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JAMA Aug 2018Alcohol consumption is associated with 88 000 US deaths annually. Although routine screening for heavy alcohol use can identify patients with alcohol use disorder... (Review)
Review
IMPORTANCE
Alcohol consumption is associated with 88 000 US deaths annually. Although routine screening for heavy alcohol use can identify patients with alcohol use disorder (AUD) and has been recommended, only 1 in 6 US adults report ever having been asked by a health professional about their drinking behavior. Alcohol use disorder, a problematic pattern of alcohol use accompanied by clinically significant impairment or distress, is present in up to 14% of US adults during a 1-year period, although only about 8% of affected individuals are treated in an alcohol treatment facility.
OBSERVATIONS
Four medications are approved by the US Food and Drug Administration to treat AUD: disulfiram, naltrexone (oral and long-acting injectable formulations), and acamprosate. However, patients with AUD most commonly receive counseling. Medications are prescribed to less than 9% of patients who are likely to benefit from them, given evidence that they exert clinically meaningful effects and their inclusion in clinical practice guidelines as first-line treatments for moderate to severe AUD. Naltrexone, which can be given once daily, reduces the likelihood of a return to any drinking by 5% and binge-drinking risk by 10%. Randomized clinical trials also show that some medications approved for other indications, including seizure disorder (eg, topiramate), are efficacious in treating AUD. Currently, there is not sufficient evidence to support the use of pharmacogenetics to personalize AUD treatments.
CONCLUSIONS AND RELEVANCE
Alcohol consumption is associated with a high rate of morbidity and mortality, and heavy alcohol use is the major risk factor for AUD. Simple, valid screening methods can be used to identify patients with heavy alcohol use, who can then be evaluated for the presence of an AUD. Patients receiving a diagnosis of the disorder should be given brief counseling and prescribed a first-line medication (eg, naltrexone) or referred for a more intensive psychosocial intervention.
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Counseling; Disulfiram; Humans; Naltrexone; Taurine
PubMed: 30167705
DOI: 10.1001/jama.2018.11406 -
Drugs Feb 2022Alcohol use disorder (AUD) is a highly prevalent but severely under-treated disorder, with only three widely-approved pharmacotherapies. Given that AUD is a very... (Review)
Review
Alcohol use disorder (AUD) is a highly prevalent but severely under-treated disorder, with only three widely-approved pharmacotherapies. Given that AUD is a very heterogeneous disorder, it is unlikely that one single medication will be effective for all individuals with an AUD. As such, there is a need to develop new, more effective, and diverse pharmacological treatment options for AUD with the hopes of increasing utilization and improving care. In this qualitative literature review, we discuss the efficacy, mechanism of action, and tolerability of approved, repurposed, and novel pharmacotherapies for the treatment of AUD with a clinical perspective. Pharmacotherapies discussed include: disulfiram, acamprosate, naltrexone, nalmefene, topiramate, gabapentin, varenicline, baclofen, sodium oxybate, aripiprazole, ondansetron, mifepristone, ibudilast, suvorexant, prazosin, doxazosin, N-acetylcysteine, GET73, ASP8062, ABT-436, PF-5190457, and cannabidiol. Overall, many repurposed and novel agents discussed in this review demonstrate clinical effectiveness and promise for the future of AUD treatment. Importantly, these medications also offer potential improvements towards the advancement of precision medicine and personalized treatment for the heterogeneous AUD population. However, there remains a great need to improve access to treatment, increase the menu of approved pharmacological treatments, and de-stigmatize and increase treatment-seeking for AUD.
Topics: Acamprosate; Alcohol Deterrents; Alcoholism; Baclofen; Disulfiram; Humans; Naltrexone; Topiramate
PubMed: 35133639
DOI: 10.1007/s40265-021-01670-3 -
JAMA Feb 2021
Topics: Acamprosate; Alcohol Deterrents; Alcoholics Anonymous; Alcoholism; Cognitive Behavioral Therapy; Disulfiram; Humans; Naltrexone
PubMed: 33560323
DOI: 10.1001/jama.2020.2012 -
Nature Dec 2017Cancer incidence is rising and this global challenge is further exacerbated by tumour resistance to available medicines. A promising approach to meet the need for...
