Treatment Of Alcohol Use Disorders Research Articles

Brain lncRNA-mRNA co-expression regulatory networks and alcohol use disorder

Prolonged alcohol consumption can disturb the expression of both coding and noncoding genes in the brain. These dysregulated genes may co-express in modules and interact within networks, consequently influencing the susceptibility to developing alcohol use disorder (AUD). In the present study, we performed an RNA-seq analysis of the expression of both long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) in 192 postmortem tissue samples collected from eight brain regions (amygdala, caudate nucleus, cerebellum, hippocampus, nucleus accumbens, prefrontal cortex, putamen, and ventral tegmental area) of 12 AUD and 12 control subjects of European ancestry. Applying the limma-voom method, we detected a total of 57 lncRNAs and 51 mRNAs exhibiting significant differential expression (Padj < 0.05 and fold-change ≥2) across at least one of the eight brain regions investigated. Machine learning analysis further confirmed the potential of these top genes in predicting AUD. Through Weighted Gene Co-expression Network Analysis (WGCNA), we identified distinct lncRNA-mRNA co-expression modules associated with AUD in each of the eight brain regions. Additionally, lncRNA-mRNA co-expression networks were constructed for each brain region using Cytoscape to reveal gene regulatory interactions implicated in AUD. Hub genes within these networks were found to be enriched in several key KEGG pathways, including Axon Guidance, MAPK Signaling, p53 Signaling, Adherens Junction, and Neurodegeneration. Our results underscore the significance of networks involving AUD-associated lncRNAs and mRNAs in modulating neuroplasticity in response to alcohol exposure. Further elucidating these molecular mechanisms holds promise for the development of targeted therapeutic interventions for AUD.

Cost-Effectiveness Analysis of Deep Brain Stimulation for the Treatment of Alcohol Use Disorder and Alcoholic Liver Disease.

Alcohol use disorder (AUD) is a major public health concern and cause of mortality and morbidity. Alcohol-associated liver disease (ALD) is a debilitating complication of AUD, mitigated by abstinence from alcohol use. Deep brain stimulation (DBS) is emerging as a potential treatment for AUD. However, its cost-effectiveness compared to the standard medical treatment is unclear. To estimate the cost-effectiveness of DBS compared to medical management for patients with AUD and ALD. We utilized a decision analytic model based on published literature to conduct a cost-effectiveness analysis of costs and health outcomes for DBS and medical management in patients with AUD and ALD. We also carried out a threshold analysis to determine the probability of success necessary for DBS to be cost-effective. Costs were measured in 2024 US dollars and effectiveness in quality-adjusted life years (QALYs). We used a time horizon of 1-2 years and adopted a societal perspective. Our results show that for AUD patients in general, DBS is not cost-effective at any DBS success rate. However, for advanced ALD patients, defined as fibrosis stage 3 or beyond DBS becomes cost-effective. For these patients, DBS is cost-effective over a two-year period at a $100,000 willingness-to-pay threshold at DBS success rates greater than 53%. For advanced decompensated ALD patients, DBS is cost-effective over a one-year period at DBS success rate greater than 35%. Should it prove efficacious, DBS may be cost-effective for patients with AUD and ALD. Thus, future randomized controlled trials to evaluate its efficacy are warranted.

Analysis of Ohio Advanced Practice Registered Nurses' Rate of Prescribing Naltrexone for Patients With Alcohol Use Disorder Since Elimination of the X-Waiver.

