Browsing by Subject "Naltrexone"
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Item Clinician Willingness to Prescribe Medications for Opioid Use Disorder to Adolescents in Indiana(American Medical Association, 2024-09-03) Aalsma, Matthew C.; Bell, Lauren A.; Schwartz, Katherine; Ouyang, Fangqian; Kolak, Marynia; Monahan, Patrick O.; Mermelstein, Sharon P.; Carson, Ian; Hulvershorn, Leslie A.; Adams, Zachary W.; Psychiatry, School of MedicineImportance: Prescribing medications for opioid use disorders (MOUD), including buprenorphine, naltrexone, and methadone, to adolescents remains an underused evidence-based strategy for reducing harms associated with opioid use. Objective: To identify potential associations between clinician- and community-level characteristics regarding clinicians' self-reported willingness to prescribe MOUD to adolescents. Design, setting, and participants: This cross-sectional study included a phone survey of Indiana clinicians and spatial analysis of community-level characteristics. Clinicians were eligible for inclusion in analyses if actively providing health care and listed on the Buprenorphine Practitioner Locator website, a publicly available national registry of clinicians possessing a waiver to legally prescribe buprenorphine (ie, waivered clinicians). Exposures: Community-level characteristics, including total population, rurality or urbanicity, percentage with incomes below the federal poverty line, and racial or ethnic makeup. Main outcomes and measures: Clinicians were asked about their willingness to prescribe MOUD to adolescents younger than 18 years if clinically indicated. Responses were recorded as no, yes, or yes with conditions. Results: Among the 871 clinicians listed on the website as of July 2022, 832 were eligible for inclusion and contacted by phone. Among waivered clinicians, 759 (91.2%) reported being unwilling to prescribe MOUD to adolescents, 73 clinicians (8.8%) reported willingness to prescribe MOUD to adolescents, and only 24 (2.9%) would do so without conditions. A multivariable logistic regression model including spatially lagged community-level variables showed that, among areas with waivered clinicians, clinicians practicing in more populated areas were significantly less likely to prescribe to adolescents (β = 0.65; 95% CI, 0.49-0.87; P = .003). Similarly, those in more rural areas were significantly more likely to prescribe to adolescents (β = 1.27; 95% CI, 1.02-1.58; P = .03). Variation in clinician willingness to prescribe was not explained by other community-level characteristics. Among all waivered clinicians, advanced practice clinicians were less likely than physicians to report willingness to prescribe (β = 0.58; 95% CI, 0.35-0.97; P = .04), as were physicians without any specialty training relevant to MOUD prescribing when compared with family medicine clinicians (β = 0.40; 95% CI, 0.18-0.89; P = .03). A small subgroup of waivered clinicians had training in pediatrics (13 clinicians [1.6%]), and none were willing to prescribe MOUD to adolescents. Conclusions and relevance: From this cross-sectional study, it appears that Indiana adolescents continued to face gaps in access to MOUD treatment, despite its well-established efficacy. Programs that support primary care practitioners, including family medicine clinicians and pediatricians, in safe and appropriate use of MOUD in adolescents may bridge these gaps.Item Combining varenicline (Chantix) with naltrexone decreases alcohol drinking more effectively than does either drug alone in a rodent model of alcoholism(Wiley, 2016-09) Froehlich, Janice C.; Fischer, Stephen M.; Dilley, Julian E.; Nicholson, Emily; Smith, Teal; Filosa, Nick; Rademacher, Logan; Cellular and Integrative Physiology, School of MedicineBackground This study examined whether varenicline (VAR), or naltrexone (NTX), alone or in combination, reduces alcohol drinking in alcohol-preferring (P) rats with a genetic predisposition toward high voluntary alcohol intake. Methods Alcohol experienced P rats that had been drinking alcohol (15% v/v) for 2 hrs/day for 4 weeks were fed either vehicle (VEH), VAR alone (0.5, 1.0 or 2.0 mg/kg BW), NTX alone (10.0, 15.0 or 20.0 mg/kg BW) or VAR + NTX in one of four dose combinations (0.5 VAR + 10.0 NTX, 0.5 VAR + 15.0 NTX, 1.0 VAR + 10.0 NTX, or 1.0 VAR + 15.0 NTX) at 1 hour prior to alcohol access for 10 consecutive days and the effects on alcohol intake were assessed. Results When administered alone, VAR in doses of 