Prazosin and cyproheptadine in combination in the treatment of alcohol use disorder: A randomized, double-blind, placebo-controlled trial.

Background And Aims: Pre-clinical studies suggest that the simultaneous blockade of the α1b and 5HT2A receptors may be effective in reducing alcohol consumption. This study aimed to assess the efficacy and safety of prazosin (α1b blocker) and cyproheptadine (5HT2A blocker) combination in decreasing total alcohol consumption (TAC) in alcohol use disorder (AUD).

Design, Setting And Participants: This was a double-blind, parallel group, placebo-controlled, Phase 2, randomized clinical trial conducted in 32 addiction treatment centres in France.

Sodium Oxybate for Alcohol Dependence: A Network Meta-Regression Analysis Considering Population Severity at Baseline and Treatment Duration.

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).

Occurrence and severity of cocaine-induced hallucinations: Two distinct phenotypes with shared clinical factors but specific genetic risk factors.

Unlabelled: Cocaine-induced transient hallucinations (CIH) are a frequent complication following cocaine intake that is associated with addiction severity.

Methods: Two hundred and forty-two non-psychotic and Caucasian lifetime cocaine users were included in a French multicentric study. Clinical variables and dopamine pathway genotype data were extracted and tested with CIH scores using a zero-inflated binomial model, which allows for the exploration of factors associated with occurrence and severity separately.

Peripheral Lymphocyte Multidrug Resistance Activity as a Predictive Tool of Biological Therapeutic Response in Rheumatoid Arthritis.

Objective: Multidrug resistance (MDR) transporters may be used as biomarkers to monitor disease progression in RA and as a predictive tool to establish responsiveness to biological therapy. In this multicenter clinical trial, we aimed to assess the predictive value of activity measurement of transporters MDR1, MD resistance protein (MRP)1, and breast cancer resistance protein (BCRP) for biological therapeutic response in RA before the initiation of biological therapy as well as 4 to 6 and 12 weeks after.

Methods: Peripheral blood samples were collected from 27 responders and 12 nonresponders to biological disease-modifying antirheumatic drugs (bDMARD) at the indicated timepoints as well as from 35 healthy controls.

Can alcohol dependent patients adhere to an 'as-needed' medication regimen?

A pooled analysis of 'as-needed medication use' data from 1,276 patients in two randomised, double-blind, placebo-controlled, parallel-group trials of nalmefene in the treatment of alcohol dependence was performed to explore whether an 'as-needed' regimen is an acceptable and feasible strategy in patients seeking help for alcohol dependence. Adherence was defined as alcohol consumption and medication intake, or no alcohol consumption (with or without medication intake). Nalmefene was taken on approximately half of the study days; placebo was taken more often than nalmefene (52.

[Changing alcohol abuse patterns].

While it has been steadily declining since the 1960s, though at a slower pace over the last 5 years, the average alcohol consumption per capita and per year in France remains one of the highest in Europe. The available general population surveys reveal that the most visible change is the type of alcohol abuse. Two emerging trends have been observed over the last ten years, and seem to be worsening: the transfer from daily drinking to weekend drinking, and the increase in isolated risk-taking related to acute alcoholization associated with more-or-less conscious inebriation episodes.

The role of brief motivational intervention on self-efficacy and abstinence in a cohort of patients with alcohol dependence.

Objectives: Brief interventions are effective in reducing heavy drinking in the general population but few studies examined whether it is also effective in alcohol dependent patients, and whether brief intervention increases self-efficacy.

Method: One hundred and seven patients with alcohol-dependence were randomized in a controlled trial examining the efficacy of a brief motivational intervention on both self-efficacy level and days of abstinence.

Results: We found that brief motivational interventions had no effect on days of abstinence, nor on self-efficacy, but that high self-efficacy was consistently correlated with a longer period of abstinence, at all assessment-points.

A haplotype of the DRD1 gene is associated with alcohol dependence.

Background: The D1 dopamine receptor has been involved in a number of brain functions, including motor control, inattentive symptoms and reward and reinforcement mechanisms. Indeed, DRD1 antagonists may reduce cocaine-seeking behavior and the acquisition of cocaine-cue associations. The D1.

The 3' part of the dopamine transporter gene DAT1/SLC6A3 is associated with withdrawal seizures in patients with alcohol dependence.

Background: Some studies have reported that the A9 allele of the variable nucleotide tandem repeat (VNTR) of the gene which encodes the dopamine transporter (DAT1/SLC6A3) is associated with alcoholism withdrawal symptoms such as alcohol withdrawal seizures (WSs), whereas others did not. We investigated whether polymorphisms within the DAT1 gene are associated with WS taking into account some of the confounding factors such as the severity of alcohol dependence.

Methods: To further assess the role of this gene in WS, we genotyped the VNTR and 7 single nucleotide polymorphisms (SNPs) encompassing the DAT1 gene in a sample of 250 alcohol-dependent subjects (175 men and 75 women), of whom 24% exhibited WSs, taking into account the severity of alcohol dependence.

[Maintaining abstinence after alcohol detoxification].

