François Paille

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

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.

A Randomized, Placebo-Controlled Study of High-Dose Baclofen in Alcohol-Dependent Patients—The ALPADIR Study

Aims Alcohol dependence is a major public health issue with a need for new pharmacological treatments. The ALPADIR study assessed the efficacy and safety of baclofen at the target dose of 180 mg/day for the maintenance of abstinence and the reduction in alcohol consumption in alcohol-dependent patients. Methods Three hundred and twenty adult patients (158 baclofen and 162 placebo) were randomized after alcohol detoxification. After a 7-week titration, the maintenance dose was provided for 17 weeks, then progressively decreased over 2 weeks before stopping. Results The percentage of abstinent patients during 20 consecutive weeks (primary endpoint) was low (baclofen: 11.9%; placebo: 10.5%) and not significantly different between groups (OR 1.20; 95%CI: 0.58 to 2.50; P = 0.618). A reduction in alcohol consumption was observed from month 1 in both groups, but the difference of 10.9 g/day at month 6 between groups, in favour of baclofen, was not statistically significant (P = 0.095). In a subgroup of patients with high drinking risk level at baseline, the reduction was greater with a difference at month 6 of 15.6 g/day between groups in favour of baclofen (P = 0.089). The craving assessed with Obsessive-Compulsive Drinking Scale significantly decreased in the baclofen group (P = 0.017). No major safety concern was observed. Conclusions This study did not demonstrate the superiority of baclofen in the maintenance of abstinence at the target dose of 180 mg/day. A tendency towards a reduction in alcohol consumption and a significantly decreased craving were observed in favour of baclofen. Short summary Baclofen was assessed versus placebo for maintenance of abstinence and reduction in alcohol consumption in alcohol-dependent patients. This study did not demonstrate the superiority of baclofen in the maintenance of abstinence. A tendency towards a reduction in alcohol consumption and a significantly decreased craving were observed in favour of baclofen.

Off-Label Baclofen Prescribing Practices among French Alcohol Specialists: Results of a National Online Survey

Objective To evaluate, among alcohol specialists belonging to the Société Française d’Alcoologie (SFA), i.e., the French Alcohol Society, the proportion of physicians who prescribed off-label baclofen for alcohol use disorders (AUDs). The secondary objective was to depict the features of individual prescribing and monitoring practices. Methods On-line survey among 484 French alcohol specialists. Physicians were asked whether they prescribed baclofen for AUDs. If they did not, the reasons for this choice were investigated. If they did, the features of the physician’s prescribing practice were explored, including the number of patients treated, the mean and maximum doses, the monitoring precautions and the pharmacovigilance reporting. Participants were also asked about their empirical findings on HDB’s efficacy and safety. Results In total, 302 physicians (response rate of 62.4%) participated in the survey. Data from 296 participants were analysed, representing 59.4% of all active prescribing physicians belonging to the SFA. HDB use was declared by 74.6% of participants (mean dose 109.5±43.6 mg/d; maximum dose 188±93.3 mg/d). However, 79.2% of prescribers had treated less than 30 patients, and 67.8% used HDB as a second-line medication. Although HDB was perceived as more efficacious than approved drugs by 54.3% of prescribers, it was also declared less safe by 62.8%. Nonetheless, 79.7% of prescribers had never filed any pharmacovigilance report. Non-prescribers (25.6%) were primarily deterred by the current lack of scientific data and official regulation. Conclusion A majority of French alcohol specialists reported using HDB, although often on a limited number of their patients. HDB was considered efficacious but also potentially hazardous. Despite this, physicians reported minimal safety data to the health security system. While French health authorities are planning to draft a specific regulatory measure for framing off-label HDB prescribing practices, the sustained education of prescribers on spontaneous pharmacovigilance reporting should be enhanced.

People with Alcohol Use Disorders in Specialized Care in Eight Different European Countries

AIM To provide a description of patients receiving alcohol treatment in eight different European countries, including the level of comorbidities and functional limitations. METHODS Drinking behaviours, DSM-IV alcohol use disorder (AUD), mental and somatic comorbidities, disability and health services utilization of 1767 patients from various specialized treatment settings were assessed as representative for regions of eight European countries. Severity of alcohol dependence (AD) in terms of drinking level was compared with a large representative US sample. RESULTS Patients in specialized care for AUDs showed high levels of consumption [average level of daily ethanol intake: 141.1 g, standard deviation (SD): 116.0 g], comorbidity [e.g. liver problems: 19.6%, 95% confidence interval (CI): 17.5-21.6%; depression: 43.2%, 95% CI: 40.7-45.8%; anxiety: 50.3%, 95% CI: 47.8-52.9%], disability and health services utilization (average number of nights spent in hospital(s) during the last 6 months: 8.8, SD: 19.5 nights). Severity of AD was similar to the US sample, but European men consumed on average more alcohol daily. CONCLUSIONS High levels of consumption, somatic and mental comorbidities, disability and functional losses were found in this representative treatment sample, indicating that treatment was initiated only at severe stages of AUDs. Earlier initiation of treatment could help avoid some of the health and social burden.

