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The formulation of microspheres involves a complex manufacturing process with multiple steps. Identifying the appropriate process parameters to achieve the desired quality attributes poses a significant challenge. This study aims to optimize the critical process parameters (CPPs) involved in the preparation of naltrexone microspheres using a Quality by Design (QbD) methodology. Additionally, the research aims to assess the drug release profiles of these microspheres under both in vivo and in vitro conditions. Critical process parameters (CPPs) and critical quality attributes (CQAs) were identified, and a Box-Behnken design was utilized to delineate the design space, ensuring alignment with the desired Quality Target Product Profile (QTPP). The investigated CPPs comprised polymer concentration, aqueous phase ratio to organic phase ratio, and quench volume. The microspheres were fabricated using the oil-in-water emulsion solvent extraction technique. Analysis revealed that increased polymer concentration was correlated with decreased particle size, reduced quench volume resulted in decreased burst release, and a heightened aqueous phase ratio to organic phase ratio improved drug entrapment. Upon analyzing the results, an optimal formulation was determined. In conclusion, the study conducted in vivo drug release testing on both the commercially available innovator product and the optimized test product utilizing an animal model. The integration of in vitro dissolution data with in vivo assessments presents a holistic understanding of drug release dynamics. The QbD approach-based optimization of CPPs furnishes informed guidance for the development of generic pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

AbstractStudies have demonstrated the benefits of LDN for various pain indications. This review describes the utilization of and response to LDN in patients with chronic pain within the William S. Middleton Memorial Veterans Hospital (Madison VA). This was a retrospective, single center, chart review of patients that were prescribed LDN for chronic pain. The primary outcome, change in subjective pain report via numeric rating scale (NRS), was analyzed through Wilcoxon Signed Rank Test and descriptive statistics. A total of 136 participants were included. Patients had an average pain score of 7.1 per NRS at baseline. At the initial follow up visit, participants had an average pain of 6.4 (p < 0.001). Additionally, 17.1% of patients had a greater than or equal to 30% pain reduction from baseline. At subsequent follow up, patients reported an average pain of 5.5 (p < 0.0001) per NRS. At the end of the study, 31.6% of patients were maintained on LDN at an average dose of 3.8 mg. This retrospective review demonstrated that LDN may be an effective modality for some chronic pain indications. Reported pain scores were significantly lower at initial follow up compared to baseline for the total population, and for patients with fibromyalgia (FM) specifically. [ABSTRACT FROM AUTHOR]

There have been no well-controlled and well-powered comparative trials of topiramate with other pharmacotherapies for alcohol use disorder (AUD), such as naltrexone. Moreover, the literature is mixed on the effects of two polymorphisms—rs2832407 (in GRIK1) and rs1799971 (in OPRM1)—on response to topiramate and naltrexone, respectively. The authors sought to examine the comparative effectiveness of topiramate and naltrexone in improving outcomes in AUD and to examine the role of the rs2832407 and rs1799971 polymorphisms, respectively, on response to these medications. In a 12-week, double-blind, placebo-controlled, randomized, multisite, genotype-stratified (rs2832407 and rs1799971) clinical trial comparing topiramate and naltrexone in treating AUD, 147 patients with AUD were randomly assigned to treatment with topiramate or naltrexone, stratified by genotype (rs2832407*CC and *AC/AA genotypes and rs1799971*AA and *AG/GG genotypes). The predefined primary outcome was number of heavy drinking days per week. Predefined secondary outcomes included standard drinks per drinking day per week, body mass index (BMI), craving, markers of liver injury, mood, and adverse events. For the number of heavy drinking days per week, there was a near-significant time-by-treatment interaction. For the number of standard drinks per drinking day per week, there was a significant time-by-treatment interaction, which favored topiramate. There were significant time-by-treatment effects, with greater reductions observed with topiramate than naltrexone for BMI, craving, and gamma-glutamyltransferase level. Withdrawal due to side effects occurred in 8% and 5% of the topiramate and naltrexone groups, respectively. Neither polymorphism showed an effect on treatment response. Topiramate is at least as effective and safe as the first-line medication, naltrexone, in reducing heavy alcohol consumption, and superior in reducing some clinical outcomes. Neither rs2832407 nor rs1799971 had effects on topiramate and naltrexone treatments, respectively. [ABSTRACT FROM AUTHOR]

