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Frontiers in Psychiatry 2021Reconsumption of ethanol after withdrawal is a hallmark for relapse in recovering patients with alcohol use disorders. We show that the preference of to reconsume...
Reconsumption of ethanol after withdrawal is a hallmark for relapse in recovering patients with alcohol use disorders. We show that the preference of to reconsume ethanol after abstinence shares mechanistic similarities to human behavior by feeding the antirelapse drug acamprosate to flies and reducing the ethanol consumption preference. The cellular stress mutant also reduced ethanol consumption preference. Together with the observation that an increasing number of candidate genes identified in a genome-wide association study on alcohol use disorders are involved in the regulation of cellular stress, the results suggest that cellular stress mechanisms might regulate the level of ethanol reconsumption after abstinence. To address this, we analyzed mutants of candidate genes involved in the regulation of cellular stress for their ethanol consumption level after abstinence and cellular stress response to free radicals. Since encodes a nuclear RNA-binding protein that regulates transcript levels, we analyzed the interactions of candidate genes on transcript and protein level. The behavioral analysis of the mutants, the analysis of transcript levels, and protein interactions suggested that at least two mechanisms regulate ethanol consumption preference after abstinence-a nuclear estrogen-related receptor-hangover-dependent complex and peroxisomal trans-2-enoyl-CoA reductase (dPECR)-dependent component in peroxisomes. The loss of estrogen-like receptor and dPECR in neurons share a protective function against oxidative stress, suggesting that the neuroprotective function of genes might be a predictor for genes involved in the regulation of ethanol reconsumption after abstinence.
PubMed: 33981260
DOI: 10.3389/fpsyt.2021.655816 -
European Journal of Internal Medicine Sep 2022In the last decades, many medications have been tested for the treatment of Alcohol Use Disorder (AUD). Among them, disulfiram, acamprosate, naltrexone, nalmefene,... (Review)
Review
INTRODUCTION
In the last decades, many medications have been tested for the treatment of Alcohol Use Disorder (AUD). Among them, disulfiram, acamprosate, naltrexone, nalmefene, sodium oxybate and baclofen have been approved in different countries, with different specific indications. Topiramate is not approved for the treatment of AUD, however, it is suggested as a therapeutic option by the American Psychiatric Association for patients who do not tolerate or respond to approved therapies.
AREAS COVERED
In this narrative review we have analyzed the main studies available in literature, investigating the efficacy and safety of these medications, distinguishing whether they were oriented towards abstinence or not. Randomized controlled studies, analyzing larger populations for longer periods were the main focus of our analysis.
CONCLUSIONS
The medications currently available for the treatment of AUD are quite effective, yet further progress can still be achieved through the personalized strategies. Also, these medications are still markedly underutilized in clinical practice and many patients do not have access to specialized treatment.
Topics: Acamprosate; Alcohol Deterrents; Alcohol Drinking; Alcoholism; Disulfiram; Humans; Naltrexone
PubMed: 35597734
DOI: 10.1016/j.ejim.2022.05.016 -
Journal of Studies on Alcohol and Drugs Jul 2022This article reviews research on post-acute alcohol withdrawal syndrome (PAWS) management.
OBJECTIVE
This article reviews research on post-acute alcohol withdrawal syndrome (PAWS) management.
METHOD
We conducted a PRISMA (Preferred Reporting Items for Systematic Revision and Meta-Analyses)-guided scoping review of the published PAWS literature, searching six electronic databases (from their inception through December 2020) for English-language randomized and nonrandomized studies.
RESULTS
A total of 16 treatment studies met the inclusion criteria. The strength of evidence overall for pharmacologic treatments is low, with often only short-term results being reported, small treatment samples used, or inconsistent results found. However, for negative affect and sleep symptoms, more evidence supports using gabapentinoids (gabapentin and pregabalin) and anticonvulsants (carbamazepine and oxcarbazepine). Although preliminary data support acamprosate, there were no controlled trials. Despite an older treatment trial showing some positive data for amitriptyline for mood, the clinical measures used were problematic, and side effects and safety profile limit its utility. Finally, there is no evidence that melatonin and other agents (homatropine, Proproten-100) show PAWS symptoms.
CONCLUSIONS
Although there is some evidence for targeted pharmacotherapy for treating specific PAWS symptoms, there are few recent, robust, placebo-controlled trials, and the level of evidence for treatment efficacy is low.
