-
Journal of Studies on Alcohol and Drugs Sep 2019U.S. Food and Drug Administration (FDA)-approved medications exist for the treatment of alcohol use disorders. However, their effectiveness depends on proper adherence... (Comparative Study)
Comparative Study
OBJECTIVE
U.S. Food and Drug Administration (FDA)-approved medications exist for the treatment of alcohol use disorders. However, their effectiveness depends on proper adherence to the prescribed regimen. Differences in adherence across medications may have implications for clinical outcomes and may provide helpful information in considering treatment options. This study aims to identify significant differences in adherence if present.
METHOD
A retrospective chart review was conducted in the Veterans Integrated Service Networks (VISN)-7 region of Veterans Affairs hospital and community-based outpatient clinics within South Carolina and Georgia. Prescriptions of FDA-approved alcohol use disorder medications from 2010 through 2015 were reviewed. Adherence was determined by the proportion of days the veteran had oral or injectable medication available over a 6-month period as noted by medication fills (reported as 0%-100% medication availability). We compared adherence for specific medications using chi-square, t test, logistic regression for dichotomous outcomes, and linear regression for continuous outcomes.
RESULTS
A total of 715 subjects and 807 medication trials were included. Mean adherence (percentage of days that medication was available) was 41.3% for disulfiram, 44.7% for acamprosate, 49.8% for oral naltrexone, and 54.6% for extended-release injectable naltrexone. The mean adherence was significantly different between disulfiram and oral naltrexone (p = .002) as well as disulfiram and extended-release injectable naltrexone (p = .004). Adherence of 80% was achieved in 11.9%, 19.4%, 22.7%, and 24.4% of treatment courses with disulfiram, acamprosate, naltrexone, and extended-release injectable naltrexone, respectively. These differences were significant for disulfiram versus oral naltrexone (p = .004) and disulfiram versus extended-release injectable naltrexone (p = .05).
CONCLUSIONS
These results demonstrate that overall adherence to medication-assisted treatment for alcohol use disorder is low across all medications. When directly compared, disulfiram had significantly lower adherence than both oral and extended-release injectable naltrexone.
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Disulfiram; Female; Humans; Male; Medication Adherence; Middle Aged; Naltrexone; Retrospective Studies; United States; United States Department of Veterans Affairs; United States Food and Drug Administration; Veterans
PubMed: 31603760
DOI: 10.15288/jsad.2019.80.572 -
Addiction (Abingdon, England) Sep 2020To examine whether World Health Organization (WHO) risk-level reductions in drinking were achievable, associated with improved functioning and maintained over time among... (Randomized Controlled Trial)
Randomized Controlled Trial
World Health Organization risk drinking level reductions are associated with improved functioning and are sustained among patients with mild, moderate and severe alcohol dependence in clinical trials in the United States and United Kingdom.
AIMS
To examine whether World Health Organization (WHO) risk-level reductions in drinking were achievable, associated with improved functioning and maintained over time among patients at varying initial alcohol dependence severity levels. Design and setting Secondary data analysis of multi-site randomized clinical trials: the US Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study and the UK Alcohol Treatment Trial (UKATT).
PARTICIPANTS
Individuals with alcohol dependence enrolled in COMBINE (n = 1383; 68.8% male) and seeking treatment for alcohol problems in UKATT (n = 742; 74.1% male). Interventions Naltrexone, acamprosate or placebo, and combined behavioral intervention or medication management in COMBINE. Social behavior network therapy or motivational enhancement therapy in UKATT.
MEASUREMENTS
WHO risk-level reductions were assessed via the calendar method. Alcohol dependence was measured by the Alcohol Dependence Scale, the Leeds Dependence Questionnaire and the Diagnostic and Statistical Manual of Mental Disorders. Measures of functioning included alcohol-related consequences (Drinker Inventory of Consequences and Alcohol Problems Questionnaire), mental health (Short Form Health Survey) and liver enzyme tests.