A novel microparticle-based extended-release local anaesthetic containing a bupivacaine/poly-lactic-co-glycolic acid (PLGA; LIQ865A) or plain bupivacaine (LIQ865B) was examined in a first-in-human trial. The objectives were to examine the dose safety/tolerability and pharmacodynamics. Randomized subcutaneous injections of LIQ865A (n = 16) or LIQ865B (n = 12) and diluent, contralaterally, were administered in a dose-ascending manner (150- to 600-mg bupivacaine). Subjects were admitted 24 h post-injection and followed for 30 days post-injection. The risk ratios (RRs; 95% CI) of erythematous reactions for LIQ865A versus diluent was 9.00 (1.81-52.23; P = 0.006) and for LIQ865B versus diluent 2.50 (0.69-9.94; P = 0.37). The RR for the development of hematomas (LIQ865A versus diluent) were 3.25 (1.52-8.16; P = 0.004) and 4.00 (0.72-24.89; P = 0.32) (LIQ865B versus diluent). Subcutaneous indurations persisting for 4-13 weeks were seen in 6/16 subjects receiving LIQ865A. One subject receiving LIQ865A (600-mg bupivacaine) developed intermittent central nervous system (CNS) symptoms of local anaesthetic systemic toxicity (85 min to 51 h post-injection) coinciding with plasma peak bupivacaine concentrations (490-533 ng/ml). Both LIQ865 formulations demonstrated dose-dependent hypoesthesia and hypoalgesia. The duration of analgesia ranged between 37 and 86 h. The overall number of local adverse events, however, prohibits clinical application without further pharmacological modifications. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze the factors associated with concurrent alcohol, tobacco and illicit drug use among Brazilian schoolchildren aged 13-17. We conducted a cross-sectional study using data from the 2019 National School-Based Health Survey. The outcome was use of the three substances during the last 30 days. Hierarchical multiple logistic regression was carried out with independent variables grouped into four blocks: sociodemographic characteristics; family context; behavioral aspects; and stressors. Variables with p<0.05 were retained in the final model. The prevalence of concurrent substance use was 3.3%. Being male, living in the Midwest, South and Southeast, skipping school without parent permission, parents not knowing what their children do in their free time, having parents who smoke, having experienced physical aggression from parents, feeling that life is not worth living, trying drinking and illicit drugs before the age of 13, and having friends who drink alcohol, smoke and use drugs in their presence remained associated with the outcome in the final model. The findings reveal high prevalence of concurrent alcohol, cigarette and illicit drug use among adolescents and that poly use is associated with sociodemographic, family, and behavioral factors and stressors. [ABSTRACT FROM AUTHOR]

Objective: There is a lack of knowledge about the relative safety and efficacy of naltrexone for the treatment of pregnant individuals with opioid and/or alcohol use disorder, including the range of outcomes, in both the pregnant individual and the infant, over the course of peripartum period. Our objective was to describe these outcomes in a cohort of pregnant individuals on naltrexone. Methods: In this prospective case series, 7 pregnant individuals with opioid use disorder (OUD) or alcohol use disorder (AUD) treated with naltrexone were followed from pregnancy through 12 months after delivery. Clinical treatment protocols and outcomes related to safety and efficacy during pregnancy, delivery, and the postpartum period are described. Results: There were 4 pregnant individuals with OUD and 3 with AUD, of which 3 were managed with oral and 4 with extended-release naltrexone. The mean gestational age at study enrollment was 21.7 (SD, 12) weeks. Of the 7 participants, there was no return to nonprescribed opioid use and 2 who experienced a return to alcohol use over the course of the study. All individuals delivered vaginally at a mean of 37 weeks gestation without any peripartum pain difficulties. Five of the individuals (71.4%) remained on naltrexone 12 months after delivery. There were no reported fetal anomalies and one preterm delivery. None of the infants developed neonatal opioid withdrawal syndrome. Conclusions: For pregnant individuals with OUD or AUD treated with naltrexone, there were low rates of return to nonprescribed use and reassuring pregnant person and infant outcomes to 12 months postpartum. [ABSTRACT FROM AUTHOR]