Topics: Alcoholism; Anticonvulsants; Benzodiazepines; Gabapentin; Humans; Substance Withdrawal Syndrome
PubMed: 35838423
DOI: 10.15288/jsad.2022.83.470 -
JAMA Network Open May 2022Alcohol-associated liver disease (ALD) is one of the most devastating complications of alcohol use disorder (AUD), an increasingly prevalent condition. Medical addiction...
IMPORTANCE
Alcohol-associated liver disease (ALD) is one of the most devastating complications of alcohol use disorder (AUD), an increasingly prevalent condition. Medical addiction therapy for AUD may play a role in protecting against the development and progression of ALD.
OBJECTIVE
To ascertain whether medical addiction therapy was associated with an altered risk of developing ALD in patients with AUD.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study used the Mass General Brigham Biobank, an ongoing research initiative that had recruited 127 480 patients between its start in 2010 and August 17, 2021, when data for the present study were retrieved. The mean follow-up duration from AUD diagnosis was 9.2 years. International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes were used to identify ALD and AUD diagnoses.
EXPOSURES
Medical addiction therapy was defined as the documented use of disulfiram, acamprosate, naltrexone, gabapentin, topiramate, or baclofen. Patients were considered to be treated if they initiated medical addiction therapy before the relevant outcome.
MAIN OUTCOMES AND MEASURES
Adjusted odds ratios (aORs) for the development of ALD and hepatic decompensation were calculated and adjusted for multiple risk factors.
RESULTS
The cohort comprised 9635 patients with AUD, of whom 5821 were male individuals (60.4%), and the mean (SD) age was 54.8 (16.5) years. A total of 1135 patients (11.8%) had ALD and 3906 patients (40.5%) were treated with medical addiction therapy. In multivariable analyses, medical addiction therapy for AUD was associated with decreased incidence of ALD (aOR, 0.37; 95% CI, 0.31-0.43; P < .001). This association was evident for naltrexone (aOR, 0.67; 95% CI, 0.46-0.95; P = .03), gabapentin (aOR, 0.36; 95% CI, 0.30-0.43; P < .001), topiramate (aOR, 0.47; 95% CI, 0.32-0.66; P < .001), and baclofen (aOR, 0.57; 95% CI, 0.36-0.88; P = .01). In addition, pharmacotherapy for AUD was associated with lower incidence of hepatic decompensation in patients with cirrhosis (aOR, 0.35; 95% CI, 0.23-0.53, P < .001), including naltrexone (aOR, 0.27; 95% CI, 0.10-0.64; P = .005) and gabapentin (aOR, 0.36; 95% CI, 0.23-0.56; P < .001). This association persisted even when medical addiction therapy was initiated only after the diagnosis of cirrhosis (aOR, 0.41; 95% CI, 0.23-0.71; P = .002).
CONCLUSIONS AND RELEVANCE
Results of this study showed that receipt of medical addiction therapy for AUD was associated with reduced incidence and progression of ALD. The associations of individual pharmacotherapy with the outcomes of ALD and hepatic decompensation varied widely.
Topics: Alcoholism; Baclofen; Female; Gabapentin; Humans; Incidence; Liver Cirrhosis; Male; Middle Aged; Naltrexone; Retrospective Studies; Topiramate
PubMed: 35594048
DOI: 10.1001/jamanetworkopen.2022.13014 -
Addiction & Health Oct 2019Among the three pharmacological agents available for alcohol de-addiction, acamprosate and naltrexone are considered anti-craving agents. Among these two, acamprosate is...
BACKGROUND
Among the three pharmacological agents available for alcohol de-addiction, acamprosate and naltrexone are considered anti-craving agents. Among these two, acamprosate is better tolerated, has low abuse potential, and is safe in overdose. But the mechanism of action of acamprosate still remains unclear.
CASE REPORT
This case report gives a description of a 46-year-old male patient diagnosed with alcohol dependence syndrome with prior admissions and failed treatments with naltrexone and baclofen. He developed skin reaction after relapsing with alcohol use while receiving acamprosate therapy. The severity of the adverse effects varied with the amount of alcohol consumed by the patient. This suggests the possibility of deterrent-like action of acamprosate in our patient. The symptoms reduced after abstinence from alcohol and the patient was continued on acamprosate and relapse prevention therapy (RPT).
CONCLUSION
Clinicians should consider the possible deterrent effect of acamprosate and manage such patients accordingly.
