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International Journal of Environmental... Jan 2023No single effective therapy for alcohol abuse has been found, despite it being a serious sociological and economic problem for hundreds of years. It seems difficult to... (Review)
Review
No single effective therapy for alcohol abuse has been found, despite it being a serious sociological and economic problem for hundreds of years. It seems difficult to find a single drug as a panacea for the alcohol problem due to the complexity of the pathophysiology of alcohol dependence. The purpose of this narrative review is to review existing and potentially future pharmaceuticals for the treatment of alcohol dependence in the most affordable way possible. Psychotherapy is the mainstay of treatment for alcoholism, while few drugs approved by legislators are available in the augmentation of this treatment, such as acamprosate, disulfiram, and naltrexone, approved by the FDA, and nalmefene by the EMA. There are recent reports in the literature on the possibility of using baclofen, topiramate, varenicline, and gabapentin in the treatment of alcohol dependence. Moreover, the results of recent clinical trials using psychoactive substances such as psilocybin and MDMA appear to be a breakthrough in the modern treatment of alcohol abuse. Despite this initial optimism, a lot of scientific effort is still needed before new pharmacological methods supporting the treatment of alcohol dependence syndrome will be widely available.
Topics: Humans; Alcoholism; Public Health; Acamprosate; Disulfiram; Pharmaceutical Preparations; Alcohol Deterrents; Taurine
PubMed: 36767234
DOI: 10.3390/ijerph20031870 -
Journal of Medical Toxicology :... Apr 2021Implementing a hospital medication for addiction treatment (MAT) and a linkage program can improve care for patients with substance use disorder (SUD); however, lack of...
INTRODUCTION
Implementing a hospital medication for addiction treatment (MAT) and a linkage program can improve care for patients with substance use disorder (SUD); however, lack of hospital funding and brick and mortar SUD resources are potential barriers to feasibility.
METHODS
This study assesses the feasibility of implementation of a SUD linkage program. Components of the program include a county-funded hospital opioid support team (HOST), a hospital-employed addiction recovery specialist (ARS), and a medical toxicology MAT induction service and maintenance program. Data for linkage by HOST, ARS, and MAT program were tracked from July 2018 to December 2019.
RESULTS
From July 2018 through December 2019, 1834 patients were linked to treatment: 1536 by HOST and 298 by the ARS. The most common disposition categories for patients linked by HOST were 16.73% to medically monitored detoxification, 9.38% to intensive outpatient, and 8.59% to short-term residential treatment. Among patients linked by the ARS, 65.66% were linked to outpatient treatment and 9.43% were linked directly to inpatient treatment. A total of 223 patients managed by the ARS were started on MAT by medical toxicology and linked to outpatient MAT clinic: 72.68% on buprenorphine/naloxone, 24.59% on naltrexone, 1.09% buprenorphine, and 0.55% acamprosate.
CONCLUSION
Implementing a MAT and linkage program in the ED and hospital setting was feasible. Leveraging medical toxicology expertise as well as community and funding partnerships was crucial to successful implementation.
Topics: Adult; Buprenorphine; Female; Humans; Interprofessional Relations; Male; Methadone; Middle Aged; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Care Team; United States
PubMed: 33146875
DOI: 10.1007/s13181-020-00813-4 -
BMC Public Health Feb 2023This study aimed to identify targeted interventions for the prevention and treatment of harmful alcohol use. Umbrella review methodology was used to summarise the... (Review)
Review
Which interventions for alcohol use should be included in a universal healthcare benefit package? An umbrella review of targeted interventions to address harmful drinking and dependence.
BACKGROUND
This study aimed to identify targeted interventions for the prevention and treatment of harmful alcohol use. Umbrella review methodology was used to summarise the effectiveness across a broad range of interventions, in order to identify which interventions should be considered for inclusion within universal health coverage schemes in low- and middle-income countries.