The fourth Society for Academic Emergency Medicine (SAEM) Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE‐4) is on the topic of the emergency department (ED) management of nonopioid use disorders and focuses on alcohol withdrawal syndrome (AWS), alcohol use disorder (AUD), and cannabinoid hyperemesis syndrome (CHS). The SAEM GRACE‐4 Writing Team, composed of emergency physicians and experts in addiction medicine and patients with lived experience, applied the Grading of Recommendations Assessment Development and Evaluation (GRADE) approach to assess the certainty of evidence and strength of recommendations regarding six priority questions for adult ED patients with AWS, AUD, and CHS. The SAEM GRACE‐4 Writing Team reached the following recommendations: (1) in adult ED patients (over the age of 18) with moderate to severe AWS who are being admitted to hospital, we suggest using phenobarbital in addition to benzodiazepines compared to using benzodiazepines alone [low to very low certainty of evidence]; (2) in adult ED patients (over the age of 18) with AUD who desire alcohol cessation, we suggest a prescription for one anticraving medication [very low certainty of evidence]; (2a) in adult ED patients (over the age of 18) with AUD, we suggest naltrexone (compared to no prescription) to prevent return to heavy drinking [low certainty of evidence]; (2b) in adult ED patients (over the age of 18) with AUD and contraindications to naltrexone, we suggest acamprosate (compared to no prescription) to prevent return to heavy drinking and/or to reduce heavy drinking [low certainty of evidence]; (2c) in adult ED patients (over the age of 18) with AUD, we suggest gabapentin (compared to no prescription) for the management of AUD to reduce heavy drinking days and improve alcohol withdrawal symptoms [very low certainty of evidence]; (3a) in adult ED patients (over the age of 18) presenting to the ED with CHS we suggest the use of haloperidol or droperidol (in addition to usual care/serotonin antagonists, e.g., ondansetron) to help with symptom management [very low certainty of evidence]; and (3b) in adult ED patients (over the age of 18) presenting to the ED with CHS, we also suggest offering the use of topical capsaicin (in addition to usual care/serotonin antagonists, e.g., ondansetron) to help with symptom management [very low certainty of evidence]. [ABSTRACT FROM AUTHOR]

Background: From 2006 to 2014, alcohol‐related visits to the emergency department (ED) increased by 76% in the United States, highlighting the need for improved ED‐driven interventions addressing alcohol use disorder (AUD). Naltrexone is an FDA‐approved medication for AUD shown to decrease craving and self‐administration of alcohol. While oral naltrexone and extended‐release naltrexone have been long utilized in primary care and inpatient hospital settings, the use of naltrexone in the ED is limited. Methods: This study implemented and analyzed a multifaceted intervention regarding ED naltrexone prescribing at a large safety net, academic, urban hospital. A baseline assessment of preintervention conditions and perspectives on naltrexone prescribing was conducted through a chart review and standardized interviews with ED providers, respectively. The interview results guided design of interventions that addressed identified barriers. These included provider education, prescribing aids, and zero‐cost naltrexone tablets supplied by the ED pharmacy to patients upon discharge. Results: Between September 1, 2019, and August 31, 2020, of 753 unique patients who had a primary diagnosis or chief complaint containing the word "alcohol," only five (0.66%) were prescribed naltrexone. ED providers identified lack of training regarding naltrexone, lack of a prescribing protocol, and limited patient and provider education materials as barriers to prescribing naltrexone. Following the intervention, among 278 eligible patients, 11 oral naltrexone prescriptions were written (3.96%) between April 13, 2021, and August 1, 2021. This represents a sixfold increase over the preintervention period. Conclusions: An intervention to increase ED oral naltrexone prescriptions for AUD was successfully implemented, addressing lack of provider education, lack of prescribing resources, and patient barriers to accessing prescribed medications. Longer‐term follow‐up is needed to assess the efficacy and sustainability of these interventions. Nevertheless, ED clinicians are well positioned to initiate naltrexone prescriptions for patients presenting with AUD. [ABSTRACT FROM AUTHOR]

The article focuses on identifying barriers and facilitators perceived by patients regarding the initiation of naltrexone (NTX) treatment for alcohol use disorder (AUD) in the emergency department (ED). It aims to understand patient perspectives to improve the treatment pathway and address missed opportunities for AUD management in the ED setting.

Objectives: Alcohol‐related concerns commonly present to the emergency department (ED), with a subset of individuals experiencing the symptoms of an alcohol use disorder (AUD). As such, examining the efficacy of pharmacological anti‐craving treatment for AUD in the ED is of increasing interest. The objective of this systematic review was to evaluate the direct evidence assessing the efficacy of providing anti‐craving medications for AUD treatment in the ED. Methods: A systematic search was conducted according to the patient‐intervention‐control‐outcome question: (P) adults (≥18 years old) presenting to the ED with an AUD (including suspected AUD); (I) anti‐craving medications (i.e., naltrexone, acamprosate, gabapentin); (C) no prescription or placebo; (O) reduction of repeat ED visits, engagement in addiction services, reductions in heavy drinking days, reductions in any drinking and amount consumed (or abstinence), and in relapse. Two reviewers independently assessed articles for inclusion and conducted risk of bias assessments for included studies. Results: From 143 potentially relevant articles, 6 met inclusion criteria: 3 clinical trials, and 3 case studies. The clinical trials identified evaluated oral versus extended‐release naltrexone, monthly extended‐release naltrexone injections, and disulfiram. Both oral and extended‐release naltrexone resulted in decreased alcohol consumption. Monthly extended‐release naltrexone injections resulted in significant improvements in drinking and quality of life. Although out of scope, the disulfiram studies identified did not result in an improvement in drinking in comparison to no medication. Conclusions: Overall, there are few studies directly examining the efficacy of anti‐craving medications for AUD in the ED, although the limited evidence that exists is supportive of naltrexone pharmacotherapy, particularly extended‐release injection formulation. Additional randomized controlled trials are necessary for substantive direct evidence on anti‐craving medication initiation in the ED. [ABSTRACT FROM AUTHOR]

