Real-world efficacy and safety of naltrexone-bupropion therapy in Chinese patients with obesity: A single-centre experience.

PURPOSE: Naltrexone-bupropion (Contrave®) has shown efficacy and safety in large randomised controlled trials, predominantly comprising Caucasians. Data are limited in Asian populations. We carried out a retrospective matched cohort study of Chinese patients with obesity to evaluate the efficacy and safety of naltrexone-bupropion in real-world clinical practice. METHODS: We performed a retrospective matched cohort study of Chinese patients with obesity managed in the Obesity Clinic of Queen Mary Hospital in Hong Kong between 1 January 2016 and 31 December 2020. Electronic health records of patients treated with naltrexone-bupropion were retrieved for body weight and height, obesity-related metabolic parameters, and adverse events over a 12-month period. Age- and sex-matched controls from the Obesity Clinic who were only on self-directed lifestyle management were identified for comparison of weight changes. General linear models were used to analyse the change in body weight over 12 months. RESULTS: Thirty-seven patients treated with naltrexone-bupropion were included (mean age 42.2 ± 8.4 years, 54.1% men, baseline body mass index 37.3 ± 4.6 kg/m2), and 37 age- and sex-matched controls were included. Among the 37 naltrexone-bupropion-treated patients, the mean weight loss was 9.2 ± 5.2% at 6 months and 9.7 ± 8.1% at 12 months, which were significantly more than in controls (p < 0.001). Improvements in the obesity-related parameters were observed in association with weight loss over 12 months. Ten patients (27.0%) discontinued naltrexone-bupropion due to side effects, mainly neurological and gastrointestinal manifestations, within the first 12 months. CONCLUSION: We demonstrated real-world efficacy and safety of naltrexone-bupropion among Chinese patients with obesity.

Weight Loss Therapies and Hypertension Benefits.

Obesity and hypertension have become an international health issue, with detrimental consequences on patients. Obesity and hypertension share common pathophysiological mechanisms, such as overactivity of the renin-angiotensin-aldosterone and the sympathetic nervous systems, insulin resistance, and disruption of the leptin pathway. Approved therapies for obesity and overweight include phentermine/topiramate, orlistat, naltrexone/bupropion, the glucagon-like peptide-1 receptor agonists liraglutide and semaglutide, tirzepatide, and bariatric surgery. This review gives the clinical data in a thorough manner and explains in detail how each of the previously mentioned therapies affects blood pressure levels.

Correlates of post-hospitalization naltrexone adherence for alcohol use disorder.

INTRODUCTION: Hospitalizations present an opportunity to initiate naltrexone for patients with alcohol use disorder (AUD). Understanding factors associated with post-hospitalization adherence could inform practice. METHODS: This study is a secondary analysis of a clinical trial in which patients with AUD were randomized to oral (PO) versus long-acting injectable (LAI) naltrexone at hospital discharge. The outcome of this secondary analysis was naltrexone adherence 3 months after discharge, defined as receipt of at least 2 out of 3 monthly injections or the equivalent days of self-reported PO medication use (60 out of 90). We used baseline socio-demographics, substance use history, health status, healthcare utilization, and randomization arm to construct multivariable logistic regression models to identify correlates of adherence. RESULTS: We evaluated patients who initiated naltrexone treatment, 124 randomized to PO and 120 to LAI (overall mean age 49 years, 80 % male, 51 % Black, 47 % unhoused, and 91 % with severe AUD). At 3 months, 50 % of patients were adherent. LAI naltrexone (aOR 3.88; 95 % CI 2.17-7.13), recent office visit (aOR 2.01; 95 % CI 1.10-3.72), and age (aOR per 10-year increase 1.37; 95 % CI 1.02-1.88) were associated with increased odds of adherence. Unhoused status (aOR 0.54; 95 % CI 0.30-0.98) and cocaine use (aOR 0.35; 95 % CI 0.17-0.71) were associated with decreased odds of adherence. CONCLUSIONS: LAI naltrexone for AUD at hospital discharge was associated with better adherence at 3 months vs PO. Access to LAI naltrexone and targeted interventions for patients with cocaine use or who are unhoused hold potential to improve naltrexone adherence.