FINDINGS
One- and two-level reductions in WHO risk levels in the last month of treatment were maintained at the 1-year follow-up [adjusted odds ratio (OR), 95% confidence interval (CI) = one-level reduction in COMBINE: 3.51 (2.73, 4.29) and UKATT: 2.65 (2.32, 2.98)] and associated with fewer alcohol-related consequences [e.g. B, 95% CI = one-level reduction COMBINE: -26.22 (-30.62, -21.82)], better mental health [e.g. B, 95% CI = one-level reduction UKATT: 9.53 (7.36, 11.73)] and improvements in γ-glutamyltransferase [e.g. B, 95% CI = one-level reduction UKATT: -89.77 (-122.50, -57.04)] at the end of treatment, even among patients with severe alcohol dependence. Results were similar when abstainers were excluded. Conclusions Reductions in World Health Organization risk levels for alcohol consumption appear to be achievable, associated with better functioning and maintained over time in both the United States and the United Kingdom.
Topics: Acamprosate; Adult; Alcohol Deterrents; Alcohol Drinking; Alcohol-Related Disorders; Alcoholism; Behavior Therapy; Female; Health Surveys; Humans; Male; Mental Health; Middle Aged; Motivational Interviewing; Naltrexone; Risk; Treatment Outcome; United Kingdom; United States; World Health Organization
PubMed: 32056311
DOI: 10.1111/add.15011 -
The Australian and New Zealand Journal... Feb 2024Alcohol use disorders confer a significant burden of disease and economic cost worldwide. However, the utilisation of pharmacotherapies to manage alcohol use disorder is... (Review)
Review
OBJECTIVE
Alcohol use disorders confer a significant burden of disease and economic cost worldwide. However, the utilisation of pharmacotherapies to manage alcohol use disorder is poor. We aimed to conduct a systematic review of economic evaluation studies of alcohol use disorder pharmacotherapies.
METHODS
A search was conducted in Embase, Medline, CINAHL, PsychINFO and EconLit (August 2019, updated September 2022). Full economic evaluations using pharmacotherapy to treat alcohol use disorders were included. Included studies were stratified by medication and summarised descriptively. The Consensus on Health Economic Criteria list was used to assess the methodological quality.
RESULTS
A total of 1139 studies were retrieved, of which 15 met the inclusion criteria. All studies were conducted in high-income countries. Four studies analysed nalmefene, four studies assessed acamprosate, three for naltrexone and four for stand-alone and/or combinations of naltrexone and acamprosate. There were 21 interventions synthesised from 15 studies as some studies evaluated multiple interventions and comparators. More than half of the included studies (73%) reported pharmacotherapy as dominant (less costly and more effective than comparators). From healthcare payer perspectives, five studies found that pharmacotherapy added to psychosocial support was dominant or cost-effective, accruing additional benefits at a higher cost but under accepted willingness to pay thresholds. Three analyses from a societal perspective found pharmacotherapy added to psychosocial support was a dominant or cost-effective strategy. Quality scores ranged from 63% to 95%.
CONCLUSION
Pharmacotherapy added to psychosocial support was cost-effective from both healthcare and societal perspectives, emphasising an increased role for pharmacotherapy to reduce the burden of alcohol use disorders.
Topics: Humans; Alcoholism; Acamprosate; Cost-Benefit Analysis; Naltrexone; Alcohol Drinking; Ethanol
PubMed: 37822267
DOI: 10.1177/00048674231201541 -
Molecular Psychiatry Jul 2021We previously reported that SNPs near TSPAN5 were associated with plasma serotonin (5-HT) concentrations which were themselves associated with selective serotonin...
We previously reported that SNPs near TSPAN5 were associated with plasma serotonin (5-HT) concentrations which were themselves associated with selective serotonin reuptake inhibitor treatment outcomes in patients with major depressive disorder (MDD). TSPAN5 SNPs were also associated with alcohol consumption and alcohol use disorder (AUD) risk. The present study was designed to explore the biological function of TSPAN5 with a focus on 5-HT and kynurenine concentrations in the tryptophan pathway. Ethanol treatment resulted in decreased 5-HT concentrations in human induced pluripotent stem cell (iPSC)-derived neuron culture media, and the downregulation of gene expression of TSPAN5, DDC, MAOA, MAOB, TPH1, and TPH2 in those cells. Strikingly, similar observations were made when the cells were treated with acamprosate-an FDA approved drug for AUD therapy. These results were replicated in iPSC-derived astrocytes. Furthermore, TSPAN5 interacted physically with proteins related to clathrin and other vesicle-related proteins, raising the possibility that TSPAN5 might play a role in vesicular function in addition to regulating expression of genes associated with 5-HT biosynthesis and metabolism. Downregulation of TSPAN5 expression by ethanol or acamprosate treatment was also associated with decreased concentrations of kynurenine, a major metabolite of tryptophan that plays a role in neuroinflammation. Knockdown of TSPAN5 also influenced the expression of genes associated with interferon signaling pathways. Finally, we determined that TSPAN5 SNPs were associated with acamprosate treatment outcomes in AUD patients. In conclusion, TSPAN5 can modulate the concentrations of 5-HT and kynurenine. Our data also highlight a potentially novel pharmacogenomic mechanism related to response to acamprosate.