Alcohol use disorder (AUD) is common and deadly. Naltrexone is a treatment for AUD. Previous research examined factors that predict Ohio Advanced Practice Registered Nurses' (APRNs) utilization of naltrexone to treat AUD. Inclusion criteria included APRNs' endorsing receipt of the X-waiver, a designation indicating providers' receipt of substance use disorder education. In 2023, the X-waiver was eliminated. The purpose of this study was to replicate the previous research design in respondents without an X-waiver and compare findings. The aims of this study were three-fold: (1) assess whether race, age, practice setting, years in practice, or work experience with an addiction specialist physician predicted prescription of naltrexone for AUD, (2) assess whether the goal of abstinence or reduced alcohol use as desired treatment affected the likelihood of naltrexone prescription for AUD, and (3) compare differences between the answers in the current respondent group without X-waiver and the previous study's X-waivered respondents. All Ohio APRNs were sent surveys. Eighty-eight responses were included in analysis. Descriptive statistics, logistic regression, and chi-square results were reported. Work experience with an addiction specialist physician was negatively associated with prescribing naltrexone for AUD. Respondents from the previous study of X-waivered APRNs were significantly more likely to prescribe naltrexone for reduced alcohol consumption as a treatment outcome than the respondents in this study. The recent policy change eliminating the X-waiver provides important context for research, adding to the substance use disorder literature.

A Brief Intervention on Alcohol Use Disorder Is Associated With Treatment Access for Inpatients With Alcohol-Associated Liver Disease.

Alcohol-associated liver disease (ALD) is the most common indication for liver transplantation in the United States. Alcohol use disorder (AUD) treatment is recommended in all patients with ALD and AUD, but it remains underutilized. To identify predictors of AUD treatment and to assess 30-day readmission, return to drinking, and 1-year transplant-free survival. Retrospective single-center cohort study of consecutive patients hospitalized with ALD and AUD between 2018 and 2020. Patients who died or were lost to follow-up at 90 days after hospitalization were excluded. AUD treatment was defined as receiving medication or participating in residential, outpatient, or support groups within 90 days of discharge. One hundred nine patients were included. Mean age was 51.7 years, and 63% were male. Fifty-six (51%) patients received AUD treatment, and 23 (21%) patients received more than one treatment. Predictors of AUD treatment were younger age (OR, 1.07 [95% CI, 1.04-1.12]; P < 0.001), gastroenterology/hepatology consult (AOR, 8.54 [95% CI, 2.55-39.50]; P = 0.0002), addiction psychiatry consult (AOR, 2.77 [95% CI, 1.16-6.84]; P = 0.02), and a brief AUD intervention (AOR, 18.19 [95% CI, 3.36-339.07]; P = 0.0001). Cirrhosis decompensation, MELD-Na score, and insurance status were not associated with treatment. Thirty-one patients (28.4%) were readmitted, and 29 (26.6%) remained abstinent 30 days from discharge. Patients who received treatment had improved transplant-free survival (HR, 0.44, P = 0.04). A brief intervention on AUD had the strongest association with receiving AUD treatment in our cohort. Further efforts to incorporate brief interventions when offering AUD treatment to patients with ALD may be beneficial.

Supervised Disulfiram Should Be Considered First-line Treatment for Alcohol Use Disorder.

Despite the prevalence of alcohol use disorder (AUD) in the United States, the armamentarium of FDA-approved medications available for AUD treatment is remarkably small. Disulfiram, 1 of only 3 approved medications, is consistently designated as a second-line option in national treatment guidelines, citing inconsistent evidence, lack of patient preference, and safety concerns. These concerns, however, stem from a misguided interpretation of the evidence that exclusively relies upon double-blind randomized controlled trials (RCT). When viewed instead as both a medication and a behavioral intervention, open-label RCTs become a more appropriate research method, yielding overwhelmingly favorable efficacy data for disulfiram, and supervised disulfiram, in particular. With these data in mind, supervised disulfiram should be redesignated as a first-line intervention in both treatment guideline creation and clinical pathway tools. The addiction medicine community can no longer afford to neglect this critical therapeutic resource.

Disulfiram Should Remain Second-line Treatment for Most Patients With Alcohol Use Disorder.

Alcohol use disorder (AUD) is responsible for a significant burden of medical, economic, and social harm globally and across the United States. Currently, only three FDA-approved medications for AUD are available, and most patients with AUD never receive pharmacotherapy. Disulfiram, the first medication that FDA approved for treatment of AUD, is recommended as a second-line treatment option by several national treatment guidelines citing safety concerns and lack of high-quality comparative studies. In this issue, Holt argues that disulfiram should be reclassified as a first-line treatment for AUD based on promising open-label randomized controlled trials (RCTs) for disulfiram as a behavioral intervention. Review of the literature suggests that disulfiram can be a useful treatment for a highly selected group of patients with no medical or psychiatric contraindications, high motivation for abstinence, and adequate family support. Unfortunately, many patients with AUD, a disorder characterized by high rates of medical and psychiatric multimorbidity and social vulnerability, fall outside of this narrow selection criteria. Prescribers should consider other FDA-approved medications as first-line treatment options for most patients with AUD, reserving disulfiram for the rare patients in whom the potential for benefit clearly outweighs risk of harm.