Objective: Alcohol use disorder (AUD) is a leading cause of preventable death and is a frequent diagnosis in the emergency department (ED). Treatment in the ED, however, typically focuses on managing the sequelae of AUD, such as acute withdrawal, rather than addressing the underlying addiction. For many patients, these ED encounters are a missed opportunity to connect with medication for AUD. In 2020, our ED created a pathway to offer patients with AUD treatment with naltrexone (NTX) during their ED visit. The aim of this study was to identify what barriers and facilitators patients perceive to NTX initiation in the ED. Methods: Adopting the theoretical framework of the behavior change wheel (BCW), we conducted qualitative interviews with patients to elicit their perspectives on ED initiation of NTX. Interviews were coded and analyzed using both inductive and deductive approaches. Themes were categorized according to patients' capabilities, opportunities, and motivations. Barriers were then mapped through the BCW to design interventions that will improve our treatment pathway. Results: Twenty‐eight patients with AUD were interviewed. Facilitators of accepting NTX included having recently experienced sequelae of AUD, rapid management of withdrawal symptoms by the ED provider, having a choice between intramuscular and oral formulations of the medication, and experiencing positive interactions in the ED that destigmatized the patient's AUD. Barriers to accepting treatment included lack of provider knowledge about NTX, dependence on alcohol as self‐treatment for psychiatric trauma and physical pain, perceived discriminatory treatment and stigma about AUD, aversion to potential side effects, and lack of access to continued treatment. Conclusions: Initiation of treatment of AUD with NTX in the ED is acceptable to patients and can be facilitated by knowledgeable ED providers who create a destigmatizing environment, effectively manage withdrawal symptoms, and connect patients to providers who will continue treatment. [ABSTRACT FROM AUTHOR]

Cognitive impairments, common sequelae of acquired brain injury (ABI), significantly affect rehabilitation and quality of life. Currently, there is no solid evidence‐base for pharmacotherapy to improve cognitive functioning after ABI, nevertheless off‐label use is widely applied in clinical practice. This meta‐analysis and meta‐regression aims to quantitatively aggregate the available evidence for the effects of pharmacological agents used in the treatment of cognitive impairments following ABI. We conducted a comprehensive search of Embase, Medline Ovid, and Cochrane Controlled Trials Register databases for randomized controlled and crossover trials. Meta‐analytic effects were calculated for each pharmaceutical agent and targeted neuromodulator system. Cognitive outcome measures were aggregated across cognitive domains. Of 8,216 articles, 41 studies (4,434 patients) were included. The noradrenergic agent methylphenidate showed a small, significant positive effect on cognitive functioning in patients with traumatic brain injury (TBI; k = 14, d = 0.34, 95% confidence interval: 0.12–0.56, P = 0.003). Specifically, methylphenidate was found to improve cognitive functions related to executive memory, baseline speed, inhibitory control, and variability in responding. The cholinergic drug donepezil demonstrated a large effect size, albeit based on a limited number of studies (k = 3, d = 1.68, P = 0.03). No significant effects were observed for other agents. Additionally, meta‐regression analysis did not identify significant sources of heterogeneity in treatment response. Our meta‐analysis supports the use of methylphenidate for enhancing cognitive functioning in patients with TBI. Although donepezil shows potential, it warrants further research. These results could guide clinical decision making, inform practice guidelines, and direct future pharmacotherapeutic research in ABI. [ABSTRACT FROM AUTHOR]

Opioid use disorder (OUD) is a chronic relapsing disorder that is a major burden for the lives of affected individuals, and society as a whole. Opioid withdrawal is characterized by strong physical symptoms, along with signs of negative affect. Negative affect due to opioid withdrawal is a major obstacle to recovery and relapse prevention. The mechanisms behind negative affect due to either spontaneous or antagonist-precipitated opioid withdrawal are not well known, and more animal models need be developed. Here, we present behavioral models of negative affect upon naloxone-precipitated morphine withdrawal in adult male mice. Social, anxiety, and despair-like deficits were investigated following naloxone administration in mice receiving morphine under three dosing regimens; acute, chronic constant dose and chronic escalating doses. Social behaviour in the three-chamber social preference test was decreased following withdrawal from chronic and escalating but not acute morphine. Anxiety-like behaviour in the open field was increased for all three treatments. Despair-like behaviour was increased following withdrawal from chronic and escalating but not acute morphine. Altogether, these animal models will contribute to study behavioural and neuronal circuitries involved in the several negative affective signs characterizing OUD. [ABSTRACT FROM AUTHOR]

