Chronic excessive alcohol consumption induces cognitive impairments mainly affecting executive functions, episodic memory, and visuospatial capacities related to multiple brain lesions. These ...cognitive impairments not only determine everyday management of these patients, but also impact on the efficacy of management and may compromise the abstinence prognosis. Maintenance of lasting abstinence is associated with cognitive recovery in these patients, but some impairments may persist and interfere with the good conduct and the efficacy of management. It therefore appears essential to clearly define neuropsychological management designed to identify and evaluate the type and severity of alcohol-related cognitive impairments. It is also essential to develop cognitive remediation therapy so that the patient can fully benefit from the management proposed in addiction medicine units.
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.
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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
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).
Energy drinks are popular beverages that are supposed to counteract sleepiness, increase energy, maintain alertness and reduce symptoms of hangover. Cognitive enhancing seems to be related to many ...compounds such as caffeine, taurine and vitamins. Currently, users mostly combine psychostimulant effects of energy drinks to counteract sedative effects of alcohol. However, recent literature suggests that this combination conducts to feel less intoxicated but still impaired. The goal of the present article is to review cognitive impact and subjective awareness in case of caffeinated alcoholic beverage (CAB) intoxication.
PubMed (January 1960 to March 2016) database was searched using the following terms: cognitive impairments, alcohol, energy drinks; cognition, alcohol, caffeine.
99 papers were found but only 12 randomized controlled studies which explored cognitive disorders and subjective awareness associated with acute CAB or AED (alcohol associated with energy drinks) intoxication were included.
The present literature review confirmed that energy drinks might counteract some cognitive deficits and adverse effects of alcohol i.e. dry mouth, fatigue, headache, weakness, and perception of intoxication due to alcohol alone. This effect depends on alcohol limb but disappears when the complexity of the task increases, when driving for example. Moreover, studies clearly showed that CAB/AEDs increase impulsivity which conducts to an overconsumption of alcohol and enhanced motivation to drink compared to alcohol alone, potentiating the risk of developing addictive behaviors. This is a huge problem in adolescents with high impulsivity and immature decision making processes.
Although energy drinks counteract some cognitive deficits due to alcohol alone, their association promotes the risk of developing alcohol addiction. As a consequence, it is necessary to better understand the neurobiological mechanisms underlying these interactions in order to better prevent the development of alcohol dependence.
•Energy drinks (ED) partly counteract cognitive deficits due to alcohol intake.•ED do not counteract alcohol-induced cognitive deficits during complex tasks.•Inhibitory failure and motivation for alcohol are increased when consumed in association with ED.•ED associated with alcohol may potentiate the risk of developing alcohol addiction.
Background:
Sodium oxybate (SMO) has been shown to be effective in the maintenance of abstinence (MoA) in alcohol-dependent patients in a series of small randomized controlled trials (RCTs). These ...results needed to be confirmed by a large trial investigating the treatment effect and its sustainability after medication discontinuation.
Aims:
To confirm the SMO effect on (sustained) MoA in detoxified alcohol-dependent patients.
Methods:
Large double-blind, randomized, placebo-controlled trial in detoxified adult alcohol-dependent outpatients (80% men) from 11 sites in four European countries. Patients were randomized to 6 months SMO (3.3–3.9 g/day) or placebo followed by a 6-month medication-free period. Primary outcome was the cumulative abstinence duration (CAD) during the 6-month treatment period defined as the number of days with no alcohol use. Secondary outcomes included CAD during the 12-month study period.
Results:
Of the 314 alcohol-dependent patients randomized, 154 received SMO and 160 received placebo. Based on the pre-specified fixed-effect two-way analysis of variance including the treatment-by-site interaction, SMO showed efficacy in CAD during the 6-month treatment period: mean difference +43.1 days, 95% confidence interval (17.6–68.5; p = 0.001). Since significant heterogeneity of effect across sites and unequal sample sizes among sites (n = 3–66) were identified, a site-level random meta-analysis was performed with results supporting the pre-specified analysis: mean difference +32.4 days, p = 0.014. The SMO effect was sustained during the medication-free follow-up period. SMO was well-tolerated.
Conclusions:
Results of this large RCT in alcohol-dependent patients demonstrated a significant and clinically relevant sustained effect of SMO on CAD.
Trial registration:
ClinicalTrials.gov Identifier: NCT04648423
Background
There is considerable unexplained variability in alcohol abstinence rates (AR) in the placebo groups of randomized controlled trials (RCTs) for alcohol dependence (AD). This is of ...particular interest because placebo responses correlate negatively with treatment effect size. Recent evidence suggests that the placebo response is lower in very heavy drinkers who show no “spontaneous improvement” prior to treatment initiation (high‐severity population) than in a mild‐severity population and in studies with longer treatment duration. We systematically investigated the relationship between population severity, treatment duration, and the placebo response in AR to inform a strategy aimed at reducing the placebo response and thereby increasing assay sensitivity in RCTs for AD.