METHODS AND FINDINGS
We included systematic reviews with meta-analysis of randomised controlled trials (RCTs) on targeted interventions addressing alcohol use in harmful drinkers or individuals with alcohol use disorder. We only included outcomes related to alcohol consumption, heavy drinking, binge drinking, abstinence, or alcohol-attributable accident, injury, morbidity or mortality. PubMed, Embase, PsycINFO, Cochrane Database of Systematic Reviews, and the International HTA Database were searched from inception to 3 September 2021. Risk of bias of reviews was assessed using the AMSTAR2 tool. After reviewing the abstracts of 9,167 articles, results were summarised narratively and certainty in the body of evidence for each intervention was assessed using GRADE. In total, 86 studies met the inclusion criteria, of which the majority reported outcomes for brief intervention (30 studies) or pharmacological interventions (29 studies). Overall, methodological quality of included studies was low.
CONCLUSIONS
For harmful drinking, brief interventions, cognitive behavioural therapy, and motivational interviewing showed a small effect, whereas mentoring in adolescents and children may have a significant long-term effect. For alcohol use disorder, social network approaches and acamprosate showed evidence of a significant and durable effect. More evidence is required on the effectiveness of gamma-hydroxybutyric acid (GHB), nalmefene, and quetiapine, as well as optimal combinations of pharmacological and psychosocial interventions. As an umbrella review, we were unable to identify the extent to which variation between studies stemmed from differences in intervention delivery or variation between country contexts. Further research is required on applicability of findings across settings and best practice for implementation. Funded by the Thai Health Promotion Foundation, grant number 61-00-1812.
Topics: Adolescent; Child; Humans; Alcohol Drinking; Alcoholism; Cognitive Behavioral Therapy; Ethanol; Systematic Reviews as Topic; Universal Health Care
PubMed: 36823618
DOI: 10.1186/s12889-023-15152-6 -
Indian Journal of Psychiatry 2020The efficacy of naltrexone, baclofen, and acamprosate in the treatment of alcohol dependence has been successfully established over the past several years. The knowledge...
BACKGROUND
The efficacy of naltrexone, baclofen, and acamprosate in the treatment of alcohol dependence has been successfully established over the past several years. The knowledge about their relative efficacies can facilitate in developing relapse prevention strategies that would give rise to a greater personal and socioeconomic benefits.
AIMS AND OBJECTIVE
To assess and compare the safety and efficacy profile of naltrexone, baclofen, and acamprosate in the treatment of alcohol dependence. In addition to this, the pattern of relapse and attitude of patients toward the treatment were also assessed.
MATERIALS AND METHODS
This was a prospective study carried out at a tertiary care center. It comprised of thirty alcohol-dependent patients each assigned to naltrexone, baclofen, and acamprosate group after detoxification. The patients were assessed for craving, relapse risk, and medication adherence using the respective scales and questionnaires.
RESULTS
In terms of Obsessive Compulsive Drinking Scale score decline, the decline seen in the naltrexone group (26.72 ± 13.05) was maximum, followed by baclofen and acamprosate. In terms of decreasing Advance Warning of Relapse (AWARE) questionnaire score, again naltrexone was most effective, with the maximum decline in AWARE score (64.72 ± 45.65), followed by baclofen and acamprosate. The attitude toward treatment with all the three medications was positive, as per the Hogan Drug Attitude Inventory score.
CONCLUSION
Naltrexone was most effective in decreasing craving and drinking behavior. Baclofen showed best tolerability in terms of liver function tests and least number of side effects reported. Naltrexone group reported the least number of relapses but maximum number of side effects. Acamprosate group had the maximum dropout rate.
PubMed: 33896969
DOI: 10.4103/psychiatry.IndianJPsychiatry_201_19 -
BMC Gastroenterology Feb 2023Alcohol cessation is the cornerstone of treatment for alcohol-related cirrhosis. This study evaluated associations between medical conversations about alcohol use...
BACKGROUND
Alcohol cessation is the cornerstone of treatment for alcohol-related cirrhosis. This study evaluated associations between medical conversations about alcohol use disorder (AUD) treatment, AUD treatment engagement, and mortality.
METHODS
This retrospective cohort study included all patients with ICD-10 diagnosis codes for cirrhosis and AUD who were engaged in hepatology care in a single healthcare system in 2015. Baseline demographic, medical, liver disease, and AUD treatment data were assessed. AUD treatment discussions and initiation, alcohol cessation, and subsequent 5-year mortality were collected. Multivariable models were used to assess the factors associated with subsequent AUD treatment and 5-year mortality.