Analyzing Dropout in Alcohol Recovery Programs: A Machine Learning Approach.

Background: Retention in treatment is crucial for the success of interventions targeting alcohol use disorder (AUD), which affects over 100 million people globally. Most previous studies have used classical statistical techniques to predict treatment dropout, and their results remain inconclusive. This study aimed to use novel machine learning tools to identify models that predict dropout with greater precision, enabling the development of better retention strategies for those at higher risk. Methods: A retrospective observational study of 39,030 (17.3% female) participants enrolled in outpatient-based treatment for alcohol use disorder in a state-wide public treatment network has been used. Participants were recruited between 1 January 2015 and 31 December 2019. We applied different machine learning algorithms to create models that allow one to predict the premature cessation of treatment (dropout). With the objective of increasing the explainability of those models with the best precision, considered as black-box models, explainability technique analyses were also applied. Results: Considering as the best models those obtained with one of the so-called black-box models (support vector classifier (SVC)), the results from the best model, from the explainability perspective, showed that the variables that showed greater explanatory capacity for treatment dropout are previous drug use as well as psychiatric comorbidity. Among these variables, those of having undergone previous opioid substitution treatment and receiving coordinated psychiatric care in mental health services showed the greatest capacity for predicting dropout. Conclusions: By using novel machine learning techniques on a large representative sample of patients enrolled in alcohol use disorder treatment, we have identified several machine learning models that help in predicting a higher risk of treatment dropout. Previous treatment for other substance use disorders (SUDs) and concurrent psychiatric comorbidity were the best predictors of dropout, and patients showing these characteristics may need more intensive or complementary interventions to benefit from treatment.

ChatGPT-4: Alcohol use disorder responses.

Alcohol use disorder (AUD) is characterized by low levels of engagement with effective treatments. Enhancing awareness of AUD treatments and how to navigate the treatment system is crucial. Many individuals use online sources (e.g. search engines) for answers to health-related questions; web-based results include a mix of high- and low-quality information. Artificial intelligence may improve access to quality health information by providing concise, high-quality responses to complex health-related questions. This study evaluated the quality of ChatGPT-4 responses to AUD-related queries. A comprehensive list of 64 AUD-related questions was developed through a combination of Google Trends analysis and expert consultation. ChatGPT-4 was prompted with each question, followed by a request to provide 3-5 peer-reviewed scientific citations supporting each response. Responses were evaluated for whether they were evidence-based, provided a referral and provided supporting documentation. ChatGPT-4 responded to all AUD-related queries, with 92.2% (59/64) of responses being fully evidence-based. Although only 12.5% (8/64) of responses included referrals to external resources, all responses (100%; 5/5) to location-specific ('near me') queries directed individuals to appropriate resources like the NIAAA Treatment Navigator. Most (85.9%; 55/64) responses to the follow-up question provided supporting documentation. ChatGPT-4 responds to alcohol use disorder-related questions with evidence-based information and supporting documentation. ChatGPT-4 could be promoted as a reasonable resource for those looking online for alcohol use disorder-related information.