"To quit drinking" is not the panacea of alcohol dependence treatment; it is only its first step. Abstinence should be considered more as a mean than a purpose of the after-withdrawal cares. The frequent resistance of the alcoholic patient to undertake in a long term abstinence can be by-passed by suggesting to fix himself renewable terms for periods during which he feels rather confident to raise the bet of a "most accomplished possible" abstinence.

Association between dopamine receptor D3 gene BalI polymorphism and cognitive impulsiveness in alcohol-dependent men.

The gene coding for the dopamine receptor D3 (DRD3) is considered as a major candidate gene in various addictive disorders. Association studies in alcohol-dependence for this gene are nevertheless controversial. We made the hypothesis that phenotypical heterogeneity of alcohol-dependence (i.

[Risk factors of early drop-out during induction of high-dose buprenorphine substitution therapy. A study of 1085 opiate addicts].

Background: The revelation of an acceptable rate of users still treated one year after initiation of a substitution program with high-dose buprenorphine (HDB) has contributed in the validation of the interest of the molecule in this indication. However the frequency of early drop-outs (after the first consultation), when treatment is set-up, is frequently evoked, although undocumented, by general practitioners.

Objective: During analysis of a survey on the follow-up of opiate addicts starting substitution therapy with HDB, we attempted to assess the frequency of early drop-outs and identify the contributing factors.

[Care network in addictive pathologies: where is it?].

Network practise is important in the care of addictive pathologies. It aims to fulfill patient needs on a social and health level, as part of a concertive approach from the different health workers. Co-ordinated practise seems to provide an adapted and proven response for more than twenty years now, but has only recently been recognised as such by the health authorities.

Five-year survival predictive factors in patients with excessive alcohol intake and cirrhosis. Effect of alcoholic hepatitis, smoking and abstinence.

Aim: To evaluate 5-year survival predictive factors in hospitalised patients with excessive alcohol intake and cirrhosis, including in a multivariate analysis the severity of the liver disease, gastrointestinal bleeding, concomitant viral B or C infection, smoking status, presence of alcoholic hepatitis at inclusion and abstinence from alcohol during follow-up.

Methods: In a non-concurrent cohort study, 122 patients with excessive alcohol intake and cirrhosis were followed up at least five years or till death. Two patients were lost to follow-up.

The A9 allele of the dopamine transporter gene is associated with delirium tremens and alcohol-withdrawal seizure.

Background: The dopamine transporter (DAT) plays a key role in homeostatic regulation of dopaminergic neurotransmission and could thus be involved in the variability of two severe alcohol-withdrawal symptoms, alcohol-withdrawal seizure (AWS) and delirium tremens (DT). Interestingly, an association was found between the DAT gene (9-copy repeat) and the risk for these symptoms in two previous case-control studies.

Methods: We reanalyzed the role of the DAT gene in the lifetime risk for AWS and DT in 120 alcohol-dependent patients, taking into account potentially confounding factors.

Economic and social effects of high-dose buprenorphine substitution therapy. Six-month results.

The purpose of this study was to analyze the impact of high-dose buprenorphine substitution therapy in opiate-dependent patients in terms of use of psychoactive substances, associated risks, social integration, and the social cost generated by the use of these substances. This was a longitudinal quantitative survey carried out in 1083 patients who were evaluated at three times: at the beginning of substitution therapy (D0), at 6 months and then at 12 months follow up (M6, M12). Data were collected with an anonymous self-administered questionnaire, completed in the presence of an investigating physician.

Reappraisal of the serotonin 5-HT(1B) receptor gene in alcoholism: of mice and men.

Because pharmacological and genetic data supported the idea that serotonin receptors of the 5-HT(1B) type can play a modulatory role in alcohol consumption in both human and rodents, the 5-HT(1B) receptor gene is considered as a candidate gene for alcohol dependence. However, contradictory results have been reported as a positive association between alcohol dependence, and either the 861C or the 861G allele of the G861C polymorphism of the 5-HT(1B) receptor gene can be found in the literature. Further investigations in a population of 136 male alcoholics compared with 72 male control subjects demonstrated that none of these alleles was actually associated with alcohol dependence.

The genetics of addiction: alcohol-dependence and D3 dopamine receptor gene.

Alcohol-dependence is a complex phenotype, with behavioral, psychological, pharmacological, medical and social dimensions. Aggregation studies, adoption and twin researches have demonstrated that the vulnerability to alcohol-dependence is at least in part linked to genetic factors, the genetic vulnerability to alcoholism being mainly not substance-specific. There are numerous candidate genes, but the D3 dopamine receptor is specifically located in the limbic area, and in particular in the nucleus accumbens, which are involved in reward and reinforcement behavior.

[Late-onset alcohol withdrawal syndrome].

The alcoholic withdrawal syndrome (AWS) arises variably within hours following the hospitalization of an alcohol dependent patient. Delay usually observed between admission and the first symptoms depends above all on alcohol serum level concentration at arrival and on the degree of severity of physical dependence. The case reported here describes the very late onset severe alcoholic withdrawal syndrome observed in a 57-year-old alcohol dependent patient hospitalized for leg trauma and operated within hours followed admission.