The Role of Repetitive Transcranial Magnetic Stimulation in Treating Alcohol Use Disorder: Neural Mechanisms, Efficacy, and Future Directions

Identifying and Reducing Bias in Genome-Wide Association Studies of Alcohol-Related Traits.

Toward Personalized Medicine in the Pharmacotherapy of Alcohol Use Disorder: Targeting Patient Genes and Patient Goals

BackgroundAlcohol use is an important issue among problem drug users. Although screening and brief intervention (SBI) are effective in reducing problem alcohol use in primary care, no research has examined this issue among problem drug users.ObjectiveThe objective of this study is to determine if a complex intervention including SBI for problem alcohol use among problem drug users is feasible and acceptable in practice. This study also aims to evaluate the effectiveness of the intervention in reducing the proportion of patients with problem alcohol use.MethodsPsychosocial intervention for alcohol use among problem drug users (PINTA) is a pilot feasibility study of a complex intervention comprising SBI for problem alcohol use among problem drug users with cluster randomization at the level of general practice, integrated qualitative process evaluation, and involving general practices in two socioeconomically deprived regions.Practices (N=16) will be eligible to participate if they are registered to prescribe methadone and/or at least 10 patients of the practice are currently receiving addiction treatment. Patient must meet the following inclusion criteria to participate in this study: 18 years of age or older, receiving addiction treatment/care (eg, methadone), or known to be a problem drug user. This study is based on a complex intervention supporting SBI for problem alcohol use among problem drug users (experimental group) compared to an “assessment-only” control group. Control practices will be provided with a delayed intervention after follow-up. Primary outcomes of the study are feasibility and acceptability of the intervention to patients and practitioners. Secondary outcome includes the effectiveness of the intervention on care process (documented rates of SBI) and outcome (proportion of patients with problem alcohol use at the follow-up). A stratified random sampling method will be used to select general practices based on the level of training for providing addiction-related care and geographical area. In this study, general practitioners and practice staff, researchers, and trainers will not be blinded to treatment, but patients and remote randomizers will be unaware of the treatment.ResultsThis study is ongoing and a protocol system is being developed for the study. This study may inform future research among the high-risk population of problem drug users by providing initial indications as to whether psychosocial interventions for problem alcohol use are feasible, acceptable, and also effective among problem drug users attending primary care.ConclusionsThis is the first study to examine the feasibility and acceptability of complex intervention in primary care to enhance alcohol SBI among problem drug users. Results of this study will inform future research among this high-risk population and guide policy and service development locally and internationally.

Glucagon-like peptide 1 (GLP-1) receptor agonists, medications commonly employed in the treatment of type 2 diabetes mellitus, have illustrated several additional benefits, including weight loss and potentially reduce addictive cravings. Several studies have indicated that GLP-1 receptor agonists may be effective in treating Alcohol Use Disorder (AUD), for which current pharmacologic therapies are often inadequate. Proposed mechanisms include modulation of dopaminergic transmission and reduced gastric emptying, both of which reduce alcohol craving and tolerance. This case report discusses dulaglutide's ability to reduce alcohol consumption. During a visit to an outpatient behavioral health clinic, a 44-year-old male was evaluated for weight loss. His medical history revealed a BMI of 41.8, hypertension, major depressive disorder, and pre-diabetes. The individual also reported the consumption of approximately ninety beers per month and was in the pre-contemplation phase of change. As part of the treatment plan, the patient was prescribed dulaglutide to manage pre-diabetes and facilitate weight loss. During subsequent appointments, the individual not only experienced weight loss but also noted a substantial reduction in alcohol cravings and consumption. However, following a lapse in insurance coverage the following year, the individual had to discontinue his dulaglutide, resulting in a return to previous drinking patterns. Future research should focus on confirming existing animal study results in humans, with the hope that GLP-1 receptor agonists can become a mainstay treatment for AUD.

