Injectable Naltrexone Research Articles

Patient predictors of substance use disorder treatment initiation in primary care

IntroductionPrimary care clinics are opportune settings in which to deliver substance use disorder (SUD) treatment, but little is known about which patients initiate treatment in these settings. MethodsUsing secondary data from a RCT that aimed to integrate SUD treatment into a federally qualified health center (FQHC) using an organizational readiness and collaborative care (CC) intervention, we examined patient-level predictors of initiation of evidence-based practices for opioid and/or alcohol use disorders (OAUDs): a brief behavioral treatment (BT) based on motivational interviewing and cognitive behavioral therapy and medication-assisted treatment (MAT) (extended-release injectable naltrexone (XR-NTX) for patients with an alcohol use disorder or opioid use disorder and buprenorphine/naloxone (BUP/NX) for patients with an opioid use disorder). Using the Andersen model of health care access, we tested bivariate and multivariate logistic regression models to assess associations between patient factors and initiation of BT and MAT. ResultsTwenty-three percent of all participants (N = 392) received BT and 13% received MAT. In the multivariate model examining factors associated with initiation of BT, being of “other” or “multiple” races compared with being White (OR = 0.45, CI = 0.22, 0.92), being homeless (OR = 0.45, CI = 0.21, 0.97) and having been arrested within 90 days of baseline (OR = 0.21 CI = 0.63, 0.69) were associated with significantly lower odds of initiating BT. Greater self-stigma (OR = 1.60, CI = 1.06, 2.42), receiving MAT (OR = 5.52, CI = 2.34, 12.98), and having received the CC study intervention (OR = 12.95, CI = 5.91, 28.37) were associated with higher odds of initiating BT. In the multivariate model examining patient factors associated with initiating MAT, older age (OR = 1.07, CI = 1.03, 1.11), female gender (OR = 3.05, CI = 1.25, 7.46), having a diagnosis of heroin abuse or dependence (with or without alcohol abuse or dependence compared with have a diagnosis of alcohol dependence only (OR = 3.03, CI = 1.17, 7.86), and having received at least one session of BT (OR = 6.42, CI = 2.59, 15.94), were associated with higher odds of initiating MAT. ConclusionsIndividuals who initiate BT for OAUDs in a FQHC are less likely to be homeless and more likely to have greater self-stigma. Those who receive MAT are more likely to be of older age, female, and to have a diagnosis of heroin abuse or dependence, with or without concomitant alcohol abuse or dependence, rather than alcohol abuse or dependence alone. Receiving collaborative care (e.g., a warm handoff, and follow-up by a care coordinator) may be critical to initiating BT. Receiving at least one session of BT is associated with higher odds of receiving MAT, and receiving MAT is associated with higher odds of receiving BT. The Andersen model of health care access provides some insight into who initiates BT and MAT for OAUD treatment in FQHC-based primary care; further research is needed to explore system-level factors that may also influence treatment initiation.

In vivo effects of μ-opioid receptor agonist/δ-opioid receptor antagonist peptidomimetics following acute and repeated administration.

Agonists at μ-opioid receptors (μ-receptors) are used for pain management but produce adverse effects including tolerance, dependence and euphoria. The co-administration of a μ-receptor agonist with a δ-opioid receptor (δ-receptor) antagonist has been shown to produce antinociception with reduced development of some side effects. We characterized the effects of three μ-receptor agonist/δ-receptor antagonist peptidomimetics in vivo after acute and repeated administration to determine if this profile provides a viable alternative to traditional opioid analgesics. Three μ-receptor agonist / δ-receptor antagonist peptidomimetics, AAH8, AMB46 and AMB47, and morphine were evaluated for the development of tolerance and dependence after 5days of twice daily treatment with escalating doses of drug (10-50mg·kg-1 ). Antinociceptive effects were measured in the warm water tail withdrawal assay before and after repeated drug treatment. Physical dependence was evaluated by naltrexone-precipitated withdrawal jumping. The rewarding effects of AAH8 were evaluated using a conditioned place preference (CPP) assay with twice daily conditioning sessions performed for 5days. Morphine, AAH8, AMB47 and AMB46 all demonstrated acute antinociceptive effects, but repeated administration only produced tolerance in animals treated with morphine and AMB46. Injection of naltrexone precipitated fewer jumps in mice treated repeatedly with AAH8 as compared with morphine, AMB47 or AMB46. Conditioning with morphine, but not AAH8, produced significant CPP. AAH8 may be a better alternative than traditional opioid analgesics, producing antinociception with less development of tolerance and dependence and may be less rewarding than morphine.