The neurobehavioural effects of cannabidiol in alcohol use disorder: Study protocol for a double-blind, randomised, cross over, placebo-controlled trial

Current treatments for alcohol use disorders (AUD) have limited efficacy. Recently, Cannabidiol (CBD) has been examined in a multitude of clinical settings. Preclinical and clinical results suggest that CBD might be particularly well suited for the treatment of AUD and may reduce alcohol cue and stress-induced craving and alcohol seeking. This study aims to investigate this new pharmacotherapy with a particular focus on neurobiological and physiological indicators of craving. Methods: In this double-blind, within-subject, randomised, placebo-controlled, cross-over study, non-treatment seekers will be randomly allocated to three days of four 200 mg CBD gel capsules (800 mg/day) or placebo, with an 18-day washout period. Cognitive, clinical, and neuroimaging assessments will be completed during these three days. The CBD and placebo assessments will be compared. The primary outcomes are i) BOLD signal as a proxy for regional activity during a cue reactivity and a fear response task measured with functional magnetic resonance imaging (fMRI), ii) heart rate variability and skin conductance levels as a proxy for psychophysiological responses to alcohol stimuli. The secondary outcomes are: i) neurometabolite levels (γ-Aminobutyric acid, ethanol, glutathione, and glutamate + glutamine (combined signal)) using magnetic resonance spectroscopy (MRS); ii) functional connectivity using resting state fMRI (rsfMRI); iii) executive functioning task results; iv) clinical outcomes such as craving, anxiety, and sleep. Discussion: This study will improve the understanding of the mechanisms of action of CBD and provide early signals of efficacy regarding the therapeutic potential of CBD in the treatment of alcohol use disorder.ClinicalTrials.gov Identifier: NCT05387148.

Frontal Brain N-Acetylaspartate at Treatment Entry is Related to Future WHO Risk Drinking Levels in Individuals with Alcohol Use Disorder.

To assess the viability of regional brain metabolite levels of individuals with alcohol use disorder (AUD) at treatment entry as a biomarker of post-treatment levels of alcohol use, categorized according to the World Health Organization risk drinking levels (WHO-RDL). Eighty-five individuals initiating treatment for AUD (16 ± 13 days after last alcohol consumption), and 45 light/non-drinking controls (LN) completed a 1.5T proton multislice magnetic resonance spectroscopic imaging study. N-acetylaspartate (NAA), a marker of neuronal viability, and other metabolites were quantitated for cortical gray matter (GM), white matter (WM) and select subcortical regions. Individuals with AUD were classified according to their post-treatment alcohol consumption, as abstainers (AB, n=42), low risk (RL, n=20), or higher risk (RH, n=23), based on the WHO-RDL taxonomy. Within frontal GM, RH exhibited significantly lower NAA levels than LN and AB but did not differ from RL. RH had significantly lower NAA concentration in frontal WM than all groups who did not significantly differ from one another. RH showed significantly lower parietal WM NAA than LN and AB; RL and RH did not differ from one another. Across RH and RL, lower frontal GM and WM NAA was related to shorter period of abstinence before first post-treatment alcohol consumption and longer post-treatment duration of alcohol resumption. There were no significant group differences in myo-inositol or choline- or creatine-containing compound concentrations. Frontal and parietal lobar NAA concentrations, near treatment entry, are associated with WHO-RDL categorized post-treatment alcohol consumption levels and may serve as predictive biomarkers of clinical outcomes following treatment for AUD.

Kappa-opioid receptor antagonism in the nucleus accumbens shell distinguishes escalated alcohol consumption and negative affective-like behavior from physiological withdrawal in alcohol-dependence

Alcohol use disorder (AUD) is a chronic relapsing disease that is deleterious at individual, familial, and societal levels. Although AUD is one of the highest preventable causes of death in the USA, therapies for the treatment of AUD are not sufficient given the heterogeneity of the disorder and the limited number of approved medications. To provide better pharmacological strategies, it is important to understand the neurological underpinnings of AUD. Evidence implicates the endogenous dynorphin (DYN)/κ-opioid receptor (KOR) system recruitment in dysphoric and negative emotional states in AUD to promote maladaptive behavioral regulation. The nucleus accumbens shell (AcbSh), mediating motivational and emotional processes that is a component of the mesolimbic dopamine system and the extended amygdala, is an important site related to alcohol's reinforcing actions (both positive and negative) and neuroadaptations in the AcbSh DYN/KOR system have been documented to induce maladaptive symptoms in AUD. We have previously shown that in other nodes of the extended amygdala, site-specific KOR antagonism can distinguish different symptoms of alcohol dependence and withdrawal. In the current study, we examined the role of the KOR signaling in the AcbSh of male Wistar rats in operant alcohol self-administration, measures of negative affective-like behavior, and physiological symptoms during acute alcohol withdrawal in alcohol-dependence. To induce alcohol dependence, rats were exposed to chronic intermittent ethanol vapor for 14 h/day for three months, during which stable escalation of alcohol self-administration was achieved and pharmacological AcbSh KOR antagonism ensued. The results showed that AcbSh KOR antagonism significantly reduced escalated alcohol intake and negative affective-like states but did not alter somatic symptoms of withdrawal. Understanding the relative contribution of these different drivers is important to understand and inform therapeutic efficacy approaches in alcohol dependence and further emphasis the importance of the KOR/DYN system as a target for AUD therapeutics.

