The identification and treatment of alcohol problems in primary care (iTAPP) study: protocol for a stepped wedge cluster randomized control trial testing the 15-method in a primary care setting.

BACKGROUND: The 15-method is a targeted screening and treatment approach for alcohol problems in primary care. The 15-method used in primary care has proven as effective as specialized treatment for mild to moderate alcohol dependence in Sweden. A feasibility study of the 15-method in Danish primary care found the method acceptable and feasible. AIMS: To evaluate the effectiveness of the 15-method in a Danish primary care setting in (1) lowering the proportion of patients exceeding the Danish low-risk alcohol consumption limit of ten standard units per week and a maximum of four standard units on a single day for men and women, and (2) increasing the likelihood of alcohol use being addressed during a consultation in general practice. Further, the rate of prescribed pharmacological treatment for alcohol problems (Disulfiram, Naltrexone, Acamprosate, and Nalmefene) will be measured along with the use of the biomarkers Alanine Transaminase and Gamma-Glutamyl Transferase. METHODS: Stepped wedge cluster randomized controlled trial in sixteen general practices in the Region of Southern Denmark. Following a three-month baseline, the practices are randomly assigned to launch dates in one of four clusters. General practitioners and nurses receive three hours of training in the 15-method before launch. Patient questionnaires will collect data on alcohol consumption levels among patients affiliated with the practices. The healthcare professionals will register consultations in which alcohol is addressed in their patient filing system. Pharmacological treatment rates and the use of biomarkers will be collected through Danish national registries. The study follows the Medical Research Council's guidelines for developing and evaluating complex interventions. DISCUSSION: From the patient's perspective, the 15-method may help identify alcohol-related problems at an earlier stage with flexible treatment offers in a familiar setting. For healthcare professionals, it addresses a traditionally challenging topic by equipping them with concrete tools, communication training, and clear treatment directives. From a societal perspective, primary care holds a unique position to identify hazardous and harmful alcohol use across different age groups, with potential public health and economic benefits through early identification and intervention. TRIAL REGISTRATION: Clinicaltrials.gov NCT05916027. Retrospectively registered 22 June 2023.

Characterizing alcohol cue reactive and non-reactive individuals with alcohol use disorder.

PURPOSE: Exposure to alcohol-related cues is thought to elicit a conditional response characterized by increased craving in individuals with alcohol use disorder (AUD). In the context of AUD research, it is important to consider that not all individuals with an AUD are alcohol cue reactive. This study systematically examined subjective alcohol cue reactivity and its clinical and drinking correlates in individuals with an AUD enrolled in a human laboratory pharmacotherapy trial. METHODS: Individuals with current moderate-to-severe AUD (N = 52) completed a standard alcohol cue exposure paradigm and individual difference assessments as part of a human laboratory pharmacotherapy trial (NCT04249882). We classified participants as cue reactive (CR+) and cue non-reactive (CR-), as indicated by self-reported, subjective alcohol urge, and examined group differences in baseline clinical characteristics and drinking outcomes over the course of the trial. RESULTS: Twenty participants (38%) were identified as CR+, while 32 participants (62%) were identified as CR-. The CR+ and CR- groups did not differ in baseline drinking and AUD clinical characteristics, but the groups differed in race composition (p = 0.02) and smoking prevalence (p = 0.04) such that the CR+ group had lower prevalence of smokers. The CR+, compared with the CR-, group drank more during the trial titration period (p = 0.03). Both groups reduced drinking across the trial (p's < 0.001), but the CR+ group exhibited a smaller reduction in drinking, compared with the CR- group (time x group, p = 0.029; CR-, p < 0.0001; CR+: p = 0.01). CONCLUSION: Results indicate that cue reactivity is a heterogenous construct. Recognizing this heterogeneity, and the clinical factors associated with it, is critical to advancing this paradigm as an early efficacy marker in AUD research.

Repurposing disulfiram, an alcohol-abuse drug, in neuroblastoma causes KAT2A downregulation and in vivo activity with a water/oil emulsion.