RESULTS
Among 436 patients with cirrhosis due to alcohol, 65 patients (15%) received AUD treatment at baseline, including 48 (11%) receiving behavioral therapy alone, 11 (2%) receiving pharmacotherapy alone, and 6 (1%) receiving both. Over the first year after a baseline hepatology visit, 37 patients engaged in AUD treatment, 51 were retained in treatment, and 14 stopped treatment. Thirty percent of patients had hepatology-documented AUD treatment recommendations and 26% had primary care-documented AUD treatment recommendations. Most hepatology (86%) and primary care (88%) recommendations discussed behavioral therapy alone. Among patients with ongoing alcohol use at baseline, AUD treatment one year later was significantly, independently associated with AUD treatment discussions with hepatology (adjusted odds ratio (aOR): 3.23, 95% confidence interval (CI): 1.58, 6.89) or primary care (aOR: 2.95; 95% CI: 1.44, 6.15) and negatively associated with having Medicaid insurance (aOR: 0.43, 95% CI: 0.18, 0.93). When treatment was discussed in both settings, high rates of treatment ensued (aOR: 10.72, 95% CI: 3.89, 33.52). Over a 5-year follow-up period, 152 (35%) patients died. Ongoing alcohol use, age, hepatic decompensation, and hepatocellular carcinoma were significantly associated with mortality in the final survival model.
CONCLUSION
AUD treatment discussions were documented in less than half of hepatology and primary care encounters in patients with alcohol-related cirrhosis, though such discussions were significantly associated with receipt of AUD treatment.
Topics: United States; Humans; Retrospective Studies; Alcoholism; Liver Cirrhosis, Alcoholic; Longitudinal Studies
PubMed: 36732709
DOI: 10.1186/s12876-023-02656-z -
Drug and Alcohol Dependence Mar 2022Precision medicine approaches attempt to reduce variability in alcohol use disorder (AUD) outcomes by identifying patient characteristics that predict response to a...
BACKGROUND
Precision medicine approaches attempt to reduce variability in alcohol use disorder (AUD) outcomes by identifying patient characteristics that predict response to a particular treatment. Recent work has examined the extent to which individuals with AUD may seek alcohol to enhance positive experiences (reward drinking) or relieve negative states (relief drinking) and shown that a high reward/low relief phenotype predicts naltrexone treatment response. Yet, limitations of reward/relief drinking measures may hamper efforts to translate findings to clinical practice. We sought to refine a brief measure of reward/relief drinking and develop cutoff scores to identify reward/relief subgroups that predict pharmacotherapy response.
METHODS
The Inventory of Drinking Situations (IDS), used in previous studies to measure reward/relief drinking, was administered to 426 participants (77% male; average age = 45.3) in a clinical trial examining naltrexone and acamprosate.
RESULTS
Item response theory and tests of differential item functioning across sex, age, and alcohol dependence severity were used to create a 10-item measure, titled the Reward and Relief IDS (RR-IDS). Cutoff scores on the RR-IDS for the reward/relief drinking subgroups were identified using latent profile and area under the curve analyses. The cutoff scores demonstrated good construct validity. Individuals in the high reward/low relief subgroup who received naltrexone or acamprosate had a decreased likelihood of heavy drinking (large effect sizes) versus those who received placebo.
CONCLUSIONS
The RR-IDS is a practical measure for identifying reward/relief subgroups and predicting pharmacotherapy response. Pending replication of these findings, the RR-IDS could be a critical precision medicine tool for prescribing AUD medications.
Topics: Acamprosate; Alcohol Deterrents; Alcohol Drinking; Alcoholism; Female; Humans; Male; Naltrexone; Psychometrics; Reward
PubMed: 35042096
DOI: 10.1016/j.drugalcdep.2021.109257 -
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 -
Neuropharmacology May 2024Repurposing regulatory agency-approved molecules, with proven safety in humans, is an attractive option for developing new treatments for disease. We identified and...
