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JAMA Nov 2023Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality. (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality.
OBJECTIVE
To compare efficacy and comparative efficacy of therapies for alcohol use disorder.
DATA SOURCES
PubMed, the Cochrane Library, the Cochrane Central Trials Registry, PsycINFO, CINAHL, and EMBASE were searched from November 2012 to September 9, 2022 Literature was subsequently systematically monitored to identify relevant articles up to August 14, 2023, and the PubMed search was updated on August 14, 2023.
STUDY SELECTION
For efficacy outcomes, randomized clinical trials of at least 12 weeks' duration were included. For adverse effects, randomized clinical trials and prospective cohort studies that compared drug therapies and reported health outcomes or harms were included.
DATA EXTRACTION AND SYNTHESIS
Two reviewers evaluated each study, assessed risk of bias, and graded strength of evidence. Meta-analyses used random-effects models. Numbers needed to treat were calculated for medications with at least moderate strength of evidence for benefit.
MAIN OUTCOMES AND MEASURES
The primary outcome was alcohol consumption. Secondary outcomes were motor vehicle crashes, injuries, quality of life, function, mortality, and harms.
RESULTS
Data from 118 clinical trials and 20 976 participants were included. The numbers needed to treat to prevent 1 person from returning to any drinking were 11 (95% CI, 1-32) for acamprosate and 18 (95% CI, 4-32) for oral naltrexone at a dose of 50 mg/d. Compared with placebo, oral naltrexone (50 mg/d) was associated with lower rates of return to heavy drinking, with a number needed to treat of 11 (95% CI, 5-41). Injectable naltrexone was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, -4.99 days; 95% CI, -9.49 to -0.49 days) Adverse effects included higher gastrointestinal distress for acamprosate (diarrhea: risk ratio, 1.58; 95% CI, 1.27-1.97) and naltrexone (nausea: risk ratio, 1.73; 95% CI, 1.51-1.98; vomiting: risk ratio, 1.53; 95% CI, 1.23-1.91) compared with placebo.
CONCLUSIONS AND RELEVANCE
In conjunction with psychosocial interventions, these findings support the use of oral naltrexone at 50 mg/d and acamprosate as first-line pharmacotherapies for alcohol use disorder.
Topics: Humans; Acamprosate; Alcohol Drinking; Alcoholism; Drug-Related Side Effects and Adverse Reactions; Naltrexone; Prospective Studies; Quality of Life; United States; Alcohol Deterrents; Psychosocial Intervention
PubMed: 37934220
DOI: 10.1001/jama.2023.19761 -
Emergency Medicine Clinics of North... Nov 2023Patients with alcohol use disorders are commonly identified and managed in the emergency department. Although the alcohol-intoxicated patient has a high risk for... (Review)
Review
Patients with alcohol use disorders are commonly identified and managed in the emergency department. Although the alcohol-intoxicated patient has a high risk for significant injury and diseases, the majority will be allowed to sober in the emergency department and can be discharged without incident. However, there are metabolic derangements in these patients, such as alcoholic ketoacidosis, Wernicke-Korsakoff, and potomania that very commonly present similar to intoxication and can be misdiagnosed by emergency clinicians.
Topics: Humans; Alcoholism; Emergencies; Wernicke Encephalopathy; Alcoholic Intoxication; Ethanol
PubMed: 37758425
DOI: 10.1016/j.emc.2023.07.003 -
Journal of Gastroenterology and... Aug 2023The microorganisms inhabiting our gastrointestinal tract are critical for human health. Chronic heavy alcohol use can modulate the composition and function of the gut... (Review)
Review
The microorganisms inhabiting our gastrointestinal tract are critical for human health. Chronic heavy alcohol use can modulate the composition and function of the gut microbiota, thereby exacerbating end-organ damage via the gut-brain axis and the gut-liver axis. In this review, we summarize the bacterial, fungal, and viral gut microbial compositional changes associated with alcohol use and alcohol-associated liver disease and discuss the mechanisms of action by which gut dysbiosis reinforces alcohol use behavior and liver inflammation and injury. We also highlight important pre-clinical and clinical trials that target gut microbial-specific mechanisms for the treatment of alcohol use disorder and alcohol-associated liver disease.
