BACKGROUND:The pharmacological management of alcohol use disorder (AUD) currently includes six medications approved by different regulatory agencies worldwide: acamprosate (ACM), naltrexone (NTX), nalmefene (NMF), disulfiram (DF), baclofen, and sodium oxybate (SO). Their optimal use should be aligned with the main aims of treatment, namely reduction of alcohol consumption and maintenance of complete abstinence. OBJECTIVES:This brief review summarizes the role of these six approved medications in AUD treatment and proposes practical treatment algorithms according to treatment goals, mechanisms of action, and clinically relevant outcomes. METHODS:A focused narrative review of the literature was conducted, prioritizing meta-analyses, systematic reviews, randomized controlled trials, and relevant regulatory documents. Evidence on efficacy, safety, tolerability, and clinical applicability was interpreted pragmatically to support first-, second-, and third-line pharmacological strategies. RESULTS:For reducing alcohol intake, NMF or NTX are proposed as first-line pharmacotherapies, with baclofen considered as a second-line option when these agents are partially effective or ineffective. For maintaining abstinence, ACM is proposed as a first-line strategy. In selected clinical settings, including severe AUD, protracted alcohol withdrawal syndrome, high motivation for aversive treatment, or liver disease, SO, baclofen, DF, or NTX may serve as second-line options. Combined pharmacotherapy may be considered in highly adherent patients, whereas off-label drugs remain third-line options for refractory cases. CONCLUSIONS:Improved knowledge of the efficacy, safety, and tolerability of the six approved medications may support more appropriate, individualized, and goal-oriented pharmacological management of patients with AUD. The proposed algorithms are intended as pragmatic tools to aid clinical decision-making rather than as formal guidelines.

Ann Ist Super Sanità 2024 | Vol. 60, No. 4: 252-257 DOI: 10.4415/ANN_24_04_03 In the originally published version of this manuscript, an error occurred in the reporting of the dosage of disulfiram (DF) (Methods section, page 253). The correct sentence should read:"All patients failed to achieve abstinence either with SO (101 patients) or DF (25 patients) alone, so they were treated with oral doses of SO (50-100 mg/kg of body weight, tid), and DF (200 mg daily) in combination for 12 weeks"instead of:"All patients failed to achieve abstinence either with SO (101 patients) or DF (25 patients) alone, so they were treated with oral doses of SO (50-100 mg/kg of body weight, tid), and DF (250 mg daily) in combination for 12 weeks."We apologize for this error and any confusion it may have caused.

Introduction. Disulfiram (DF), acamprosate, naltrexone, baclofen and sodium oxybate (SO) are currently the medications approved for the treatment of alcohol use disorder (AUD). In this context, combined pharmacological interventions and sex differences are an interesting area in the treatment of non-responder AUD patients. Aim. To evaluate the efficacy of SO in combination with DF in maintaining alcohol abstinence in patients with AUD who failed to achieve abstinence either with SO or DF alone. Methods and results. 126 detoxified AUD patients, previously treated with only SO or DF, were retrospectively enrolled from 2018 to 2022. At the end of treatment, a higher number of females than males (74.1% vs 66.3%: p=0.03) maintained continuous abstinence from alcohol, and all the females responded completely or partially to the treatment. Conclusions. This study shows that the combination of SO and DF may be considered a further pharmacological opportunity for AUD patients (particularly in females) who do not respond to mono-therapy.