Neuroblastoma, the most common type of pediatric extracranial solid tumor, causes 10% of childhood cancer deaths. Despite intensive multimodal treatment, the outcomes of high-risk neuroblastoma remain poor. We urgently need to develop new therapies with safe long-term toxicity profiles for rapid testing in clinical trials. Drug repurposing is a promising approach to meet these needs. Here, we investigated disulfiram, a safe and successful chronic alcoholism treatment with known anticancer and epigenetic effects. Disulfiram efficiently induced cell cycle arrest and decreased the viability of six human neuroblastoma cell lines at half-maximal inhibitory concentrations up to 20 times lower than its peak clinical plasma level in patients treated for chronic alcoholism. Disulfiram shifted neuroblastoma transcriptome, decreasing MYCN levels and activating neuronal differentiation. Consistently, disulfiram significantly reduced the protein level of lysine acetyltransferase 2A (KAT2A), drastically reducing acetylation of its target residues on histone H3. To investigate disulfiram's anticancer effects in an in vivo model of high-risk neuroblastoma, we developed a disulfiram-loaded emulsion to deliver the highly liposoluble drug. Treatment with the emulsion significantly delayed neuroblastoma progression in mice. These results identify KAT2A as a novel target of disulfiram, which directly impacts neuroblastoma epigenetics and is a promising candidate for repurposing to treat pediatric neuroblastoma.

Disulfiram's journey from rubber vulcanization to T-cell activation.

Disulfiram, a drug prescribed for the treatment of alcohol use disorders for more than 60 years, has recently been repurposed for cancer treatment. New work in The EMBO Journal now describes a disulfiram role in immunotherapy of cancer, involving direct binding to Lck to mediate activation of tumor-infiltrating T cells.

Identifying chronic alcoholism drug disulfiram as a potent DJ-1 inhibitor for cancer therapeutics.

As a key regulator involved in tumor development and progression, DJ-1 has been proposed as a potential therapeutic target against cancer. Also, the development of DJ-1 inhibitors holds great interests in cancer treatment. In the current study, by utilizing a small molecule covalent compounds library screening, we found that disulfiram (DSF), an FDA-approved chronic alcoholism drug, is a potent DJ-1 inhibitor. Glyoxalase assay and microscale thermophoresis analysis suggested that DSF exhibits strong inhibitory activity and high affinity to DJ-1 protein. Additionally, DSF similarly inhibited the methylglyoxal detoxification function of DJ-1 protein at the intracellular level. Notably, we discovered that DSF could significantly enhance N-(4-hydroxyphenyl) retinamide-based proliferation inhibition and apoptosis induction in different types of cancer cell lines, but not in normal tissue lines. Thus, our data suggest DSF functions as a potential inhibitor targeting DJ-1, which may provide a potential synergistic treatment option for cancer therapy.

Efficacy of Combining Varenicline and Naltrexone for Smoking Cessation and Drinking Reduction: A Randomized Clinical Trial.

OBJECTIVE: Pharmacological treatments that can concomitantly address cigarette smoking and heavy drinking stand to improve health care delivery for these highly prevalent co-occurring conditions. This superiority trial compared the combination of varenicline and naltrexone against varenicline alone for smoking cessation and drinking reduction among heavy-drinking smokers. METHODS: This was a phase 2 randomized double-blind clinical trial. Participants (N=165) who were daily smokers and drank heavily received either 2 mg/day of varenicline plus 50 mg/day of naltrexone or 2 mg/day of varenicline plus matched placebo pills for 12 weeks. Primary outcomes were 7-day point prevalence of nicotine abstinence (bioverified by a breath CO reading ≤5 ppm) at the 26-week follow-up and number of drinks per drinking day during the 12-week treatment phase. RESULTS: Smoking abstinence at week 26 was significantly higher in the varenicline plus placebo condition than in the varenicline plus naltrexone condition (N=37 [45.1%] compared with N=22 [26.5%]). For drinks per drinking day, there was a medication effect favoring the combination of varenicline and naltrexone over varenicline alone across the 12-week treatment phase, although it did not meet the significance threshold. CONCLUSIONS: These findings suggest that smoking cessation and drinking reduction can be concomitantly targeted with pharmacotherapy and that while varenicline alone may be sufficient as a smoking cessation aid in heavy-drinking smokers, the combination of varenicline and naltrexone may confer benefits with regard to drinking outcomes, particularly during the 12-week period of active medication treatment.

The Persistent Challenge of Developing Addiction Pharmacotherapies.

There are currently effective Food and Drug Administration (FDA)-approved therapies for alcohol, nicotine, and opioid use disorders. This article will review the development of eight compounds used in the treatment of drug addiction with an emphasis on pharmacological mechanisms and the utility of preclinical animal models of addiction in therapeutic development. In contrast to these successes, animal research has identified a number of promising medications for the treatment of psychostimulant use disorder, none of which have proven to be clinically effective. A specific example of an apparently promising pharmacotherapeutic for cocaine that failed clinically will be examined to determine whether this truly represents a challenge to the predictive validity of current models of cocaine addiction. In addition, the development of promising cocaine use disorder therapeutics derived from animal research will be reviewed, with some discussion regarding how preclinical studies might be modified to better inform clinical outcomes.