PubMed: 32206220
DOI: 10.22122/ahj.v11i4.248 -
The Application of Clinical Genetics 2019Genetics of alcohol addiction is currently a contradictive and complex field, where data in the most studies reflect methods' limitations rather than meaningful and...
Genetics of alcohol addiction is currently a contradictive and complex field, where data in the most studies reflect methods' limitations rather than meaningful and complementary results. In our review, we focus on the genetics of alcohol addiction, leaving genetics of acute alcohol intoxication out of the scope. A review of the literature on pharmacogenetic biomarkers development for the pharmacotherapy personalization reveals that today the evidence base concerning these biomarkers is still insufficient. In particular, now the researches with the design of randomized controlled trials and meta-analysis investigating the effect of the SNPs as biomarkers on the therapy efficacy are available for naltrexone only. For other medications, there are only a few studies in small samples. It decreases the possibilities to implement the pharmacogenetic algorithms for the pharmacotherapy personalization in patients with alcohol use disorders (AUD). In view of the importance of the precision approaches development not in addiction medicine only, but in other fields of medicine also to increase the efficacy and safety of the therapy, studies on pharmacogenetic biomarkers development for the medications used in patients with AUD (eg, naltrexone, disulfiram, nalmefene, acamprosate, etc.) remain relevant to this day.
PubMed: 31372024
DOI: 10.2147/TACG.S206745 -
Molecular Pharmaceutics Nov 2019In drug development, estimating fraction absorbed () in man for permeability-limited compounds is important but challenging. To model of such compounds from apparent...
In drug development, estimating fraction absorbed () in man for permeability-limited compounds is important but challenging. To model of such compounds from apparent permeabilities () across filter-grown Caco-2 cell monolayers, it is central to elucidate the intestinal permeation mechanism(s) of the compound. The present study aims to refine a computational permeability model to investigate the relative contribution of paracellular and transcellular routes to the across Caco-2 monolayers of the permeability-limited compound acamprosate having a bioavailability of ∼11%. The values of acamprosate and of several paracellular marker molecules were measured. These values were used to refine system-specific parameters of the Caco-2 monolayers, that is, paracellular pore radius, pore capacity, and potential drop. The refined parameters were subsequently used as an input in modeling the permeability () of the tested compounds using mathematical models collected from two published permeability models. The experimental data show that acamprosate across Caco-2 monolayers is low and similar in both transport directions. The obtained acamprosate , 1.56 ± 0.28 × 10 cm·s, is similar to the of molecular markers for paracellular permeability, namely, mannitol (2.72 ± 0.24 × 10 cm·s), lucifer yellow (1.80 ± 0.35 × 10 cm·s), and fluorescein (2.10 ± 0.28 × 10 cm·s), and lower than that of atenolol (7.32 ± 0.60 × 10 cm·s; mean ± SEM, = 3-6), while the end-point amount of acamprosate internalized by the cell monolayer, , was lower than that of mannitol. Acamprosate did not influence the barrier function of the monolayers since it altered neither the of the three paracellular markers nor the transepithelial electrical resistance (TEER) of the cell monolayer. The for all the paracellular markers and acamprosate was dominated by the component and matched the experimentally obtained . Furthermore, acamprosate did not inhibit the uptake of probe substrates for solute carriers PEPT1, TAUT, PAT1, EAAT1, BAT/rBAT, OATP2B1, and ASBT expressed in Caco-2 cells. Thus, the estimated well , and the paracellular route appears to be the predominant mechanism for acamprosate across Caco-2 monolayers, while the alternative transcellular routes, mediated by passive diffusion or carriers, are suggested to only play insignificant roles.
Topics: Acamprosate; Atenolol; Biological Availability; Biological Transport; Caco-2 Cells; Cell Line, Tumor; Diffusion; Fluorescein; Humans; Isoquinolines; Mannitol; Permeability
PubMed: 31560549
DOI: 10.1021/acs.molpharmaceut.9b00733 -
Cold Spring Harbor Perspectives in... Nov 2021There are currently effective Food and Drug Administration (FDA)-approved therapies for alcohol, nicotine, and opioid use disorders. This article will review the...