Outpatient transition to extended-release injectable naltrexone for patients with opioid use disorder: A phase 3 randomized trial

BackgroundInjectable extended-release naltrexone (XR-NTX), approved to prevent relapse to opioid dependence, requires initial abstinence. This multisite outpatient clinical trial examined the efficacy and safety of low-dose oral naltrexone (NTX), combined with a brief buprenorphine (BUP) taper and standing ancillary medications, for detoxification and induction onto XR-NTX. MethodsPatients (N = 378) were randomized, stratified by primary short-acting opioid-of-use, to one of three regimens: NTX + BUP; NTX + placebo BUP (PBO-B); placebo NTX (PBO-N) + PBO-B. Patients received 7 days of ascending NTX or placebo, concurrent with a 3-day BUP or placebo taper, and ancillary medications in an outpatient setting. Daily psychoeducational counseling was provided. On Day 8, patients passing a naloxone challenge received XR-NTX. ResultsRates of transition to XR-NTX were comparable across groups: NTX/BUP (46.0%) vs. NTX/PBO-B (40.5%) vs. PBO-N/PBO-B (46.0%). Thus, the study did not meet its primary endpoint. Adverse events, reported by 32.5% of all patients, were mild to moderate in severity and consistent with opioid withdrawal. A first, second, and third XR-NTX injection was received by 44.4%, 29.9%, and 22.5% of patients, respectively. Compared with the PBO-N/PBO-B group, the NTX/BUP group demonstrated higher opioid abstinence during the transition and lower post-XR-NTX subjective opioid withdrawal scores. ConclusionsA 7-day detoxification protocol with NTX alone or NTX + BUP provided similar rates of induction to XR-NTX as placebo. For those inducted onto XR-NTX, management of opioid withdrawal symptoms prior to induction was achieved in a structured outpatient setting using a well-tolerated, fixed-dose ancillary medication regimen common to all three groups.

Review of Case Narratives from Fatal Overdoses Associated with Injectable Naltrexone for Opioid Dependence.

An extended-release injectable naltrexone suspension (Vivitrol®) was approved in USA in 2010 for the prevention of relapse to opioid dependence. Concerns, raised at the time of approval, about rebound overdose risk following the last dose, have not been adequately studied. We sought to determine the time period of concern for fatal overdose associated with Vivitrol. We performed a retrospective case review of Vivitrol spontaneous reports (October 2010-March 2016) in the US Food and Drug Administration Adverse Event Reporting System via the Freedom of Information Act. Case narratives were manually reviewed to identify overdose deaths amongst current and former patients, extracting information on the time from discontinuation, followed by causality assessment. Narratives on 263 deaths and overdose-related outcomes were obtained. One hundred and forty-five death reports were assessed for causality. Among these reports, cause of death was unknown in 46%, while 52 fatal overdoses met the case definition. Of 52 overdoses, time between the last dose and death was known for 28; 22 (84.6%) occurred within 2months of the last Vivitrol injection [median 46days (interquartile range 29.5-82)]. The sponsor's causality assessment in 75% of fatal overdoses repeated verbatim text that placed responsibility on underlying opioid dependence and precluded a link between medication and overdose or ignored rebound risk following treatment discontinuation. Vivitrol adverse event reports suggest the need to investigate twomonths following the last medicine injection as a period of particular concern for overdose. A registry study would best quantify risk. Providers should report suspected post-discontinuation overdoses to government authorities.

