventions. MethodsWe searched PubMed for peer-reviewed studies in English from August 2015 through December 2019 as an update to a 2015 review. We used the Drummond checklist to evaluate and categorize economic evaluation study quality. We summarized results by economic evaluation methodology and pharmacologic treatment modality. ResultsWe identified 105 articles as potentially relevant and included 21 (4 cost-offset studies and 17 cost-effectiveness/cost-benefit studies). We found strengthened evidence on buprenorphine and methadone, indicating that these treatments are economically advantageous compared with no pharmacotherapy, but found limited evidence on XR-NTX. Only half of the cost-effectiveness studies used a generic preference-based measure of effectiveness, limiting broad comparison across diseases/disorders. The disease/disorder-specific cost-effectiveness measures vary widely, suggesting a lack of consensus on the value of substance use disorder treatment. ConclusionWe found studies that provide new evidence supporting the cost-effectiveness of buprenorphine compared with no pharmacotherapy. We found a lack of evidence supporting superior economic value for buprenorphine versus methadone, suggesting that both are attractive alternatives. Further economic research is needed on XR-NTX, as well as other emerging pharmacotherapies, treatment modalities, and dosage forms.

Veteran adherence to oral versus injectable AUD medication treatment.

IntroductionAUD medication treatment has been shown to improve outcomes compared with placebo when confined to per-protocol analysis. The same outcomes, however, have not always been maintained in intent-to-treat analysis, thus suggesting adherence may have a significant impact on efficacy outcomes. There is conflicting evidence present in the literature comparing adherence to oral versus injectable AUD pharmacotherapy and a paucity of information in the veteran population on risk factors for low adherence.MethodsThe primary end point of this retrospective chart review was to determine whether adherence rates differ between oral and injectable AUD treatments in veterans during the first year of treatment (at 3, 6, 9, and 12 months) using the portion of days covered model. Secondary end points were to determine differing characteristics between patients with high versus low adherence and compare alcohol-related readmission rates and discontinuation rates between groups.ResultsAdherence to injectable extended-release (XR) naltrexone was significantly higher than oral naltrexone at all time points and was significantly higher than disulfiram at 3, 6, and 9 months, but it was not significantly different from acamprosate at any time point. At months 9 and 12, acamprosate had significantly higher adherence compared with oral naltrexone. Patients with higher adherence were seen more frequently in the mental health clinic and had previously tried more AUD medications. The discontinuation rates and alcohol-related admission rates were not significantly different between groups at 1 year.DiscussionXR naltrexone may improve adherence rates compared with oral naltrexone or disulfiram, but not acamprosate based on these outcomes. Patients may have increased adherence if they are seen more often in clinic and have trialed more AUD medications.

Assessment of Attitudes Towards Medication-Assisted Drug Treatment Options among an Incarcerated Population

ABSTRACT Medication-assisted treatment (MAT) is the state-of-the-art approach to treating opioid use disorder (OUD). Although OUD is prevalent among justice-involved populations, their attitudes toward MAT are largely unknown. Injectable extended release naltrexone (XR-NTX) is a MAT option, that is, unlike others, an opioid antagonist. We assess beliefs about XR-NTX as compared to methadone, a gold-standard pure opioid agonist MAT modality, in a sample of incarcerated men and women. Self-report data were collected from randomly selected adults (n = 1,570) residing in therapeutic communities (TCs) in 23 state correctional facilities. Distinct instruments addressed XR-NTX (n = 830) and methadone (n = 741). Prior knowledge and exposure to XR-NTX, and race, were significantly associated with positive beliefs about XR-NTX. Addiction history, race, beliefs about behavioral change, and a preference for injection over oral medications were positively associated with the average likelihood of opting for post-release XR-NTX treatment. Implications for health and correctional policy are discussed.

Cost-effectiveness of Treatments for Opioid Use Disorder

Opioid use disorder (OUD) is a significant cause of morbidity and mortality in the US, yet many individuals with OUD do not receive treatment. To assess the cost-effectiveness of OUD treatments and association of these treatments with outcomes in the US. This model-based cost-effectiveness analysis included a US population with OUD. Medication-assisted treatment (MAT) with buprenorphine, methadone, or injectable extended-release naltrexone; psychotherapy (beyond standard counseling); overdose education and naloxone distribution (OEND); and contingency management (CM). Fatal and nonfatal overdoses and deaths throughout 5 years, discounted lifetime quality-adjusted life-years (QALYs), and costs. In the base case, in the absence of treatment, 42 717 overdoses (4132 fatal, 38 585 nonfatal) and 12 660 deaths were estimated to occur in a cohort of 100 000 patients over 5 years, and 11.58 discounted lifetime QALYs were estimated to be experienced per person. An estimated reduction in overdoses was associated with MAT with methadone (10.7%), MAT with buprenorphine or naltrexone (22.0%), and when combined with CM and psychotherapy (range, 21.0%-31.4%). Estimated deceased deaths were associated with MAT with methadone (6%), MAT with buprenorphine or naltrexone (13.9%), and when combined with CM, OEND, and psychotherapy (16.9%). MAT yielded discounted gains of 1.02 to 1.07 QALYs per person. Including only health care sector costs, methadone cost $16 000/QALY gained compared with no treatment, followed by methadone with OEND ($22 000/QALY gained), then by buprenorphine with OEND and CM ($42 000/QALY gained), and then by buprenorphine with OEND, CM, and psychotherapy ($250 000/QALY gained). MAT with naltrexone was dominated by other treatment alternatives. When criminal justice costs were included, all forms of MAT (with buprenorphine, methadone, and naltrexone) were associated with cost savings compared with no treatment, yielding savings of $25 000 to $105 000 in lifetime costs per person. The largest cost savings were associated with methadone plus CM. Results were qualitatively unchanged over a wide range of sensitivity analyses. An analysis using demographic and cost data for Veterans Health Administration patients yielded similar findings. In this cost-effectiveness analysis, expanded access to MAT, combined with OEND and CM, was associated with cost-saving reductions in morbidity and mortality from OUD. Lack of widespread MAT availability limits access to a cost-saving medical intervention that reduces morbidity and mortality from OUD. Opioid overdoses in the US likely reached a record high in 2020 because of COVID-19 increasing substance use, exacerbating stress and social isolation, and interfering with opioid treatment. It is essential to understand the cost-effectiveness of alternative forms of MAT to treat OUD.

Recent Advances in the Treatment of Opioid Use Disorder.

Opioid use disorder (OUD) remains a national epidemic with an immense consequence to the United States' healthcare system. Current therapeutic options are limited by adverse effects and limited efficacy. Recent advances in therapeutic options for OUD have shown promise in the fight against this ongoing health crisis. Modifications to approved medication-assisted treatment (MAT) include office-based methadone maintenance, implantable and monthly injectable buprenorphine, and an extended-release injectable naltrexone. Therapies under investigation include various strategies such as heroin vaccines, gene-targeted therapy, and biased agonism at the G protein-coupled receptor (GPCR), but several pharmacologic, clinical, and practical barriers limit these treatments' market viability. This manuscript provides a comprehensive review of the current literature regarding recent innovations in OUD treatment.