Topics: Acamprosate; Alcohol Drinking; Alcoholism; Depressive Disorder, Major; Humans; Induced Pluripotent Stem Cells; Kynurenine; Neuroinflammatory Diseases; Pharmacogenetics; Serotonin; Tetraspanins; Tryptophan Hydroxylase
PubMed: 32753686
DOI: 10.1038/s41380-020-0855-9 -
Neurological Research Dec 2021Alcohol abuse causes several neurological disorders. Resveratrol is a natural polyphenol that occurs as a phytoalexin. In different studies, it has been investigated...
OBJECTIVE
Alcohol abuse causes several neurological disorders. Resveratrol is a natural polyphenol that occurs as a phytoalexin. In different studies, it has been investigated that resveratrol has positive effects on various mechanisms that are important in drug addiction or substance use disorder. The objective of the present study was to examine the effect of resveratrol on alcohol-induced conditioned place preference (CPP) in mice.
METHODS
CPP was induced by intraperitoneal (i.p.) administration of ethanol (2 g/kg) in an 8-day conditioning program. The influence of reference drug, acamprosate and resveratrol on the rewarding properties of ethanol was tested in mice given treatment of acamprosate (300 mg/kg, i.p.) and resveratrol (25, 50, and 75 mg/kg, i.p.) 30 minutes prior to ethanol administration. Once established, CPP was extinguished by repeated testing, through which conditioned mice were administered acamprosate, various doses of resveratrol or saline daily. Subsequently, the potency of acamprosate and resveratrol in preventing reinstatement of CPP provoked by priming with low-dose ethanol (0.4 g/kg, i.p.) was also evaluated.
RESULTS
The present findings confirm that resveratrol impairs acquisition, reinstatement and precipitates the extinction of preference for alcohol-induced CPP. Resveratrol presented a similar effect in the CPP phases to the acamprosate.
CONCLUSIONS
The effect of resveratrol on ethanol-induced CPP in mice demonstrated for the first time. As a conclusion, these findings may shed light on the fact that resveratrol can be utilized as an agent which is potentially beneficial to prevent the various harmful effects of ethanol, however, more research is needed to completely elucidate this attribute.
Topics: Animals; Behavior, Animal; Central Nervous System Depressants; Conditioning, Operant; Ethanol; Male; Mice; Resveratrol
PubMed: 34210247
DOI: 10.1080/01616412.2021.1948749 -
Journal of General Internal Medicine Apr 2022Hospitalizations related to the consequences of substance use are rising yet most hospitalized patients with substance use disorder do not receive evidence-based...
INTRODUCTION
Hospitalizations related to the consequences of substance use are rising yet most hospitalized patients with substance use disorder do not receive evidence-based addiction treatment. Opportunities to leverage the hospitalist workforce could close this treatment gap.
AIM
To describe the development, implementation, and evaluation of a hospitalist-directed addiction consultation service (ACS) to provide in-hospital addiction treatment.
SETTING
Six hundred fifty-bed university hospital in Aurora, Colorado.
PROGRAM DESCRIPTION
Hospitalists completed buprenorphine waiver training, participated in a 13-part addiction lecture series, and completed a minimum of 40 hours of online addiction training. Hospitalists participated in shadow shifts with an addiction-trained physician. Dedicated addiction social workers developed relationships with local addiction treatment services.
PROGRAM EVALUATION METRICS
Physician-related metrics included education, training, and clinical time spent in addiction practice. Patient and encounter-related metrics included a description of ACS care provision.