Repurposing regulatory agency-approved molecules, with proven safety in humans, is an attractive option for developing new treatments for disease. We identified and assessed the efficacy of 3 drugs predicted by an in silico screen as having the potential to treat l-DOPA-induced dyskinesia (LID) in Parkinson's disease. We analysed ∼1.3 million Medline abstracts using natural language processing and ranked 3539 existing drugs based on predicted ability to reduce LID. 3 drugs from the top 5% of the 3539 candidates; lorcaserin, acamprosate and ganaxolone, were prioritized for preclinical testing based on i) having a novel mechanism of action, ii) having not been previously validated for the treatment of LID, iii) being blood-brain-barrier penetrant and orally bioavailable and iv) being clinical trial ready. We assessed the efficacy of acamprosate, ganaxolone and lorcaserin in a rodent model of l-DOPA-induced hyperactivity, with lorcaserin affording a 58% reduction in rotational asymmetry (P < 0.05) compared to vehicle. Acamprosate and ganaxolone failed to demonstrate efficacy. Lorcaserin, a 5HT2C agonist, was then further tested in MPTP lesioned dyskinetic macaques where it afforded an 82% reduction in LID (P < 0.05), unfortunately accompanied by a significant increase in parkinsonian disability. In conclusion, although our data do not support the repurposing of lorcaserin, acamprosate or ganaxolone per se for LID, we demonstrate value of an in silico approach to identify candidate molecules which, in combination with an in vivo screen, can facilitate clinical development decisions. The present study adds to a growing literature in support of this paradigm shifting approach in the repurposing pipeline.
Topics: Humans; Animals; Levodopa; Artificial Intelligence; Drug Repositioning; Acamprosate; Dyskinesia, Drug-Induced; Macaca; Antiparkinson Agents; Disease Models, Animal
PubMed: 38412888
DOI: 10.1016/j.neuropharm.2024.109880 -
Brain, Behavior, and Immunity Jun 2024Acamprosate is a Food and Drug Administration (FDA) approved medication for the treatment of alcohol use disorder (AUD). However, only a subset of patients achieves...
Acamprosate is a Food and Drug Administration (FDA) approved medication for the treatment of alcohol use disorder (AUD). However, only a subset of patients achieves optimal treatment outcomes. Currently, no biological measures are utilized to predict response to acamprosate treatment. We applied our established pharmaco-omics informed genomics strategy to identify potential biomarkers associated with acamprosate treatment response. Specifically, our previous open-label acamprosate clinical trial recruited 442 patients with AUD who were treated with acamprosate for three months. We first performed proteomics using baseline plasma samples to identify potential biomarkers associated with acamprosate treatment outcomes. Next, we applied our established "proteomics-informed genome-wide association study (GWAS)" research strategy, and identified 12 proteins, including interleukin-17 receptor B (IL17RB), associated with acamprosate treatment response. A GWAS for IL17RB concentrations identified several genome-wide significant signals. Specifically, the top hit single nucleotide polymorphism (SNP) rs6801605 with a minor allele frequency of 38% in the European American population mapped 4 kilobase (Kb) upstream of IL17RB, and intron 1 of the choline dehydrogenase (CHDH) gene on chromosome 3 (p: 4.8E-20). The variant genotype (AA) for the SNP rs6801605 was associated with lower IL17RB protein expression. In addition, we identified a series of genetic variants in IL17RB that were associated with acamprosate treatment outcomes. Furthermore, the variantgenotypes for all of those IL17RB SNPs were protective for alcohol relapse. Finally, we demonstrated that the basal level of mRNA expression of IL17RB was inversely correlated with those of nuclear factor-κB (NF-κB) subunits, and a significantly higher expression of NF-κB subunits was observed in AUD patients who relapsed to alcohol use. In summary, this study illustrates that IL17RB genetic variants might contribute to acamprosate treatment outcomes. This series of studies represents an important step toward generating functional hypotheses that could be tested to gain insight into mechanisms underlying acamprosate treatment response phenotypes. (The ClinicalTrials.gov Identifier: NCT00662571).
