Use of pharmacological treatments by a sample of Italian patients affected by alcohol use disorders

Title: USE OF PHARMACOLOGICAL TREATMENTS BY A SAMPLE OF ITALIAN PATIENTS AFFECTED BY ALCOHOL USE DISORDERS Author name(s): R. Agabio; E.M. Diana; D. Grazzini; R. Pirastu; G.L. Gessa Institution: Department of Biochemical Sciences, Section of Neuroscience, Preclinical and Clinical Pharmacology, University of Cagliari, Italy Text Background: It has often been reported that the majority of patients affected by Alcohol Use Disorders (AUDs) do not receive any pharmacological treatment. This study was aimed at investigating the use of the medications available in Italy (disulfiram, naltrexone, acamprosate, and γ-hydroxybutyric acid) by a sample of outpatients affected by AUDs. Methods: Four trained psychologists interviewed outpatients affected by AUDs in an area of Sardinia, Italy, of approximately 550.000 adult inhabitants. Results: A total sample of 208 outpatients affected by AUDs was interviewed (~1/3 of total outpatients affected by AUDs of that area). Their main features were: 166 males (79.5%); mean age=48.6±0.6 year; duration of AUDs=15.8±0.7 years; number of drinks per drinking days=19.4±1.3; number of criteria of DSM-IV-Tr=5.8±0.1. Before the admission into specific services, 13 patients (6.2%) had already received medication for AUDs; 7 patients (3.4%) had received disulfiram and 6 patients (2.9%) γ-hydroxybutyric acid. Over the same period, 22 patients (10.6%) had already attended self-help groups and 4 patients (1.9%) had received thiamine (Vitamine B1). After the admission into specific medical settings for the treatment of AUDs, 113 patients (54.3%) received medication for AUDs: 58 patients (27.9%) received disulfiram, 65 patients (31.2%) γ-hydroxybutyric acid, 2 patients (1.0%) naltrexone, and 6 patients (2.9%) acamprosate. In the same period, 54 patients (26.0%) frequented self-help associations, and 21 patients (10.1%) received thiamine. Conclusions: The results of this study confirm that the number of patients who receive a treatment for AUDs continues to be surprisingly low. Despite the long duration and the high level of severity of the AUDs, the majority of patients affected by AUDs did not receive any treatment before their admission in specific medical settings for the treatment of AUDs (10% of patients frequented self-help groups, 6% received a medication for AUDs, and 2% thiamine). After the admission into specific medical settings, the number of patients who received a treatment increased: 26% frequented self-help associations, 54% received a specific medication, and 10% received thiamine. However, approximately half of the patients did not receive any pharmacological treatment even if they frequented medical settings for the treatment of AUDs. Additional work is needed to understand the reasons of such a scarce use of treatments. Acknowledgements: This study was supported by a grant from Regione Autonoma della Sardegna

Unawareness of Alcoholic Content of Alcopops among 13-Year Old Italian Teenagers.

Aims: Alcopops are ready-mixed drinks containing approximately the same amount of alcohol as beer, usually sweet, and flavoured, particularly appealing to young people. The present study was aimed to investigate whether young adolescents aged 12-14 years, corresponding to the average age of the first drink, are capable of identifying the presence of alcohol in these beverages. Methods: Administration of a questionnaire comprising 8 questions investigating knowledge and consumption of different alcoholic and non-alcoholic beverages to a sample of 13-year old Italian students. Results: More than 20% of a sample of 224 students reported that they were unaware of the alcoholic content of alcopops at the age of the first drink. The number of students unable to distinguish alcopops from non-alcoholic beverages was significantly higher than students who were not able to distinguish beer from alcohol-free beverages. Conclusions: At the age of the first drink, the identification of alcopops as alcoholic beverages is more difficult than that of other beverages containing the same amount of alcohol. Information aimed at increasing the ability of adolescents to distinguish between alcoholic and non-alcoholic beverages should be provided to young adolescent students before they start drinking

GABAB receptor as therapeutic target for drug addiction: from baclofen to positive allosteric modulators

The present paper summarizes experimental and clinical data indicating the therapeutic potential of the GABAB receptor agonist, baclofen, in the treatment of alcohol use disorder (AUD) and substance use disorder (SUD). Multiple preclinical studies have demonstrated the ability of baclofen to suppress alcohol drinking (including binge – and relapse-like drinking), oral alcohol self-administration, and intravenous self-administration of cocaine, nicotine, amphetamine, methamphetamine, morphine, and heroin in rodents. Some randomized, controlled trials (RCTs) and case reports support the efficacy of baclofen in suppressing alcohol consumption, craving for alcohol, and alcohol withdrawal symptomatology in alcohol-dependent patients. Data from RCTs and open studies investigating baclofen efficacy on SUD are currently less conclusive. Interest in testing high doses of baclofen in AUD and SUD treatment has recently emerged. Preclinical research has extended the anti-addictive properties of baclofen to positive allosteric modulators of the GABAB receptor (GABAB PAMs). In light of their more favourable side effect profile (compared to baclofen), GABAB PAMs may represent a major step forward in a GABAB receptor-based pharmacotherapy of AUD and SUD