Cancer incidence is rising and this global challenge is further exacerbated by tumour resistance to available medicines. A promising approach to meet the need for improved cancer treatment is drug repurposing. Here we highlight the potential for repurposing disulfiram (also known by the trade name Antabuse), an old alcohol-aversion drug that has been shown to be effective against diverse cancer types in preclinical studies. Our nationwide epidemiological study reveals that patients who continuously used disulfiram have a lower risk of death from cancer compared to those who stopped using the drug at their diagnosis. Moreover, we identify the ditiocarb-copper complex as the metabolite of disulfiram that is responsible for its anti-cancer effects, and provide methods to detect preferential accumulation of the complex in tumours and candidate biomarkers to analyse its effect on cells and tissues. Finally, our functional and biophysical analyses reveal the molecular target of disulfiram's tumour-suppressing effects as NPL4, an adaptor of p97 (also known as VCP) segregase, which is essential for the turnover of proteins involved in multiple regulatory and stress-response pathways in cells.
Topics: Adult; Alcohol Deterrents; Alcoholism; Animals; Antineoplastic Agents; Copper; Denmark; Disulfiram; Drug Repositioning; Female; Heat-Shock Response; Humans; Male; Mice; Middle Aged; Molecular Targeted Therapy; Neoplasms; Nuclear Proteins; Protein Aggregates; Protein Binding; Proteolysis
PubMed: 29211715
DOI: 10.1038/nature25016 -
Clinics in Liver Disease Aug 2016Unhealthy alcohol use is common and routine screening is essential to identify patients and initiate appropriate treatment. At-risk or hazardous drinking is best managed... (Review)
Review
Unhealthy alcohol use is common and routine screening is essential to identify patients and initiate appropriate treatment. At-risk or hazardous drinking is best managed with brief interventions, which can be performed by any provider and are designed to enhance patients' motivations and promote behavioral change. Alcohol withdrawal can be managed, preferably with benzodiazepines, using a symptom-triggered approach. Twelve-step programs and provider-driven behavioral therapies have robust data supporting their effectiveness and patients with alcohol use disorder should be referred for these services. Research now support the use of several FDA-approved medications that aid in promoting abstinence and reducing heavy drinking.
Topics: Alcohol Abstinence; Alcohol Deterrents; Alcohol Drinking; Alcoholism; Crisis Intervention; Humans; Psychotherapy; Risk Factors; Substance Withdrawal Syndrome
PubMed: 27373607
DOI: 10.1016/j.cld.2016.02.003 -
Alcohol and Alcoholism (Oxford,... 1999Alcohol and histamine metabolic pathways in the body have the common enzymes aldehyde dehydrogenase and aldehyde oxidase. The metabolite of ethanol, acetaldehyde, can... (Review)
Review
Alcohol and histamine metabolic pathways in the body have the common enzymes aldehyde dehydrogenase and aldehyde oxidase. The metabolite of ethanol, acetaldehyde, can effectively compete with the metabolites of histamine, methylimidazole acetaldehyde, and imidazole acetaldehyde. At the periphery, alcohol and acetaldehyde liberate histamine from its store in mast cells and depress histamine elimination by inhibiting diamine oxidase, resulting in elevated histamine levels in tissues. Histamine mediates alcohol-induced gastric and intestinal damage and bronchial asthma as well as flushing in Orientals. On the other hand, alcohol provokes food-induced histaminosis and histamine intolerance, which is an epidemiological problem. There are many controversial reports concerning the effect of H2 receptor antagonists on ethanol metabolism and the activity of alcohol dehydrogenase in the stomach. In addition, alcohol affects histamine levels in the brain by modulating histamine synthesis, release, and turnover. Histamine receptor antagonists can affect ethanol metabolism and change the sensitivity of animals to the hypnotic effects of alcohol. In contrast to other neurotransmitters, the involvement of the brain histamine system in the mechanisms of the central actions of alcohol and in the pathogenesis of alcoholism is poorly studied and understood.