Topics: Humans; Gastrointestinal Microbiome; Ethanol; Liver; Liver Diseases, Alcoholic; Alcoholism; Dysbiosis
PubMed: 37096652
DOI: 10.1111/jgh.16199 -
JAMA Psychiatry Nov 2023Reward circuitry dysfunction is a candidate mechanism of co-occurring bipolar disorder and alcohol use disorder (BD + AUD) that remains understudied. This functional...
IMPORTANCE
Reward circuitry dysfunction is a candidate mechanism of co-occurring bipolar disorder and alcohol use disorder (BD + AUD) that remains understudied. This functional magnetic resonance imaging (fMRI) research represents the first evaluation of alcohol cue reward processing in BD + AUD.
OBJECTIVE
To determine how alcohol cue processing in individuals with BD + AUD may be distinct from that of individuals with AUD or BD alone.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional case-control study (April 2013-June 2018) followed a 2 × 2 factorial design and included individuals with BD + AUD, AUD alone, BD alone, and healthy controls. A well-validated visual alcohol cue reactivity fMRI paradigm was administered to eligible participants following their demonstration of 1 week or more of abstinence from alcohol and drugs assessed via serial biomarker testing. Study procedures were completed at the Medical University of South Carolina. Analysis took place between June and August 2022.
MAIN OUTCOMES AND MEASURES
Past-week mood symptoms were rated by clinicians using the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale. The Alcohol Dependence Scale, Obsessive-Compulsive Drinking Scale, and Barratt Impulsiveness Scale were included questionnaires. Functional MRI whole-brain data were analyzed along with percent signal change within a priori regions of interest located in the ventral striatum, dorsal striatum, and ventromedial prefrontal cortex. Exploratory analyses of associations between cue reactivity and select behavioral correlates (alcohol craving, impulsivity, maximum number of alcohol drinks on a single occasion, and days since last alcohol drink) were also performed.
RESULTS
Of 112 participants, 28 (25.0%) had BD + AUD, 26 (23.2%) had AUD alone, 31 (27.7%) had BD alone, and 27 (24.1%) were healthy controls. The mean (SD) age was 38.7 (11.6) years, 50 (45.5%) were female, 33 (30%) were smokers, and 37 (34.9%) reported recent alcohol consumption. Whole-brain analyses revealed a BD × AUD interaction (F = 10.64; P = .001; η2 = 0.09) within a cluster spanning portions of the right inferior frontal gyrus and insula. Region of interest analyses revealed a main association of BD (F = 8.02; P = .006; η2 = 0.07) within the dorsal striatum. In each instance, individuals with BD + AUD exhibited reduced activation compared with all other groups who did not significantly differ from one another. These hypoactivations were associated with increased impulsivity and obsessive-compulsive alcohol craving exclusively among individuals with BD + AUD.
CONCLUSION AND RELEVANCE
The findings of this study suggest conceptualizing reward dysfunction in BD + AUD by the potential interaction between blunted reward responsivity and deficient inhibitory control may help guide treatment development strategies. To this end, reduced right inferior frontal gyrus and insula alcohol cue reactivity represents a novel candidate biomarker of BD + AUD that may respond to pharmacological interventions targeting impulsivity-related neural mechanisms for improved executive control.
Topics: Humans; Female; Adult; Male; Alcoholism; Bipolar Disorder; Cross-Sectional Studies; Case-Control Studies; Cues; Alcohol Drinking; Ethanol; Biomarkers; Magnetic Resonance Imaging
PubMed: 37556131
DOI: 10.1001/jamapsychiatry.2023.2726 -
International Review of Neurobiology 2024Alcohol is a major cause of pre-mature death and individual suffering worldwide, and the importance of diagnosing and treating AUD cannot be overstated. Given the global...