Open-label pilot study of injectable naltrexone for cannabis dependence

ABSTRACTBackground: There are no FDA-approved pharmacotherapies for cannabis use disorders (CUD), despite the evaluation of numerous medications. Notably, chronic dosing of oral naltrexone decreases self-administration of cannabis in human laboratory studies.Objectives: To test the feasibility of long-acting injectable naltrexone for the treatment of CUD, while obtaining preliminary safety and efficacy data.Methods: Twelve adult participants (seven male) meeting DSM-IV-TR criteria for cannabis dependence enrolled into an 8-week, open-label pilot study conducted at an academic treatment research clinic. They received 380 mg intramuscular injections of long-acting naltrexone on study day 1 and at the start of study week 5. Outcome measures included percentages of study completers and participants who received the second injection, frequency of adverse events (AEs), and cannabis consumption measured by average daily grams, dollars, and using days per week as measured by timeline follow-back and urine oral delta-9-tetrahydrocannabinol (THC) concentrations.Results: Of the 12 participants enrolled in the study, 9 completed the study and 6 received the second injection. There were no severe AEs but an unexpected AE led to the addition of supportive medications to the protocol. Number of cannabis use days per week significantly decreased over the course of the study (p = .001). Creatinine-corrected urine THC concentrations and average daily cannabis use per study week in grams and in dollars did not decrease over the course of the study.Conclusions: Long-acting injectable naltrexone is a feasible intervention for CUD worthy of further study in a placebo-controlled, double-blinded randomized clinical trial.

Effects of motivational interviewing fidelity on substance use treatment engagement in primary care

ObjectivePrimary care (PC) may be an opportune setting to engage patients with opioid and alcohol use disorders (OAUDs) in treatment. We examined whether motivational interviewing (MI) fidelity was associated with engagement in primary care-based OAUD treatment in an integrated behavioral health setting. MethodsWe coded 42 first session therapy recordings and examined whether therapist MI global ratings and behavior counts were associated with patient engagement, defined as the patient receiving one shot of extended-release injectable naltrexone or any combination of at least two additional behavioral therapy, sublingual buprenorphine/naloxone prescriptions, or OAUD-related medical visits within 30days of their initial behavioral therapy visit. ResultsAutonomy/support global ratings were higher in the non-engaged group (OR=0.28, 95%CI: 0.09–0.93; p=0.037). No other MI fidelity ratings were significantly associated with engagement. ConclusionWe did not find positive associations between MI fidelity and engagement in primary care-based OAUD treatment. More research with larger samples is needed to examine how providing autonomy/support to patients who are not ready to change may affect engagement. Practice implicationsTraining providers to strategically use MI to reinforce change as opposed to the status quo is needed. This may be especially important in primary care where patients may not be specifically seeking help for their OAUDs.

Injectable naltrexone found as effective as buprenorphine in noninferiority trial

A 12‐week trial conducted in Norway has found injectable extended‐release naltrexone to be noninferior to oral buprenorphine‐naloxone on a number of outcomes for opioid‐dependent patients, including treatment retention and opioid‐negative drug tests. These results have significant implications because the study represents one of the first direct comparisons between injectable naltrexone and what has become the standard‐of‐care treatment for opioid dependence in several countries. Study results were published online Oct. 18 in JAMA Psychiatry.