Changes in Serum Retinol, α-Tocopherol, Vitamin C, Carotenoids, Zinc and Selenium after Micronutrient Supplementation during Alcohol Rehabilitation

Objective: To test the effect of a 21-day supplementation with moderate doses of antioxidant nutrients on biochemical indicators of vitamin, carotenoid and trace element levels in alcohol-dependent patients during a program of alcohol rehabilitation. Design: A randomized double-blind trial was performed comparing two groups receiving daily either a combination of micronutrients (beta-carotene: 6 mg, vitamin C: 120 mg, vitamin E: 30 mg, zinc: 20 mg, selenium: 100 μg) or a placebo. Subjects: 106 alcohol-dependent patients 20 to 60 years of age without severe liver disease, hospitalized for a 21-day rehabilitation program. Measure of Outcome: Vitamin C, retinol, α-tocopherol, zeaxanthin/lutein, β-cryptoxanthin, lycopene, α- and β-carotene, zinc and selenium were measured in serum, initially and after supplementation. Results: (1) In the placebo group, after 21 days of rehabilitation, serum concentrations of vitamin C and all five carotenoids significantly increased, whereas retinol and α-tocopherol concentrations decreased; zinc and selenium levels were unaffected. (2) At the end of the hospital stay, serum indicators were significantly improved in the supplement group as compared to the placebo group for vitamin C, α-tocopherol, β-carotene, zinc and selenium; conversely, lycopene changes were higher in the placebo group than in supplement group. (3) Of the serum antioxidants measured at entrance, only vitamin C was significantly depleted in heavy smokers, and, after the supplementation period, vitamin C was efficiently repleted in this later group. Conclusion: Our results indicate that a short-term supplementation with physiological doses of antioxidant vitamins, carotenoids and trace elements during alcohol rehabilitation clearly improves micronutrient status indicators. Heavy smokers in particular seem to respond to vitamin C supplementation.

The 2015 French guidelines on alcohol misuse, issued in partnership with the European Federation of Addiction Societies: a focus on children and adolescents

The new French good practice recommendations (GPRs) for the screening, diagnosis, and treatment of alcohol misuse have recently been issued in both French and English [2]. Updating the French GPRs was warranted owing to several recent advances in the field. These points, which have been previously detailed elsewhere [3], essentially consisted of promoting the public health benefits of drinking reduction strategies, addressing the need to reduce the important treatment gap observed in the field, and offering recommendations on the off-label prescribing of baclofen, which has become widespread in France. These GPRs were conducted under the aegis of the Société Française d’Alcoologie (SFA, French Alcohol Society), with support and peer-review from members of the European Federation of Addiction Societies (EUFAS) [3]. The GPRs’ writing and peer-reviewing processes involved a steering committee, a working group, and two successive reviewing groups. The final GPRs were based on both the international scientific literature and the national aspects of the clinical practice and health system. The strength of each recommendation was graded: (1) A, based on randomized clinical trials of correct power or on meta-analyses; (2): B, based on low power comparative trials; (3): C, based on non-randomized trials, cohort studies, or case series; or (4) expert consensus (EC), using a standardized grading system [3]. The details of the GPR issuing process can be found elsewhere [2, 5]. In France, as in many other European countries, experimentation with alcohol use and drunkenness mainly occurs during adolescence [6]. Alcohol misuse may occur during adolescence, occasionally shortly after experimentation. Recent data suggest that the occurrence of alcohol misuse during adolescence may significantly disrupt the brain maturation processes and neuropsychological development during this period, which might subsequently worsen the

Serial evaluation of dilated cardiomyopathy with exercise thallium-201 tomography: correlation with the evolution of left ventricular parameters

