Treatment Of Alcohol Use Disorders Research Articles

Beyond mediators: A critical review and methodological path forward for studying mechanisms in alcohol use treatment research.

Understanding how treatments for alcohol use disorder (AUD) facilitate behavior change has long been recognized as an important area of research for advancing clinical care. However, despite decades of research, the specific mechanisms of change for most AUD treatments remain largely unknown because most prior work in the field has focused only on statistical mediation. Statistical mediation is a necessary but not sufficient condition to establish evidence for a mechanism of change. Mediators are intermediate variables that account statistically for the relationship between independent and dependent variables, whereas mechanisms provide more detailed explanations of how an intervention leads to a desired outcome. Thus, mediators and mechanisms are not equivalent. To advance mechanisms of behavior change research, in this critical review we provide an overview of methodological shortfalls of existing AUD treatment mechanism research and introduce an etiologically informed precision medicine approach that facilitates the testing of mechanisms of behavior change rather than treatment mediators. We propose a framework for studying mechanisms in alcohol treatment research that promises to facilitate our understanding of behavior change and precision medicine (i.e., for whom a given mechanism of behavior change operates and under what conditions). The framework presented in this review has several overarching goals, one of which is to provide a methodological roadmap for testing AUD recovery mechanisms. We provide two examples of our framework, one pharmacological and one behavioral, to facilitate future efforts to implement this methodological approach to mechanism research. The framework proposed in this critical review facilitates the alignment of AUD treatment mechanism research with current theories of etiologic mechanisms, precision medicine efforts, and cross-disciplinary approaches to testing mechanisms. Although no framework can address all the challenges related to mechanisms research, our goal is to help facilitate a shift toward more rigorous and falsifiable behavior change research.

Narrowing the Patient-Physician Gap Based on Self-Reporting and Monthly Hepatologist Feedback for Patients With Alcohol-Related Liver Disease: Interventional Pilot Study Using a Journaling Smartphone App.

Screening and intervention for alcohol use disorders (AUDs) are recommended to improve the prognosis of patients with alcohol-related liver disease (ALD). Most patients' smartphone app diaries record drinking behavior for self-monitoring. A smartphone app can be expected to also be helpful for physicians because it can provide rich patient information to hepatologists, leading to suitable feedback. We conducted this prospective pilot study to assess the use of a smartphone app as a journaling tool and as a self-report-based feedback source for patients with ALD. The aims of this study were assessment of whether journaling (self-report) and self-report-based feedback can help patients maintain abstinence and improve liver function data. This pilot study used a newly developed smartphone journaling app for patients, with input data that physicians can review. After patients with ALD were screened for harmful alcohol use, some were invited to use the smartphone journaling app for 8 weeks. Their self-reported alcohol intake, symptoms, and laboratory data were recorded at entry, week 4, and week 8. Biomarkers for alcohol use included gamma glutamyl transferase (GGT), percentage of carbohydrate-deficient transferrin to transferrin (%CDT), and GGT-CDT (GGT-CDT= 0.8 × ln[GGT] + 1.3 × ln[%CDT]). At each visit, their recorded data were reviewed by a hepatologist to evaluate changes in alcohol consumption and laboratory data. The relation between those outcomes and app usage was also investigated. Of 14 patients agreeing to participate, 10 completed an 8-week follow-up, with diary input rates between 44% and 100% of the expected days. Of the 14 patients, 2 withdrew from clinical follow-up, and 2 additional patients never used the smartphone journaling app. Using the physician's view, a treating hepatologist gave feedback via comments to patients at each visit. Mean self-reported alcohol consumption dropped from baseline (100, SD 70 g) to week 4 (13, SD 25 g; P=.002) and remained lower at week 8 (13, SD 23 g; P=.007). During the study, 5 patients reported complete abstinence. No significant changes were found in mean GGT and mean %CDT alone, but the mean GGT-CDT combination dropped significantly from entry (5.2, SD 1.2) to the week 4 visit (4.8, SD 1.1; P=.02) and at week 8 (4.8, SD 1.0; P=.01). During the study period, decreases in mean total bilirubin (3.0, SD 2.4 mg/dL to 2.4, SD 1.9 mg/dL; P=.01) and increases in mean serum albumin (3.0, SD 0.9 g/dL to 3.3, SD 0.8 g/dL; P=.009) were recorded. These pilot study findings revealed that a short-term intervention with a smartphone journaling app used by both patients and treatment-administering hepatologists was associated with reduced drinking and improved liver function. UMIN CTR UMIN000045285; http://tinyurl.com/yvvk38tj.