Naltrexone and its Effects on Craving and Alcohol Use among Patients with Alcohol Dependence Syndroms: A Report.

Background: Naltrexone is a Food and Drug Administration (FDA)-approved anti-craving agent for the long-term treatment of alcohol dependence syndrome (ADS). However, it may not be equally effective in all patients. This study aims to assess naltrexone treatment response over four weeks in a national-level tertiary care setting. Methods: Male patients with ADS (n=100) who were initiated on naltrexone were included in the study. The clinical data, including the drinking pattern and craving, were recorded at baseline. At the end of the one-month follow-up, the drinking status and compliance with naltrexone were recorded. Findings: At the end of one month, more than half of the patients (n=53) were retained in the study. All the treatment-retained patients (n=53) reported naltrexone consumption for more than 24 days in the last month. Those who retained in the study reported significantly less craving among 72% of patients, while an almost 50% reduction in alcohol use was observed. Conclusion: This study adds to the evidence of outcomes with naltrexone in terms of reduced craving and alcohol use.

The Pre-Operative Evaluation Clinic: An Underutilized Service in Optimizing Analgesic Outcomes in Patients on Buprenorphine, Methadone, and Naltrexone for Substance Use Disorder or Chronic Pain.

Background: Patients receiving methadone, buprenorphine, and naltrexone for either chronic pain or substance use disorder (SUD) pose perioperative challenges. Due to their complex pharmacology, perioperative recommendations continue to evolve. Deviations from these recommendations may result in worse perioperative outcomes. A formal preoperative evaluation (POE) and optimization of patients on these medications are recommended to address these concerns. Methods: A single-center retrospective electronic health record review was performed with adult patients on methadone, buprenorphine, and naltrexone undergoing elective surgery between January 1, 2010 and December 31, 2020. The primary outcome of interest was the percentage of patients referred to the POE clinic for evaluation prior to the scheduled elective surgery. In addition, we assessed differences in variables (perioperative opioid, hospital length of stay, perioperative multimodal analgesics, perioperative complications, inpatient pain service consult, readmission within 30 days, cancellation of surgery, addiction medicine consult) based on POE clinic evaluation. This analysis was performed separately for patients prescribed these medications for SUD versus chronic pain. Continuous outcomes were analyzed using linear regression with generalized estimating equations (GEE) and robust variance estimates. Results: A total of 714 patients were included in the final analysis, of which 572 (80%) took buprenorphine, methadone, or naltrexone for chronic pain and 142 (20%) took these medications for SUD. Within the chronic pain and SUD subpopulations, 193 (34%) and 35 (25%) patients had formal POE clinic assessments, respectively. Among those taking these medications for chronic pain, POE clinic evaluation was associated with a higher likelihood for receiving non-opioid multimodal analgesics perioperatively (p = 0.016). Conclusion: Formal preoperative evaluations are currently underutilized in patients who take buprenorphine, methadone, or naltrexone for chronic pain or SUD. These patients may benefit from POE clinic assessment to optimize perioperative outcomes.

Alcohol pharmacotherapy dispensing trends in Australia between 2006 and 2023.