Effects of ethanol, naltrexone, nicotine and varenicline in an ethanol and nicotine co-use model in Sprague-Dawley rats.

BACKGROUND: As alcohol and nicotine use disorders are entwined, it may be possible to develop a single medication to treat both. We previously developed a model for ethanol (EtOH) and nicotine co-use in female selectively bred alcohol-preferring (P) rats. To model co-use in a genetically diverse population, we adapted the model to outbred Sprague-Dawley rats of both sexes and assessed the effect of drug pretreatments. METHODS: In phase 1, rats were trained in a 2-bottle choice between water and a sweetened or unsweetened EtOH solution in operant chambers. In phase 2, rats were trained in nicotine self-administration under an increasing fixed ratio (FR) schedule with 2 bottles containing water or saccharin-sweetened EtOH also available. In phase 3, rats were pretreated with EtOH (0.5, 1.5 g/kg), naltrexone (0.3 mg/kg), nicotine (0.2, 0.6 mg/kg), varenicline (3.0 mg/kg) or vehicle before the session. RESULTS: Sweetening the EtOH solution was required to obtain pharmacologically relevant levels of consumption in Phase 1, with males showing increased sweetened EtOH preference compared to females. In Phase 2, increasing the FR requirement for nicotine decreased nicotine infusions, but increased EtOH consumption. In Phase 3, EtOH, naltrexone, and nicotine failed to alter EtOH consumption; however, varenicline decreased both EtOH and nicotine intake. CONCLUSIONS: The co-use model was successfully adapted to Sprague-Dawley rats by adding saccharin to the EtOH solution. In contrast to previous results in P rats, varenicline reduced both EtOH and nicotine intake, indicating it may be a useful monotherapy for co-use in a genetically diverse population.

Very Low Frequency of Drug Therapy of Alcohol Dependence in Germany - Analysis of Data of A Statutory Health Insurance.

Acamprosate and naltrexone are medications of proven efficacy in the treatment of alcohol dependence. In order to investigate the prescription of these drugs in outpatient routine treatment in Germany (frequency of prescription, duration, medical specialty of prescribing physician), data of a large statutory health insurance were analyzed. Persons were included who were discharged from inpatient treatment with an alcohol-related disorder among their diagnoses during a one year observation period and with no diagnosed additional substance-related disorder (apart from nicotine- and cannabis-related disorders). Thus 12.958 patients were identified (mainly male, 77.9%; at average 51.4 years [+/-12.7] of age). 44.3% of these patients were treated in a psychiatric hospital, the remaining patients in hospitals of other specialties (e. g. 9.2% in departments of surgery). During an observation period of 6 months after discharge, acamprosate or naltrexone were prescribed at least once to 98 persons (0.76% of 12.958 patients; acamprosate n=80, 0.62%; naltrexone n=18, 0.14%). 16 (0.12%) patients were prescribed acamprosate or naltrexone for more than 3 months. Half of the prescriptions were issued by general practitioners. Possible reasons for this under-prescription are lack of knowledge about the drug treatment of alcohol dependence outside of addiction psychiatry, neglect of biological aspects (including medication) regarding etiology and treatment of substance-related disorders, and stigma of patients with substance-related disorders.

Alcohol-related chronic exocrine pancreatic insufficiency: diagnosis and therapeutic management. A proposal for treatment by the Italian Association for the Study of the Pancreas (AISP) and the Italian Society of Alcohology (SIA).

Current estimates of the prevalence of chronic pancreatitis, one of the most common causes of exocrine pancreatic insufficiency, are in the range of 3-10 per 100,000 people in many parts of the world. Alcohol consumption is a very important risk factor for exocrine pancreatic insufficiency and is involved in nearly half of all cases. The main hypothesis regarding the role of chronic alcohol consumption in pancreatitis is that there must be additional environmental or genetic risk factors involved for ongoing damage to occur. Treatment of patients with alcohol-related exocrine pancreatic insufficiency is complex, as the patient has two concomitant pathologies, alcohol-use disorder (AUD) and exocrine pancreatic insufficiency/chronic pancreatitis. Alcohol abstinence is the starting point for treatment, although even this along with the most advanced therapies allow only a slowdown in progression rather than restoration of function. This position paper of the Italian Association for the Study of the Pancreas and the Italian Society of Alcohology provides an overview of the pathogenesis of alcohol-related pancreatitis and discuss diagnostic issues. Treatment options for both exocrine pancreatic insufficiency/chronic pancreatitis (with a focus on pancreatic enzyme replacement therapy) and AUD (acamprosate, disulfiram, oral naltrexone, long-acting injectable naltrexone, sodium oxybate, nalmefene, baclofen, and psychosocial interventions) are also reviewed.