AIMS:Alcohol use disorder (AUD) is a common mental disorder characterized by sex-gender differences (SGDs). The present study was aimed at evaluating attitudes displayed by Italian AUD treatment services towards investigating the presence of SGDs in their patients and implementing gender-specific treatments for female AUD patients. METHODS:Potential SGDs were initially investigated in a sample of AUD outpatients, subsequently followed by a national survey on the adoption of specific interventions for female AUD outpatients. RESULTS:The presence of SGDs was confirmed in a sample of 525 (332 men; 193 women) AUD outpatients, including a higher prevalence of anxiety and mood disorders, and episodes of violence and trauma among female AUD outpatients compared to males. Despite the presence of these SGDs, only <20% of a total of 217 Italian AUD treatment services reported the implementation of specific strategies for female AUD outpatients. The majority of services (94%) reported investigating episodes of violence and/or trauma, largely resorting to specific procedures only when these issues were detected. CONCLUSIONS:Our findings confirm the presence of SGDs among AUD outpatients, including a higher prevalence of anxiety and mood disorders and episodes of violence and trauma among females compared with males. However, only a small number of services have adopted a gender medicine approach in AUD treatment. These results underline the urgency of investigating the specific needs of female, male, and non-binary AUD patients in order to personalize and enhance the effectiveness and appeal of AUD treatment.

Il disturbo da uso di alcol (DUA) è tra i più diffusi disturbi mentali in tutto il mondo (American Psychiatric Association, 2013), con 3 milioni di decessi all’anno causati dal consumo di alcol, rappresentando il 5,3% di tutti i decessi. Il DUA è altamente invalidante e si associa a molte comorbidità fi siche e psichiche, quest’ultime in particolar modo hanno visto un’esacerbazione durante la recente pandemia di Covid-19 (Chiappini et al., 2020; Martinotti et al., 2020); nel complesso, oltre alle conseguenze per la salute, il DUA comporta problematiche relazionali e sociali, non solo per l’individuo ma anche per la comunità (Associazione psichiatrica americana, 2013). Quando si parla di DUA non ci si può esimere dal parlare del craving concetto che negli ultimi 20 anni ha ricevuto un’attenzione signifi cativa come sintomo chiave di tutte le dipendenze (Leggio, 2009) fi no ad essere inserito nei criteri per la defi nizione di DUA nel DSM V. È presente nel 54-72% dei pazienti con DUA (Westerberg, 2000; Yoon et al., 2006), giocando un ruolo cruciale sia nello sviluppo della DUA (Robinson e Berridge, 1993) che nel meccanismo determinante la ricaduta (Bottlender e Soyka, 2004). Il craving per l’alcol, defi nito come desiderio apparentemente incontrollabile di assumere bevande alcoliche, compare quando il paziente con DUA cerca di mantenere l’astensione ed è generato da una sproporzione tra la spinta impulsiva o compulsiva (a seconda degli stadi del DUA) ad assumere alcolici e lo sforzo cognitivo per controllarla, gestirla e ridefi nirla (Bernard et al., 2021). Inoltre, il craving per alcol, soprattutto se presente all’inizio del trattamento, è associato a una ricaduta precoce (Bottlender e Soyka, 2004; Oslin et al., 2009). Il craving per l’alcol nei pazienti con DUA astinenti è esacerbato dall’esposizione alla sostanza e a triggers ad essa associati (O’Brien et al., 1998). Questi includono triggers interni come stati emotivi (es. ansia) o sintomi astinenziali e triggers esterni come l’esposizione ad ambienti o oggetti correlati all’alcol (ad es. bottiglie di bevande alcoliche o pubblicità). La valutazione e quantifi cazione del craving sono spesso diffi cili a causa della sua natura soggettiva e inoltre l’intensità e le caratteristiche del desiderio possono variare secondo caratteristiche personali, ambientali e circostanze (Martinotti et al., 2013). Dal punto di vista qualitativo sono stati proposti diversi modelli interpretativi del craving, tra cui uno di quelli che ha avuto più successo e che risulta essere più completo è un modello “three-way” di craving, che include craving di tipo reward, craving di tipo relief e craving di tipo obsessive, ipotizzato già nel 1999 da Verhuel (Verheul et al., 1999). Board editoriale e Comitato scientifi co: Giovanni Addolorato, Roberta Agabio, Fabio Caputo, Giorgio Cerizza, Mauro Cibin, Giovanni Galimberti, Ina Hinnenthal, Ezio Manzato, Antonio Mosti, Felice Nava, Biagio Sanfi lippo, Teo Vignoli, Valeria Zavan

