Medications for treating alcohol use disorder: A narrative review

Chronic heavy alcohol use impacts all major neurotransmitter systems and is associated with multiple medical, psychiatric, and social problems. Available evidence-based medications to treat alcohol use disorder (AUD) are underutilized in clinical practice. These medications promote abstinence or reduce alcohol consumption, though there are questions regarding their optimal dosage, length of treatment, and utility in combination with one another. Pharmacogenetic approaches, which use a patient's genetic make-up to inform medication selection, have garnered great interest but have yet to yield results robust enough to incorporate them in routine clinical care. This narrative review summarizes the evidence both for medications approved by the Food and Drug Administration (disulfiram, oral naltrexone, acamprosate, and extended-release naltrexone) and those commonly used off-label (e.g., gabapentin, baclofen, and topiramate) for AUD treatment. We discuss these drugs' mechanisms of action, clinical use, pharmacogenetic findings, and treatment recommendations. We conclude that the most consistent evidence supporting the pharmacotherapy of AUD is for the opioid antagonists, naltrexone and nalmefene (which is not approved in the United States), and topiramate. These medications demonstrate consistent small or moderate effects in reducing the frequency of drinking and/or heavy drinking. Lastly, we make suggestions for research needed to refine and expand the current literature on effective pharmacotherapy for AUD.     

Longitudinal gut microbiome changes in alcohol use disorder are influenced by abstinence and drinking quantity

ABSTRACT

Many patients with alcohol use disorder (AUD) consume alcohol chronically and in large amounts that alter intestinal microbiota, damage the gastrointestinal tract, and thereby injure other organs via malabsorption and intestinal inflammation. We hypothesized that alcohol consumption and subsequent abstinence would change the gut microbiome in adults admitted to a treatment program. Stool and oral specimens, diet data, gastrointestinal assessment scores, anxiety, depression measures and drinking amounts were collected longitudinally for up to 4 weeks in 22 newly abstinent inpatients with AUD who were dichotomized as less heavy drinkers (LHD, <10 drinks/d) and very heavy drinkers (VHD, 10 or more drinks/d). Next-generation 16 S rRNA gene sequencing was performed to measure the gut and oral microbiome at up to ten time points/subject and LHD and VHD were compared for change in principal components, Shannon diversity index and specific genera. The first three principal components explained 46.7% of the variance in gut microbiome diversity across time and all study subjects, indicating the change in gut microbiome following abstinence. The first time point was an outlier in three-dimensional principal component space versus all other time points. The gut microbiota in LHD and VHD were significantly dissimilar in change from day 1 to day 5 (p = .03) and from day 1 to week 3 (p = .02). The VHD drinking group displayed greater change from baseline. The Shannon diversity index of the gut microbiome changed significantly during abstinence in five participants. In both groups, the Shannon diversity was lower in the oral microbiome than gut. Ten total genera were shared between oral and stool in the AUD participants. These data were compared with healthy controls from the Human Microbiome Project to investigate the concept of a core microbiome. Rapid changes in gut microbiome following abstinence from alcohol suggest resilience of the gut microbiome in AUD and reflects the benefits of refraining from the highest levels of alcohol and potential benefits of abstinence.     

Improvement in quality of life among women and men aged 60 years and older following treatment for alcohol use disorder

Background

Previous studies have yielded mixed results on the association between gender and alcohol use disorder (AUD) treatment outcomes. Thus, additional research is needed to determine the effect of gender on AUD treatment outcomes, including quality of life (QoL), particularly among older adults.

Aims

In a clinical sample of older adults with DSM-5 AUD, we examined changes in QoL from the beginning of AUD treatment through 1 year of follow-ups. We also examined the effect of gender and explored interaction effects with gender on QoL.

Methods

We utilized data from the “Elderly Study,” a multi-national, single-blind, randomized, controlled trial of 693 adults aged 60+ with DSM-5 AUD. Alcohol use was assessed with the Form-90, and QoL with the brief version of the World Health Organization QoL measure. Information was collected at treatment initiation and at 4-, 12-, 26-, and 52-week follow-ups. Multilevel mixed-effects logistic and linear regression models were used to examine QoL changes and the effect of gender on changes in QoL.

Results

Following treatment, small, but significant improvements were seen over time in overall perceived health (p < 0.05). Improvements that persisted over the 1-year follow-up period were seen in the QoL domains of physical health (β: 2.6, 95% CI: 1.4–3.9), psychological health (β: 3.5, 95% CI: 3.3–3.8), social relationships (β: 4.0, 95% CI: 2.5–5.6), and environmental health (β: 1.4, 95% CI: 0.4–2.4). No significant changes were seen over time in overall perceived QoL (p = 0.58). Gender was not associated with changes in any of the QoL outcome measures (all p ≥ 0.05).

Conclusions

Among 60+ year-old adults receiving treatment for DSM-5 AUD, improvements in QoL were achievable and maintained over time, but were not associated with gender.     

Lifetime alcohol intake and pattern of alcohol consumption in patients with alcohol-induced pancreatitis in comparison with patients with alcohol use disorder

Objective: To examine lifetime drinking patterns in men and women with alcohol-induced pancreatitis (AIP) in comparison with patients with alcoholic use disorder (AUD) without pancreatic disease.

Methods: Alcohol consumption patterns were assessed using a validated questionnaire, the Lifetime Drinking History (LDH), during an outpatient visit. Patients diagnosed with AIP were matched for gender and age (+/? 5 years) with patients with AUD in addiction treatment.

Results: A total of 45 patients with AIP (35 males, 10 females) and 45 AUD patients were included. Alcohol consumption patterns were not significantly different between males and females with AIP and those with history of acute AIP and chronic pancreatitis (CP). Alcohol consumption patterns of AIP and AUD patients were similar in terms of onset age and duration of alcohol consumption, lifetime alcohol intake and drinks per drinking day. A higher proportion of binge drinking was found among patients with AUD than those with AIP (median 1.00 vs. 0.94, p?=?.01). Males with AUD had lower onset age (15 vs. 16 years, p?=?.03), higher total amount of spirits (35520 vs. 10450 drinks, p?=?.04) and higher proportion of binge drinking (1.00 vs. 0.97, p?=?.01) than males with AIP, whereas females with AIP and AUD had similar drinking patterns.

Conclusions: Alcohol drinking patterns and lifetime drinking history was similar in patients with AIP and patients with AUD. Males with AIP had lower total amount of spirits and lower proportion of binge drinking than those with AUD, suggesting the idiosyncratic etiology of AIP.