0.5 or 1.0 mg/kg BW did not alter alcohol intake but a dose of 2.0 mg/kg BW decreased alcohol intake. This effect disappeared when drug treatment was terminated. NTX in doses of 10.0 and 15.0 mg/kg BW did not alter alcohol intake but a dose of 20.0 mg/kg BW decreased alcohol intake. Combining low doses of VAR and NTX into a single medication reduced alcohol intake as well as did high doses of each drug alone. Reduced alcohol intake occurred immediately after onset of treatment with the combined medication and continued throughout prolonged treatment. Conclusions Low doses of VAR and NTX, when combined in a single medication, reduce alcohol intake in a rodent model of alcoholism. This approach has the advantage of reducing potential side effects associated with each drug. Lowering the dose of NTX and VAR in a combined treatment approach that maintains efficacy while reducing the incidence of negative side-effects may increase patient compliance and improve clinical outcomes for alcoholics and heavy drinkers who want to reduce their alcohol intake.Item Exploring Potential Pharmacologic Treatments for Alcoholism: Can the Use of Drugs Selective for the µ-, δ-, and κ- Opioid Receptors Differentially Modulate Alcohol Drinking?(2013-07-12) Henderson, Angela Nicole; Czachowski, Cristine; Grahame, Nicholas J.; Stewart, Robert; Kinzig, Kimberly P.; Hazer, JohnNaltrexone (NTX) is clinically efficacious at attenuating alcohol intake in non-abstinent alcoholics and, to a lesser extent, craving, independent of intake. While generally regarded as a non-selective opioid antagonist, NTX has been shown to have concentration dependent selectivity with lower doses (< 1.0 mg/kg) selective for the mu receptor and doses exceeding 1.0 mg/kg capable of binding to delta and kappa receptors. Like the mu system, the delta receptor system has also been implicated in mediating the rewarding effects of EtOH. In contrast, the role of the kappa system is less clear though recent evidence suggests that kappa activation may mediate EtOH aversion. Thus, the present study sought to evaluate the effects of both mu-selective and non-selective doses of naltrexone, the selective delta antagonist naltrindole (NTI), and the selective kappa agonist U50,488H (U50) in a paradigm that procedurally separates the motivation to seek versus consume a reinforcer to assess whether these receptor-selective drugs differentially affects these behaviors in both selected (alcohol-preferring P rats) and non-selected (Long Evans) rats, and whether these effects are specific to EtOH. Rats were trained to complete a single response requirement that resulted in access to either 2% sucrose or 10% EtOH for a 20-min drinking session. In three separate experiments, rats were injected (using a balanced design) with either vehicle or 1 of 3 doses of drug: U50 (IP; 2.5, 5.0, or 10.0mg/kg), NTI (IP; 2.5, 5.0, or 10.0 mg/kg), low NTX (SC; 0.1, 0.3, or 1.0 mg/kg) or high NTX (SC; 1.0, 3.0, or 10.0 mg/kg) on both consummatory and appetitive treatment days. Following either a 20 (U50), 15 (NTI), or 30 minute (NTX) pretreatment, rats were placed into an operant chamber and intake (consummatory) or lever responses (appetitive) and response latencies were recorded. The results showed that overall: U50, NTI, and NTX attenuated intake and responding for sucrose and EtOH. Independent of reinforcer, LE rats were more sensitive to U50’s effects on intake while P rats were more sensitive to the effects on seeking. P rats reinforced with EtOH were more sensitive to NTI’s effects on intake and seeking than all other rat groups. P rats were more sensitive overall to lower doses of NTX than LE rats and lower doses of NTX were more selective in attenuating EtOH responding vs. sucrose. Higher doses of NTX suppressed intake and responding across both lines and reinforcers. These results demonstrate that craving and intake may be differentially regulated by the kappa, delta, and mu opioid receptor systems as a function of “family history” and suggest that different mechanisms of the same (opioid) system may differentially affect craving and intake.Item Greater inhibition of female rat binge alcohol intake by adrenergic receptor blockers using a novel Two-Shot rat binge drinking model(Springer Nature, 2024-06-18) De Oliveira Sergio, Thatiane; Smith, Rebecca Jane; Wean, Sarah E.; Engleman, Eric A.; Hopf, Frederic W.; Psychiatry, School of MedicineBinge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and to better understand