The combination of donepezil and cognitive training for improving treatment outcomes for alcohol use disorder: Design of a randomized controlled trial

BackgroundThe development of alcohol use disorder (AUD) is a major concern in public health, and cognitive impairments caused by alcohol are involved in this process. Emerging neurobiological evidence suggests that donepezil, an anticholinesterase agent, may improve AUD treatment outcomes by enhancing neurocognitive functioning. Previous research has also suggested that cognitive remediation therapy (CRT) could potentially improve cognitive function and AUD treatment outcomes. We present the rationale and design of a trial to evaluate the combination of donepezil and cognitive remediation therapy (donepezil + CRT) as an intervention for AUD. MethodsWe propose a 13-week, randomized, double-blind, placebo-controlled, between-subjects trial comparing 4 groups (donepezil + CRT vs. donepezil alone vs. CRT alone vs. placebos) as an intervention for AUD. The main goal of the study is to evaluate if donepezil + CRT is superior to placebo in reducing heavy drinking days and improving neurocognitive functioning. A total of 160 patients (4 groups, 40 per each group) with AUD between the ages of 18–80 years will be recruited at Yale University and the VA Connecticut Healthcare System. Primary outcome measures include 1) heavy drinking by Timeline Follow Back (TLFB) over 13 weeks and 2) global neurocognitive functioning by a global index of neurocognitive function score at 7 and 13 weeks. DiscussionThis protocol paper describes the rationale and proposed methods for the randomized controlled trial for improving AUD treatment outcomes. This project has significant clinical potential to help patients suffering from AUD by improving their cognition and reducing alcohol consumption.Trial Registration:NCT05042102

Treatment of substance use disorders in adolescence and early school leaving.

To examine early school leaving in a longitudinal cohort of all high school students treated for substance use disorder (SUD) and their demographic counterparts in Norway. From the National Patient and National Population Registries, we extracted (a) all high school students born in 1991-1992 who received SUD treatment during 2009-2010 (N = 648; nalcohol = 95, ncannabis = 327, and nother drugs = 226) and (b) their age-and-gender matched counterparts (n = 647). From the National Educational Database, we obtained enrollment and graduation status for these two cohorts throughout the designated school period of 5 years. We estimated the hazards of early school leaving as a function of students' treatment for alcohol, cannabis, and other drug use disorders and other known risk factors. Nine out of 10 adolescents receiving SUD treatment left high school early (89%) compared with one in four (27%) from the matched cohort; 422 (73.5%) of these left high school during or after the treatment year. Multivariate discrete-time models revealed significant and ordered associations between receiving SUD treatment and early school leaving, HRalcohol = 3.09 [1.96, 4.89], HRcannabis = 3.83 [2.64, 5.56], HRother drugs = 5.16 [3.32, 8.03], even after accounting for individual-level (sex, immigrant background, criminal charges, and mental health treatment), family-level (family structure, parental education, and family income), and structural risk factors (municipal size, county employment, and dropout rates). Adolescents receiving SUD treatment remain especially vulnerable for early school leaving. These findings underscore the importance of improving and coordinating health and educational services for youth in SUD treatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Use of sodium oxybate for the treatment of alcohol withdrawal syndrome in patients with acute alcohol-associated hepatitis: A 4-patient case report.