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessVarenicline Shows Promise for Reducing Alcohol UseVabren WattsVabren WattsPublished Online:18 Jun 2015https://doi.org/10.1176/appi.pn.2015.6b17AbstractResults from a phase 2 clinical trial show that in addition to curbing smoking, the drug varenicline reduces alcohol craving and consumption.For almost a decade, the drug varenicline—marketed by Pfizer as Chantix—has been spotlighted as a pharmacotherapy intended to help smokers quit smoking. Now the drug is in the spotlight for a different reason—its ability to reduce alcohol use. Daniel Falk, Ph.D., believes that compounds that target nicotinic acetylcholine receptors may serve as a therapy to help people reduce alcohol consumption.NIAAADuring APA's 2015 annual meeting last month in Toronto, Daniel Falk, Ph.D., a health science administrator for the National Institute on Alcohol Abuse and Alcoholism (NIAAA), presented results from a phase 2 clinical trial that assessed the effectiveness and safety of varenicline in the treatment of alcohol use disorder."There is a high comorbidity between nicotine use and alcohol use," said Falk, who explained to Psychiatric News that one-third of Americans who use nicotine also use alcohol. Falk told Psychiatric News that he and his colleagues decided to study the off-label use of varenicline after the results of animal studies and small clinical trials found that the drug reduces alcohol craving and intake. Since the launch of varenicline as Chantix, Pfizer, the drug manufacturer, has paid out more than $275 million to settle thousands of lawsuits claiming that the drug caused adverse psychiatric symptoms such as suicidal ideation. In 2009, a black-box warning for the drug was mandated by the Food and Drug Administration. Falk and colleagues' phase 2 trial included 200 adult smokers and nonsmokers with alcohol use disorder, in accordance with DSM-IV, who were administered 2 mg of varenicline daily or a placebo for 13 weeks. According to Falk, the study participants consisted mostly of males who had been engaging in frequent heavy drinking (five or more drinks a day) for an average of 20 years. The participants had no history of other drug use or psychiatric disorders.The results showed that participants taking varenicline had an average of 33 percent fewer heavy drinking days over the course of the trial compared with the placebo group. In addition, the varenicline cohort was on average 13 percent more likely to abstain from daily alcohol use. Participants reported symptoms of nausea, constipation, and chest pains, but no psychiatric symptoms. "The treatment worked well in both nonsmokers and smokers," said Falk, who mentioned during his session presentation that smokers involved in the study were also able to reduce smoking as expected. Falk hypothesized that the nicotinic acetylcholine receptor, which has been shown to be involved in the rewarding effects of both nicotine and alcohol use, may be responsible for this outcome. "We are definitely interested in doing more research with compounds that target the nicotinic acetylcholine receptor, like varenicline, in the treatment of alcohol use disorder, and we encourage other alcohol use disorder researchers to do the same."Falk informed Psychiatric News that, as far as he knows, Pfizer is not planning to market varenicline as a therapy to treat alcohol use disorder. ■A video interview of Falk discussing varenicline's use in the treatment of alcohol disorders can be viewed here. ISSUES NewArchived

Psychedelic drugs may help treat alcohol use disorder (AUD). This study evaluated BPL-003, a novel intranasal powder formulation of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) benzoate salt, in people with moderate-severe AUD enrolled in a standard of care, 10-week programme of relapse-prevention oriented Cognitive Behavioural Therapy (CBT). Open-label, phase 2a, single-dose, clinical trial with 12-week follow-up (Day 84 endpoint) with a target of 12 participants. Two clinics in England between 29 March 2023 and 2 July 2024. Thirteen participants were enrolled. Most were male (n = 10; 76.9%), of White-UK origin (n = 12; 92.3%), with a mean age of 49.3years. Twelve participants completed the study (efficacy analysis set). Participants received a single intranasal dose of 10mg BPL-003 in a controlled environment with psychological support. Participants received three pre-dose preparation sessions and three post-dose integration sessions before CBT. Primary endpoints were safety and tolerability (by physical examination, laboratory evaluations, cardiac telemetry and treatment emergent adverse events [TEAEs]). Exploratory endpoints included Timeline Follow-Back recording of alcohol use (abstinent days, units per day/week, heavy drinking days [HDDs; defined according to the UK government definition of binge drinking: ≥7units per day women, ≥9units per day men]) to Week 12 follow-up (study endpoint); craving, alcohol-related problems; and patient- and clinician-reported measures of well-being and health-related quality of life (HRQoL). Over 12 weeks, 41 TEAEs (all mild or moderate in severity) were reported by 11 of 12 (84.6%) participants (no TEAE-related withdrawals). The most common TEAEs were study drug administration site pain (four participants; 30.8%); transient elevations in blood pressure after drug administration (four participants; 30.8%); and flashbacks (reactivations), nightmares, and nausea (two participants; 15.4%). At Week 12, the mean (standard deviation [SD]) percentage of abstinent days increased from 33.2% (22.8) at baseline to 80.8% (28.2) and HDDs reduced from 56.2% (SD 26.4) at baseline to 13.2% (SD 21.8). Six of 12 participants (50%) were continuously abstinent, three (25%) had meaningful reductions in alcohol consumption, and three (25%) had no change or a limited change in their drinking patterns. Overall, measures of the negative consequences of alcohol, craving, well-being and HRQoL indicated improvement. A first phase 2a clinical trial of 5-methoxy-N,N-dimethyltryptamine (BPL-003 10mg) in the context of a 10-week programme of CBT demonstrated acceptable safety and tolerability and provided preliminary evidence of efficacy for reducing alcohol craving and consumption. These findings support progression to larger, controlled trials of BPL-003 for the treatment of alcohol use disorder.