Baclofen in the Treatment of Patients With Alcohol Use Disorder and Other Mental Health Disorders

A limited number of medications are approved to treat Alcohol Use Disorder (AUD). Furthermore, the magnitude of their therapeutic effect is relatively modest, suggesting the potential for subtypes of patients who respond to a specific medication. The use of these medications is also limited in clinical practice by a series of contraindications such as medical comorbidities and/or concurrent use of other medications. In recent years, animal and human studies have been conducted to evaluate the efficacy of baclofen, a GABAB receptor agonist approved for clinical use as a muscle relaxant, in the treatment of AUD. However, these studies have yielded contrasting results. Despite this discrepancy, baclofen is often used off-label to treat AUD, especially in some European countries and Australia. Recently, several factors have been considered to try to shed light on the potential reasons and mechanisms underlying the inconsistent results obtained until now. The presence of a psychiatric comorbidity may be amongst the abovementioned factors playing a role in explaining different responses to baclofen treatment in terms of alcohol drinking outcomes. Therefore, the aim here was to conduct a narrative review of the scientific literature related to the use of baclofen in AUD, both in patients with and without concomitant psychiatric disorders. All clinical studies (randomized and controlled, open-label, retrospective, human laboratory studies, and case reports) were analyzed and discussed, bearing in mind other potential factors that may have influenced baclofen response, including dose administered, severity of AUD, use of other psychosocial therapies, and the presence of physical disorders. This review indicates that the most frequent psychiatric comorbidities in patients affected by AUD undergoing baclofen treatment are anxiety and mood disorders. Unfortunately, no definitive conclusions can be drawn due to the lack of specific analyses on whether baclofen efficacy is different in AUD patients with comorbid psychiatric disorders vs. those without. Therefore, it will be critical that psychiatric comorbidities are considered in the planning of future studies and in the analysis of the data, with the ultimate goal of understanding whether subtypes of AUD patients may respond best to baclofen

Oxytocin Nasal Spray in the Treatment of Binge Eating Disorder and Obesity: A pilot, Randomized, Double Blind Trial

1.1. Background Preclinical studies suggest that the neuropeptide oxytocin reduces food intake and body weight, but only a few clinical studies have investigated the translatability of these findings in humans. The present study investigated the safety and efficacy of oxytocin nasal spray in patients affected by binge eating disorder and obesity. 1.2. Methods Seventeen outpatients affected by binge eating disorder and obesity participated in a 8 week double-blind trial and received oxytocin (n=8; 24 IU, four times a day, 20 min before each of three meals and before going to bed) or placebo (n=9) with an energy-restricted diet. Primary outcomes included adverse events and the number of binge eating episodes per week. Secondary measures included body weight, BMI, severity of BED, craving for food, quality of sleep, quality of life, anxiety, and depressive symptoms. 1.3. Results One patient of oxytocin group discontinued prematurely the trial before the first post-randomization efficacy measure. Among the other 16 participants, 13 (81.2%) completed the trial, and 3 (18.8%) discontinued [3 in the oxytocin group; 0 in the placebo group (p=0.0625, Fisher’s exact test)]. No significant difference between groups was found in any outcome evaluated. Patients of the placebo group performed slightly better than patients of the oxytocin group in some secondary outcomes, but these differences were not significant. 1.4. Conclusion Oxytocin nasal spray resulted to be safe, including in women of childbearing age but did not significantly reduce the number of binge eating episodes per week in outpatients affected by binge eating disorder and obesity. These findings are discussed in light of the human oxytocin literature. Keyword

The Use of Baclofen as a Treatment for Alcohol Use Disorder: A Clinical Practice Perspective

Alcohol use disorder (AUD) is a brain disorder associated with high rates of mortality and morbidity worldwide. Baclofen, a selective gamma-aminobutyric acid-B (GABA-B) receptor agonist, has emerged as a promising drug for AUD. The use of this drug remains controversial, in part due to uncertainty regarding dosing and efficacy, alongside concerns about safety. To date there have been 15 randomized controlled trials (RCTs) investigating the use of baclofen in AUD; three using doses over 100 mg/day. Two additional RCTs have been completed but have not yet been published. Most trials used fixed dosing of 30–80 mg/day. The other approach involved titration until the desired clinical effect was achieved, or unwanted effects emerged. The maintenance dose varies widely from 30 to more than 300 mg/day. Baclofen may be particularly advantageous in those with liver disease, due to its limited hepatic metabolism and safe profile in this population. Patients should be informed that the use of baclofen for AUD is as an “off-label” prescription, that no optimal fixed dose has been established, and that existing clinical evidence on efficacy is inconsistent. Baclofen therapy requires careful medical monitoring due to safety considerations, particularly at higher doses and in those with comorbid physical and/or psychiatric conditions. Baclofen is mostly used in some European countries and Australia, and in particular, for patients who have not benefitted from the currently used and approved medications for AUD