Alcohol is a major cause of pre-mature death and individual suffering worldwide, and the importance of diagnosing and treating AUD cannot be overstated. Given the global burden and the high attributable factor of alcohol in a vast number of diseases, the need for additional interventions and the development of new medicines is considered a priority by the World Health Organization (WHO). As of today, AUD is severely under-treated with a treatment gap nearing 90%, strikingly higher than that for other psychiatric disorders. Patients often seek treatment late in the progress of the disease and even among those who seek treatment only a minority receive medication, mirroring the still-prevailing stigma of the disease, and a lack of access to effective treatments, as well as a reluctance to total abstinence. To increase adherence, treatment goals should focus not only on maintaining abstinence, but also on harm reduction and psychosocial functioning. A personalised approach to AUD treatment, with a holistic view, and tailored therapy has the potential to improve AUD treatment outcomes by targeting the heterogeneity in genetics and pathophysiology, as well as reason for, and reaction to drinking. Also, the psychiatric co-morbidity rates are high in AUD and dual diagnosis can worsen symptoms and influence treatment response and should be considered in the treatment strategies.
Topics: Humans; Alcoholism; Treatment Outcome; Comorbidity
PubMed: 38555113
DOI: 10.1016/bs.irn.2024.03.003 -
The American Journal of Psychiatry Aug 2023
Topics: Humans; Alcoholism; Alcohol Drinking; Phenotype; Substance-Related Disorders
PubMed: 37525606
DOI: 10.1176/appi.ajp.20230456 -
Drug and Alcohol Dependence Oct 2023We investigated whether genetic risk for insomnia and sleep duration abnormalities are associated with AUD and alcohol consumption. We also evaluated the causal...
STUDY OBJECTIVES
We investigated whether genetic risk for insomnia and sleep duration abnormalities are associated with AUD and alcohol consumption. We also evaluated the causal relationships between sleep- and alcohol-related traits.
METHODS
Individual-level phenotype and genotype data from the Million Veteran Program were used. Polygenic risk scores (PRS) were computed using summary statistics from two recent discovery GWAS of insomnia (N= 453,379 European-ancestry (EA) individuals) and sleep duration (N= 446,118 EAs) and tested for association with lifetime AUD diagnosis (N= 34,658 EA cases) and past-year Alcohol Use Disorders Identification Test-Consumption scale scores (AUDIT-C, N= 200,680 EAs). Bi-directional two-sample Mendelian Randomization (MR) analyses assessed causal associations between the two sleep traits and the two alcohol-related traits.
RESULTS
The insomnia PRS was positively associated with AUD at 2/9 PRS thresholds, with p<0.01 being the most significant (OR = 1.02, p = 3.48 × 10). Conversely, insomnia PRS was negatively associated with AUDIT-C at 6/9 PRS thresholds (most significant threshold being p = 0.001 (β = -0.02, p = 5.6 × 10). Sleep duration PRS was positively associated with AUDIT-C at 2/9 PRS thresholds, with the most significant threshold being p = 1 × 10 (β = 0.01, p = 0.0009). MR analyses supported a significant positive causal effect of insomnia on AUD (14 SNPs; β = 104.14; SE = 16.19; p = 2.22 × 10), although with significant heterogeneity. MR analyses also showed that shorter sleep duration had a causal effect on the risk of AUD (27 SNPs; β = -63.05; SE = 3.54; p = 4.55 × 10), which was robust to sensitivity analyses.
CONCLUSION
The genetic risk for insomnia shows pleiotropy with AUD, and sleep continuity abnormalities have a causal influence on the development of AUD.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Alcoholism; Mendelian Randomization Analysis; Risk Factors; Sleep; Phenotype; Genome-Wide Association Study
PubMed: 37591043
DOI: 10.1016/j.drugalcdep.2023.110912 -
American Family Physician Jan 2024Excessive alcohol use is a leading cause of preventable death in the United States, with alcohol-related deaths increasing during the pandemic. The Substance Abuse and...