The efficiency of the medical rehabilitation program with the use of injectable naltrexone for alcohol addicted patients who are at risk of parental rights deprivation

To evaluate the efficacy of treatment of patients at risk of deprivation of parental rights due to alcohol dependence under the 'Point of Soberness' program including psychotherapy and intramuscular injections of extended-release naltrexone (vivitrol). Results of therapy of 45 patients, 39 women and 6 men, are presented. Out of 45 patients, 42 (93.3%) received a full course of injections of prolonged naltrexone (6 or more) as part of a comprehensive outpatient rehabilitation program. Thirty-six (80.0%) patients maintained a remission. In 9 patients (20.0%), single breakdowns and breakdowns, resulting in a relapse of the disease were recorded. Forty-two patients (93.3%) retained their parental rights. The return of children was made in one case. The 'Point of Soberness' program makes it possible to achieve long remission of alcohol dependence, and to keep parental rights for these patients.

State-Targeted Funding and Technical Assistance to Increase Access to Medication Treatment for Opioid Use Disorder.

As the United States grapples with an opioid epidemic, expanding access to effective treatment for opioid use disorder is a major public health priority. Identifying effective policy tools that can be used to expand access to care is critically important. This article examines the relationship between state-targeted funding and technical assistance and adoption of three medications for treating opioid use disorder: oral naltrexone, injectable naltrexone, and buprenorphine. This study draws from the 2013-2014 wave of the National Drug Abuse Treatment System Survey, a nationally representative, longitudinal study of substance use disorder treatment programs. The sample includes data from 695 treatment programs (85.5% response rate) and representatives from single-state agencies in 49 states and Washington, D.C. (98% response rate). Logistic regression was used to examine the relationships of single-state agency targeted funding and technical assistance to availability of opioid use disorder medications among treatment programs. State-targeted funding was associated with increased program-level adoption of oral naltrexone (adjusted odds ratio [AOR]=3.14, 95% confidence interval [CI]=1.49-6.60, p=.004) and buprenorphine (AOR=2.47, 95% CI=1.31-4.67, p=.006). Buprenorphine adoption was also correlated with state technical assistance to support medication provision (AOR=1.18, 95% CI=1.00-1.39, p=.049). State-targeted funding for medications may be a viable policy lever for increasing access to opioid use disorder medications. Given the historically low rates of opioid use disorder medication adoption in treatment programs, single-state agency targeted funding is a potentially important tool to reduce mortality and morbidity associated with opioid disorders and misuse.

Journal Digest

Journal Digest

Assessing and improving organizational readiness to implement substance use disorder treatment in primary care: findings from the SUMMIT study

BackgroundMillions of people with substance use disorders (SUDs) need, but do not receive, treatment. Delivering SUD treatment in primary care settings could increase access to treatment because most people visit their primary care doctors at least once a year, but evidence-based SUD treatments are underutilized in primary care settings. We used an organizational readiness intervention comprised of a cluster of implementation strategies to prepare a federally qualified health center to deliver SUD screening and evidence-based treatments (extended-release injectable naltrexone (XR-NTX) for alcohol use disorders, buprenorphine/naloxone (BUP/NX) for opioid use disorders and a brief motivational interviewing/cognitive behavioral –based psychotherapy for both disorders). This article reports the effects of the intervention on key implementation outcomes.MethodsTo assess changes in organizational readiness we conducted pre- and post-intervention surveys with prescribing medical providers, behavioral health providers and general clinic staff (N = 69). We report on changes in implementation outcomes: acceptability, perceptions of appropriateness and feasibility, and intention to adopt the evidence-based treatments. We used Wilcoxon signed rank tests to analyze pre- to post-intervention changes.ResultsAfter 18 months, prescribing medical providers agreed more that XR-NTX was easier to use for patients with alcohol use disorders than before the intervention, but their opinions about the effectiveness and ease of use of BUP/NX for patients with opioid use disorders did not improve. Prescribing medical providers also felt more strongly after the intervention that XR-NTX for alcohol use disorders was compatible with current practices. Opinions of general clinic staff about the appropriateness of SUD treatment in primary care improved significantly.ConclusionsConsistent with implementation theory, we found that an organizational readiness implementation intervention enhanced perceptions in some domains of practice acceptability and appropriateness. Further research will assess whether these factors, which focus on individual staff readiness, change over time and ultimately predict adoption of SUD treatments in primary care.

