Giorgio Zoli

Alcohol use disorders in the elderly: A brief overview from epidemiology to treatment options

Alcohol-use-disorders (AUDs) afflict 1-3% of elderly subjects. The CAGE, SMAST-G, and AUDIT are the most common and validated questionnaires used to identify AUDs in the elderly, and some laboratory markers of alcohol abuse (AST, GGT, MCV, and CDT) may also be helpful. In particular, the sensitivity of MCV or GGT in detecting alcohol misuse is higher in older than in younger populations. The incidence of medical and neurological complications during alcohol withdrawal syndrome in elderly alcoholics is higher than in younger alcoholics. Chronic alcohol abuse is associated with tissue damage to several organs. Namely, an increased level of blood pressure is more frequent in the elderly than in younger adults, and a greater vulnerability to the onset of alcoholic liver disease, and an increasing risk of breast cancer in menopausal women have been described. In addition, the prevalence of dementia in elderly alcoholics is almost 5 times higher than in non-alcoholic elderly individuals, approximately 25% of elderly patients with dementia also present AUDs, and almost 20% of individuals aged 65 and over with a diagnosis of depression have a co-occurring AUD. Moreover, prevention of drinking relapse in older alcoholics is, in some cases, better than in younger patients; indeed, more than 20% of treated elderly alcohol-dependent patients remain abstinent after 4 years. Considering that the incidence of AUDs in the elderly is fairly high, and AUDs in the elderly are still underestimated, more studies in the fields of epidemiology, prevention and pharmacological and psychotherapeutic treatment of AUDs in the elderly are warranted.

Gamma hydroxybutyric acid (GHB) for the treatment of alcohol dependence: a review.

Gamma-hydroxybutyric acid (GHB) is a short-chain fatty acid structurally similar to the inhibitory neurotransmitter γ-aminobutyric acid. Clinical trials have demonstrated that 50–100 mg/kg of GHB fractioned into three or six daily doses is able to suppress alcohol withdrawal symptoms and facilitates the maintenance of abstinence from alcohol. These studies have also shown that GHB craving episodes are a very limited phenomenon (about 10–15%). Thus, physicians with access should consider the clinical efficacy of GHB as a valid pharmacological tool for the treatment of alcohol addiction.

A randomized controlled study comparing elemental diet and steroid treatment in Crohn's disease

Background: Elemental diet is considered an effective primary treatment for active Crohns disease, but it is usually given by a feeding tube.

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.

Impaired tuftsin activity in cirrhosis: relationship with splenic function and clinical outcome

Background: Cirrhotic patients show increased susceptibility to bacterial infections. It is not known whether tuftsin deficiency, which is associated with an increased incidence of infections in many disease states, is present in cirrhosis. Our aims were to determine whether tuftsin activity is deficient in cirrhosis and if so, whether this deficiency is related to splenic function, contributes to altered neutrophil granulocyte function, or influences the occurrence of bacterial infections and patient survival. Methods: Tuftsin activity and splenic function were assessed in 31 patients with liver cirrhosis and 31 healthy subjects. The phagocytic activity of neutrophil granulocytes from 23 patients was tested in vitro with addition of both autologous and pooled sera from healthy subjects. In 10 patients and eight controls it was also tested with addition of synthetic tuftsin. Patients were followed up until death or liver transplantation. Results: Patients had reduced tuftsin activity (median 8% (range 3–24.5)) compared with controls (17% (11.5–37)) (p<0.001) and a higher pitted red cell count (p<0.001). Tuftsin activity was correlated with pitted cell count (p=0.02) and the Child-Pugh score (p=0.002). Nineteen of 23 patients showed deficient phagocytic activity of neutrophil granulocytes, which was correlated with tuftsin activity (p<0.001), improved in all cases but one with addition of serum from healthy subjects, and normalised with addition of synthetic tuftsin. Reduced tuftsin activity did not influence patient survival but was associated with a higher incidence of bacterial infections (p=0.029). Comment: Tuftsin activity was reduced in cirrhosis, and contributed to impaired phagocytic activity of neutrophil granulocytes. Such an abnormality appears to be related to impaired splenic function and severity of cirrhosis, and probably favours the occurrence of bacterial infections.

Sodium oxybate in maintaining alcohol abstinence in alcoholic patients with and without psychiatric comorbidity.

Sodium oxybate (SMO) is a GABA-ergic drug currently used for the treatment of alcohol-dependence in some European countries. In particular, clinical studies have shown a role of SMO in promoting alcohol abstinence, as well as in relieving withdrawal symptoms. The aim of this study was to describe alcohol abstinence and the onset of craving for and abuse of SMO in alcohol-dependent subjects with and without psychiatric co-morbidity. Forty-eight patients were enrolled and classified into two groups: group A (20 alcoholics without any psychiatric co-morbidity) and group B (28 alcoholics with a psychiatric co-morbidity). All patients were treated with oral SMO (50 mg/kg of body weight t.i.d.) for 12 weeks. Alcohol abstinence as well as alcohol drinking during the 12 weeks of treatment did not differ between the two groups at the end of treatment (p=0.9). In addition, a reduction of alcohol intake in both groups has been observed (p<0.0001). On the other hand, craving for SMO was significantly more frequent in group B than group A (p=0.001). Cases of SMO abuse were observed in almost 10% of group B patients. In conclusion, alcohol abstinence achieved through SMO administration does not differ in patients with and without psychiatric co-morbidity. However, alcoholics with co-morbid borderline disorders appear to be at high risk of developing craving for and abuse of the drug; therefore, SMO may not be indicated in these patients.

