F. Caputo

A case of gamma-hydroxybutyric acid withdrawal syndrome during alcohol addiction treatment: utility of diazepam administration.

Gamma-hydroxybutyric acid (GHB) is an emerging drug for alcoholism therapy. We present a case of GHB withdrawal syndrome secondary to GHB addiction during alcoholism treatment. A complete disappearance of drug withdrawal syndrome was achieved with oral diazepam and the symptoms resolved without sequelae. GHB has been used for alcoholism therapy for only a few years now, but the trend is increasing, and other cases similar to this one are foreseeable. This risk could be higher in some countries in which GHB use is increasing not for alcoholism therapy, but for its euphoric and anabolic effects. The present experience indicates that administration of benzodiazepines would seem to be sufficient to achieve total regression of the withdrawal syndrome in a short time, at least if recognized early.

Gamma-hydroxybutyric acid versus naltrexone in maintaining alcohol abstinence: an open randomized comparative study.

Maintaining abstinence from alcohol is the main goal in the treatment of alcohol dependence. Naltrexone (NTX) and gamma-hydroxybutyric acid (GHB) have proved able to maintain alcohol abstinence in alcoholic subjects. The aim of our study was to evaluate the efficacy of GHB compared with NTX in maintaining abstinence from alcohol after 3 months of treatment. A total of 35 alcohol-dependent outpatients were randomly enrolled in two groups: the GHB group consisted of 18 patients treated with oral doses of GHB (50 mg/kg of body weight t.i.d) for 3 months; the NTX group consisted of 17 patients treated with oral doses of NTX (50 mg/day) for 3 months. At the end of the study, a statistically significant difference (P=0.02) was found in the number of abstinent patients between the GHB and the NTX groups. In patients who failed to be abstinent, no relapses in heavy drinking were observed in the NTX group, while in the GHB group all patients relapsed. The results of the present study show that GHB is more effective than NTX in maintaining abstinence from alcohol in a short-term treatment period; on the other hand, NTX confirmed its ability to reduce alcohol relapses.

Baclofen promotes alcohol abstinence in alcohol dependent cirrhotic patients with hepatitis C virus (HCV) infection

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 baclofens 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.

Three months of abstinence from alcohol normalizes energy expenditure and substrate oxidation in alcoholics: a longitudinal study

Objective:The aim of this study was to evaluate the energy expenditure, substrate oxidation, and body composition in alcoholics during addiction and after several months of abstinence.Methods:A total of 32 alcoholics without liver cirrhosis and malabsorption were consecutively recruited. A total of 55 social drinkers, matched for gender and height, were studied as a control group. Anthropometry and bioimpedance analysis were performed to assess body composition, and indirect calorimetry was used to measure basal metabolic rate (BMR) and substrate oxidation. Total abstinence was then achieved in 15 subjects. At 1, 2, 3, and 6 months of abstinence, the metabolic variables and the energy intake were re-examined.Results:At enrollment (T0) alcoholics compared to controls showed a significant decrease in body mass index (22.2 ± 2.71 vs 23.6 ± 1.3 kg/m2; p < 0.05), fat mass (14.1 ± 4.5 vs 16.7 ± 3.3 kg; p < 0.01), an increased BMR normalized by fat-free mass (34.5 ± 3.7 vs 32.1 ± 2.01 kcal/kg/day; p < 0.01), a lower nonprotein respiratory quotient (npRQ: 0.76 ± 0.03 vs 0.83 ± 0.03; p < 0.001), with a consequently higher lipid oxidation (0.08 ± 0.02 vs 0.04 ± 0.02 g/min; p < 0.01), and a lower carbohydrate oxidation (0.05 ± 0.02 vs 0.10 ± 0.03 g/min; p < 0.01). Although at 1 and 2 months of abstinence the metabolic parameters had improved, only after 3 months of abstinence did alcoholics show values of body mass index (23.2 ± 2.6 kg/m2), fat mass (17.0 ± 5.34 kg), BMR/fat-free mass (33.1 ± 2.78 kcal/kg/day), npRQ (0.82 ± 0.02), lipid oxidation (0.05 ± 0.03 g/min) and carbohydrate oxidation (0.11 ± 0.04 g/min) comparable to those of controls; these values remained constant at 6 months.Conclusions:Three months of abstinence from alcohol could represent the minimum time necessary to obtain a normalization of the metabolic variables considered and of the nutritional status for these patients, probably related to a regression of the functional alterations of the microsomal ethanol oxidizing system and of mitochondria secondary to chronic ethanol abuse.

Incidence of craving for and abuse of gamma-hydroxybutyric acid (GHB) in different populations of treated alcoholics: an open comparative study

Gamma-hydroxybutyric acid (GHB) is a drug currently used for the treatment of alcohol dependence. The aim of our study was to investigate the incidence of craving for and abuse of GHB in 47 patients enrolled and divided into four groups: group A (pure alcoholics), group B (alcoholics with a sustained full remission from cocaine dependence), group C (alcoholics with a sustained full remission from heroin dependence) and group D (alcoholics in a methadone maintenance treatment [MMT] programme). All patients were treated with an oral dose of GHB (50 mg/kg of body weight t.i.d.) for three months. Craving for GHB was statistically significant higher in group B than in group A (P < 0.001), C (P = 0.01) and D (P < 0.001), and in group C than in group D (P < 0.05). Abuse of GHB proved to be statistically significant higher in group B than in group A (P < 0.001) and D (P < 0.01), and in group C than in group A (P = 0.01) and D (P < 0.05). Thus, the administration of GHB in alcoholics with a sustained full remission from heroin or cocaine dependence is not recommended; however, this should not discourage physicians from using GHB for the treatment of pure alcoholics or alcohol dependents following a MMT.