This study examined routine computerized screening for alcohol and drug use of men and women seeking outpatient psychiatric services (excluding chemical dependency treatment) and prevalence based on electronic medical records of consecutive admissions. The sample of 422 patients, ages 18-91, completed a self-administered questionnaire. Measures included 30-day, one-year, and lifetime substance use and alcohol-related problems. Seventy-five percent of patients completed electronic intakes during the study period. Prior-month alcohol use was reported by 90 men (70%) and 180 women (62%). Of these patients, heavy drinking (five or more drinks on one occasion) was reported by 37 men (41%) and 41 women (23%). Prior-month cannabis use was reported by 17 men (13%) and 32 women (11%). Computerized intake systems that include alcohol and drug screening can be integrated into outpatient psychiatric settings. Heavy drinking and use of nonprescribed drugs are commonly reported, which provides an important intervention opportunity.

Objective-This study examined routine computerized screening for alcohol and drug use of men and women seeking outpatient psychiatric services (excluding chemical dependency treatment) and prevalence based on electronic medical records of consecutive admissions.Methods-The sample of 422 patients, ages 18-91, completed a self-administered questionnaire.Measures included 30-day, one-year, and lifetime substance use and alcohol-related problems.Results-Seventy-five percent of patients completed electronic intakes during the study period.Prior-month alcohol use was reported by 90 men (70%) and 180 women (62%).Of these patients, heavy drinking (five or more drinks on one occasion) was reported by 37 men (41%) and 41 women (23%).Prior-month cannabis use was reported by 17 men (13%) and 32 women (11%).Conclusions-Computerized intake systems that include alcohol and drug screening can be integrated into outpatient psychiatric settings.Heavy drinking and use of nonprescribed drugs are commonly reported, which provides an important intervention opportunity.

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EASL Clinical Practice Guidelines: Management of alcohol-related liver disease

The prevalence of hepatitis C (HCV) infection among veterans treated within Veterans Affairs Medical Centers (VAMCs) is 3 to 4 times higher than the general population prevalence of 1.8%. Approximately 50 to 60% of patients with HCV are at risk for progression to end-stage liver disease. The risk for progression to end-stage liver disease is significantly increased in individuals with heavy alcohol consumption and veterans with HCV have a high rate of co-morbid alcohol use. Treatments that reduce or eliminate alcohol consumption among HCV-positive veterans may reduce the impact of the disease for the individual. Motivational enhancement treatments (MET) have shown the greatest efficacy in treating alcohol use disorders in general. Further, medications that reduce alcohol craving and consumption, that are also not metabolized in the liver are equally beneficial. The objectives of this presentation are to detail two ongoing studies at the Veterans Affairs Medical Center that aim to reduce alcohol consumption for veterans with hepatitis C. The first study assesses the efficacy of MET to reduce number of drinking days over the period of six months. This study is being conducted in two VA Medical Centers and compares a four session MET intervention to a four session educational (control) intervention. The second study being conducted at three VA medical centers assesses the use baclofen, a generic medication approved for use in muscle spasm that has been shown in initial trials to reduce alcohol craving and consumption. Baclofen is not metabolized in the liver and is potentially ideal for patients with HCV. Both non-medication and medication interventions are crucial strategies for improving the health of veterans with HCV who have co-morbid alcohol use.