AIMS: This study aimed to investigate acamprosate and naltrexone dispensing patterns in Australia. METHODS: A 10% representative sample of medications subsidized by the Australian Pharmaceutical Benefits Scheme (PBS) was used to identify individuals who were dispensed naltrexone or acamprosate between January 2006 and December 2023. Data were used to examine concurrent dispensing, medication switching and treatment episode length, as well as changes in prevalence and incidence over time. RESULTS: During the study, we identified 22 745 individuals with a total of 117 548 dispensed prescriptions (45.3% naltrexone, 43.0% acamprosate, and 11.7% concurrent dispensing). Alcohol pharmacotherapy dispensing occurred in 1354 per 100 000 individuals. It is estimated that 2.9% of individuals with an alcohol use disorder in Australia are receiving a PBS-listed pharmacological treatment. For both pharmacotherapies, individuals were most likely to be male (60.0%) and 35-54 years of age (56.0%). Individuals were more likely to switch from acamprosate to naltrexone rather than the reverse. From 2006 and 2023, the number of prevalent individuals treated with an alcohol pharmacotherapy significantly increased, driven mainly the use of naltrexone, which more than doubled over the study period. Incident naltrexone-treated individuals were more likely to remain on treatment for the recommended minimum 3-month period compared to acamprosate treated individuals, although overall dispensing for at least 3 months was low (5.1%). CONCLUSIONS: In Australia between 2006 and 2023, rates of naltrexone dispensing have substantially increased, while acamprosate dispensing showed minimal changes. However, the use of alcohol pharmacotherapies remains low compared with the likely prevalence of alcohol use disorders.

An eco-friendly smartphone based HPTLC method versus conventional densitometric one for determination of Naltrexone and Bupropion.

The rapid uprising technologies of smartphone applications and software introduced a new era for analytical detection techniques. It has transformed bench-top laboratory methods into simpler ones depending on cost-effective, portable, and widely accessible devices. In this work, two high performance thin layer chromatographic (HPTLC) methods were developed based on smartphone's camera detection and either ImageJ desktop software or Color-Picker smartphone's application as alternative techniques to conventional densitometric detection. A mixture of Naltrexone hydrochloride (NAL) and Bupropion hydrochloride (BUP) was chromatographed on HPTLC- plates using ethyl acetate, methanol, acetone, and glacial acetic acid (3:6:1:0.5, by volume) as a developing system. The developed plates were scanned at 203 nm for the densitometric analysis, then visualized by modified Dragendorff's reagent and shot by a smartphone's camera. The captured images were uploaded to either ImageJ software or Color-Picker application to detect the separated spots. The results derived from the three detection methods were compared over the concentration range of 0.4-24 & 0.6-18 µg/band for the densitometric method, 0.4-24 & 2-24 µg/band for ImageJ built method and 0.8-20 & 5-20 µg/band for Color Picker built method for NAL and BUP, respectively. The methods were found to be appropriate for assaying both active drug substances in pure forms and combined in marketed pharmaceutical formulations. The excellent sustainability of densitometric and ImageJ-based methods enabled also the assessment of their dosage form content uniformity. The greenness and sustainability of the methods were assessed by three metric tools, namely Green Analytical Procedure Index (GAPI), Analytical GREEnness Metric Approach (AGREE), and White Analytical Chemistry (WAC). The assessments results confirmed the sustainability and superiority of the proposed methods in terms of sample treatment, waste mount, energy consumption, cost, and number of analyzed samples per an hour.

Naltrexone augmented with prazosin for alcohol use disorder: results from a randomized controlled proof-of-concept trial.

AIMS: We conducted a proof-of-concept randomized controlled trial of the mu-opioid receptor antagonist, naltrexone, augmented with the alpha-1 adrenergic receptor antagonist, prazosin, for alcohol use disorder in veterans. We sought a signal that the naltrexone plus prazosin combination regimen would be superior to naltrexone alone. METHODS: Thirty-one actively drinking veterans with alcohol use disorder were randomized 1:1:1:1 to naltrexone plus prazosin (NAL-PRAZ [n = 8]), naltrexone plus placebo (NAL-PLAC [n = 7]), prazosin plus placebo (PRAZ-PLAC [n = 7]), or placebo plus placebo (PLAC-PLAC [n = 9]) for 6 weeks. Prazosin was titrated over 2 weeks to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS. Naltrexone was administered at 50 mg QD. Primary outcomes were the Penn Alcohol Craving Scale (PACS), % drinking days (PDD), and % heavy drinking days (PHDD). RESULTS: In the NAL-PRAZ condition, % reductions from baseline for all three primary outcome measures exceeded 50% and were at least twice as large as % reductions in the NAL-PLAC condition (PACS: 57% vs. 26%; PDD: 51% vs. 22%; PHDD: 69% vs. 15%) and in the other two comparator conditions. Standardized effect sizes between NAL-PRAZ and NAL-PLAC for each primary outcome measure were >0.8. All but one participant assigned to the two prazosin containing conditions achieved the target prazosin dose of 16 mg/day and maintained that dose for the duration of the trial. CONCLUSION: These results suggest that prazosin augmentation of naltrexone enhances naltrexone benefit for alcohol use disorder. These results strengthen rationale for an adequately powered definitive randomized controlled trial.