Topics: Alcohol Deterrents; Animals; Drug Interactions; Ethanol; Ethnicity; Flushing; Histamine; Histamine Agonists; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Receptors, Histamine
PubMed: 10344773
DOI: 10.1093/alcalc/34.2.141 -
American Family Physician Mar 2016The U.S. Preventive Services Task Force recommends that clinicians screen adults for alcohol misuse and provide persons engaged in risky or hazardous drinking behaviors... (Review)
Review
The U.S. Preventive Services Task Force recommends that clinicians screen adults for alcohol misuse and provide persons engaged in risky or hazardous drinking behaviors with brief behavioral counseling to reduce alcohol misuse. However, only a minority of American adults with high-risk alcohol use receive treatment. Three medications are approved by the U.S. Food and Drug Administration to treat alcohol use disorder: acamprosate, disulfiram, and naltrexone. Acamprosate and naltrexone reduce alcohol consumption and increase abstinence rates, although the effects appear to be modest. Disulfiram has been used for years, but evidence supporting its effectiveness is inconsistent. Other medications may be beneficial to reduce heavy alcohol use. The anticonvulsants topiramate and gabapentin may reduce alcohol ingestion, although long-term studies are lacking. Antidepressants do not decrease alcohol use in patients without mood disorders, but sertraline and fluoxetine may help depressed patients decrease alcohol ingestion. Ondansetron may reduce alcohol use, particularly in selected subpopulations. Further study is needed for genetically targeted or as-needed medications to reduce alcohol use.
Topics: Alcohol Deterrents; Alcohol-Related Disorders; Antidepressive Agents; Counseling; Humans; Practice Guidelines as Topic
PubMed: 26977830
DOI: No ID Found -
JAMA Mar 2024
Topics: Humans; Alcohol Drinking; Alcoholism; Alcohol Deterrents
PubMed: 38441587
DOI: 10.1001/jama.2023.28408 -
The Medical Clinics of North America Jul 2018Alcohol use disorder is a common, destructive, and undertreated disease. As understanding of alcohol use disorder has evolved, so has our ability to manage patients with... (Review)
Review
Alcohol use disorder is a common, destructive, and undertreated disease. As understanding of alcohol use disorder has evolved, so has our ability to manage patients with pharmacotherapeutic agents in addition to nondrug therapy, including various counseling strategies. Providers now have a myriad of medications, both approved and not approved by the US Food and Drug Administration, to choose from and can personalize care based on treatment goals, comorbidities, drug interactions, and drug availability. This review explores these treatment options and offers the prescriber practical advice regarding when each option may or may not be appropriate for a specific patient.
Topics: Alcohol Deterrents; Alcoholism; Anticonvulsants; Comorbidity; Drug Therapy, Combination; Humans; Medication Adherence; Narcotic Antagonists; Nicotinic Agonists; Off-Label Use; Patient Care Planning; United States
PubMed: 29933821
DOI: 10.1016/j.mcna.2018.02.008 -
Progress in Neuro-psychopharmacology &... Feb 2016Alcohol addiction is one of the most common and devastating diseases in the world. Given the tremendous heterogeneity of alcohol addicted individuals, it is unlikely... (Review)
Review
Alcohol addiction is one of the most common and devastating diseases in the world. Given the tremendous heterogeneity of alcohol addicted individuals, it is unlikely that one medication will help nearly all patients. Thus, there is a clear need to develop predictors of response to existing medications. Naltrexone is a mu-opioid receptor antagonist which has been approved in the United States for treatment of alcohol addiction since 1994. It has limited efficacy, in part due to noncompliance, but many patients do not respond despite high levels of compliance. There are reports that a mis-sense single nucleotide polymorphism (rs179919 or A118G) in the mu-opioid receptor gene predicts a favorable response to naltrexone if an individual carries a 'G' allele. This chapter will review the evidence for this hypothesis. The data are promising that the 'G' allele predisposes to a beneficial naltrexone response among alcohol addicted persons, but additional research is needed to prove this hypothesis in prospective clinical trials.
Topics: Alcohol Deterrents; Alcoholism; Humans; Receptors, Opioid, mu
PubMed: 26226591
DOI: 10.1016/j.pnpbp.2015.07.011