Excessive alcohol use is a leading cause of preventable death in the United States, with alcohol-related deaths increasing during the pandemic. The Substance Abuse and Mental Health Services Administration recommends that physicians offer pharmacotherapy with behavioral interventions for patients diagnosed with alcohol use disorder. Several medications are available to help patients reduce drinking and maintain abstinence; however, in 2019, only 7.3% of Americans with alcohol use disorder received any treatment, and only 1.6% were prescribed medications to treat the disorder. Strong evidence shows that naltrexone and gabapentin reduce heavy-drinking days and that acamprosate prevents return-to-use in patients who are currently abstinent; moderate evidence supports the use of topiramate in decreasing heavy-drinking days. Disulfiram has been commonly prescribed, but little evidence supports its effectiveness outside of supervised settings. Other medications, including varenicline and baclofen, may be beneficial in reducing heavy alcohol use. Antidepressants do not decrease alcohol use in patients who do not have mood disorders, but they may help patients who meet criteria for depression to decrease their alcohol intake. Systematic policies are needed to expand the use of medications when treating alcohol use disorder in inpatient and outpatient populations.
Topics: Humans; Alcoholism; Alcohol Deterrents; Acamprosate; Alcohol Drinking; Naltrexone; Disulfiram
PubMed: 38227873
DOI: No ID Found -
Frontiers in Neural Circuits 2023Alcohol is one of the most widely used substances. Alcohol use accounts for 5.1% of the global disease burden, contributes substantially to societal and economic costs,... (Review)
Review
Alcohol is one of the most widely used substances. Alcohol use accounts for 5.1% of the global disease burden, contributes substantially to societal and economic costs, and leads to approximately 3 million global deaths yearly. Alcohol use disorder (AUD) includes various drinking behavior patterns that lead to short-term or long-lasting effects on health. Ethanol, the main psychoactive molecule acting in alcoholic beverages, directly impacts the GABAergic system, contributing to GABAergic dysregulations that vary depending on the intensity and duration of alcohol consumption. A small number of interventions have been developed that target the GABAergic system, but there are promising future therapeutic avenues to explore. This review provides an overview of the impact of alcohol on the GABAergic system, the current interventions available for AUD that target the GABAergic system, and the novel interventions being explored that in the future could be included among first-line therapies for the treatment of AUD.
Topics: Humans; Alcoholism; Alcohol Drinking; Ethanol
PubMed: 37929054
DOI: 10.3389/fncir.2023.1218737 -
Clinical Therapeutics Dec 2023Alcohol use disorder (AUD) is a growing public health concern and an important contributor to global morbidity and mortality. While the hepatotoxic effects of alcohol... (Review)
Review
PURPOSE
Alcohol use disorder (AUD) is a growing public health concern and an important contributor to global morbidity and mortality. While the hepatotoxic effects of alcohol are well known, the adverse effects of alcohol are manifested in almost every organ system. With the growing public health impact of AUD, the aim of this narrative review is to highlight the epidemiology and burden of AUD and its association with extrahepatic diseases including malignancy and disorders of the gastrointestinal (GI), cardiovascular, immunologic, neurologic, endocrine, and hematologic systems.
METHODS
A narrative review of the literature was performed to identify studies addressing the epidemiology, pathophysiology, clinical manifestations, and therapy of extrahepatic health manifestations of alcohol use.
FINDINGS
In the United States, an estimated 14.5 million people have AUD and approximately 88,000 adults die yearly due to alcohol-related causes. The consumption of alcohol and AUD is associated with injuries, violence, cancers, nonmalignant conditions of the GI system, infections, effects on the cardiovascular system, and neurodegenerative diseases. These conditions contribute to the increased mortality associated with AUD and are burdensome to patients and caregivers.
IMPLICATIONS
Increased awareness of the extrahepatic manifestations of AUD, screening for AUD using validated screening tools, such as the Alcohol Use Disorders Identification Test-Concise (AUDIT-C) score, and offering evidence-based interventions to patients with AUD is imperative to reduce the public health burden of AUD. Although historically controversial, recent evidence suggests that any level of alcohol consumption can have negative health consequences. Further research is warranted to determine if any amount of alcohol is safe for consumption. Public health efforts are warranted to help curtail the growing burden of AUD.
Topics: Adult; Humans; United States; Alcoholism; Alcohol Drinking; Liver Diseases
PubMed: 37806811
DOI: 10.1016/j.clinthera.2023.08.018