Background: Considering the conflicting effects of bupropion on parameters related to metabolic syndrome including glucose metabolism and lipid profile, in this meta‐analysis study, we investigated the effects of this drug alone or in combination with naltrexone on glucose metabolism and lipid profile. Methods: Scopus, PubMed/Medline, Web of Science and Embase databases were searched using standard keywords to identify all controlled trials investigating effects of bupropion alone and combined with naltrexone on the glucose and lipid profile. Pooled weighted mean difference and 95% confidence intervals were achieved by random‐effects model. Results: Twelve studies with 5152 participants' were included in this article. The pooled findings showed that bupropion alone or in combination with naltrexone would significantly reduce glucose (weighted mean difference (WMD): −2.25 mg/dL, 95% confidence interval (CI): −4.10, −0.40), insulin (WMD: −4.06 μU/mL, 95% CI: −6.09, −2.03), homeostatic model assessment for insulin resistance (HOMA‐IR) (WMD: −0.58, 95% CI: −0.98, −0.19), triglyceride (TG) (WMD: −11.78 mg/dL, 95% CI: −14.48 to −9.08) and increase high‐density lipoprotein (HDL) (WMD: 2.68 mg/dL, 95% CI: 2.13 to 3.24). A Greater reduction in glucose levels was observed with duration >26 weeks. Dose of bupropion intake ≤360 mg and intervention for more than 26 weeks decreased insulin level significantly. With regard to lipid profile, reduction of triglycerides is more significant with dose of bupropion greater than 360 mg and a shorter intervention length equal to 26 weeks. Conclusions: The addition of combination therapies such as bupropion and naltrexone to lifestyle modification can significantly improve glucose metabolism and some lipid parameters. [ABSTRACT FROM AUTHOR]

Background: Cancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the pharmacological agents relative to each other is still unclear. Therefore, medications that may potentially contribute to improving CRF will be investigated in this head-to-head trial. Our main objective is to compare the efficacy of methylphenidate vs. bupropion vs. ginseng vs. amantadine vs. placebo in patients with advanced cancer. Methods: The 5-EPIFAT study is a 5-arm, randomized, multi-blind, placebo-controlled, multicenter trial that will use a parallel-group design with an equal allocation ratio comparing the efficacy and safety of four medications (Methylphenidate vs. Bupropion vs. Ginseng vs. Amantadine) versus placebo for management of CRF. We will recruit 255 adult patients with advanced cancer who experience fatigue intensity ≥ 4 based on a 0–10 scale. The study period includes a 4-week intervention and a 4-week follow-up with repeated measurements over time. The primary outcome is the cancer-related fatigue level over time, which will be measured by the functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. To evaluate safety, the secondary outcome is the symptomatic adverse events, which will be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in cancer clinical trials (PRO-CTCAE). Also, a subgroup analysis based on a decision tree-based machine learning algorithm will be employed for the clinical prediction of different agents in homogeneous subgroups. Discussion: The findings of the 5-EPIFAT trial could be helpful to guide clinical decision-making, personalization treatment approach, design of future trials, as well as the development of CRF management guidelines. Trial registration: IRCT.ir IRCT20150302021307N6. Registered on 13 May 2023. [ABSTRACT FROM AUTHOR]

Problematic pornography use remains a debatable entity, with features overlapping behavioral addictions and impulse control disorders. The controversial nosological status also provides challenges in formulating management plans as there exists no proven pharmacotherapy. We reviewed the bio-physiological basis and available evidence for naltrexone for the management of pornography addiction. Evidence supporting naltrexone as a standalone or adjunctive treatment in pornography addiction is limited. The case report suggesting positive outcomes represents a heterogeneous clinical entity and thus cannot be generalized. More rigorous clinical trials are needed to establish naltrexone's efficacy in the management of problematic pornography use. [ABSTRACT FROM AUTHOR]