The purpose of this prospective study was to correlate (1) the initial findings of exercise thallium-201 tomography with the evolution of left ventricular parameters at long term follow-up in patients with dilated cardiomyopathy and (2) the changes of exercise thallium-201 tomography repeated 1 year later. We studied 19 men with dilated cardiomyopathy and normal coronary angiogram. Two patients died and three patients had heart transplantation during follow-up. The other 14 patients were assessed at baseline and 1-year follow-up. Thallium-201 tomograms were divided into 20 segments for each patient. Two groups were defined according to the evolution of left ventricular ejection fraction: group 1 (n = 7) had unchanged or decreased ejection fraction at follow-up (24 +/- 11% at baseline versus 22 +/- 11% at follow-up, ns) and group 2 (n = 7) had improved ejection fraction at follow-up (25 +/- 9% at baseline versus 49 +/- 8% at follow-up, P < 0.03). The number of total abnormal segments at stress were not statistically different at baseline between groups 1 and 2, and in group 1 between baseline and follow-up. Group 2 at follow-up had a reduced number of total abnormal segments (P < 0.03). The percentage of reversibility was similar in both groups at baseline and follow-up. On exercise thallium-201 tomography, neither the presence nor the reversibility of stress myocardial perfusion abnormalities can predict improvement of left ventricular ejection fraction in dilated cardiomyopathy. However, regression of dilated cardiomyopathy is accompanied by a reduction of stress myocardial perfusion abnormalities.

How useful is aminolevulinic acid dehydratase as a marker of recent alcohol intake

Abstract Erythroycte delta aminolevulinic acid dehydratase (ALAD) has been suggested as a marker for detecting recent alcohol intake. Unlike other markers, ALAD activity decreases after alcohol intake. Review of the literature suggests that the main interest in this marker is because it increases rapidly after withdrawal. The present study investigated the changes in erythrocyte ALAD and serum gamma‐glutamyltransferase activities after alcohol withdrawal in 120 alcoholics. Our data showed that ALAD is less sensitive than GGT as an indicator of recent alcohol intake (56% and 84% abnormal, respectively). The increase in ALAD activity was greater between day 12 and 18 after withdrawal (11%) than between day 1 and 12 after withdrawal (5%). There were as many patients returning to normal values 12 and 18 days after withdrawal, for GGT as for ALAD. Thus, our results contradict the claim that ALAD rises rapidly after withdrawal. ALAD shows no advantage over GGT as a marker of recent alcohol intake.

Efficacy and safety of sodium oxybate in alcohol-dependent patients with a very high drinking risk level: Efficacy and safety of sodium oxybate in alcohol-dependent patients with a very high drinking risk level

Medication development for alcohol relapse prevention or reduction of consumption is highly challenging due to methodological issues of pharmacotherapy trials. Existing approved medications are only modestly effective with many patients failing to benefit from these therapies. Therefore, there is a pressing need for other effective treatments with a different mechanism of action, especially for patients with very high (VH) drinking risk levels (DRL) because this is the most severely affected population of alcohol use disorder patients. Life expectancy of alcohol‐dependent patients with a VH DRL is reduced by 22 years compared with the general population and approximately 90 000 alcohol‐dependent subjects with a VH DRL die prematurely each year in the EU (Rehm et al. ). A promising new medication for this population is sodium oxybate, a compound that acts on GABAB receptors and extrasynaptic GABAA receptors resulting in alcohol‐mimetic effects. In this article, a European expert group of alcohol researchers and clinicians summarizes data (a) from published trials, (b) from two new—as yet unpublished—large clinical trials (GATE 2 (n = 314) and SMO032 (n = 496), (c) from post hoc subgroup analyses of patients with different WHO‐defined DRLs and (d) from multiple meta‐analyses. These data provide convergent evidence that sodium oxybate is effective especially in a subgroup of alcohol‐dependent patients with VH DRLs. Depending on the study, abstinence rates are increased up to 34 percent compared with placebo with risk ratios up to 6.8 in favor of sodium oxybate treatment. These convergent data are supported by the clinical use of sodium oxybate in Austria and Italy for more than 25 years. Sodium oxybate is the sodium salt of γ‐hydroxybutyric acid that is also used as a recreational (street) drug suggestive of abuse potential. However, a pharmacovigilance database of more than 260 000 alcohol‐dependent patients treated with sodium oxybate reported very few adverse side effects and only few cases of abuse. We therefore conclude that sodium oxybate is an effective, well‐tolerated and safe treatment for withdrawal and relapse prevention treatment, especially in alcohol‐dependent patients with VH DRL.

Consommation d'alcool et myocardiopathie dilatée primitive. Comparaison avec une population de patients coronariens

Alcohol consumption was compared between 23 men admitted to hospital with idiopathic dilated myocardiopathy (DCM) and 46 men with coronary artery disease. Duration of regular daily alcohol, heavy daily alcohol, mean daily alcohol consumption, in particular consumption of wine were higher in patients with DCM. Among the biological markers, only serum levels of immunoglobulin A and bilirubin were increased in pts with DCM.