Engaging healthcare teams to increase access to medications for opioid use disorder.

OBJECTIVE: To assess the effectiveness of evidence-based quality improvement (EBQI) as an implementation strategy to expand the use of medications for opioid use disorder (MOUD) within nonspecialty settings. DATA SOURCES AND STUDY SETTING: We studied eight facilities in one Veteran Health Administration (VHA) region from October 2015 to September 2022 using administrative data. STUDY DESIGN: Initially a pilot, we sequentially engaged seven of eight facilities from April 2018 to September 2022 using EBQI, consisting of multilevel stakeholder engagement, technical support, practice facilitation, and data feedback. We established facility-level interdisciplinary quality improvement (QI) teams and a regional-level cross-facility collaborative. We used a nonrandomized stepped wedge design with repeated cross sections to accommodate the phased implementation. Using aggregate facility-level data from October 2015 to September 2022, we analyzed changes in patients receiving MOUD using hierarchical multiple logistic regression. DATA COLLECTION/EXTRACTION METHODS: Eligible patients had an opioid use disorder (OUD) diagnosis from an outpatient or inpatient visit in the previous year. Receiving MOUD was defined as having been prescribed an opioid agonist or antagonist treatment or a visit to an opioid substitution clinic. PRINCIPAL FINDINGS: The probability of patients with OUD receiving MOUD improved significantly over time for all eight facilities (average marginal effect [AME]: 0.0057, 95% CI: 0.0044, 0.0070) due to ongoing VHA initiatives, with the probability of receiving MOUD increasing by 0.577 percentage points, on average, each quarter, totaling 16 percentage points during the evaluation period. The seven facilities engaging in EBQI experienced, on average, an additional 5.25 percentage point increase in the probability of receiving MOUD (AME: 0.0525, 95%CI: 0.0280, 0.0769). EBQI duration was not associated with changes. CONCLUSIONS: EBQI was effective for expanding access to MOUD in nonspecialty settings, resulting in increases in patients receiving MOUD exceeding those associated with temporal trends. Additional research is needed due to recent MOUD expansion legislation.

Adverse Events at 1 Month Following Medication Initiation for Opioid Use Disorder Among Adolescents and Young Adults.

BACKGROUND: We assess adverse events (AEs) following medication initiation for adolescents and young adults with opioid use disorder (OUD). METHODS: This is a secondary analysis of a clinical trial of long-acting injectable naltrexone (LAI-naltrexone) among youth with OUD aged 15 to 21 years. Participants were recruited from residential treatment and placed into 1 of 3 treatment groups based on medication receipt at time of discharge (no medication, sublingual buprenorphine-naloxone [buprenorphine], or LAI-naltrexone). Frequencies and percentages of AEs by body system were compared by medication group at the 1-month follow-up visit. Logistic regression was used to compare groups on their likelihood of reporting an AE, overall and excluding injection site reactions. RESULTS: Of 199 participants, 71 (36%) received no medication, 59 (30%) buprenorphine, and 69 (35%) LAI-naltrexone at discharge. Participants who received LAI-naltrexone experienced more AEs, primarily due to injection site reactions (62%, accounting for 43% of all AEs among participants who received LAI-naltrexone). There were 6 reports of nonlethal overdose, 5 in the no medication, 1 in the buprenorphine, and none in the LAI-naltrexone group. Participants receiving LAI-naltrexone were more likely to report an AE compared to the other groups (P = .04), but this difference was no longer significant when excluding injection site reactions (P = .82). CONCLUSIONS: Excluding injection site reactions, there were no significant differences in the likelihood of reporting an AE 1 month after receiving LAI-NTX, buprenorphine, and no medications. LAI-naltrexone should be among the medications offered for the treatment of OUD in youth.