A large body of research demonstrates the safety and efficacy of medication for opioid use disorder to reduce opioid misuse and related harms. However, stigma is a substantial barrier to broader use of these medications. This endpage reviews the impact of stigma toward medication for opioid use disorder on treatment access, uptake, retention, and outcomes. I then suggests areas for future research and social change. As one of the primary service providers for people with opioid use disorder, social workers should be at the forefront of efforts to destigmatize medication treatments. Social workers are well positioned to address the consequences of stigma toward medication for opioid use disorder through research, education, practice, and systems change. VIDEO ABSTRACT SCRIPT Methadone, buprenorphine, and extended-release naltrexone, the three FDA-approved medications for opioid use disorder, are among the most powerful tools we have in our fight against the rising drug overdose crisis. A large body of research demonstrates the safety and efficacy of these medications to reduce opioid cravings, improve treatment outcomes, and prevent overdose death. However, stigma is a major barrier to their use. Despite a strong evidence base, medications for opioid use disorder are commonly viewed as ineffective and illegitimate treatments that simply 'substitute one drug for another.' Stigma is encoded in stringent laws and regulations which limit access to medication. For people with opioid use disorder, stigma can influence beliefs about medications and affect the likelihood that one will initiate and maintain treatment. Stigma also erodes self-esteem and social support, two important predictors for recovery outcomes. In this way, stigma toward medications for opioid use disorder has become a pressing social justice issue. As one of the primary service providers for people with opioid use disorder, social workers should be at the forefront of efforts to destigmatize medication treatments. This endpage is a call to action for social workers to address stigma toward medication treatments through research, education, practice, and systems change. [ABSTRACT FROM AUTHOR]

Abstract The aim of this study is to determine if extended‐release, bioabsorbable, subcutaneous naltrexone (NTX) implants can mitigate respiratory depression after an intravenous injection (IV) of fentanyl. Six different BIOabsorbable Polymeric Implant Naltrexone (BIOPIN) formulations, comprising combinations of Poly‐d,l‐Lactic Acid (PDLLA) and/or Polycaprolactone (PCL‐1 or PCL‐2), were used to create subcutaneous implants. Both placebo and naltrexone implants were implanted subcutaneously in male dogs. The active naltrexone implants consisted of two doses, 644 mg and 1288 mg. A challenge with IV fentanyl was performed in 33 male dogs at 97–100 days after implantation. Following the administration of a 30 μg/kg intravenous fentanyl dose, the placebo cohort manifested a swift and profound respiratory depression with a ~50% reduction in their pre‐dose respiratory rate (RR). The BIOPIN NTX‐implanted dogs were exposed to escalating doses of intravenous fentanyl (30 μg/kg, 60 μg/kg, 90 μg/kg, and 120 μg/kg). In contrast, the dogs implanted with the BIOPIN naltrexone implants tolerated doses up to 60 μg/kg without significant respiratory depression (

Cirrhosis is the consequence of chronic liver injury Considering the crucial role of oxidative stress in the progression of liver cirrhosis, we aimed to investigate the ameliorative effect of NTX against oxidative stress in carbon tetrachloride (CCl4)-induced cirrhotic rats. Eighty-four male Wistar rats were randomly assigned into 4 groups (21 rats /group I) receiving CCl4; (II) NTX+CCl4; (III) mineral oil (M) (as the control); (IV) NTX+M. The animals in each group were sacrificed in 3 different time-points 2 weeks, 6 weeks (early cirrhosis) and 8 weeks (advanced cirrhosis). Liver function tests, NO metabolites, GSH level, as well as the activity of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxides (GPX), and hexokinase (HK) were assessed. NTX was able to ameliorate liver injury, revealed by attenuation of ALT activity, which was significantly enhanced due to cirrhosis induction, as well as pathological evaluation. HK was also increased significantly after treatment with CCl₄ while NTX moderated this increase. Although CCl4 treatment did not have a significant effect on GSH levels, NTX was able to considerably increase GSH in blood. The activity of CAT and SOD as well as NO levels were all augmented by NTX in CCl4-treated rats. Naltrexone demonstrates antioxidative effects in liver cirrhosis and may confer a protective effect against hepatic cirrhosis through modulation of oxidative stress.