A Brief Up-Date of the Use of Sodium Oxybate for the Treatment of Alcohol Use Disorder

The treatment of alcohol use disorder (AUD) with sodium oxybate (SMO) or gamma-hydroxybutyric acid (GHB) was introduced in Italy and Austria more than 20 years and 15 years ago, respectively, and it is now widely employed to treat alcohol withdrawal syndrome (AWS) and to maintain alcohol abstinence. These indications derive from its similar structure to the inhibitory neurotransmitter γ-amino-butyric acid (GABA), exerting an ethanol-mimicking effect, because it binds to GABAB receptors. Craving for, and abuse of, SMO remain a controversial issue; even though these unfavorable effects are evident in poly-drug addicted patients and in those with psychiatric diagnosis of borderline personality disorder. In addition, despite cases of severe intoxication and deaths being widely documented when GHB is used as “street drug”; its clinical use remains safe. Thus, the aim of the present review is to examine the role of SMO in the treatment of AUD, its possible implications in reducing alcohol consumption, and cases of abuse, and severe intoxication due to SMO during its clinical use in the treatment of AUD.

Sodium oxybate in maintaining alcohol abstinence in alcoholic patients according to Lesch typologies: a pilot study.

Sodium oxybate (SO) is a γ-amino-butyric acid (GABA)-ergic drug currently used for the treatment of alcohol dependence (AD) in some European countries. The aim of this study was to describe the effect of SO administration in alcoholics classified according to Lesch alcoholism typology (LAT). Forty-eight patients were enrolled and classified into four groups according to LAT. All patients were treated with oral SO (50 mg/kg of body weight t.i.d.) for 12 weeks. All patients significantly reduced their alcohol intake (p<0.001). Alcohol abstinence during the 12 weeks of treatment did not differ between the four groups at the end of treatment. Craving for SO did not significantly differ amongst groups; cases of SO abuse were very limited and were observed in almost 10% of patients. In conclusion, our study showed an overall efficacy of SO in the treatment of AD irrespective of LAT categories. However, our results confirm that alcoholics with psychiatric co-morbidity, particularly with a borderline personality disorder of Axis II, are at a greater risk of developing craving for and abuse of the drug: until craving for alcohol and craving for SO are characterized in depth, SO should be used with caution in these patients.

Sodium oxybate plus nalmefene for the treatment of alcohol use disorder: A case series.

The treatment of alcohol use disorder still remains a challenge. The efficacy of the combined pharmacological treatment for alcohol use disorder has been widely investigated with controversial results. The aim of our case series was to investigate the effect of nalmefene in patients not responding to sodium oxybate therapy. We describe seven cases of consecutive patients affected by alcohol use disorder, and treated with sodium oxybate (50 mg/kg per day) who did not achieve complete alcohol abstinence after at least one month of pharmacological treatment. Then, in partial- and non-responder patients to sodium oxybate treatment, administration of nalmefene, 18 mg as needed, was commenced. Our data show that, during the first month of the combined treatment of sodium oxybate plus nalmefene, patients were able to achieve alcohol abstinence (two patients), to suppress (five cases) or reduce (two patients) episodes of heavy drinking days, and to suppress the onset of craving for sodium oxybate (one patient). Likely, nalmefene may act in modulating the excessive reward effect of sodium oxybate, which may be responsible for the persistence of alcohol intake and for the onset of craving for sodium oxybate. However, controlled clinical trials to confirm the safety and efficacy of sodium oxybate plus nalmefene in treating alcohol use disorder are warranted.

Alcohol use disorder and GABAB receptor gene polymorphisms in an Italian sample: haplotype frequencies, linkage disequilibrium and association studies

Abstract Background: Alcohol use disorder (AUD) is a complex trait with genetic and environmental influences. Several gene variants have been associated with the risk for AUD, including genes encoding the sub-units of the γ-aminobutyric acid (GABA) receptors. Aim: This study evaluated whether specific single nucleotide polymorphisms (SNPs) in genes encoding GABAB receptor sub-units can be considered as candidates for the risk of AUD. Subjects and methods: Seventy-four AUD subjects and 128 Italian controls were genotyped for 10 SNPs in genes encoding GABA-B1 and GABA-B2 sub-units (GABBR1 and GABBR2). Allele, genotype, and haplotype frequencies were tested for the association with the AUD trait. Results: A significant difference between AUD individuals and controls was observed at genotype level for rs2900512 of GABBR2 gene. The homozygous T/T genotype was not found in the controls, whereas it was over-represented in the AUD individuals. Under the recessive model (T/T vs C/T + C/C) this result was statistically significant, as well as the Odds Ratio for the association with the AUD trait. Conclusions: The results provide preliminary data on the association between GABAB receptor gene variation and risk of AUD. To confirm this finding, studies with larger samples and additional characterisation of the phenotypic AUD trait are required.