Subjective stress and any drinking during alcohol treatment: Disentangling within and between person autoregressive effects

Alcohol use has been shown to increase stress, and there is some evidence that stress predicts subsequent alcohol use during treatment for alcohol use disorder (AUD), particularly among females who are more likely to report coping-motivated drinking. Gaining a better understanding of the processes by which stress and alcohol use are linked during treatment could potentially inform AUD treatment planning. The current study aimed to characterize the association between stress and drinking during the course of AUD treatment and whether there were sex differences in these associations. Secondary data analyses of the COMBINE study (N = 1375; 69% male, 76.3% non-Hispanic and white, average age of 44.4 years) were conducted to examine self-reported perceived stress and alcohol consumption across 16 weeks of treatment for AUD using a Bayesian random-intercept cross-lagged panel model. There was stronger evidence for any alcohol use predicting greater than typical stress in subsequent weeks and less strong evidence for stress increasing the subsequent probability of alcohol use, particularly among males. For females, greater stress predicted subsequent drinking earlier in the treatment period, and a lower probability of subsequent drinking in the last week of treatment. Interventions might specifically focus on targeting reductions in stress following drinking occasions.

A qualitative exploration of young adults’ perceptions of a new intervention for alcohol use disorder

Background Due to the rising prevalence of alcohol use disorders among young adults, the need for effective and accessible interventions has become increasingly imperative. In acknowledgment of this issue, we developed a novel intervention known as contingency management plus problem solving therapy (CM-PST). The aim of the current study was to gain insight into the perspectives on the effectiveness of the newly developed CM-PST using focus group discussion among young adults who consume alcohol regularly. Materials and Methods The study employed a qualitative research design, utilizing focus group discussions as the primary data collection method. Participants described their perceptions regarding the newly developed CM-PST. Semi-structured focus group sessions were conducted via Zoom in November 2022. A total of 19 young adults, aged 18-24 years old, participated in five focus group sessions. Data were analyzed using deductive content analysis. Results Participants demonstrated overall positive attitudes toward the novel intervention, recognizing the potential benefits, it could offer in terms of alcohol use reduction and emotional well-being. They emphasized the importance of incentives in motivating behavioral changes, as well as the practicality of problem-solving techniques in addressing everyday challenges. Additionally, participants provided valuable insights into potential barriers and implementation challenges, highlighting the need for flexible and personalized approaches to accommodate individual preferences and needs. Conclusions The results of this study contribute to the growing body of literature on innovative intervention approaches for young adults facing alcohol use issues. The findings shed light on the acceptability and perceived effectiveness of the CM-PST intervention from the perspective of the target population.

Associations between alcohol use disorder polygenic score andremission in participants from high-risk families and the Indiana Biobank.