Cirrhosis induced by bile duct ligation alleviates acetic acid intestinal damages in rats: Involvements of nitrergic and opioidergic systems.

Colitis, a colonic inflammatory condition, showed a linkage with hepatobiliary disorders such as cirrhosis. It has been reported that both endogenous opioids and nitric oxide (NO) play critical roles in colitis pathogenesis. Moreover, opioid and NO levels showed elevation in patients with cirrhosis. The aim of this study was to evaluate the effect of cirrhosis on the experimental model of colitis and the possible involvement of opioidergic/nitrergic systems in rats. Colitis was induced by acetic acid 28days after bile duct ligation (BDL). L-NAME, as an inhibitor of NO synthase and naltrexone, as an antagonist of opioid receptors were administered intraperitoneally to animals during 3days after induction of colitis. Macroscopic colitis lesion area, inflammatory mediators change, NO metabolite levels, and colon microscopic injuries were assessed 3days after induction. Cirrhosis significantly reduced the severity of damages to the colon. Administration of L-NAME (10mg/kg), naltrexone (10mg/kg) and co-administration of L-NAME (1mg/kg) and naltrexone (5mg/kg) significantly decreased the protective effect of BDL on colitis. Nitrite elevated levels in BDL rats were significantly diminished in L-NAME- and naltrexone-treated animals. Histopathology parameters and cytokines level alterations in the colon of acetic acid-treated animals after BDL was reversed after injection of L-NAME, naltrexone, and co-administration of L-NAME (1mg/kg) + naltrexone (5mg/kg). Cirrhosis improved the intestinal damages induced by acetic acid in rats which may be mediated through interaction of nitrergic and opioidergic systems.

Collaborative Care May Improve Outcomes in Patients With Substance Use Disorder

Collaborative Care May Improve Outcomes in Patients With Substance Use Disorder

Medications for opioid use disorder: bridging the gap in care

For the past two decades, the USA has been in the throes of an opioid crisis marked by a rising number of deaths; in 2016, opioids were responsible for most of the nation's estimated 64 000 fatal drug overdoses. 1 US Centers for Disease Control and PreventionNational Center for Health StatisticsNational Vital Statistics SystemProvisional counts of drug overdose deaths, as of 8/6/2017. https://www.cdc.gov/nchs/data/health_policy/monthly-drug-overdose-death-estimates.pdfDate: 2017 Google Scholar The problem began with overprescribing of opioid analgesics in the 1990s, which exposed pain patients to the risks of addiction and produced large surpluses of pain pills that were diverted for misuse by the larger community. Additionally, the escalating numbers of opioid-addicted Americans led to increased HIV and hepatitis C transmission among people who misuse these drugs by injecting them 2 Van Handel MM Rose CE Hallisey EJ et al. County-level vulnerability assessment for rapid dissemination of HIV or HCV infections among persons who inject drugs, United States. J Acquir Immune Defic Syndr. 2016; 73: 323-331 Crossref PubMed Scopus (278) Google Scholar and increased numbers of infants born dependent on opioids as a result of the mother's opioid use (neonatal abstinence syndrome). 3 Brown JD Goodin AJ Talbert JC Rural and Appalachian disparities in neonatal abstinence syndrome incidence and access to opioid abuse treatment. J Rural Health. 2017; (published online July 7.)DOI: 10.1111/jrh.12251 Google Scholar Extended-release naltrexone: good but not a panaceaUnlike other addictions, opioid-use disorder has several highly effective medication treatments available, in particular methadone, buprenorphine, and naltrexone.1–3 Methadone is the least accessible or acceptable of these in many settings, so providers and patients are often faced with a choice between buprenorphine-naloxone (BUP-NX) and extended-release naltrexone injection (XR-NTX). Full-Text PDF Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trialIn this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications. Full-Text PDF