Off-Label Use of Naltrexone in Pica and Other Compulsive Behaviors: A Report of Two Cases.

Pica is known to the medical community as an eating disorder in which individuals may ingest non-food items due to a nutritional deficiency and cause unintentional physical harm to themselves. This article discusses the cases of children with pica in addition to other comorbidities such as trichotillomania, depression, autism, and anxiety. Both patients were trialed on typical first-line treatments to address pica symptoms, including antidepressants, psychotherapy, and neurology consults, which were ineffective in treating pica symptoms. The introduction of naltrexone resulted in significant improvements, including decreased pica symptoms and improvements in depression, anxiety, and overall behaviors. These effects of naltrexone were further bolstered by the effects that occurred when both patients discontinued naltrexone for some time.

Efficacy and safety of low-dose naltrexone for the management of fibromyalgia: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis.

Background: Fibromyalgia is characterized by the presence of chronic widespread pain that may impair patient's quality of life. Currently, the use of naltrexone as a therapeutic agent for fibromyalgia is not supported by enough evidence, especially from randomized controlled trials (RCTs). This study aims to analyze the efficacy and safety of low-dose naltrexone (LDN) for the management of fibromyalgia. Methods: A comprehensive search was conducted on the Scopus, Medline, ClinicalTrials.gov, and Cochrane Library databases up until May 20th, 2024. This review incorporates RCTs that examine the comparison between LDN and placebo in fibromyalgia patients. We employed random-effect models to analyze the odds ratio and mean difference (MD) for presentation of the outcomes. Results: A total of 4 RCTs with 222 fibromyalgia patients were incorporated. The results of our meta-analysis showed a significant reduction in pain scores (MD: -0.86, 95% confidence interval [CI]: -1.20, -0.51, P < 0.001, I2 = 33%) and higher increment in pressure pain threshold (MD: 0.17, 95% CI: 0.08, 0.25, P < 0.001, I2 = 0%) among fibromyalgia patients who received LDN than those who only received a placebo. The fibromyalgia impact questionnaire revised and pain catastrophizing scale did not differ significantly between the two groups. LDN was also associated with higher incidence of vivid dreams and nausea, but showed no significant difference with the placebo in terms of serious adverse events, headache, diarrhea, and dizziness. Conclusions: This study suggests the efficacy of LDN in mitigating pain symptoms for fibromyalgia patients with a relatively good safety profile.

Effects of chronic naltrexone treatment on relapse-related behavior and neural responses to fentanyl in awake nonhuman primates.

Naltrexone, an opioid antagonist that blocks the reinforcing properties of opioid agonists, is often prescribed to preclude relapse to opioid use disorder (OUD) following detoxification. However, few laboratory studies have directly investigated the ability of naltrexone to alter relapse-inducing effects of opioid agonists, including their priming strength in reinstatement studies and their impact in brain regions known to be involved in drug-induced reinforcement in MRI studies. Here we directly address this issue by investigating the effects of continuous exposure to naltrexone on 1) fentanyl-induced reinstatement of drug-seeking behavior, 2) fentanyl-induced patterns of blood oxygenation level dependent (BOLD) activation in the nucleus accumbens (NAcc), and 3) fentanyl-induced changes in NAcc functional connectivity (FC) in awake non-human primates that are engaged in ongoing opioid self-administration studies. We found that naltrexone antagonizes the priming strength of fentanyl as shown by a rightward shift in its reinstatement dose-effect curve and that naltrexone surmountably antagonizes the BOLD response induced by fentanyl. However, while naltrexone also countered fentanyl's effects on NAcc FC, the effects were not surmounted by a higher dose of fentanyl. Together, these data suggest that, in contrast to naltrexone's modulation of fentanyl's effects on behavior and BOLD responses, their interactive effects on FC between multiple brain regions do not reflect their receptor-mediated activity. Additionally, we demonstrated opposing effects in the absence and presence of naltrexone on NAcc FC at baseline (i.e., in the absence of any fentanyl prime) suggesting that naltrexone alters FC at baseline, even though naltrexone appears behaviorally silent in the absence of an agonist prime. Together these data provide additional insight into ways in which naltrexone interacts with opioid agonists, both behaviorally and in the brain. Further understanding the effects of opioid agonists on patterns of FC could help elucidate our understanding of the neural processes that contribute to the initiation of and relapse to opioid-seeking behavior in OUD.