In the United States, ~50% of individuals who meet criteria for alcohol use disorder (AUD) during their lifetimes do not remit. We previously reported that a polygenic score for AUD (PGSAUD ) was positively associated with AUD severity as measured by DSM-5 lifetime criterion count, and AUD severity was negatively associated with remission. Thus, we hypothesized that PGSAUD would be negatively associated with remission. Individuals of European (EA) and African ancestry (AA) from the Collaborative Study on the Genetics of Alcoholism (COGA) who met lifetime criteria for AUD, and two EA cohorts ascertained for studies of liver diseases and substance use disorders from the Indiana Biobank were included. In COGA, 12-month remission was defined as any period of ≥12 consecutive months without meeting AUD criteria except craving and was further categorized as abstinent and non-abstinent. In the Indiana Biobank, remission was defined based on ICD codes and could not be further distinguished as abstinent or non-abstinent. Sex and age were included as covariates. COGA analyses included additional adjustment for AUD severity, family history of remission, and AUD treatment history. In COGA EA, PGSAUD was negatively associated with 12-month and non-abstinent remission (p ≤ 0.013, βs between -0.15 and -0.10) after adjusting for all covariates. In contrast to the COGA findings, PGSAUD was positively associated with remission (p = 0.004, β = 0.28) in the Indiana Biobank liver diseases cohort but not in the Indiana Biobank substance use disorder cohort (p = 0.17, β = 0.15). PGSAUD was negatively associated with 12-month and non-abstinent remission in COGA EA, independent of behavioral measures of AUD severity and family history of remission. The discrepant results in COGA and the Indiana Biobank could reflect different ascertainment strategies: the Indiana Biobank participants were older and had higher rates of liver disease, suggesting that these individuals remitted due to alcohol-related health conditions that manifested in later life.

Patterns of health care interactions of individuals with alcohol use disorder: A latent class analysis

IntroductionGiven the high rates at which individuals with alcohol use disorder (AUD) utilize health care for co-existing conditions, health systems are promising venues for interventions that will facilitate access to AUD treatment. However, how individuals with AUD interact with such systems and, thus, how systems should intervene is unclear. In this study, we seek to identify patterns in how individuals diagnosed with AUD within an academic health system interacted with the system prior to diagnosis. MethodsWe use electronic health records from a single academic health system in a major US metropolitan area to create a deidentified retrospective cohort including all individuals age 18+ diagnosed with AUD 2010–2019 (n = 26,899). Latent class analysis (LCA) identified subgroups defined by aspects of previous system interaction and health status, including having an in-system primary care provider, previous utilization of primary and specialty care, diagnosis setting, payer, and presence of other chronic conditions. We then assessed subgroup differences in demographics and associations with in-system AUD treatment receipt in the year following diagnosis, adjusting for demographics. ResultsThe population was on average 38.6 years old (standard deviation = 15.4) and predominantly male (66.1 %), White (64.5 %), and not of Hispanic/Latino ethnicity (87.8 %). Only 4.7 % received in-system treatment following diagnosis. We deemed the four-class model the optimal LCA model. This model identified subgroups that can be described as 1) average utilization (20.7 % of population), 2) low utilization (54.5 %), 3) high health burden and low utilization (14.2 %), and 4) high health burden and high utilization (10.6 %). Predicted membership in the high health burden and high utilization subgroup and low utilization subgroup were associated with higher and lower odds of treatment receipt, respectively, compared with predicted membership in the average utilization subgroup (odds ratio (OR) for high/high subgroup = 1.21, 95 % confidence interval (CI) = 1.01, 1.27; OR for low subgroup = 0.29 95 % CI = 0.24, 0.34). ConclusionIndividuals diagnosed with AUD within a health system interact with that system in markedly different ways and are unlikely to benefit uniformly from system-based interventions to facilitate treatment. Group-tailored interventions are more likely to have impact and provide returns on investments for systems.

Inpatient Screening, Brief Intervention, and Referral to Treatment for Alcohol Use Disorder in Patients Admitted with Alcohol-associated Liver Disease Is Not Universally Implemented in Practice, But Can Reduce Readmissions for Alcohol-associated Hepatitis.