RESULTS
Eleven hospitalists completed an average of 95 hours of addiction-related didactics. Once addiction training was complete, hospitalists spent an average of 30 days over 12 months staffing a weekday ACS. Between October 2019 and November 2020, the ACS completed 1620 consultations on 1350 unique patients. Alcohol was the most common substance (n = 1279; 79%), followed by tobacco (979; 60.4%), methamphetamines/amphetamines (n = 494; 30.5%), and opioids (n = 400; 24.7%). Naltrexone was the most frequently prescribed medication (n = 350; 21.6%), followed by acamprosate (n = 93; 5.7%), and buprenorphine (n = 77, 4.8%). Trauma was a frequent discharge diagnoses (n = 1564; 96.5%). Leaving prior to treatment completion was commonly noted (n = 120, 7.4%). The ACS completed 47 in-hospital methadone enrollments.
DISCUSSION
The hospitalist-directed ACS is a promising clinical initiative that could be implemented to expand hospital-based addiction treatment. Future research is needed to understand challenges to disseminating this model into other hospital settings, and to evaluate intended and unintended effects of broad implementation.
Topics: Addiction Medicine; Hospitalists; Hospitalization; Humans; Medicine; Referral and Consultation
PubMed: 34013473
DOI: 10.1007/s11606-021-06849-8 -
Alcoholism, Clinical and Experimental... Oct 2020One of the challenges in early-stage clinical research aimed at developing novel treatments for alcohol use disorder (AUD) is that the enrolled participants are heavy... (Randomized Controlled Trial)
Randomized Controlled Trial
Differences in Sociodemographic and Alcohol-Related Clinical Characteristics Between Treatment Seekers and Nontreatment Seekers and Their Role in Predicting Outcomes in the COMBINE Study for Alcohol Use Disorder.
BACKGROUND
One of the challenges in early-stage clinical research aimed at developing novel treatments for alcohol use disorder (AUD) is that the enrolled participants are heavy drinkers, but do not seek treatment for AUD.
AIMS
To compare nontreatment seekers with alcohol dependence (AD) from 4 human laboratory studies conducted at Brown University (N = 240; 65.4% male) to treatment seekers with AD from the multisite COMBINE study (N = 1,383; 69.1% male) across sociodemographic and alcohol-related clinical variables and to evaluate whether the variables that significantly differentiate the 2 samples predict the 3 main COMBINE clinical outcomes: time to relapse, percent days abstinent (PDA), and good clinical outcome.
METHODS
Sample characteristics were assessed by parametric and nonparametric testing. Three regression models measured the association between the differing variables and the 3 main COMBINE clinical outcomes.
RESULTS
The nontreatment seekers, compared to the treatment seekers, were more ethnically diverse, less educated, single, and working part-time or unemployed (p's < 0.05); they met fewer DSM-IV AD criteria and had significantly lower scores on alcohol-related scales (p's < 0.05); they were less likely to have a father with alcohol problems (p < 0.0001) and had a significantly earlier age of onset and longer duration of AD (p's < 0.05); they also had significantly more total drinks, drinks per drinking day, heavy drinking days (HDD), and lower PDA in the 30 days prior to baseline (p's < 0.0001 to <0.05). Having more HDD in the 30 days prior to baseline predicted all of the 3 COMBINE clinical outcomes. All the other characteristics mentioned above that differed significantly between the 2 groups predicted at least 1 of the 3 COMBINE clinical outcomes, except for level of education, age of onset, and duration of AD.
CONCLUSIONS
The observed differences between groups should be considered in efforts across participant recruitment at different stages of the development of new treatments for AUD.
Topics: Acamprosate; Adult; Age of Onset; Alcohol Deterrents; Alcoholism; Case-Control Studies; Drug Therapy, Combination; Female; Humans; Male; Naltrexone; Patient Acceptance of Health Care; Socioeconomic Factors; Treatment Outcome
PubMed: 32997422
DOI: 10.1111/acer.14428 -
Alcoholism, Clinical and Experimental... Jun 2022Investigations show that medications for alcohol use disorders (MAUD) reduce heavy drinking and relapses. However, only 1.6% of individuals with alcohol use disorders...
RATIONALE
Investigations show that medications for alcohol use disorders (MAUD) reduce heavy drinking and relapses. However, only 1.6% of individuals with alcohol use disorders (AUD) receive MAUD across care settings. The epidemiology of MAUD prescribing in the acute care setting is incompletely described. We hypothesized that MAUD would be under prescribed in inpatient acute care hospital settings compared to the outpatient, emergency department (ED), and inpatient substance use treatment settings.