Background & Aims: Treatment of alcohol use disorder (AUD) improves survival in patients with alcohol-related cirrhosis. However, medications for alcohol use disorder (MAUD) are underutilized in this population, partially due to concerns regarding drug-induced liver injury (DILI). Our aim was to evaluate the safety of naltrexone in patients with cirrhosis. Methods: This was a retrospective study of patients with cirrhosis who were prescribed naltrexone using the VOCAL (Veterans Outcomes and Costs Associated with Liver Disease) database. Patients with new initiation of naltrexone after diagnosis of cirrhosis who had liver enzymes checked within a 3-month time frame were included. A chart review was performed on patients who developed alanine aminotransferase or alkaline phosphatase elevations to more than 2× or 5× the upper limit of normal, respectively. The RUCAM (Roussel Uclaf causality assessment method) was used to determine if DILI occurred. Results: A total of 3,285 patients with cirrhosis were initiated on naltrexone, of whom 2,940 had laboratory testing during the high-risk DILI period. Only 2% of patients had liver enzyme elevations, and among those, 30 (48%) were classified as “DILI excluded” and 32 (52%) were classified as “DILI unlikely”. No patients were classified as possible, probable, or highly probable DILI. No deaths or new decompensations were attributed to naltrexone. Conclusions: Naltrexone in patients with cirrhosis was not associated with development of DILI using RUCAM scoring. Naltrexone appears to be safe in patients with compensated and decompensated cirrhosis. Impact and Implications: Naltrexone is an effective medication for treating alcohol use disorder but is underutilized in patients with underlying liver disease due to historical concerns regarding hepatotoxicity. This retrospective study shows no drug-induced liver injury in a large cohort of patients with cirrhosis with new initiation of naltrexone. This study may encourage providers to prescribe naltrexone to patients with existing liver disease with ongoing alcohol use disorder.

ObjectiveThe authors sought to determine the efficacy of targeted naltrexone in sexual and gender minority men (SGM) who binge drink and have mild to moderate alcohol use disorder.MethodsIn a double-blind placebo-controlled trial, a total of 120 SGM who binge drink and have mild to moderate alcohol use disorder were randomized in a 1:1 ratio to receive targeted oral naltrexone (50 mg) or placebo with weekly counseling for 12 weeks. The study's primary endpoints were binge-drinking intensity, defined as 1) number of drinks in the past 30 days; 2) any binge drinking in the past week; 3) number of binge-drinking days in the past week; and 4) number of drinking days in the past week. The study also measured changes in alcohol use with two alcohol biomarker measures: ethyl glucuronide in urine samples and phosphatidylethanol (PEth) in dried blood spot samples.ResultsNinety-three percent completed the trial, with 85% of weekly follow-up visits completed. In intention-to-treat analyses, naltrexone was associated with a significantly reduced reported number of binge-drinking days (incidence rate ratio [IRR]=0.74, 95% CI=0.56, 0.98; number needed to treat [NNT]=2), weeks with any binge drinking (IRR=0.83, 95% CI=0.72, 0.96; NNT=7.4), number of drinks per month (IRR=0.69, 95% CI=0.52, 0.91; NNT=5.7 for 10 drinks), and alcohol craving scores (coefficient=-9.25, 95% CI=-17.20, -1.31). In as-treated analyses among those who took their medication on average at least 2.5 days per week (the median frequency in the study), naltrexone reduced any binge drinking (IRR=0.84, 95% CI=0.71, 0.99), number of binge-drinking days (IRR=0.67, 95% CI=0.47, 0.96), and PEth concentrations (coefficient=-55.47, 95% CI=-110.75, -0.20). At 6 months posttreatment, naltrexone had sustained effects in number of drinks per month (IRR=0.69, 95% CI=0.50, 0.97), number of binge-drinking days (IRR=0.67, 95% CI=0.47, 0.95), and any binge drinking in the past week (IRR=0.79, 95% CI=0.63, 0.99).ConclusionsTargeted naltrexone significantly reduced drinking outcomes among SGM with mild to moderate alcohol use disorder during treatment, with sustained effects at 6 months posttreatment. Naltrexone may be an important pharmacotherapy to address binge drinking in populations with mild to moderate alcohol use disorder.

BackgroundAlcohol use disorder (AUD) is ubiquitous and its sequelae contribute to high levels of healthcare utilization, yet AUD remains undertreated. The ED encounter represents a missed opportunity to initiate medication assisted treatment (MAT) for patients with AUD. The aims of this study are to identify barriers and facilitators to the treatment of AUD in the ED, and to design interventions to address identified barriers.MethodsUsing an implementation science approach based on the Behavior Change Wheel framework, we conducted qualitative interviews with staff to interrogate their perspectives on ED initiation of AUD treatment. Subjects included physicians, nurses, nurse practitioners, clinical social workers, and pharmacists. Interviews were thematically coded using both inductive and deductive approaches and constant comparative analysis. Themes were further categorized as relating to providers' capabilities, opportunities, or motivations. Barriers were then mapped to corresponding intervention functions.ResultsFacilitators at our institution included time allotted for continuing education, the availability of clinical social workers, and favorable opinions of MAT based on previous experiences implementing buprenorphine for opioid use disorder. Capability barriers included limited familiarity with naltrexone and difficulty determining which patients are candidates for therapy. Opportunity barriers included the limited supply of naltrexone and a lack of clarity as to who should introduce naltrexone and assess readiness for change. Motivation barriers included a sense of futility in treating patients with AUD and stigmas associated with alcohol use. Evidence-based interventions included multi-modal provider education, a standardized treatment algorithm and order set, selection of clinical champions, and clarification of roles among providers on the team.ConclusionsA large evidence-practice gap exists for the treatment of AUD with Naltrexone, and the ED visit is a missed opportunity for intervention. ED providers are optimistic about implementing AUD treatment in the ED but described many barriers, especially related to knowledge, clarification of roles, and stigma associated with AUD. Applying a formal implementation science approach guided by the Behavior Change Wheel allowed us to transform qualitative interview data into evidence-based interventions for the implementation of an ED-based program for the treatment of AUD.