Sustained opioid antagonism modulates striatal sensitivity to baby schema in opioid use disorder

BackgroundChronic opioid misuse is associated with reduced sensitivity to natural rewards and social motivation deficits that include impaired caregiving. The neurobiological mechanisms underlying these deficits and their response to treatment are not well understood. Baby schema (Kindchenschema) is a set of juvenile physical features, which is perceived as “cute” and triggers motivation for caregiving. Recent studies suggest that the “baby schema effect” is mediated by the brain “reward” network. We studied the impact of opioid antagonist treatment on the baby schema response in patients with opioid use disorder. MethodsForty-seven (24 F) recently detoxified patients with opioid use disorder underwent functional magnetic resonance imaging (fMRI) while viewing infant portraits that were parametrically manipulated for baby schema content and rating them for cuteness, at baseline and during treatment with the injectable extended release opioid antagonist naltrexone (XRNTX). The study was not placebo-controlled. ResultsThe behavioral effect of baby schema, indexed by “cuteness” ratings, was present and unaffected by XRNTX. The brain response to baby schema was absent at baseline, but present in the bilateral ventral striatum after two weeks of XRNTX treatment. The decline in self-reported craving for opioids was positively correlated with the brain fMRI response to baby schema in the bilateral ventral striatum. ConclusionsOpioid antagonist treatment modulated the brain reward system response to a marker of caregiving motivation in patients with opioid use disorder. Neural response to baby schema may offer a novel probe of social motivation and affiliative behaviors in this population.

Bioavailability Differences in Naltrexone: Oral and Injectable, Extended Release

Undoubtedly the rise of opioid use in the United States is a frightening upsurge When exogenous opioids are ingested they mimic the same pathways in the body that naturally occurring morphine would For this reason if used in a manner that is not prescribed opioids can be dangerous Looking at opioid use disorder several pharmacotherapies exist One such pharmacotherapy that is studied in high volumes in the use of naltrexone an opioid antagonist This article looks at the significantly advantageous bioavailability factors of injectable extended release naltrexone over daily oral administration

Collaborative Care for Opioid and Alcohol Use Disorders in Primary Care

Primary care offers an important and underutilized setting to deliver treatment for opioid and/or alcohol use disorders (OAUD). Collaborative care (CC) is effective but has not been tested for OAUD. To determine whether CC for OAUD improves delivery of evidence-based treatments for OAUD and increases self-reported abstinence compared with usual primary care. A randomized clinical trial of 377 primary care patients with OAUD was conducted in 2 clinics in a federally qualified health center. Participants were recruited from June 3, 2014, to January 15, 2016, and followed for 6 months. Of the 377 participants, 187 were randomized to CC and 190 were randomized to usual care; 77 (20.4%) of the participants were female, of whom 39 (20.9%) were randomized to CC and 38 (20.0%) were randomized to UC. The mean (SD) age of all respondents at baseline was 42 (12.0) years, 41(11.7) years for the CC group, and 43 (12.2) yearsfor the UC group. Collaborative care was a system-level intervention, designed to increase the delivery of either a 6-session brief psychotherapy treatment and/or medication-assisted treatment with either sublingual buprenorphine/naloxone for opioid use disorders or long-acting injectable naltrexone for alcohol use disorders. Usual care participants were told that the clinic provided OAUD treatment and given a number for appointment scheduling and list of community referrals. The primary outcomes were use of any evidence-based treatment for OAUD and self-reported abstinence from opioids or alcohol at 6 months. The secondary outcomes included the Healthcare Effectiveness Data and Information Set (HEDIS) initiation and engagement measures, abstinence from other substances, heavy drinking, health-related quality of life, and consequences from OAUD. At 6 months, the proportion of participants who received any OAUD treatment was higher in the CC group compared with usual care (73 [39.0%] vs 32 [16.8%]; logistic model adjusted OR, 3.97; 95% CI, 2.32-6.79; P < .001). A higher proportion of CC participants reported abstinence from opioids or alcohol at 6 months (32.8% vs 22.3%); after linear probability model adjustment for covariates (β = 0.12; 95% CI, 0.01-0.23; P = .03). In secondary analyses, the proportion meeting the HEDIS initiation and engagement measures was also higher among CC participants (initiation, 31.6% vs 13.7%; adjusted OR, 3.54; 95% CI, 2.02-6.20; P < .001; engagement, 15.5% vs 4.2%; adjusted OR, 5.89; 95% CI, 2.43-14.32; P < .001) as was abstinence from opioids, cocaine, methamphetamines, marijuana, and any alcohol (26.3% vs 15.6%; effect estimate, β = 0.13; 95% CI, 0.03-0.23; P = .01). Among adults with OAUD in primary care, the SUMMIT collaborative care intervention resulted in significantly more access to treatment and abstinence from alcohol and drugs at 6 months, than usual care. clinicaltrials.gov Identifier: NCT01810159.