Effects of time-varying changes in tobacco and alcohol use on depressive symptoms following pharmaco-behavioral treatment for smoking and heavy drinking.

BACKGROUND: Complete abstinence from alcohol as well as smoking cessation have been shown to predict reductions in depressive symptoms over time. However, whether reducing alcohol use or smoking positively affect depressive symptoms has yet to be examined. The current study examined depressive symptoms as a function of time-varying changes in alcohol use and smoking status following a pharmaco-behavioral treatment addressing smoking cessation and alcohol reduction. METHODS: Participants were heavy-drinking smokers (n = 150) followed for 26 weeks after their quit smoking date, with assessments of smoking, alcohol use, and depressive symptoms at baseline and 2, 8, 16, and 26 weeks. RESULTS: Abstinence from smoking was associated with significantly lower depressive symptoms, as compared to little to no reduction in smoking (B = -6.1) as well as significant reductions in smoking (B = 4.01). Exploratory analyses, which excluded observations in which a participant was abstinent, revealed a significant effect of percent change in cigarettes smoked, modeled continuously, on depressive symptoms, (B = 4.39). By contrast, no differences were observed in depressive symptoms in relation to changes in alcohol use. CONCLUSION: It appears that smoking abstinence is associated with improvements in depression as compared to any level of sustained or reduced use and that the magnitude of smoking reduction may be associated with lower depressive symptoms among those who did not quit successfully. If replicated, these findings may inform treatment for individuals for whom depression is a major barrier to cessation and who have been unable or are unwilling to be completely abstinent from smoking.

An improved model of ethanol and nicotine co-use in female P rats: Effects of naltrexone, varenicline, and the selective nicotinic α6ß2* antagonist r-bPiDI.

Background Although pharmacotherapies are available for alcohol (EtOH) or tobacco use disorders individually, it may be possible to develop a single pharmacotherapy to treat heavy drinking tobacco smokers by capitalizing on the commonalities in their mechanisms of action. Methods Female alcohol-preferring (P) rats were trained for EtOH drinking and nicotine self-administration in two phases: (1) EtOH alone (0 vs. 15% EtOH, 2-bottle choice) and (2) concomitant access, during which EtOH access continued with access to nicotine (0.03 mg/kg/infusion, i.v.) using a 2-lever choice procedure (active vs. inactive lever) in which the fixed ratio (FR) requirement was gradually increased to FR30. When stable co-use was obtained, rats were pretreated with varying doses of naltrexone, varenicline, or r-bPiDI, an α6ß2* subtype-selective nicotinic acetylcholine receptor antagonist shown previously to reduce nicotine self-administration. Results While EtOH intake was initially suppressed in phase 2 (co-use), pharmacologically relevant intake for both substances was achieved by raising the "price" of nicotine to FR30. In phase 2, naltrexone decreased EtOH and water consumption but not nicotine intake; in contrast, naltrexone in phase 1 (EtOH only) did not significantly alter EtOH intake. Varenicline and r-bPiDI in phase 2 both decreased nicotine self-administration and inactive lever pressing, but neither altered EtOH or water consumption. Conclusions These results indicate that increasing the "price" of nicotine increases EtOH intake during co-use. Additionally, the efficacy of naltrexone, varenicline, and r-bPiDI was specific to either EtOH or nicotine, with no efficacy for co-use. Nevertheless, future studies on combining these treatments may reveal synergistic efficacy.

Systematic review evaluating randomized controlled trials of smoking and alcohol cessation interventions in people with head and neck cancer and oral dysplasia.