individual and sex differences in neurobiological mechanisms related to BD, the use of outbred rat strains would be valuable. Here, we developed a novel BD model where after 3+ months of intermittent access to 20% alcohol Wistar rats drank, twice a week, with two 5-min intake (what we called Two-shot) separated by a 10-min break. Our findings showed during Two-Shot that most animals reached ≥ 80 mg% BAC levels (when briefly food-restricted). However, when increasing alcohol concentrations from 20 to 30%, 40%, or 50%, rats titrated to similar intake levels, suggesting rapid sensing of alcohol effects even when front-loading. Two-Shot drinking was reduced in both sexes by naltrexone (1 mg/kg), validating intake suppression by a clinical therapeutic agent for human problem drinking. Further, both propranolol (β-adrenergic receptor antagonist) and prazosin (α1-adrenergic receptor antagonist) reduced female but not male BD at the lower dose. Thus, our results provide a novel model for BD in outbred rats and suggest that female binging is more sensitive to adrenergic modulation than males, perhaps providing a novel sex-related therapy.Item Medication for Adolescents and Young Adults with Opioid Use Disorder(Elsevier, 2021) Hadland, Scott E.; Aalsma, Matthew C.; Akgül, Sinem; Alinsky, Rachel H.; Bruner, Ann; Chadi, Nicholas; Galagali, Preeti M.; Kreida, Ellen C.; Robinson, Camille A.; Wilson, J. Deanna; Pediatrics, School of MedicineOpioid-related morbidity and mortality have risen in many settings globally. It is critical that practitioners who work with adolescents and young adults (AYAs) provide timely, evidence-based treatment for opioid use disorder (OUD). Such treatment should include medications for opioid use disorder (MOUD), including buprenorphine, naltrexone, and methadone. Medication treatment is associated with reduced mortality, fewer relapses to opioid use, and enhanced recovery and retention in addiction care, among other positive health outcomes. Unfortunately, the vast majority of AYAs with OUD do not receive medication. The Society for Adolescent Health and Medicine recommends that AYAs be offered MOUD as a critical component of an integrated treatment approach. Barriers to receipt of medications are widespread; many are common to high-, middle-, and low-income countries alike, whereas others differ. Such barriers should be minimized to ensure equitable access to youth-friendly, affirming, and confidential addiction treatment that includes MOUD. Robust education on OUD and medication treatment should be provided to all practitioners who work with AYAs. Strategies to reduce stigma surrounding medication-and stigma experienced by individuals with substance use disorders more generally-should be widely implemented. A broad research agenda is proposed with the goal of expanding the evidence base for the use and delivery of MOUD for AYAs.Item Prazosin + Naltrexone Decreases Alcohol Drinking More Effectively Than Does Either Drug Alone in P Rats with a Protracted History of Extensive Voluntary Alcohol Drinking, Dependence, and Multiple Withdrawals(Wiley, 2015-09) Rasmussen, Dennis D.; Kincaid, Carrie L.; Froehlich, Janice C.; Department of Medicine, IU School of MedicineBackground Prazosin (PRZ, an α1-adrenergic receptor antagonist) and naltrexone (NTX, a non-specific opioid receptor antagonist) each decrease alcohol drinking when administered to rats selectively-bred for high voluntary alcohol drinking (alcohol-preferring, or “P”), and the combination of PRZ+NTX decreases alcohol drinking more effectively than does either drug alone. Since drug responsiveness can depend on history of alcohol drinking and dependence, we investigated whether various schedules of PRZ and NTX administration, alone or in combination, are effective in decreasing alcohol drinking in male P rats with a history of protracted voluntary alcohol drinking, dependence and repeated withdrawals closely resembling human alcoholism. Methods Male P rats became alcohol-dependent during 1 year of ad libitum 24 h/day access to food, water and 20% alcohol with repetitive temporary alcohol withdrawals. Four sequential studies then addressed effects of oral PRZ (2 mg/kg) and NTX (10 mg/kg), alone or together, on alcohol drinking during: 1) daily alcohol access with daily drug treatment, 2) intermittent alcohol access with daily drug treatment, 3) intermittent alcohol access with occasional drug treatment, and 4) post-deprivation reinstatement of alcohol access. Results