A novel non-opioid protocol for medically supervised opioid withdrawal and transition to antagonist treatment

ABSTRACTBackground: The clinical feasibility of a novel non-opioid and benzodiazepine-free protocol was assessed for the treatment of medically supervised opioid withdrawal and transition to subsequent relapse prevention strategies. Methods: A retrospective chart review of DSM-IV diagnosed opioid-dependent patients admitted for inpatient medically supervised withdrawal examined 84 subjects (52 males, 32 females) treated with a 4-day protocol of scheduled tizanidine, hydroxyzine, and gabapentin. Subjects also received ancillary medications as needed, and routine counseling. Primary outcomes were completion of medically supervised withdrawal, and initiation of injectable extended release (ER) naltrexone treatment. Secondary outcomes included the length of hospital stay, Clinical Opiate Withdrawal Scale (COWS) scores, and facilitation to substance use disorder treatment intervention. Ancillary medication use and adverse effects were also assessed. Results: A total of 79 (94%) of subjects completed medically supervised withdrawal. A total of 27 (32%) subjects chose to pursue transition to ER naltrexone, and 24 of the 27 (89%) successfully received the injection prior to hospital discharge. The protocol subjects had a mean length of hospital stay of 3.6 days, and the mean COWS scores was 3.3, 3.4, 2.8, and 2.4 on Day 1, 2, 3, and 4, respectively. Furthermore, 71 (85%) engaged in an inpatient or outpatient substance use disorder (SUD) treatment program following protocol completion. Conclusion: This retrospective chart review suggests the feasibility of a novel protocol for medically supervised opioid withdrawal and transition to relapse prevention strategies, including injectable ER naltrexone. This withdrawal protocol does not utilize opioid agonists or other controlled substances.‬‬‬‬

Variation in receipt of pharmacotherapy for alcohol use disorders across racial/ethnic groups: A national study in the U.S. Veterans Health Administration

ObjectivePharmacologic treatment is recommended for alcohol use disorders (AUD), but most patients do not receive it. Although racial/ethnic minorities have greater AUD consequences than whites, whether AUD medication receipt varies across race/ethnicity is unknown. We evaluate this in a national sample. MethodsElectronic health records data were extracted for all black, Hispanic, and/or white patients who received care at the U.S. Veterans Health Administration (VA) during Fiscal Year 2012 and had a documented AUD diagnosis. Mixed effects regression models, with a random effect for facility, determined the likelihood of receiving AUD pharmacotherapy (acamprosate, disulfiram, topirimate or oral or injectable naltrexone ≤180days after AUD diagnosis) for black and Hispanic patients relative to white patients. Models were unadjusted and then adjusted for patient- and facility-level factors. Results297,506 patients had AUD; 26.4% were black patients, 7.1% were Hispanic patients and 66.5% were white patients; 5.1% received AUD medications. Before adjustment, black patients were less likely than white [Odds Ratio (OR) 0.77; 95% Confidence Interval (CI) 0.75 −0.82; (p<0.001)], while Hispanic patients were more likely than white (OR 1.09; 95% CI 1.01–1.16) to receive AUD medications. After adjustment, black patients remained less likely than white to receive AUD medications (OR 0.68; 95% CI 0.65–0.71; p<0.0001); no difference between Hispanic and white patients was observed (OR 0.94; 95% CI 0.87–1.00; p=0.07). ConclusionsIn this national study of patients with AUD, blacks were less likely to receive AUD medications than whites. Future research is needed to identify why these disparities exist.