METHODS
We evaluated electronic health record (EHR) data from adult patients with an International Classification of Diseases, 10th revision (ICD-10) alcohol-related diagnosis in the University of Colorado Health (UCHealth) system between January 1, 2016 and 31 December, 2019. Data from patients with an ICD-10 diagnosis code for opioid use disorder and those receiving MAUD prior to their first alcohol-related episode were excluded. The primary outcome was prescribing of MAUD, defined by prescription of naltrexone, acamprosate, and/or disulfiram. We performed bivariate and multivariate analyses to identify independent predictors of MAUD prescribing at UCHealth.
RESULTS
We identified 48,421 unique patients with 136,205 alcohol-related encounters at UCHealth. Encounters occurred in the ED (42%), inpatient acute care (17%), inpatient substance use treatment (18%), or outpatient primary care (12%) settings. Only 2270 (5%) patients received MAUD across all settings. Female sex and addiction medicine consults positively predicted MAUD prescribing. In contrast, encounters outside inpatient substance use treatment, Hispanic ethnicity, and black or non-white race were negative predictors of MAUD prescribing. Compared to inpatient substance use treatment, inpatient acute care hospitalizations for AUD was associated with a 93% reduced odds of receiving MAUD.
CONCLUSIONS
AUD-related ED and inpatient acute care hospital encounters in our healthcare system were common. Nevertheless, prescriptions for MAUD were infrequent in this population, particularly in inpatient settings. Our findings suggest that the initiation of MAUD for patients with alcohol-related diagnoses in acute care settings deserves additional evaluation.
Topics: Adult; Alcoholism; Colorado; Delivery of Health Care; Ethanol; Female; Humans; Naltrexone; Opioid-Related Disorders
PubMed: 35723682
DOI: 10.1111/acer.14837 -
Academic Emergency Medicine : Official... May 2024Alcohol-related concerns commonly present to the emergency department (ED), with a subset of individuals experiencing the symptoms of an alcohol use disorder (AUD). As... (Review)
Review
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.
Topics: Humans; Emergency Service, Hospital; Alcoholism; Alcohol Deterrents; Naltrexone; Acamprosate; Craving; Adult
PubMed: 37735346
DOI: 10.1111/acem.14806 -
Cureus Apr 2024Background Alcohol use disorder (AUD) is one of the most common substance use disorders globally. It is a chronic mental illness characterized by frequent...
Background Alcohol use disorder (AUD) is one of the most common substance use disorders globally. It is a chronic mental illness characterized by frequent relapses. Hence, preventing relapse is one of the most important aspects of the management of patients with AUD. Aims This study aimed to compare the role of acamprosate and baclofen as anti-craving agents in patients diagnosed with AUD. Settings and design This was a 12-week interventional follow-up study conducted in the Department of Psychiatry of S N Medical College, a tertiary care teaching hospital in Agra, Uttar Pradesh, India. Methods and materials Patients with AUD were enrolled in the study. Following medical management of alcohol withdrawal symptoms, patients were alternately assigned to receive either acamprosate or baclofen and were then followed up for 12 weeks. Measures to compare the effectiveness of the two medications were craving as measured using the Penn Alcohol Craving Scale (PACS), days to first alcohol consumption, days to relapse, number of drinks consumed at one occasion, number of patients who completed the study, and number of patients who remained abstinent throughout the duration of the study. Descriptive statistics were used to present the data while unpaired t-test and Fisher's exact test were used to compare the two groups. Results A total of 63 patients were enrolled in the study. Following medical management of alcohol withdrawal symptoms for one week, 50 (79.37%) patients were retained in the study. Hence, these 50 patients were assigned to treatment with either acamprosate or baclofen alternately in a 1:1 ratio. Only 32 (64%) of the patients who were started on these medications completed the study and were available for analysis at the end of 12 weeks. Acamprosate-treated patients were found to have less severe cravings (p < 0.01) for alcohol at the end of the study and also had consumed less number of drinks on a single occasion (p < 0.05). For other variables being considered in the study, namely, days to first alcohol consumption, days to relapse to previous drinking pattern, number of patients who dropped from the study versus those who completed the study, and those who were abstinent versus those who relapsed, no statistically significant difference was noted. Conclusion Acamprosate-treated patients had significantly lesser cravings for alcohol and consumed a lesser number of drinks on one occasion compared to baclofen-treated patients in this 12-week study.
PubMed: 38741835
DOI: 10.7759/cureus.58174