During the treatment of alcohol use disorder, alcohol withdrawal syndrome (AWS) can occur. Benzodiazepines remain the "gold standard" for the pharmacological treatment of AWS. However, other drugs have been approved in some European Countries for the treatment of AWS: namely, clomethiazole in Spain and Germany and sodium oxybate in Italy and Austria. Acute alcohol-associated hepatitis (AAH) is a distinct clinical syndrome characterized by the recent onset of jaundice with or without other signs of liver decompensation in patients with ongoing alcohol consumption. We report 4 paradigmatic clinical cases to analyze the efficacy, safety, and tolerability of the very short half-life (30-45 minutes) sodium oxybate (SO) in the management of AWS with moderate to severe AAH. Compared to SO, "as needed" short-acting benzodiazepines, currently prescribed to treat AWS in patients with AAH, have a much longer half-life (5-25 hours) which increases the risk of drug accumulation. The very short half-life of SO provides a fixed dose approach allowing for a more effective control of AWS than "as needed" therapy throughout the 24 hours. Patients reported anxiety, agitation, diffuse abdominal pain, loss of appetite, and nausea with elevation in serum bilirubin and 2 of them had abdomen distension due to ascites. Patients were affected by moderate or severe AWS and moderate or severe AAH on alcohol-related liver cirrhosis. In order to suppress AWS, all patients were treated with oral sodium oxybate at a dose of 25 mg/kg/day, progressively increased to 50 to 100 mg/kg/day, divided into 3 to 5 administrations. SO was efficient, safe and tolerable in suppressing AWS even in patients with severe AAH. All treated patients showed a rapid improvement of all symptom (via the Clinical Institute of Withdrawal Assessment for Alcohol Scale) and liver test scores (Model for End-Stage Liver Disease). Because of its short half-life, SO can be considered a safe and effective pharmacological option for the AWS in patients with moderate to severe AAH even in comparison to short-acting benzodiazepines, thus avoiding the risk of accumulation. Notably, SO guarantees a fixed approach to cover the possible onset of AWS throughout the 24 hours.

Negative affect variability as a potential mechanism of behavior change in alcohol use disorder treatment.

Negative affect and affect variability figure prominently in models of addictive behaviors but are not without controversy. Negative affect variability may better capture a mechanism of behavior change in alcohol use disorder (AUD) treatment because it contains information about affect regulation, a common clinical target. The aims of this study are to examine the change in: (a) trajectory of negative affect variability, (b) association of negative affect variability and abstinence, and (c) association of negative affect variability and heavy drinking during AUD treatment. This article is a secondary analysis of data drawn from a randomized clinical trial. N = 181 participants diagnosed with Diagnostic and Statistical Manual of Mental Disorders, fifth edition AUD (Mage = 50.8, SDage = 10.6; 51.4% female) received 12 sessions of Cognitive Behavioral Coping Skills Therapy for AUD. Participants completed one daily diary prompt per day for 84 consecutive days. Each day, participants reported on negative affect and number of alcoholic drinks consumed the previous day. Time-varying effect models examined changes in negative affect variability and its associations with abstinence and heavy drinking. Negative affect variability decreased throughout treatment. The positive association between negative affect variability and heavy drinking became nonsignificant (decoupled) midway through treatment. The inverse association between negative affect variability and daily abstinence became nonsignificant (decoupled) at approximately day 75 of 84. When mean levels of NA were added as a covariate, the effects were in the same direction but no longer statistically significant. Reductions in negative affect variability may capture an important change mechanism of behavioral treatments for AUD because it contains information about affect regulation as compared with mean levels of negative affect. Negative affect variability warrants further consideration as a mechanism of behavior change. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Role of relative-reinforcement value of alcohol-free activities during recovery from alcohol use disorder in an adult clinical sample.