Bioabsorbable, subcutaneous naltrexone implants mitigate fentanyl-induced respiratory depression at 3 months-A pilot study in male canines.

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 (<50%) but had severe respiratory depression with fentanyl doses of 90 µg/kg and especially at 120 µg/kg. Bioabsorbable, extended-release BIOPIN naltrexone implants are effective in mitigating fentanyl-induced respiratory depression in male canines at about 3 months after implantation. This technology may also have potential for mitigating fentanyl-induced respiratory depression in humans.

A historical perspective on clonidine as an alpha-2A receptor agonist in the treatment of addictive behaviors: Focus on opioid dependence.

Clonidine operates through agonism at the alpha-2A receptor, a specific subtype of the alpha-2-adrenergic receptor located predominantly in the prefrontal cortex. By inhibiting the release of norepinephrine, which is responsible for withdrawal symptoms, clonidine effectively addresses withdrawal-related conditions such as anxiety, hypertension, and tachycardia. The groundbreaking work by Gold et al. demonstrated clonidine's ability to counteract the effects of locus coeruleus stimulation, reshaping the understanding of opioid withdrawal within the field. In the 1980s, the efficacy of clonidine in facilitating the transition to long-acting injectable naltrexone was confirmed for individuals motivated to overcome opioid use disorders (OUDs), including physicians and executives. Despite challenges with compliance, naltrexone offers sustained blockade of opioid receptors, reducing the risk of overdose, intoxication, and relapse in motivated patients in recovery. The development of clonidine and naltrexone as treatment modalities for OUDs, and potentially other addictions, including behavioral ones, underscores the potential for translating neurobiological advancements from preclinical models (bench) to clinical practice (bedside), ushering in innovative approaches to addiction treatment.

Analysis of Ohio Advanced Practice Registered Nurses' Rate of Prescribing Naltrexone for Patients With Alcohol Use Disorder Since Elimination of the X-Waiver.

BACKGROUND: Alcohol use disorder (AUD) is common and deadly. Naltrexone is a treatment for AUD. Previous research examined factors that predict Ohio Advanced Practice Registered Nurses' (APRNs) utilization of naltrexone to treat AUD. Inclusion criteria included APRNs' endorsing receipt of the X-waiver, a designation indicating providers' receipt of substance use disorder education. In 2023, the X-waiver was eliminated. The purpose of this study was to replicate the previous research design in respondents without an X-waiver and compare findings. AIMS: The aims of this study were three-fold: (1) assess whether race, age, practice setting, years in practice, or work experience with an addiction specialist physician predicted prescription of naltrexone for AUD, (2) assess whether the goal of abstinence or reduced alcohol use as desired treatment affected the likelihood of naltrexone prescription for AUD, and (3) compare differences between the answers in the current respondent group without X-waiver and the previous study's X-waivered respondents. METHOD: All Ohio APRNs were sent surveys. Eighty-eight responses were included in analysis. Descriptive statistics, logistic regression, and chi-square results were reported. RESULTS: Work experience with an addiction specialist physician was negatively associated with prescribing naltrexone for AUD. Respondents from the previous study of X-waivered APRNs were significantly more likely to prescribe naltrexone for reduced alcohol consumption as a treatment outcome than the respondents in this study. CONCLUSION: The recent policy change eliminating the X-waiver provides important context for research, adding to the substance use disorder literature.