The management of alcohol-related liver disease requires a multidisciplinary approach to treat alcohol use disorder. We aimed to determine the proportion of actively drinking patients admitted for alcohol-associated hepatitis (AAH) or decompensated alcohol-related cirrhosis (DARLC) who were offered or underwent screening, brief intervention, and referral to treatment (SBIRT) for alcohol use disorder during admission and if inpatient SBIRT is associated with reduced readmissions for alcohol-related liver disease. We conducted a retrospective cohort study of actively drinking patients admitted to our institution from January 2017 to December 2021 with AAH or DARLC. Logistic regression was used to identify factors, such as conducting SBIRT, that were associated with 30-day and 90-day readmissions for recurrent AAH or DARLC. There were 120 AAH admissions (mean age 47.7 ± 13.6 years), and 177 DARLC admissions (mean age 58.2 ± 9.5 years). SBIRT was conducted in only 51.7% of AAH admissions, and 23.7% of DARLC admissions. For AAH, conducting SBIRT was associated with significantly reduced 30-day (OR 0.098, P = 0.001, 95% CI 0.024-0.408) and 90-day (OR 0.166, P = 0.003, 95% CI 0.052-0.534) readmissions. For DARLC, there was no association between conducting SBIRT and 30-day or 90-day readmissions. SBIRT was conducted with actively drinking patients in only 51.7% of AAH admissions and 23.7% of DARLC admissions. Patients admitted for AAH who received inpatient SBIRT had decreased 30-day and 90-day readmission rates for AAH or DARLC.

GLP-1 receptor agonists are promising but unproven treatments for alcohol and substance use disorders.

GLP-1 receptor agonists are promising but unproven treatments for alcohol and substance use disorders.

Affective and cognitive Theory of Mind in patients with alcohol use disorder: Associations with symptoms of depression, anxiety, and somatization

IntroductionTheory of Mind (ToM) is the ability to ascribe thoughts (cognitive ToM) and feelings (affective ToM) to others. Ample evidence exists for impairments of affective and cognitive ToM in individuals with alcohol use disorder (AUD); however, evidence regarding changes of these impairments during AUD treatment and their possible relationship to comorbid symptoms is ambiguous. The current study analyzed changes in ToM during treatment and tested associations with comorbid symptoms of depression, anxiety, somatization, and social functioning. MethodsWe analyzed data from 175 individuals with AUD. The study assessed ToM and comorbid symptoms of depression, anxiety, somatization, and social functioning at the time of admission and at the time of discharge from an approximately 60 days long abstinence-oriented inpatient treatment. We assessed affective and cognitive ToM using the Movie for the Assessment of Social Cognition, a measure with high ecological validity. ResultsAll symptoms, total and cognitive ToM improved following treatment; however, affective ToM did not improve. Moreover, cognitive ToM at the beginning of treatment was associated with improved symptoms of depression and somatization, while affective ToM was not. ConclusionsOur study shows improvements in total and cognitive ToM as well as symptoms of depression, anxiety, somatization, and social functioning following long-term treatment. Furthermore, cognitive ToM was related to improvements in comorbid symptoms. This finding suggests that ToM may be an important treatment target in patients with AUD.

Prefrontal cortex glutamatergic adaptations in a mouse model of alcohol use disorder

Alcohol use disorder (AUD) produces cognitive deficits, indicating a shift in prefrontal cortex (PFC) function. PFC glutamate neurotransmission is mostly mediated by α-amino-3‑hydroxy-5-methyl-4-isoxazolepropionic acid-type ionotropic receptors (AMPARs); however preclinical studies have mostly focused on other receptor subtypes. Here we examined the impact of early withdrawal from chronic ethanol on AMPAR function in the mouse medial PFC (mPFC). Dependent male C57BL/6J mice were generated using the chronic intermittent ethanol vapor-two bottle choice (CIE-2BC) paradigm. Non-dependent mice had access to water and ethanol bottles but did not receive ethanol vapor. Naïve mice had no ethanol exposure. We used patch-clamp electrophysiology to measure glutamate neurotransmission in layer 2/3 prelimbic mPFC pyramidal neurons. Since AMPAR function can be impacted by subunit composition or plasticity-related proteins, we probed their mPFC expression levels. Dependent mice had higher spontaneous excitatory postsynaptic current (sEPSC) amplitude and kinetics compared to the Naïve/Non-dependent mice. These effects were seen during intoxication and after 3–8 days withdrawal, and were action potential-independent, suggesting direct enhancement of AMPAR function. Surprisingly, 3 days withdrawal decreased expression of genes encoding AMPAR subunits (Gria1/2) and synaptic plasticity proteins (Dlg4 and Grip1) in Dependent mice. Further analysis within the Dependent group revealed a negative correlation between Gria1 mRNA levels and ethanol intake. Collectively, these data establish a role for mPFC AMPAR adaptations in the glutamatergic dysfunction associated with ethanol dependence. Future studies on the underlying AMPAR plasticity mechanisms that promote alcohol reinforcement, seeking, drinking and relapse behavior may help identify new targets for AUD treatment.