There are currently effective Food and Drug Administration (FDA)-approved therapies for alcohol, nicotine, and opioid use disorders. This article will review the development of eight compounds used in the treatment of drug addiction with an emphasis on pharmacological mechanisms and the utility of preclinical animal models of addiction in therapeutic development. In contrast to these successes, animal research has identified a number of promising medications for the treatment of psychostimulant use disorder, none of which have proven to be clinically effective. A specific example of an apparently promising pharmacotherapeutic for cocaine that failed clinically will be examined to determine whether this truly represents a challenge to the predictive validity of current models of cocaine addiction. In addition, the development of promising cocaine use disorder therapeutics derived from animal research will be reviewed, with some discussion regarding how preclinical studies might be modified to better inform clinical outcomes.
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Bupropion; Central Nervous System Stimulants; Cocaine-Related Disorders; Drug Therapy; Humans; Naltrexone; Narcotic Antagonists; Nicotinic Agonists; Smoking Cessation Agents; Substance-Related Disorders; Varenicline
PubMed: 32601131
DOI: 10.1101/cshperspect.a040311 -
Journal of General Internal Medicine Nov 2023Alcohol use disorder (AUD) is the most prevalent substance use disorder, but evidence-based medications to treat AUD (MAUD), including naltrexone and acamprosate, are...
BACKGROUND
Alcohol use disorder (AUD) is the most prevalent substance use disorder, but evidence-based medications to treat AUD (MAUD), including naltrexone and acamprosate, are substantially underutilized. Hospitalization provides an opportunity to start MAUD for patients who may not otherwise seek treatment. Addiction consultation services (ACSs) have been increasingly utilized to ensure appropriate treatment. There is little research examining the effect of an ACS on health outcomes among patients with AUD.
OBJECTIVE
To determine the association between an ACS consultation and provision of MAUD during admission and MAUD at discharge among admissions with AUD.
DESIGN
Retrospective study comparing admissions which received an ACS consult and propensity score-matched historical control admissions. Subjects A total of 215 admissions with a primary or secondary diagnosis of AUD who received an ACS consult and 215 matched historical control admissions. Intervention ACS consultation from a multidisciplinary team offering withdrawal management, substance use disorder treatment, patient-centered counseling, discharge planning, and linkage to outpatient care for patients with substance use disorders, including AUD. Main Measures Primary outcomes were initiation of new MAUD during admission and new MAUD at discharge. Secondary outcomes were patient-directed discharge, time to 7- and 30-day readmission, and time to 7- and 30-day post-discharge ER visit. Key Results Among 430 admissions with AUD, those that received an ACS consultation were significantly more likely to receive new inpatient MAUD (33.0% vs 0.9%; OR 52.5 [CI 12.6-218.6]) and significantly more likely to receive new MAUD at discharge (41.4% vs 1.9%; OR 37.3 [13.3-104.6]), compared with historical controls. ACS was not significantly associated with patient-directed discharge, time to readmission, or time to post-discharge ER visit.
CONCLUSIONS
ACS was associated with a large increase in provision of new inpatient MAUD and new MAUD at discharge when compared to propensity-matched historical controls.
Topics: Humans; Alcoholism; Inpatients; Patient Discharge; Retrospective Studies; Aftercare; Substance-Related Disorders; Referral and Consultation
PubMed: 37100986
DOI: 10.1007/s11606-023-08202-7 -
La Revue Du Praticien Oct 2019Medical management of alcohol use disorders. Psychosocial support remains the key element of treatment of patients with an alcohol use disorder in order to either...
Medical management of alcohol use disorders. Psychosocial support remains the key element of treatment of patients with an alcohol use disorder in order to either decrease or cease their alcohol consumption. However two drugs can now be used to reduce alcohol consumption: nalmefene and baclofen. Currently available studies have shown weak to moderate effect sizes in this indication. Four molecules are available to help patients maintain abstinence: acamprosate, naltrexone, disulfiram and baclofen (off-label use). Effect sizes calculated by various metaanalyses are also low to moderate. Disulfiram appears to be more effective when the patient has understood its mechanism of action and when it is used under supervision. However, the use of disulfiram is limited by the risk of rare, but potentially serious adverse effects. Identification of patient subgroups obtaining better responses to certain drugs constitutes a major research challenge, but only a few criteria have been defined to date. However, regardless of the drug considered, heavy drinking and difficulty to maintain abstinence significantly improve the efficacy of the drugs. After an initially promising period, identification of genetic markers has not yet resulted in any clinical applications. Promising molecules currently under evaluation include sodium oxybate and topiramate.
Topics: Acamprosate; Alcohol Deterrents; Alcohol Drinking; Alcoholism; Baclofen; Humans
PubMed: 32237660
DOI: No ID Found