BACKGROUND Alcohol use disorder (AUD) is a condition characterized by uncontrollable alcohol use despite negative social, occupational, or health consequences. AUD affects major organ systems in the body including the eyes in different ways. Current research displays mixed findings on the correlation between alcohol consumption and glaucoma, and little has been investigated in the AUD population. This paper outlines a protocol for a scoping review that aims to explore research on the connection between alcohol use disorder, and its related conditions such as alcohol dependence and alcohol misuse, with glaucoma and its associated symptoms, including increased intraocular pressure, optic nerve damage, and vision loss. OBJECTIVE The overarching goal of this scoping review is to synthesize an extensive overview of the current literature surrounding alcohol use disorder or alcohol consumption and glaucoma. We aim to (1) map the existing literature on alcohol and glaucoma, (2) identify how alcohol consumption is associated with glaucoma, and (3) synthesize evidence concerning the association between alcohol use disorder or alcohol consumption (including drinking frequency, quantity, and type) with glaucoma. METHODS A biomedical librarian will do a systematic search of PubMed/MEDLINE, Embase, and Web of Science. A two-step process will be used to screen the results, using Covidence as the screening software. All unique records retrieved from the database and supplemental searches will be screened by two reviewers independently using the eligibility criteria. This will be followed by data charting. This evidence synthesis will summarize findings in narrative and table formats. RESULTS This scoping review was started in Covidence in Nov 2024 and is currently funded by NIH’s Intramural Research Program. The projected end date for data collection and submission is August 2025. CONCLUSIONS By performing this scoping review, our team aims to address the mixed findings on the association between alcohol use disorder and or alcohol consumption and glaucoma. Our review will lay a foundation for future investigation on the topic.

There is growing interest in neuromodulation-based therapeutics as tools for individuals with alcohol use disorder (AUD). Through electromagnetic induction, techniques such as transcranial magnetic stimulation (TMS) can noninvasively depolarize cortical cells in the induced electrical field and monosynaptic afferents. The ability of TMS to modulate the brain is dependent upon two factors, which may be compromised in individuals with AUD: (1) gray matter volume (GMV) at the site of stimulation and (2) scalp-to-cortex (STC) distance. This study tested the hypotheses that these aspects of neural architecture are compromised in AUD patients, and thus AUD patients may need a higher TMS dose to depolarize the cortex. High-resolution magnetic resonance images were acquired from 44 individuals with AUD and 44 age-matched healthy controls (n=88). Whole-brain voxel-based morphometry was conducted. Subsequent region-of-interest analysis was performed at three EEG 10-20 sites commonly used in TMS for AUD: FP1 (left frontal pole), F3 (left DLPFC), and C3 (left motor cortex). STC distance and TMS electric fields were assessed at these EEG sites. Individuals with AUD had significantly lower GMV in the bilateral orbitofrontal cortices, supramarginal gyri, and the left DLPFC (voxel-threshold p<0.05, cluster-threshold p<0.05) and within all 3 TMS target locations, F (1, 264)=14.12, p=0.0002. There was no significant difference in STC distance between the AUD and the healthy control group at any tested cortical location, F (3, 252)=1.906, p=0.129. Individuals with AUD had significantly lower GMV in multiple areas of interest for TMS treatment; however, these volumetric reductions did not impact STC distance. Given previous studies that have shown TMS-evoked changes in cortical and subcortical activity to be dependent on GMV, these data suggest that individuals with AUD may require higher doses of TMS to sufficiently modulate the neural circuits of interest.

The degree to which alcohol use is associated with the risk of all-cause mortality and hepatic decompensation after hepatitis C (HCV) diagnosis, treatment, and cure remains unknown. We sought to address this question among patients achieving sustained virologic response (SVR) after direct-acting antiviral treatment in the largest HCV health system in the United States. We extracted data on alcohol use, HCV treatment, SVR, HIV co-infection, demographics, risk behaviours, hepatic decompensation, and mortality from all patients in the 1945 to 1965 VA Birth Cohort. Alcohol use categories were generated using responses to the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and diagnostic codes for alcohol use disorder (AUD): abstinent without a history of AUD, abstinent with a history of AUD, current lower-risk consumption, current moderate-risk consumption, and current high-risk consumption with or without AUD. Cox proportional hazard models were used to examine associations between alcohol category and the risk of hepatic decompensation and all-cause mortality. Among 50,581 patients in the analytic cohort, compared to current drinkers exhibiting lower risk alcohol consumption (referent), current high-risk consumption with or without AUD was associated with increased risk of all-cause mortality (aHR: 1.40, 95% CI: 1.21-1.63) and hepatic decompensation (HR: 2.15, 95% CI: 1.60-2.89) as was abstinence with a history of AUD diagnosis (mortality aHR: 1.63, 95% CI: 1.41-1.89; hepatic decompensation aHR: 1.85, 95% CI: 1.36-2.51). AUD and high-risk alcohol consumption are associated with the risk of hepatic decompensation and all-cause mortality among Veterans who have achieved SVR, including those categorised as being currently abstinent. Interventions for alcohol consumption and use disorder among individuals treated for HCV infection may reduce morbidity and mortality in this population.

Addiction as a Coping Response: Hyperkatifeia, Deaths of Despair, and COVID-19.