Alcohol use disorder in alcohol-associated liver disease: Two sides of the same coin.

Alcohol-associated liver disease (ALD) has emerged as the leading indication for liver transplantation (LT) worldwide, with 40% of LTs in the United States performed for ALD in 2019. The ALD-related health care burden accelerated during the COVID-19 pandemic, especially in young individuals. Alcohol use disorder (AUD), which focuses on the negative effects of alcohol on psychosocial, physical, and mental health, is present in the majority of patients with ALD, with moderate to severe AUD in 75%-80%. During the last decade, early liver transplantation (eLT) has emerged as a lifesaving treatment for selected patients with alcohol-associated hepatitis; these patients may have a higher risk of using alcohol after LT. The risk of alcohol use recurrence may be reduced during the pretransplant or post-transplant period with AUD treatment using behavioral and/or pharmacological therapies and with regular monitoring for alcohol use (self-reported and complemented with biomarkers like phosphatidylethanol). However, AUD treatment in patients with ALD is challenging due to patient, clinician, and system barriers. An integrated model to provide AUD and ALD care by hepatologists and addiction experts in a colocated clinic starting from LT evaluation and selection to monitoring listed candidates and then to following up on recipients of LT should be promoted. However, the integration of addiction and hepatology teams in an LT program in the real world is often present only during evaluation and candidate selection for LT. Data are emerging to show that a multidisciplinary integrated AUD treatment within an LT program reduces recurrent alcohol use after LT. If we want to continue using early liver transplantation for patients with severe alcohol-associated hepatitis, LT programs should focus on building integrated multidisciplinary care teams for the integrated treatment of both AUD and ALD.

Russian Version of the Reasons for Heavy Drinking Questionnaire: the study of psychometric properties and validation

The heterogeneity of the clinical presentation of alcohol use disorder significantly affects the effectiveness of a standardized approach to the treatment of the disease and requires the use of targeted interventions based on an understanding of the underlying mechanisms and processes. Experimental studies of using drinking motive phenotypes for developing personalized treatment approaches had promising results and have demonstrated the theoretical and practical relevance of their further investigation and assessment.The purpose of this paper is to explore the psychometric properties of the Russian version of the Reasons for Heavy Drinking Questionnaire. For this study 163 patients (108 men (71%), mean age 43.00 years [38.00;43.00] (Mdn [Q1; Q3]), mean disease duration 10 years [4.00;17.00] (Mdn[Q1; Q3]) undergoing inpatient treatment for alcohol use disorder were recruited. The following instruments were used: clinical interview, Reward, Relief, Habit Drinking Scale, Penn Alcohol Craving Scale, Hospital Anxiety and Depression Scale, Snaith-Hamilton Pleasure Scale, and Carver and White’s BIS/BAS scale.The results did not confirm the factor structure proposed by the authors of the questionnaire. However, two factors - "Positive Reinforcement" and "Normalization and Habit" - were identified. Multiple significant correlations were also identified between drinking motivation phenotypes and clinical and psychological characteristics (previous treatment experience and periods of alcohol remission, emotional impairment, behavioral activation and inhibition in response to reward and punishment, and another scale for assessment of reward, relief, and habit drinking motives).

Modeling the impact of a long-term horizon and multiple treatment episodes on estimates of the cost-effectiveness of alcohol treatment in the United States.