The combination of PRZ+NTX consistently suppressed alcohol drinking during daily or intermittent alcohol access conditions and when drug treatment was either daily or occasional. PRZ+NTX was consistently more effective than either drug alone. The reduction in alcohol drinking was not due to sedation, motor effects or malaise. Conclusions Both daily and “as-needed” treatment with PRZ+NTX are highly effective in suppressing daily, intermittent and post-deprivation alcohol drinking in male P rats with a protracted history of alcohol dependence and repeated withdrawals. This drug combination may be especially effective for treating individuals with long histories of heavy alcohol abuse, dependence and repeated relapse, as commonly encountered in clinical practice.Item Racial and Ethnic Disparities in Buprenorphine and Extended-Release Naltrexone Filled Prescriptions During the COVID-19 Pandemic(American Medical Association, 2022) Nguyen, Thuy; Ziedan, Engy; Simon, Kosali; Miles, Jennifer; Crystal, Stephen; Samples, Hillary; Gupta, Sumedha; Economics, School of Liberal ArtsImportance: COVID-19 disrupted delivery of buprenorphine and naltrexone treatment for opioid use disorder (OUD), and during the pandemic, members of racial and ethnic minority groups experienced increased COVID-19 and opioid overdose risks compared with White individuals. However, whether filled buprenorphine and naltrexone prescriptions varied across racial and ethnic groups during the COVID-19 pandemic remains unknown. Objective: To investigate whether disruptions in filled buprenorphine and naltrexone prescriptions differed by race and ethnicity and insurance status or payer type. Design, setting, and participants: This cross-sectional study used retail pharmacy claims from May 2019 to June 2021 from the Symphony Health database, which includes 92% of US retail pharmacy claims, with race and ethnicity data spanning all insurance status and payer categories. Interrupted time series were used to estimate levels and trends of dispensed buprenorphine and naltrexone prescriptions before and after pandemic onset. Included individuals were those who filled buprenorphine and extended-release naltrexone prescriptions. Data were analyzed from July 2021 through March 2022. Main outcomes and measures: Weekly rates of dispensed buprenorphine and extended-release naltrexone prescription fills per 1000 patients and proportion of longer (ie, ≥14 days' supply) buprenorphine prescription fills were calculated. Analyses were stratified by patient race and ethnicity and further by insurance status and payer type for White and Black patients. Results: A total of 1 556 860 individuals who filled buprenorphine prescriptions (4359 Asian [0.3%], 94 657 Black [6.1%], 55 369 Hispanic [3.6%], and 664 779 White [42.7%]) and 127 506 individuals who filled extended-release naltrexone prescriptions (344 Asian [0.3%], 8186 Black [6.4%], 5343 Hispanic [4.2%], and 53 068 White [41.6%]) from May 6, 2019, to June 5, 2021, were analyzed. Prepandemic increases in buprenorphine fill rate flattened for all groups after COVID-19 onset (30.5 percentage point difference in trend; P < .001) compared with prepandemic trends. Significant level decreases in buprenorphine fills (ranging from 2.5% for Black patients; P = .009 to 4.0% for Hispanic patients; P = .009) at pandemic onset were observed for members of racial and ethnic minority groups but not White patients. At pandemic onset, rate of buprenorphine fills decreased in level for Medicare and cash-paying patients but with greater decreases for Black patients (Medicare: 10.0%; P < .001; cash: 20.0%; P < .001) than White patients (Medicare: 3.5%; P = .004; cash: 15.0%; P < .001). No decreases were found among Medicaid patients. Unlike buprenorphine, extended-release naltrexone had uniform level (from 10.0% for White patients with private insurance; P < .001 to 23.3% for Black patients with Medicare; P < .001) and trend (from 15.5 percentage points for White patients with Medicaid; P = .001 to 52.0 percentage points for Black patients with private insurance; P < .001) decreases across groups. Conclusions and relevance: This study found that the COVID-19 pandemic was associated with immediate decreases in filled buprenorphine prescriptions by members of racial and ethnic minority groups but not White individuals. These findings suggest that members of racial and ethnic minority groups had larger losses in buprenorphine access during the pandemic across payer types.