BACKGROUND: Smoking and alcohol increase the risk of head and neck cancer and affect treatment outcomes. Interventions modifying these behaviors may improve posttreatment outcomes and survival. We systematically reviewed evidence of the effectiveness of smoking/alcohol interventions in head and neck cancer and oral dysplasia. METHODS: The AMED, CINAHL, Embase, MEDLINE, and Web of Science databases were searched for randomized controlled trials (RCTs) of smoking/alcohol interventions in people with head and neck cancer. A qualitative synthesis of the studies was conducted. RESULTS: Three RCTs were identified: 2 smoking interventions and 1 smoking and alcohol intervention. One intervention, which was comprised of a smoking intervention based on Cognitive Behavioral Therapy and pharmacologic management compared to usual care, reduced smoking prevalence. CONCLUSION: Further research is required into the underlying mechanisms that lead to cessation and interventions that include both pharmacological and behavioral therapy. Future RCTs should include suitable control conditions and sufficient power to assess clinical outcomes.

Nicotine-Use/Smoking Is Associated with the Efficacy of Naltrexone in the Treatment of Alcohol Dependence.

BACKGROUND: The opioid antagonist naltrexone is not efficacious for every alcohol treatment seeker. However, various individual factors, such as genetic differences and nicotine-use/smoking status, have been suggested as predictors of naltrexone response. In a randomized clinical trial, we previously reported that nicotine-use/smoking status might be a stronger predictor of naltrexone efficacy than OPRM1 A118G single nucleotide polymorphism (SNP) genotype. In this report, we further characterize the nicotine-users in that trial, examine other drinking outcomes, examine the influence of smoking change on naltrexone effects on drinking, and validate the result in smokers with disialo carbohydrate-deficient transferrin (%dCDT) change as an independent biomarker of response. METHODS: Individuals (n = 146) meeting DSM-IV criteria for alcohol dependence who were genotyped for the OPRM1 A118G SNP and who did, or did not, use nicotine/cigarettes were randomized, in a balanced fashion, to naltrexone (50 mg/d) or placebo and provided medical management (MM) over a 16-week clinical trial. Alcohol use and smoking during the trial were assessed and analyzed. RESULTS: Nicotine-use/smoking status significantly interacted with medication in reducing percent heavy drinking days (PHDD) during the trial (p = 0.003), such that nicotine-users/smokers showed significantly lower PHDD on naltrexone versus placebo (p = 0.0001, Cohen's d = 0.89), while nonusers showed no significant difference between naltrexone and placebo (p = 0.95, Cohen's d = 0.02). Similar effects were shown for drinks per day and percent days drinking. The superiority of naltrexone over placebo on PHDD reduction in nicotine-users/smokers was confirmed with %dCDT (Cohen's d range 0.3 to 0.9 over the study). Naltrexone did not significantly change cigarette use in smokers, and change in use did not influence naltrexone's effect on PHDD. CONCLUSIONS: These data confirm past findings that naltrexone is more efficacious in those who use nicotine/cigarettes. Compared to previous work on the OPRM1 A118G SNP, it appears that nicotine-use might be a more salient predictor of naltrexone treatment response. While naltrexone did not change cigarette use during the study, and smoking change was not related to alcohol reduction, it should be noted that participants were not seeking smoking cessation and MM did not address this issue.

Addressing unhealthy alcohol use among people living with HIV: recent advances and research directions.

PURPOSE OF REVIEW: Unhealthy alcohol use is prevalent among people living with HIV (PLWH). We sought to identify the most current literature examining the impact of unhealthy alcohol on health outcomes and latest developments on how to best intervene. RECENT FINDINGS: New research shows that PLWH have heightened morbidity and mortality at lower levels of alcohol consumption compared with HIV-uninfected persons. Studies published since 2016 have further elucidated the effects of persistent unhealthy alcohol use on HIV treatment outcomes over time. Screening and brief interventions, as well as pharmacologic treatment, can reduce unhealthy alcohol use among PLWH. SUMMARY: Unhealthy alcohol use is an important and modifiable risk factor for poor health and HIV treatment outcomes among PLWH. More research is needed to encourage and maintain engagement in alcohol-related interventions and improve implementation.

Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4.

Cancer incidence is rising and this global challenge is further exacerbated by tumour resistance to available medicines. A promising approach to meet the need for improved cancer treatment is drug repurposing. Here we highlight the potential for repurposing disulfiram (also known by the trade name Antabuse), an old alcohol-aversion drug that has been shown to be effective against diverse cancer types in preclinical studies. Our nationwide epidemiological study reveals that patients who continuously used disulfiram have a lower risk of death from cancer compared to those who stopped using the drug at their diagnosis. Moreover, we identify the ditiocarb-copper complex as the metabolite of disulfiram that is responsible for its anti-cancer effects, and provide methods to detect preferential accumulation of the complex in tumours and candidate biomarkers to analyse its effect on cells and tissues. Finally, our functional and biophysical analyses reveal the molecular target of disulfiram's tumour-suppressing effects as NPL4, an adaptor of p97 (also known as VCP) segregase, which is essential for the turnover of proteins involved in multiple regulatory and stress-response pathways in cells.