Most clinical studies of alcohol use disorder (AUD) treatment have short follow-up periods, underestimating the full benefits of alcohol treatment. Furthermore, clinical studies only consider one treatment cycle and do not account for the need for multiple episodes to treat a chronic recurrent condition. A validated microsimulation model of the long-term drinking patterns of people with AUD in the United States simulated 10,000 individuals resembling those from a large clinical trial. The model was used to assess the impact of (1) 1-year, 5-year, and lifetime horizon on alcohol treatment cost-effectiveness estimates and (2) no, one, two, four, and unlimited additional treatment episodes on alcohol treatment cost-effectiveness estimates. Model outcomes included healthcare costs, crime costs, labor market productivity, life expectancy, quality-adjusted life years (QALYs), alcohol-related hospitalizations, and deaths. Cost-effectiveness analyses were conducted for two perspectives: a healthcare perspective that included costs from hospitalization and AUD treatment, and a broader societal perspective that also included crime costs and productivity. The incremental cost per additional QALY gained for alcohol treatment compared with no treatment decreased from $55,590 after 1 year to $78 when healthcare costs and QALYs were tracked over the lifetime, that is, treatment became more cost effective. Treatment was cost saving for any time frame when the impacts on crime and labor productivity were also accounted for in a societal perspective. Access to multiple treatment episodes dominated (i.e., it was more effective and less costly) than no-treatment and one-episode scenarios. From a healthcare perspective, incremental costs per additional QALY for increasing from a maximum of two to four treatment episodes was $499 and from four to unlimited episodes was $5049. The unlimited treatment scenario dominated all others from a societal perspective. Results were robust in sensitivity analyses. A long-term perspective and multiple episodes of alcohol treatment improve cost-effectiveness estimates. When societal impacts are included, alcohol treatment is cost saving. Results support the value of alcohol treatment.

Impact of a Rounding Tool and Clinical Champion on Trauma Patient Screening, Brief Intervention, and Referral to Treatment for Alcohol Use Disorder.

Early identification and treatment of alcohol misuse among trauma patients is the standard of care for trauma centers. Yet, trauma programs face significant barriers in adherence to sustained alcohol misuse screening. This study aims to evaluate the impact of a rounding tool and clinical champion on screening, brief intervention, and referral to treatment compliance rates for alcohol use disorder in trauma patients. This is a single-center, retrospective cohort design measuring the impact of a nursing rounding tool and clinical champion on screening, brief intervention, and referral to treatment for alcohol use disorder in trauma patients older than 14 years. Retrospective reviews were conducted over a 5-year period from 2017 to 2021 for all admitted trauma patients as defined by the National Trauma Data Standard. More than 5,000 trauma patients were included during the study period. The nurses' rounding tool and clinical champion intervention led to an increase in the alcohol use disorder screening rate from an average of 59% for the first 3 months of the study (May to July 2017) to 95% for the last 3 months of the study (March to May 2021). Our findings show that a dedicated clinical champion and nurse rounding tool increase compliance for screening, brief intervention, and referral to treatment for alcohol use disorder in trauma patients.

Alcohol use disorder treatment via video conferencing compared with in-person therapy during COVID-19 social distancing : A non-inferiority comparison of three cohorts.

Social distancing measures during the COVID-19 pandemic forced an abrupt transformation of treatment delivery for mental health care. In mid-March 2020, nearly all in-person contact was replaced with video conferencing. The pandemic thus offered a natural experiment and a unique opportunity to conduct an observational study of whether alcohol use disorder treatment through video conferencing is non-inferior to in-person treatment. In a large urban substance use disorder treatment center in the Netherlands, treatment evaluation is routine practice. Outcome data are regularly collected to support shared decision making and monitor patient progress. For this study, pre-test and post-test data on alcohol use (Measurements in the Addictions for Triage and Evaluation), psychopathology (Depression Anxiety Stress Scales), and quality of life (Manchester Short Assessment of Quality of Life) were used to compare outcomes of cognitive behavioral therapy treatment for three cohorts: patients who received treatment for a primary alcohol use disorder performed prior to (n = 628), partially during (n = 557), and entirely during (n = 653) the COVID-19 lockdown. Outcome was similar across the three cohorts: No inferior outcomes were found for treatments that were conducted predominantly through video conferencing during lockdown or treatments that started in-person, but were continued through video conferencing, compared to in-person treatments that were conducted prior to COVID-19. The number of drop-outs were also similar between cohorts. However, there was a difference in average treatment intensity between cohorts, with treatment partially or fully conducted during the COVID-19 pandemic lasting longer. Treatment for a primary alcohol use disorder, provided partially or predominantly through video conferencing during the COVID-19 pandemic resulted in abstinence rates and secondary outcomes similar to traditional in-person care, in spite of the potentially negative effects of the COVID-related lockdown measures themselves. These results from everyday clinical practice corroborate findings of randomized controlled studies and meta-analyses in which video conferencing appeared non-inferior to in-person care in clinical effectiveness.