Injectable naltrexone, oral naltrexone, and buprenorphine utilization and discontinuation among individuals treated for opioid use disorder in a United States commercially insured population

We investigated prescribing patterns for four opioid use disorder (OUD) medications: 1) injectable naltrexone, 2) oral naltrexone, 3) sublingual or oralmucosal buprenorphine/naloxone, and 4) sublingual buprenorphine as well as transdermal buprenorphine (which is approved for treating pain, but not OUD) in a nationally representative claims-based database (Truven Health MarketScan®) of commercially insured individuals in the United States. We calculated the prevalence of OUD in the database for each year from 2010 to 2014 and the proportion of diagnosed patient months on OUD medication. We compared characteristics of individuals diagnosed with OUD who did and did not receive these medications with bivariate descriptive statistics. Finally, we fit a Cox proportional hazards model of time to discontinuation of therapy as a function of therapy type, controlling for relevant confounders.From 2010 to 2014, the proportion of commercially insured individuals diagnosed with OUD grew by fourfold (0.12% to 0.48%), but the proportion of diagnosed patient-months on medication decreased from 25% in 2010 (0.05% injectable naltrexone, 0.4% oral naltrexone, 23.1% sublingual or oralmucosal buprenorphine/naloxone, 1.5% sublingual buprenorphine, and 0% transdermal buprenorphine) to 16% in 2014 (0.2% injectable naltrexone, 0.4% oral naltrexone, 13.8% sublingual or oralmucosal buprenorphine/naloxone, 1.4% sublingual buprenorphine, and 0.3% transdermal buprenorphine). Individuals who received medication therapy were more likely to be male, younger, and have an additional substance use disorder compared with those diagnosed with OUD who did not receive medication therapy. Those prescribed injectable naltrexone were more often male, younger, and diagnosed with additional substance use disorders compared with those prescribed other medications for opioid use disorder (MOUDs). At 30 days after initiation, 52% for individuals treated with injectable naltrexone, 70% for individuals treated with oral naltrexone, 31% for individuals treated with sublingual or oralmucosal buprenorphine/naloxone, 58% for individuals treated with sublingual buprenorphine, and 51% for individuals treated with transdermal buprenorphine discontinued treatment. In the Cox proportional hazard model, use of injectable naltrexone, oral naltrexone, sublingual buprenorphine, and transdermal buprenorphine were all associated with significantly greater hazard of discontinuing therapy beginning >30days after MOUD initiation (HR=2.17, 2.54, 1.15, and 2.21, respectively, 95% CIs 2.04–2.30, 2.45–2.64, 1.10–1.19, and 2.11–2.33), compared with the use of sublingual or oralmucosal buprenorphine/naloxone.This analysis demonstrates that the use of evidence-based medication therapies has not kept pace with increases in OUD diagnoses in commercially insured populations in the United States. Among those who have been treated, discontinuation rates >30days after initiation are high. The proportion treated with injectable naltrexone, oral naltrexone, and transdermal buprenorphine grew over time but remains small, and the discontinuation rates are higher among those treated with these medications compared with those treated with sublingual or oralmucosal buprenorphine/naloxone. In the face of the opioid overdose and addiction crisis, new efforts are needed at the provider, health system, and policy levels so that MOUD availability and uptake keep pace with new OUD diagnoses and OUD treatment discontinuation is minimized.