Methods
We conducted a systematic literature review on placebo‐controlled RCTs for AD.We assigned retained RCTs to high‐ or mild‐severity groups of studies based on baseline drinking risk levels and abstinence duration before treatment initiation. We tested the effects of population severity and treatment duration on the placebo response in AR using meta‐regression analysis.
Results
Among the 19 retained RCTs (comprising 1996 placebo‐treated patients), 11 trials were high‐severity and 8 were mild‐severity RCTs. The between‐study variability in AR was lower in the high‐severity than in the mild‐severity studies (interquartile range: 7.4% vs. 20.9%). The AR in placebo groups was dependent on population severity (p = 0.004) and treatment duration (p = 0.017) and was lower in the high‐severity studies (16.8% at 3 months) than the mild‐severity studies (36.7% at 3 months).
Conclusions
Pharmacological RCTs for AD should select high‐severity patients to decrease the magnitude and variability in the placebo effect and and improve the efficiency of drug development efforts for AD.
Abstract
Aims
The estimated effect of sodium oxybate (SMO) in the treatment of alcohol dependence is heterogeneous. Population severity and treatment duration have been identified as potential effect ...modifiers. Population severity distinguishes heavy drinking patients with <14 days of abstinence before treatment initiation (high-severity population) from other patients (mild-severity population). Treatment duration reflects the planned treatment duration. This study aimed to systematically investigate the effect of these potential effect moderators on SMO efficacy in alcohol-dependent patients.
Methods
Network meta-regression allows for testing potential effect modifiers. It was selected to investigate the effect of the above factors on SMO efficacy defined as continuous abstinence (abstinence rate) and the percentage of days abstinent (PDA). Randomized controlled trials for alcohol dependence with at least one SMO group conducted in high-severity and mild-severity populations were assigned to a high-severity and mild-severity group of studies, respectively.
Results
Eight studies (1082 patients) were retained: four in the high-severity group and four in the mild-severity group. The high-severity group was associated with larger SMO effect sizes than the mild-severity group: abstinence rate risk ratio (RR) 3.16, P = 0.004; PDA +26.9%, P < 0.001. For PDA, longer treatment duration was associated with larger SMO effect size: +11.3% per extra month, P < 0.001. In the high-severity group, SMO showed benefit: abstinence rate RR 2.91, P = 0.03; PDA +16.9%, P < 0.001. In the mild-severity group, SMO showed benefit only in PDA for longer treatment duration: +23.9%, P < 0.001.
Conclusions
In the retained studies with alcohol-dependent patients, high-severity population and longer treatment duration were associated with larger SMO effect sizes.
Short Summary: We tested the moderating effect of population severity and treatment duration on SMO efficacy in the treatment of alcohol dependence using network meta-regression analysis. SMO efficacy was seen in high-severity populations and, in mild-severity populations, with long-term treatments.
The survey aimed to estimate, in the presence of alcohol use disorder, the frequency of systematic prescription of thiamine, the factors associated with it, and those related to the administration ...(oral, intravenous, intramuscular) when Wernicke's encephalopathy is suspected.
A self-questionnaire available on Internet was sent by e-mail to doctors and nurses taking care patients with alcohol use disorder.
In all, 565 professionals responded. The systematic prescription frequency of thiamine was 84.8 %, addiction care centers and medical-psychological centers prescribed it 5 times less than in psychiatric hospitals (OR=0.2 IC 0.1-0.5 P<0.0001), and medicine/surgery/obstetrics (MSO) services 10 times more than psychiatric hospitals (OR=10.7 IC 2.5-45.3 P<0.0001). The prescription decreased with the exercise period, the interns prescribing it 10 times more systematically (OR=10.9 IC 3.6-32.9 P<0.0001). In the presence of symptoms related to Wernicke's encephalopathy, thiamine administration was mainly oral (67.1 %). Intravenous administration was used more by the MSO services (OR=18.3 IC 10.2-32.7 P<0.0001), while the intramuscular injection was used more in psychiatric hospitals (OR=4.6 IC 1.7-11.9 P=0.0353).
The prescription of thiamine is rather systematic. In contrast, intravenous administration is underused, in the presence of symptoms related to Wernicke's encephalopathy, in favor of oral administration, and the more specific use of the intramuscular injection in psychiatry.
...alcohol misuse during adolescence is associated with an enhanced risk of unprotected/regretted sexual activity, criminal and disorderly behavior, suicide and deliberate self-harm, injury, drunk ...driving, alcohol poisoning, and accidental death 8. ...the early onset of alcohol misuse is associated with a risk of poor-prognosis AUD later in adulthood and with more psychiatric comorbidities and other addictive disorders 9. The occurrence of misuse in adolescence is frequently associated with social and family issues 12 and other substance misuse and with psychiatric comorbid disorders in the adolescent. ...it should be emphasized that the occurrence of alcohol misuse in children and adolescents is more frequently associated with psychiatric disorders or psychological distress than in adults. ...it is up to addiction specialists, and adult and child psychiatrists to constantly raise awareness of this very frequent association among professionals who work with this population.
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