Comparative effectiveness of extended-release naltrexone and sublingual buprenorphine for treatment of opioid use disorder among Medicaid patients.

BACKGROUND AND AIMS: Extended-release naltrexone (XR-NTX) and sublingual buprenorphine (SL-BUP) are both approved for opioid use disorder (OUD) treatment in any medical setting. We aimed to compare the real-world effectiveness of XR-NTX and SL-BUP. DESIGN AND SETTING: This was an observational active comparator, new user cohort study of Medicaid claims records for patients in New Jersey and California, USA, 2016-19. PARTICIPANTS/CASES: The participants were adult Medicaid patients aged 18-64 years who initiated XR-NTX or SL-BUP for maintenance treatment of OUD and did not use medications for OUD in the 90 days before initiation. Our cohort included 1755 XR-NTX and 9886 SL-BUP patients. MEASUREMENTS: We examined two outcomes up to 180 days after medication initiation: (1) composite of medication discontinuation and death and (2) composite of overdose and death. FINDINGS: In adjusted analyses, treatment with XR-NTX was more likely to result in discontinuation or death by the end of follow-up than treatment with SL-BUP: cumulative risk 75.9% [95% confidence interval (CI) = 73.9%, 77.9%] versus 62.2% (95% CI = 61.2%, 63.2%), respectively (risk difference = 13.7 percentage points, 95% CI = 11.4, 16.0). There was minimal difference in the cumulative risk of overdose or death by the end of follow-up: XR-NTX 3.9% (95% CI = 3.0%, 4.8%) versus SL-BUP 3.3% (95% CI = 2.9%, 3.7%); risk difference = 0.5 percentage points, 95% CI = -0.4, 1.5. Results were consistent across sensitivity analyses. CONCLUSIONS: Medicaid patients in California and New Jersey, USA, receiving treatment for opioid use disorder stayed in treatment longer on sublingual buprenorphine than on extended-release naltrexone, but the risk of overdose was similar. Most patients in this study discontinued medication within 6 months, regardless of which medication was initiated.

Characterizing reward and relief/habit drinking profiles in a study of naltrexone, varenicline, and placebo.

INTRODUCTION: This study aims to clarify differences in mood, craving, and treatment response between reward and relief/habit individuals in a study of naltrexone, varenicline, and placebo. We hypothesized that relief/habit individuals would have a poorer mood during early abstinence and higher levels of alcohol craving than reward individuals. We hypothesized that reward individuals would demonstrate better drinking outcomes on naltrexone versus placebo. METHODS: Data were culled from a randomized, double-blind, placebo-controlled human trial of 53 individuals (18F/16M) with alcohol use disorder randomized to varenicline (n = 19), naltrexone (n = 15), or matched placebo (n = 19). In this 6-day practice quit trial, participants attempted to abstain from drinking and completed daily diaries. Participants were classified into reward or relief/habit subgroups based on self-reported motivation for drinking. Multilinear models tested differences in mood and alcohol craving between reward and relief/habit individuals. General linear models tested differences between reward and relief/habit individuals' drinking outcomes on each medication versus placebo. RESULTS: Relief/habit individuals showed decreases in positive mood and increases in negative mood over the quit attempt across medications, compared to reward individuals (P's < .05). Reward individuals' tension decreased on naltrexone, while relief/habit individuals' tension remained stable (F = 3.64, P = .03). Reward individuals in the placebo group had higher percent days abstinent than relief individuals in the placebo group (P < .001). DISCUSSION: This study suggests relief/habit individuals' mood worsens during early abstinence. Our finding that reward individuals' tension decreased on naltrexone and increased on placebo may suggest a clinical response to the medication.

Therapeutic Potential of Naltrexone in the Niche of Psychopharmacology.

NTX is FDA-approved for opiate and alcohol use disorders as anti-craving agent. It has been used successfully off-label in other psychiatric indications. Here, we shed some light on these while examining the extant evidence.