Coronavirus disease 2019 (COVID-19) first emerged in China in November 2019. Most governments have responded to the COVID-19 pandemic by imposing a lockdown. Some evidence suggests that a period of isolation might have led to a spike in alcohol misuse, and in the case of patients with alcohol use disorder (AUD), social isolation can favour lapse and relapse. The aim of our position paper is to provide specialists in the alcohol addiction field, in psychopharmacology, gastroenterology and in internal medicine, with appropriate tools to better manage patients with AUD and COVID-19,considering some important topics: (a) the susceptibility of AUD patients to infection; (b) the pharmacological interaction between medications used to treat AUD and to treat COVID-19; (c) the reorganization of the Centre for Alcohol Addiction Treatment for the management of AUD patients in the COVID-19 era (group activities, telemedicine, outpatients treatment, alcohol-related liver disease and liver transplantation, collecting samples); (d) AUD and SARS-CoV-2 vaccination. Telemedicine/telehealth will undoubtedly be useful/practical tools even though it remains at an elementary level; the contribution of the family and of caregivers in the management of AUD patients will play a significant role; the multidisciplinary intervention involving experts in the treatment of AUD with specialists in the treatment of COVID-19 disease will need implementation. Thus, the COVID-19 pandemic is rapidly leading addiction specialists towards a new governance scenario of AUD, which necessarily needs an in-depth reconsideration, focusing attention on a safe approach in combination with the efficacy of treatment.

Proposal for the enhancement of alcohology (prevention, treatment and rehabilitation of alcohol problems): the position of Società Italiana di Alcologia (SIA), Federazione Italiana degli Operatori dei Dipartimenti e dei Servizi delle Dipendenze (FeDerSerD) and Società Italiana Tossicodipendenze (SITD)

BACKGROUND:Alcohol withdrawal syndrome (AWS) is characterized by different phases (acute, early and protracted). Protracted alcohol withdrawal (PAW) presents some symptoms, which may persist for several weeks, months or even years after drinking cessation.METHODS:We conducted a systematic review of the literature in major scientific databases on selected AWS symptoms (craving, sleep disorders, and anhedonia) in patients with alcohol use disorder.RESULTS:Of the 102 eligible publications (70 RCTs and 32 cohort studies), 88 provided data on craving, 21 on sleep disorders, and 1 on anhedonia. Overall, 37 studies assessed craving using the Obsessive Compulsive Drinking Scale (OCDS). Pooled OCDS decreased from 24.2 at baseline to 18.8 at 1 week, 10.3 at 1 month and 9.7 at 3 months. The corresponding estimates for treated individuals were 23.9, 18.8, 8.7, and 8.8, and for non-treated subjects, they were 25.3, 13.9, 13.2, and 11.4, respectively. In 4 studies assessing sleep disorders using the Epworth Sleeping Scale (ESS), the scale remained stable in time, i.e., 7.3 at baseline, 7.3 at 1 week, 7.2 at 1 month, and 7.1 at 3 months.CONCLUSION:This study confirms the presence of PAW after the resolution of the acute phase of AWS. The pharmacological approach to managing PAW may ensure a more rapid reduction of symptoms in three weeks. We highlight the importance of studying PAW and the ability of pharmacological treatment to reduce its symptoms. This review protocol is registered in Prospero (registration number: CRD42020211265).SUMMARY:This systematic review summarizes literature on major symptoms of protracted alcohol withdrawal in patients with alcohol use disorder. The pharmacological approach to manage protracted alcohol withdrawal ensures a more rapid reduction of symptoms (craving in particular), achieving in three weeks similar results obtained only after almost 6 months without treatment.