Neurobiology and the Treatment of Alcohol Use Disorder: A Review of the Evidence Base.

Alcohol use disorder (AUD) is a significant public health concern, accounting for a majority of substance use disorder cases in the United States. Treatment for AUD is complex, with multiple intervention points that may be further complicated by genotype and phenotype, resulting in diverse outcomes. In order to better understand the current landscape of AUD treatment, the present review considers different etiological models of AUD and assesses the evidence base of current treatment options. The first section of this review summarizes various etiological models of AUD and presents different approaches to classifying the disorder. Various theories, including neurobiological models, are discussed. The second section presents a comprehensive analysis of available treatment options for AUD, encompassing behavioral and pharmacological interventions and their current evidence base. Finally, this review discusses the ongoing treatment gap and significant factors contributing to low treatment utilization. Together, this review provides an overview of different etiological processes and mechanisms of AUD, as well as summarizes the literature on key treatment approaches. By integrating historical, theoretical, and empirical data, this review aims to inform both researchers and providers with valuable insights to advance AUD treatment approaches and narrow the treatment gap.

Management of Patients After Treatment of Severe Alcohol-associated Hepatitis.

Alcohol-associated liver disease is the leading indication for hospitalization among patients with chronic liver disease. Rates of hospitalization for alcohol-associated hepatitis have been rising over the last 2 decades. Patients with alcohol-associated hepatitis carry significant morbidity and mortality, but there is a lack of standardized postdischarge management strategies to care for this challenging group of patients. Patients warrant management of not only their liver disease but also their alcohol use disorder. In this review, we will discuss outpatient management strategies for patients who were recently hospitalized and discharged for alcohol-associated hepatitis. We will discuss short management of their liver disease, long-term follow-up, and review-available treatment options for alcohol use disorder and challenges associated with pursuing treatment for alcohol use disorder.

Update on Pharmacological Treatment for Comorbid Major Depressive and Alcohol Use Disorders: The Role of Extended-release Trazodone.

Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD) are major public health concerns because of their high prevalence and clinical and functional severity. MDD and AUD commonly co-occur, but effective therapeutic approaches for comorbidity are still scarce. Available evidence on selective serotonin reuptake inhibitors and tricyclic antidepressants held mixed results, and further pharmacological categories have been less investigated. Trazodone is an approved antidepressant drug for adults and has shown efficacy on symptoms like anxiety and insomnia observed in AUD patients as well. Thus, this study aims to evaluate the effect of extended-release trazodone on clinical and functional features in MDD + AUD subjects. One hundred MDD + AUD outpatients were retrospectively evaluated at 1, 3, and 6 months of treatment with extended-release trazodone (150-300 mg/day, flexibly dosed). Improvement in depressive symptoms was the primary outcome measure. Changes in anxiety, sleep, functioning, quality of life, clinical global severity, and alcohol craving were also investigated. Trazodone reduced depressive symptoms (p < 0.001) with 54.5% remission at the endpoint. Similar improvements were observed in all secondary outcomes, including anxiety, sleep alterations, and craving (p < 0.001). Only mild side effects were reported and disappeared over time. Extended-release trazodone displayed good antidepressant properties in MDD + AUD patients, ameliorating overall symptomatology, functioning, and quality of life, with a good safety/ tolerability profile. Further, it significantly improved sleep disturbances and craving symptoms, which are associated with drinking relapse and worse outcomes. Therefore, trazodone might represent a promising pharmacological option for MDD + AUD patients.

Repurposing Drugs for Inhibition against ALDH2 via a 2D/3D Ligand-Based Similarity Search and Molecular Simulation.