Behavioral economic theory has been extensively applied to understand alcohol use disorder (AUD). Applications of behavioral economic theory conceptualize AUD as a pattern of harmful alcohol use over extended periods of time in which choices between drinking or engaging in alcohol-free activities favor drinking. Recovery, in contrast, entails a sustained shift toward a pattern of selecting rewarding alcohol-free activities. The present study examined whether alcohol-free activity engagement and the relative-reinforcement value (RRV) of engaging in those activities predicted AUD treatment outcomes via secondary analysis of data from Project MATCH, a multisite randomized clinical trial examining behavioral treatments for AUD (N = 1,279, 75.8% male, 81.0% non-Hispanic White, 9.5% Black, 7.7% Hispanic/Latino, 1.5% American Indian/Alaska Native, < 1% Asian American, and other race/ethnicity). Regression analyses indicated that every additional alcohol-free activity reported at 6 months posttreatment was associated with 7% fewer drinking days, 5% fewer heavy drinking days, and approximately one less drink per drinking day, as well as with significant improvements in depression, purpose in life, and psychosocial functioning at 12 months following treatment. Consistent with behavioral economic theory, higher RRV of alcohol-free activities also predicted significant reductions in drinking and improvements in functioning, and these associations were stronger compared to results for alcohol-free activity frequency only. The findings highlight the importance of understanding environmental contexts conducive to recovery and support the value of increasing alcohol-free activity engagement and the RRV of engaging in such activities to facilitate reductions in drinking and improved functioning among individuals with AUD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Use of Transdermal Alcohol Sensors in Conjunction With Contingency Management to Reduce Alcohol Consumption in People With Alcohol Dependence Attending Alcohol Treatment Services: Protocol for a Pilot Feasibility Randomized Controlled Trial.

Wearable technology for objective, continuous, and reliable alcohol monitoring has been developed. These are known as transdermal alcohol sensors (TASs). They can be worn on the wrist or ankle with the sensor pressed against the skin and can measure sweat vapors being emitted from the skin, to record transdermal alcohol concentration (TAC). Previous studies have investigated the accuracy and acceptability of the available TAS brands, but there has been little research into their use in people with alcohol use disorders (AUD). This feasibility randomized controlled trial aims to explore the feasibility, strengths, and limitations of using a TAS to monitor alcohol consumption in individuals in treatment for AUD with or without contingency management (CM) to promote abstinence or low-level alcohol consumption. The target sample size is 30 (15 randomized to each group). Participants will be recruited through poster adverts at alcohol services. Both groups (control and CM) will wear the TAS (BACtrack Skyn) for 2 weeks in the context of their usual treatment, meeting with the researcher every other weekday. In the last meeting, the participants will complete a postwear survey on their experience of wearing the TAS. The CM group will also receive small financial incentives for low or no alcohol consumption, as measured by the TAS. On days where the TAC peak is below a set threshold (<115.660 g/L), CM group participants will be rewarded with a £5 (US $6.38) voucher. There are financial bonuses if this target is achieved on consecutive days. The researcher will monitor TAC for each day of the study at each research visit and allocate financial incentives to participants according to a set reinforcement schedule. The first participant was enrolled in June 2023, and the last in December 2023. Data analysis is underway and is estimated to be completed by June 2024. A total of 32 participants were enrolled. Most TAS brands have had limited application in clinical settings, and most studies have included healthy adults rather than people with AUD. TAS has the potential to enhance treatment outcomes in clinical alcohol treatment. The accuracy, acceptability, and feasibility of TAS for people with AUD in clinical settings need to be investigated. This is the first study to use TAS in specialized alcohol services with diagnosed AUD individuals currently receiving treatment from a south London alcohol service. ISRCTN Registry ISRCTN46845361; https://www.isrctn.com/ISRCTN46845361. DERR1-10.2196/57653.

Validation of predicted individual treatment effects in out of sample respondents.

