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The purpose of this exploratory study was to examine the interaction of 5-HTTLPR and DRD4 exon III polymorphisms with gender in non-treatment seeking alcohol-dependent (AD) individuals while alternately taking ondansetron and sertraline. Evidence suggests that alcohol dependence may be influenced by a genetic interaction that may be gender-specific with temporal changes making pharmacological treatment with serotonergic drugs complex. The main trial was a within-subject double-blind placebo-controlled human laboratory study with 77 non-treatment-seeking AD individuals randomized (55 completed, 49 complete data) to receive 200 mg/day of sertraline or 0.5 mg/day of ondansetron for 3 weeks followed by an alcohol self-administration experiment (ASAE), then placebo for 3 weeks followed by a second ASAE, then receive the alternate drug, in a counterbalanced order, for 3 weeks followed by a third ASAE. Results for men were not significant. Women with the LL 5-HTTLPR genotype receiving ondansetron and SS/SL 5-HTTLPR genotype receiving sertraline (matched), drank significantly fewer drinks per drinking day (DDD) during the 7 days prior to the first and third ASAEs than women receiving the mismatched medication (i.e., sertraline to LL and ondansetron to SS/SL). In a 3-way interaction, 5-HTTLPR alleles by DRD4 alleles by medications, women with the LL genotype who received ondansetron and had DRD4≥7 exon III repeats drank significantly fewer DDD as did SS/SL women who received sertraline but conversely had DRD4<7 repeats in the 7-day period leading up to the first and third ASAEs. Consistent with these data was a significant reduction of milliliters consumed ad libitum during these same ASAEs. These exploratory findings add possible support to gender and genetic differences among AD individuals in response to serotonergic pharmacotherapies. Future trials should be powerful enough to take into account that endophenotypes and a targeting of serotonergic interactions may be essential to successfully treat alcohol dependence., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Hepatitis C virus (HCV) and alcoholic liver disease (ALD), either alone or in combination, count for more than two thirds of all liver diseases in the Western world. There is no safe level of drinking in HCV-infected patients and the most effective goal for these patients is total abstinence. Baclofen, a GABA(B) receptor agonist, represents a promising pharmacotherapy for alcohol dependence (AD). Previously, we performed a randomized clinical trial (RCT), which demonstrated the safety and efficacy of baclofen in patients affected by AD and cirrhosis. The goal of this post-hoc analysis was to explore baclofen's effect in a subgroup of alcohol-dependent HCV-infected cirrhotic patients. Any patient with HCV infection was selected for this analysis. Among the 84 subjects randomized in the main trial, 24 alcohol-dependent cirrhotic patients had a HCV infection; 12 received baclofen 10mg t.i.d. and 12 received placebo for 12-weeks. With respect to the placebo group (3/12, 25.0%), a significantly higher number of patients who achieved and maintained total alcohol abstinence was found in the baclofen group (10/12, 83.3%; p=0.0123). Furthermore, in the baclofen group, compared to placebo, there was a significantly higher increase in albumin values from baseline (p=0.0132) and a trend toward a significant reduction in INR levels from baseline (p=0.0716). In conclusion, baclofen was safe and significantly more effective than placebo in promoting alcohol abstinence, and improving some Liver Function Tests (LFTs) (i.e. albumin, INR) in alcohol-dependent HCV-infected cirrhotic patients. Baclofen may represent a clinically relevant alcohol pharmacotherapy for these patients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Both animal and human studies suggest that volume-regulating hormones could play a role in alcohol dependence as well as in alcohol craving. The role of the volume-regulating hormones, renin, aldosterone, and the N-terminal pro B-type natriuretic peptide (NT-proBNP) in alcohol craving was therefore evaluated in the present study. Twenty-five actively drinking alcohol-dependent patients satisfied the inclusion criteria and were enrolled into the study. The volume-regulating hormones, renin, aldosterone, and the NT-proBNP, and craving measurements--Obsessive-Compulsive Drinking Scale (OCDS) and Penn Alcohol Craving Scale (PACS)--were performed at baseline and after 12 weeks. Sixteen patients remained totally abstinent for the entire 12 weeks and were available for the second assessments. At baseline, no correlations between hormones and craving scores were found with either the 25 patients initially enrolled or the 16 abstinent patients. At 12 weeks, a significant increase of renin and a significant decrease of aldosterone were observed. Aldosterone showed a significant direct correlation with the obsessive OCDS subscore (r=0.59, P=.016) and a trend toward a significant direct correlation with the PACS score (r=0.48, P=.057). Renin demonstrated a significant direct correlation with the obsessive OCDS subscore (r=0.51, P=.041) and with the PACS score (r=0.56, P=.025). The NT-proBNP never correlated with craving measurements. In conclusion, the renin-aldosterone axis could play a role in craving in medium-term abstinent patients and thereby leading to the hypothesis that alcohol craving could be influenced by the fluid volume intake.

The Drinker Inventory of Consequences (DrInC) was developed for Project MATCH to assess the consequences of drinking in five domains. The present study, using baseline data from the 1382 participants involved in the COMBINE Study, analyzed the psychometrics of the 50-item DrInC and its shorter form, the 15-item SIP. Findings indicate the DrInC is reliable, valid, and clinically useful and that DrInC subscales are internally consistent and non-redundant. In an examination of the shorter version of the DrInC, findings suggest that the SIP is suitable when assessing the overall level of drinking-related consequences.