Background Coronavirus Disease 2019 (COVID-19), firstly reported in China last November 2019, became a global pandemic. It has been shown that periods of isolation may induce a spike in alcohol use disorder (AUD). In addition, alcohol-related liver disease (ALD) is the most common consequence of excessive alcohol consumption worldwide. Moreover, liver impairment has also been reported as a common manifestation of COVID-19. Aims The aim of our position paper was to consider some critical issues regarding the management of ALD in patients with AUD in the era of COVID-19. Methods A panel of experts of the Italian Society of Alcohology (SIA) met via “conference calls” during the lockdown period to draft the SIA’s criteria for the management of ALD in patients with COVID-19 as follows: (a) liver injury in patients with ALD and COVID-19 infection; (b) toxicity to the liver of the drugs currently tested to treat COVID-19 and the pharmacological interaction between medications used to treat AUD and to treat COVID-19; (c) reorganization of the management of compensated and decompensated ALD and liver transplantation in the COVID-19 era. Results and Conclusions The COVID-19 pandemic has rapidly carried us toward a new governance scenario of AUD and ALD which necessarily requires an in-depth review of the management of these diseases with a new safe approach (management of out-patients and in-patients following new rules of safety, telemedicine, telehealth, call meetings with clinicians, nurses, patients, and caregivers) without losing the therapeutic efficacy of multidisciplinary treatment.

Background: People who inject drugs (PWID) are the largest group at risk for HCV infection. Despite the direct acting antivirals (DAA) advancements, HCV elimination has been hindered by real-life difficulties in PWID. Aims: This study aimed to assess the impact of a multidisciplinary intervention strategy where HCV screening, treatment and follow-up were performed at the same location on efficacy and safety of DAA-therapy in real-life PWID population. Methods: All HCV-infected PWID referred to five specialized outpatient centers for drug addicts (SerDs) in Northern Italy were prospectively enrolled from May 2015 to December 2019. Hepatologists and SerDs healthcare workers collaborated together in the management of PWID inside the SerDs. Sustained virologic response (SVR), safety of treatment, proportion of patients lost to follow-up and reinfection rate were evaluated. Results: A total of 358 PWID started antiviral treatment. About 50% of patients had advanced fibrosis/cirrhosis, 69% received opioid substitution treatment, and 20.7% self-reported recent injecting use. SVR was achieved in 338 (94.4%) patients. Two patients died during treatment; one prematurely discontinued, resulting in a non-responder; twelve were lost during treatment/follow-up; and five relapsed. No serious adverse events were reported. SVR was lower in recent PWID than in former ones (89.2% vs. 95.8%; p = 0.028). Seven reinfections were detected, equating to an incidence of 1.25/100 person-years. Reinfection was associated with recent drug use (OR 11.07, 95%CI 2.10–58.38; p = 0.005). Conclusion: Our embedded treatment model could be appropriate to increase the linkage to care of HCV-infected PWID. In this setting, DAA regimens are well tolerated and highly effective, achieving a lower rate of reinfection.

Worldwide, the prevalence of alcohol use disorder (AUD) is 20–30% in men and 10–15% in women, and cirrhosis due to alcohol-related liver disease (ALD) is responsible for 0.9% of global deaths and 47.9% of cirrhosis-related deaths. End-stage ALD (ESALD) is the final condition of alcohol-related cirrhosis, and severe acute alcohol-related hepatitis (SAAH) is a distinct clinical syndrome associated with the consumption of large amounts of alcohol. In some cases, ESALD, and SAAH may need liver transplantation (LT). Thus, the management of ESALD and SAAH in patients affected by AUD may be an essential part of the clinical skills for hepatologists. For these reasons, the national board of the Italian Society on Alcohol have reviewed the most recent data on the management of ESALD, SAAH and LT for ALD in patients with AUD, formulating a position paper with related recommendations regarding four issues of specific clinical interest in this field: (a) the management of hepatic encephalopathy in patients with AUD, and LT in patients with ESALD; (b) the management of SAAH; (c) the management of AUD in patients with ESALD and SAAH; (d) special populations: polydrug addicts.