Aldehyde dehydrogenase-2 (ALDH2) is a crucial enzyme participating in intracellular aldehyde metabolism and is acknowledged as a potential therapeutic target for the treatment of alcohol use disorder and other addictive behaviors. Using previously reported ALDH2 inhibitors of Daidzin, CVT-10216, and CHEMBL114083 as reference molecules, here we perform a ligand-based virtual screening of world-approved drugs via 2D/3D similarity search methods, followed by the assessments of molecular docking, toxicity prediction, molecular simulation, and the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analysis. The 2D molecular fingerprinting of ECFP4 and FCFP4 and 3D molecule-shape-based USRCAT methods show good performances in selecting compounds with a strong binding behavior with ALDH2. Three compounds of Zeaxanthin (q = 0), Troglitazone (q = 0), and Sequinavir (q = +1 e) are singled out as potential inhibitors; Zeaxanthin can only be hit via USRCAT. These drugs displayed a stronger binding strength compared to the reported potent inhibitor CVT-10216. Sarizotan (q = +1 e) and Netarsudil (q = 0/+1 e) displayed a strong binding strength with ALDH2 as well, whereas they displayed a shallow penetration into the substrate-binding tunnel of ALDH2 and could not fully occupy it. This likely left a space for substrate binding, and thus they were not ideal inhibitors. The MM-PBSA results indicate that the selected negatively charged compounds from the similarity search and Vina scoring are thermodynamically unfavorable, mainly due to electrostatic repulsion with the receptor (q = -6 e for ALDH2). The electrostatic attraction with positively charged compounds, however, yielded very strong binding results with ALDH2. These findings reveal a deficiency in the modeling of electrostatic interactions (in particular, between charged moieties) in the virtual screening via the 2D/3D similarity search and molecular docking with the Vina scoring system.

Leadership Styles Experienced During Military Service Predict Later Anhedonic Depressive Symptoms andSelf-Efficacy inVeterans With Alcohol Use Disorder.

Lifetime and past-year alcohol use disorder (AUD) prevalence is significantly higher in US Armed Services Veterans than in non-veterans across adulthood. This study examined the associations of perceived transformational leadership styles (TLS) experienced during military service and anhedonic depression and self-efficacy related to confidence to abstain or reduce alcohol consumption in Veterans seeking treatment for AUD. The ramifications of perceived leadership styles on multiple aspects of follower psychiatric functioning, including depressive and PTSD symptomatology, during and after military service, may be substantial and enduring. Higher anhedonic depression and lower abstinence self-efficacy are related to increased risk of relapse after treatment. We predicted Veterans, in treatment for AUD, who reported higher perceived levels of transformational leadership during military service, demonstrate lower anhedonic depressive symptoms and higher alcohol abstinence self-efficacy. Veterans with AUD (n = 60; 50 ± 14 years of age) were recruited from residential treatment at the VA Palo Alto Health Care System. All procedures were approved by the VA Palo Alto Health Care System and Stanford University institutional review boards. A series of mediation analyses were completed with The Multifactor Leadership Questionnaire measures of TLS (average across leadership measures [transformational leadership average; TLS average]) as predictor and the Alcohol Abstinence Self-Efficacy Scale, Mood and Anxiety Symptom Questionnaire, anhedonic depression subscale, as dependent measures. PTSD Checklist for DSM-5 score was tested as a mediator variable. Higher reported perceived TLS average during military service was significantly related to lower anhedonic depressive symptoms. Higher TLS average was related to higher self-efficacy to resist alcohol use in contexts involving experience of physical issues and withdrawal/cravings and urges. These relationships were not mediated by PTSD symptomatology or duration of military service, age, education, time since military service, military branch, combat exposure, or current psychiatric diagnosis. The significant associations of perceived TLS during military service with anhedonic depression and alcohol use self-efficacy are clinically relevant because these measures are associated with relapse risk after AUD treatment. Further study of the implications of perceived TLS during military service for AUD and other substance use disorder treatment outcome is warranted in Veterans.