Long-Term Management of Alcoholic Liver Disease.

The key to management of alcoholic liver disease (ALD) is early recognition by the patient and physician. Excessive alcohol consumption, ranging from drinking more than recommended amounts to abuse, is one of the most preventable causes of death and disability. The US Preventive Services Task Force guidelines recommend screening for alcoholism in the primary care setting. Abstinence is the cornerstone of therapy and it decreases mortality and morbidity significantly. Alcoholic cirrhosis can cause varices that need to be followed closely with upper endoscopy to prevent or treat hemorrhage. In this review, we describe an approach to long-term management of ALD.

Pharmacotherapy for Substance Use Disorders.

This article reviews the current pharmacotherapy options available for the treatment of patients with substance use disorders. In the United States there are medications available to treat tobacco use disorders (nicotine replacement, bupropion, and varenicline), alcohol use disorders (naltrexone and acamprosate), and opioid use disorders (methadone and buprenorphine). These medications are likely underused and physicians should more readily prescribe for eligible patients.

Pharmacotherapy for Alcohol Dependence: The 2015 Recommendations of the French Alcohol Society, Issued in Partnership with the European Federation of Addiction Societies.

BACKGROUND: The latest French good practice recommendations (GPRs) for the screening, prevention, and treatment of alcohol misuse were recently published in partnership with the European Federation of Addiction Societies (EUFAS). This article aims to synthesize the GPRs focused on the pharmacotherapy of alcohol dependence. METHODS: A four-member European steering committee defined the questions that were addressed to an 18-member multiprofessional working group (WG). The WG developed the GPRs based on a systematic, hierarchical, and structured literature search and submitted the document to two review processes involving 37 French members from multiple disciplines and 5 non-French EUFAS members. The final GPRs were graded A, B, or C, or expert consensus (EC) using a reference recommendation grading system. RESULTS: The treatment of alcohol dependence consists of either alcohol detoxification or abstinence maintenance programs or drinking reduction programs. The therapeutic objective is the result of a decision made jointly by the physician and the patient. For alcohol detoxification, benzodiazepines (BZDs) are recommended in first-line (grade A). BZD dosing should be guided by regular clinical monitoring (grade B). Residential detoxification is more appropriate for patients with a history of seizures, delirium tremens, unstable psychiatric comorbidity, or another associated substance use disorder (grade B). BZDs are only justified beyond a 1-week period in the case of persistent withdrawal symptoms, withdrawal events or associated BZD dependence (grade B). BZDs should not be continued for more than 4 weeks (grade C). The dosing and duration of thiamine (vitamin B1) during detoxification should be adapted to nutritional status (EC). For relapse prevention, acamprosate and naltrexone are recommended as first-line medications (grade A). Disulfiram can be proposed as second-line option in patients with sufficient information and supervision (EC). For reducing alcohol consumption, nalmefene is indicated in first line (grade A). The second-line prescription of baclofen, up to 300 mg/day, to prevent relapse or reduce drinking should be carried out according to the "temporary recommendation for use" measure issued by the French Health Agency (EC). During pregnancy, abstinence is recommended (EC). If alcohol detoxification is conducted during pregnancy, BZD use is recommended (grade B). No medication other than those for alcohol detoxification should be initiated in pregnant or breastfeeding women (EC). In a stabilized pregnant patient taking medication to support abstinence, the continuation of the drug should be considered on a case-by-case basis, weighing the benefit/risk ratio. Only disulfiram should be always stopped, given the unknown risks of the antabuse effect on the fetus (EC). First-line treatments to help maintain abstinence or reduce drinking are off-label for people under 18 years of age and should thus be considered on a case-by-case basis after the repeated failure of psychosocial measures alone (EC). Short half-life BZDs should be preferred for the detoxification of elderly patients (grade B). The initial doses of BZDs should be reduced by 30 to 50% in elderly patients (EC). In patients with chronic alcohol-related physical disorders, abstinence is recommended (EC). Any antidepressant or anxiolytic medication should be introduced after a psychiatric reassessment after 2-4 weeks of alcohol abstinence or low-risk use (grade B). A smoking cessation program should be offered to any smokers involved in an alcohol treatment program (grade B).