PubMed: 38852760
DOI: 10.1016/j.bbi.2024.06.007 -
PLoS Medicine Nov 2019Patients with opioid dependency prescribed opioid agonist treatment (OAT) may also be prescribed sedative drugs. This may increase mortality risk but may also increase... (Observational Study)
Observational Study
Prescription of benzodiazepines, z-drugs, and gabapentinoids and mortality risk in people receiving opioid agonist treatment: Observational study based on the UK Clinical Practice Research Datalink and Office for National Statistics death records.
BACKGROUND
Patients with opioid dependency prescribed opioid agonist treatment (OAT) may also be prescribed sedative drugs. This may increase mortality risk but may also increase treatment duration, with overall benefit. We hypothesised that prescription of benzodiazepines in patients receiving OAT would increase risk of mortality overall, irrespective of any increased treatment duration.
METHODS AND FINDINGS
Data on 12,118 patients aged 15-64 years prescribed OAT between 1998 and 2014 were extracted from the Clinical Practice Research Datalink. Data from the Office for National Statistics on whether patients had died and, if so, their cause of death were available for 7,016 of these patients. We identified episodes of prescription of benzodiazepines, z-drugs, and gabapentinoids and used linear regression and Cox proportional hazards models to assess the associations of co-prescription (prescribed during OAT and up to 12 months post-treatment) and concurrent prescription (prescribed during OAT) with treatment duration and mortality. We examined all-cause mortality (ACM), drug-related poisoning (DRP) mortality, and mortality not attributable to DRP (non-DRP). Models included potential confounding factors. In 36,126 person-years of follow-up there were 657 deaths and 29,540 OAT episodes, of which 42% involved benzodiazepine co-prescription and 29% concurrent prescription (for z-drugs these respective proportions were 20% and 11%, and for gabapentinoids 8% and 5%). Concurrent prescription of benzodiazepines was associated with increased duration of methadone treatment (adjusted mean duration of treatment episode 466 days [95% CI 450 to 483] compared to 286 days [95% CI 275 to 297]). Benzodiazepine co-prescription was associated with increased risk of DRP (adjusted HR 2.96 [95% CI 1.97 to 4.43], p < 0.001), with evidence of a dose-response effect, but showed little evidence of an association with non-DRP (adjusted HR 0.91 [95% CI 0.66 to 1.25], p = 0.549). Co-prescription of z-drugs showed evidence of an association with increased risk of DRP (adjusted HR 2.75 [95% CI 1.57 to 4.83], p < 0.001) but little evidence of an association with non-DRP (adjusted HR 0.79 [95% CI 0.49 to 1.28], p = 0.342). There was no evidence of an association of gabapentinoid co-prescription with DRP (HR 1.54 [95% CI 0.60 to 3.98], p = 0.373) but evidence of an association with increased non-DRP (HR 1.83 [95% CI 1.28 to 2.62], p = 0.001). Concurrent benzodiazepine prescription also increased mortality risk after consideration of duration of OAT (adjusted HR for DRP with benzodiazepine concurrent prescription 3.34 [95% CI 2.14 to 5.20], p < 0.001). The main limitation of this study is the possibility that unmeasured confounding factors led to an association between benzodiazepine prescription and DRP that is not causal.
CONCLUSIONS
In this study, co-prescription of benzodiazepine was specifically associated with increased risk of DRP in opioid-dependent individuals. Co-prescription of z-drugs and gabapentinoids was also associated with increased mortality risk; however, for z-drugs there was no evidence for a dose-response effect on DRP, and for gabapentinoids the increased mortality risk was not specific to DRP. Concurrent prescription of benzodiazepine was associated with longer treatment but still increased risk of death overall. Clinicians should be cautious about prescribing benzodiazepines to opioid-dependent individuals.
Topics: Adult; Analgesics, Opioid; Benzodiazepines; Drug Overdose; Female; GABA-A Receptor Agonists; Humans; Male; Middle Aged; Opioid-Related Disorders; Proportional Hazards Models; Receptors, GABA-A; Risk Factors; United Kingdom
PubMed: 31770388
DOI: 10.1371/journal.pmed.1002965