The chronic use of alcohol can lead to the onset of an alcohol use disorder (AUD). About 50% of subjects with an AUD may develop alcohol withdrawal syndrome (AWS) when they reduce or discontinue their alcohol consumption and, in 3–5% of them, convulsions and delirium tremens (DTs), representing life-threatening complications, may occur. Unfortunately, few physicians are adequately trained in identifying and treating AWS. The Italian Society on Alcohol has, therefore, implemented a task force of specialists to draw up recommendations for the treatment of AWS with the following main results: (1) while mild AWS may not require treatment, moderate and severe AWS need to be pharmacologically treated; (2) out-patient treatment is appropriate in patients with mild or moderate AWS, while patients with severe AWS need to be treated as in-patients; (3) benzodiazepines, BDZs are the “gold standard” for the treatment of AWS and DTs; (4) alpha-2-agonists, beta-blockers, and neuroleptics may be used in association when BDZs do not completely resolve specific persisting symptoms of AWS; (5) in the case of a refractory form of DTs, the use of anaesthetic drugs (propofol and phenobarbital) in an intensive care unit is appropriate; (6) alternatively to BDZs, sodium oxybate, clomethiazole, and tiapride approved in some European Countries for the treatment of AWS may be employed for the treatment of moderate AWS; (7) anti-convulsants are not sufficient to suppress AWS, and they may be used only in association with BDZs for the treatment of refractory forms of convulsions in the course of AWS.

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.

Background: Alcohol use disorder (AUD) is a complex trait with genetic and environmental influences. Several gene variants have been associated with the risk for AUD, including genes encoding the sub-units of the -aminobutyric acid (GABA) receptors.Aim: This study evaluated whether specific single nucleotide polymorphisms (SNPs) in genes encoding GABA(B) receptor sub-units can be considered as candidates for the risk of AUD.Subjects and methods: Seventy-four AUD subjects and 128 Italian controls were genotyped for 10 SNPs in genes encoding GABA-B1 and GABA-B2 sub-units (GABBR1 and GABBR2). Allele, genotype, and haplotype frequencies were tested for the association with the AUD trait.Results: A significant difference between AUD individuals and controls was observed at genotype level for rs2900512 of GABBR2 gene. The homozygous T/T genotype was not found in the controls, whereas it was over-represented in the AUD individuals. Under the recessive model (T/T vs C/T+C/C) this result was statistically significant, as well as the Odds Ratio for the association with the AUD trait.Conclusions: The results provide preliminary data on the association between GABA(B) receptor gene variation and risk of AUD. To confirm this finding, studies with larger samples and additional characterisation of the phenotypic AUD trait are required.

The treatment of alcohol use disorder (AUD) with sodium oxybate (SMO) or gamma-hydroxybutyric acid (GHB) was introduced in Italy and Austria more than 20 years and 15 years ago, respectively, and it is now widely employed to treat alcohol withdrawal syndrome (AWS) and to maintain alcohol abstinence. These indications derive from its similar structure to the inhibitory neurotransmitter γ-amino-butyric acid (GABA), exerting an ethanol-mimicking effect, because it binds to GABAB receptors. Craving for, and abuse of, SMO remain a controversial issue; even though these unfavorable effects are evident in poly-drug addicted patients and in those with psychiatric diagnosis of borderline personality disorder. In addition, despite cases of severe intoxication and deaths being widely documented when GHB is used as “street drug”; its clinical use remains safe. Thus, the aim of the present review is to examine the role of SMO in the treatment of AUD, its possible implications in reducing alcohol consumption, and cases of abuse, and severe intoxication due to SMO during its clinical use in the treatment of AUD.