Personalized medicine promises the ability to improve patient outcomes by tailoring treatment recommendations to the likelihood that any given patient will respond well to a given treatment. It is important that predictions of treatment response be validated and replicated in independent data to support their use in clinical practice. In this paper, we propose and test an approach for validating predictions of individual treatment effects with continuous outcomes across samples that uses matching in a test (validation) sample to match individuals in the treatment and control arms based on their predicted treatment response and their predicted response under control. To examine the proposed validation approach, we conducted simulations where test data is generated from either an identical, similar, or unrelated process to the training data. We also examined the impact of nuisance variables. To demonstrate the use of this validation procedure in the context of predicting individual treatment effects in the treatment of alcohol use disorder, we apply our validation procedure using data from a clinical trial of combined behavioral and pharmacotherapy treatments. We find that the validation algorithm accurately confirms validation and lack of validation, and also provides insights into cases where test data were generated under similar, but not identical conditions. We also show that the presence of nuisance variables detrimentally impacts algorithm performance, which can be partially reduced though the use of variable selection methods. An advantage of the approach is that it can be widely applied to different predictive methods.

Ecological momentary assessment and cue-elicited drug craving as primary endpoints: study protocol for a randomized, double-blind, placebo-controlled clinical trial testing the efficacy of a GLP-1 receptor agonist in opioid use disorder

BackgroundDespite continuing advancements in treatments for opioid use disorder (OUD), continued high rates of relapse indicate the need for more effective approaches, including novel pharmacological interventions. Glucagon-like peptide 1 receptor agonists (GLP-1RA) provide a promising avenue as a non-opioid medication for the treatment of OUD. Whereas GLP-1RAs have shown promise as a treatment for alcohol and nicotine use disorders, to date, no controlled clinical trials have been conducted to determine if a GLP-1RA can reduce craving in individuals with OUD. The purpose of the current protocol was to evaluate the potential for a GLP-1RA, liraglutide, to safely and effectively reduce craving in an OUD population in residential treatment.MethodThis preliminary study was a randomized, double-blinded, placebo-controlled clinical trial designed to test the safety and efficacy of the GLP-1RA, liraglutide, in 40 participants in residential treatment for OUD. Along with taking a range of safety measures, efficacy for cue-induced craving was evaluated prior to (Day 1) and following (Day 19) treatment using a Visual Analogue Scale (VAS) in response to a cue reactivity task during functional near-infrared spectroscopy (fNIRS) and for craving. Efficacy of treatment for ambient craving was assessed using Ecological Momentary Assessment (EMA) prior to (Study Day 1), across (Study Days 2–19), and following (Study Days 20–21) residential treatment.DiscussionThis manuscript describes a protocol to collect clinical data on the safety and efficacy of a GLP-1RA, liraglutide, during residential treatment of persons with OUD, laying the groundwork for further evaluation in a larger, outpatient OUD population. Improved understanding of innovative, non-opioid based treatments for OUD will have the potential to inform community-based interventions and health policy, assist physicians and health care professionals in the treatment of persons with OUD, and to support individuals with OUD in their effort to live a healthy life. Trial registration: ClinicalTrials.gov: NCT04199728. Registered 16 December 2019, https://clinicaltrials.gov/study/NCT04199728?term=NCT04199728.Protocol Version10 May 2023

Antidepressants and alcohol use disorder: A multicenter study on the mediating role of depression symptom changes.

Alcohol use disorder (AUD) and depression are highly prevalent and tied to significant psychological, physiological, social and economic consequences. Their co-occurrence presents a complex clinical challenge, as the impact of antidepressant medication on AUD outcomes remains equivocal. In this multicenter, longitudinal study we investigated the relationship between antidepressant medication and changes in depression symptoms and alcohol use in AUD patients. We analyzed data from 153 detoxified AUD patients who attended a 12-week residential treatment program between 2015 and 2019. Within a mediation analysis, adopting a bootstrapping approach and a quasi-Bayesian framework, we estimated the total, direct, and mediated effects of antidepressants on the percentage of daysabstinent to assess the role of changes in depression symptoms as a mediating factor. The mediation analysis revealed a dual impact pathway model with a negative direct effect of antidepressants on abstinence (p = 0.004) and a positive indirect effect, mediated through the reduction of depression symptoms (p = 0.002). The findings of the mediation analysis show that patients treated with antidepressants and whose depression symptoms do not improve over time show more relapses, while patients treated with antidepressants who achieve a reduction in depression symptoms show fewer relapses over time. Thus, to optimize treatment outcome, depression symptoms should be vigilantly monitored when antidepressants are prescribed during AUD treatment.