Victor Koltenyuk,1 Ismat Mrad,2 Ian Choe,1 Mohamad Ibrahim Ayoub,3 Sangeeta Kumaraswami,4 Jeff L Xu4 1School of Medicine, New York Medical College, Valhalla, NY, USA; 2Anesthesiology and Perioperative Medicine, University of Rochester, Rochester, NY, USA; 3Department of Anesthesiology, New York University Grossman School of Medicine, New York, NY, USA; 4Department of Anesthesiology, Westchester Medical Center/New York Medical College, Valhalla, NY, USACorrespondence: Jeff L Xu, Department of Anesthesiology, Westchester Medical Center/New York Medical College, 100 Woods Road, Valhalla, NY, 10595, USA, Tel +1 914 493 7693, Fax +1 914 493 7927, Email jeff.xu@wmchealth.orgAbstract: The opioid epidemic in the United States has led to an increasing number of pregnant patients with opioid use disorder (OUD) presenting to obstetric units. Caring for this complex patient population requires an interdisciplinary approach involving obstetricians, anesthesiologists, addiction medicine physicians, psychiatrists, and social workers. The management of acute pain in the parturient with OUD can be challenging due to several factors, including respiratory depression, opioid tolerance, and opioid-induced hyperalgesia. Patients with a history of OUD can present in one of three categories: 1) those with untreated OUD; 2) those who are currently abstinent from opioids; 3) those being treated with medications to prevent withdrawal. A patient-centered, multimodal approach is essential for optimal peripartum pain relief and prevention of adverse maternal and neonatal outcomes. Medications for opioid use disorder (MOUD), previously referred to as medication-assisted therapy (MAT), include opioids like methadone, buprenorphine, and naltrexone. These are prescribed for pregnant patients with OUD, but appropriate dosing and administration of these medications are critical to avoid withdrawal in the mother. Non-opioid analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) can be used in a stepwise approach, and regional techniques like neuraxial anesthesia and truncal blocks offer opioid-sparing options. Other medications like ketamine, clonidine, dexmedetomidine, nitrous oxide, and gabapentinoids show promise for pain management but require further research. Overall, a comprehensive pain management strategy is essential to ensure the well-being of both the mother and the fetus in pregnant patients with OUD.Keywords: opioids, pregnancy, buprenorphine, methadone, naltrexone

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Semaglutide (Ozempic, Wegovy), a medication for type 2 diabetes that has also been popular with people trying to lose weight because it decreases appetite, has been shown to reduce the desire to drink, which has raised interest in the use of the drug to treat alcohol use disorder (AUD). A recent study, "Associations of semaglutide with incidence and recurrence of alcohol use disorder in real‐world population," based on 83,825 patients with obesity, has found that these patients reduced their risk of AUD incidence or recurrence by 50%–56%. The study, published in the May issue of Nature Communications, found that consistent reductions were seen for a 12‐month period. The findings provide evidence of the potential benefit of these drugs, now commonly called weight‐loss drugs, to treat AUD, and the researchers (lead author William Wang, second author Nora D. Volkow, M.D., director of the National Institute on Drug Abuse) have called for clinical trials. [ABSTRACT FROM AUTHOR]

The article discusses the medical use of ethanol in patients with alcohol use disorder. It highlights the prevalence of alcohol-related deaths and the challenges faced by healthcare professionals in treating these patients. The historical approach to treating alcohol withdrawal is explored, as well as the physiological explanation for the limitations of benzodiazepines in treating withdrawal symptoms. The ethics of forced detoxification are also discussed, and the article suggests harm-reduction strategies as an alternative to a zero-tolerance approach. The article concludes by presenting a retrospective review that suggests the potential benefits of medically supervised ethanol use in certain practice models. [Extracted from the article]