Almost 10% of the world's population is affected by alcohol use disorders, and the treatment of alcohol dependence (AD) still remains a challenge. Patients with AD can differ in many traits. Three drugs (disulfiram, naltrexone, and acamprosate) have been approved by the FDA for the treatment of AD, and in some European countries sodium oxybate is also approved for this purpose. Combined pharmacological therapy has not provided such convincing results. Considering the fact that the "ideal" and effective drug for all types of alcoholic patients does not exists, the future challenge will be to identify a personalized approach. Recent data has shown that this objective can be achieved by investigating the genetic variability of the patient. Moreover, the use of replacement molecules can probably be considered an advantageous therapeutic opportunity (i.e. sodium oxybate). In addition, reduction of alcohol consumption is increasingly accepted as a viable treatment goal, and the use of nalmefene "as-needed" (a pharmacological approach similar to naltrexone, but, possibly, with lower hepatotoxicity) may help in the treatment of AD. Thus, it is important to stress that a pharmacological approach to treat AD should be preceded by the definition of patient characteristics; this may help in the choice of the most appropriate drug and it can be done more easily when more pharmacological options approved for the treatment of AD are also available.

Sodium oxybate (SO) is a γ-amino-butyric acid (GABA)-ergic drug currently used for the treatment of alcohol dependence (AD) in some European countries. The aim of this study was to describe the effect of SO administration in alcoholics classified according to Lesch alcoholism typology (LAT). Forty-eight patients were enrolled and classified into four groups according to LAT. All patients were treated with oral SO (50 mg/kg of body weight t.i.d.) for 12 weeks. All patients significantly reduced their alcohol intake ( p<0.001). Alcohol abstinence during the 12 weeks of treatment did not differ between the four groups at the end of treatment. Craving for SO did not significantly differ amongst groups; cases of SO abuse were very limited and were observed in almost 10% of patients. In conclusion, our study showed an overall efficacy of SO in the treatment of AD irrespective of LAT categories. However, our results confirm that alcoholics with psychiatric co-morbidity, particularly with a borderline personality disorder of Axis II, are at a greater risk of developing craving for and abuse of the drug: until craving for alcohol and craving for SO are characterized in depth, SO should be used with caution in these patients.

Alcohol-use-disorders (AUDs) afflict 1–3% of elderly subjects. The CAGE, SMAST-G, and AUDIT are the most common and validated questionnaires used to identify AUDs in the elderly, and some laboratory markers of alcohol abuse (AST, GGT, MCV, and CDT) may also be helpful. In particular, the sensitivity of MCV or GGT in detecting alcohol misuse is higher in older than in younger populations. The incidence of medical and neurological complications during alcohol withdrawal syndrome in elderly alcoholics is higher than in younger alcoholics. Chronic alcohol abuse is associated with tissue damage to several organs. Namely, an increased level of blood pressure is more frequent in the elderly than in younger adults, and a greater vulnerability to the onset of alcoholic liver disease, and an increasing risk of breast cancer in menopausal women have been described. In addition, the prevalence of dementia in elderly alcoholics is almost 5 times higher than in non-alcoholic elderly individuals, approximately 25% of elderly patients with dementia also present AUDs, and almost 20% of individuals aged 65 and over with a diagnosis of depression have a co-occurring AUD. Moreover, prevention of drinking relapse in older alcoholics is, in some cases, better than in younger patients; indeed, more than 20% of treated elderly alcohol-dependent patients remain abstinent after 4 years. Considering that the incidence of AUDs in the elderly is fairly high, and AUDs in the elderly are still underestimated, more studies in the fields of epidemiology, prevention and pharmacological and psychotherapeutic treatment of AUDs in the elderly are warranted.

Gamma-hydroxybutyric acid (GHB) is a short-chain fatty acid structurally similar to the inhibitory neurotransmitter γ-aminobutyric acid. Clinical trials have demonstrated that 50-100 mg/kg of GHB fractioned into three or six daily doses is able to suppress alcohol withdrawal symptoms and facilitates the maintenance of abstinence from alcohol. These studies have also shown that GHB craving episodes are a very limited phenomenon (about 10-15%). Thus, physicians with access should consider the clinical efficacy of GHB as a valid pharmacological tool for the treatment of alcohol addiction.