SAT2SODIUM OXYBATE, A BREAKTHROUGH TREATMENT OF ALCOHOL WITHDRAWAL SYNDROME AND MAINTENANCE OF ALCOHOL ABSTINENCE (D&A)SAT2.1Sodium Oxybate in Alcohol Withdrawal – Results from the GATE 1 StudySAT2.2SODIUM OXYBATE IN THE PREVENTION OF ALCOHOL RELAPSES IN ALCOHOL DEPENDENT PATIENTS (GATE 2 STUDY)SAT2.3PHARMACODYNAMIC INTERACTIONS OF A SOLID FORMULATION OF SODIUM OXYBATE AND ALCOHOL IN HEALTHY VOLUNTEERSSAT2.4A RETROSPECTIVE STUDY ON THE USE OF SODIUM OXYBATE IN NORTHERN ITALY

# SAT2.1 Sodium Oxybate in Alcohol Withdrawal – Results from the GATE 1 Study {#article-title-2} Background. Alcohol withdrawal can be a difficult challenge as most substances available are of limited efficacy according to withdrawal and relapse prevention in early stages. We aimed to investigate safety and efficacy of sodium 4-hydroxybutyrate (sodium oxybate or GHB) in the withdrawal treatment of alcohol dependent patients. Method. 126 patients with a diagnosis of alcohol dependence according to DSM-IV criteria with severe withdrawal (CIWA-Ar Scale: 18.71 vs. 18.00) were randomly recruited from 9 European sites and allocated to treatment with sodium oxybate (n = 61) or oxazepam (n = 65) in a double blind, double dummy design. Daily dosage in the first 5 days was 5.25 g (i.e.30 ml) for sodium oxybate and 210 mg for oxazepam, adjusted for body weight. The medication dropped down until day 10. Primary outcome variable was severity of withdrawal as determined with CIWA-Ar-scale. Findings. Patients were comparable in demographic details and there was no difference in the distribution of Lesch's types or the severity of withdrawal symptoms between groups (also in biological markers and craving for alcohol). In both groups withdrawal and craving for alcohol decreased significantly, with no difference between the treatment groups. In both groups nearly all patients stayed sober the whole treatment and follow up period (90.2% vs. 84.6 %). The biological markers normalized in both groups significantly without any group differences. Neither cognitive impairment nor adverse events were found more often in one of the groups. Interpretation. sodium oxybate and oxazepam are both effective and safe in treating alcohol withdrawal and in reducing craving for alcohol. Any kind of craving after discontinuation of sodium oxybate or of oxazepam was not an issue. Motivation process could be started early in both groups. # SAT2.2 SODIUM OXYBATE IN THE PREVENTION OF ALCOHOL RELAPSES IN ALCOHOL DEPENDENT PATIENTS (GATE 2 STUDY) {#article-title-3} Background. Maintenance of abstinence from alcohol represents the most important, but also the most challenging objective in the treatment of alcohol dependent patients. We aimed to investigate the long-term safety and efficacy of sodium oxybate in the long-term treatment of recently detoxified alcohol-dependent patients. Method. 314 patients with a diagnosis of alcohol dependence according to DSM-IV criteria were randomly enrolled from 11 European sites and allocated to two treatment groups: sodium oxybate (n = 154) and placebo (n = 160). Study duration was of 12 months (6 months of double-blind treatment period and 6 months of untreated follow-up). The primary outcome was the Cumulative Abstinence Duration (CAD). Findings. Sodium oxybate was superior to placebo in achieving and maintaining abstinence from alcohol (p = 0.05). Specifically, sodium oxybate was particularly effective in Lesch type II patients (p = 0.035), but also in Lesch type III and IV patients (not statistically significant because of a lower sample size). Moreover, the incidence of craving for and abuse of the drug, and of other safety endpoints did not differ between sodium oxybate and placebo groups. Interpretation. This long-term study confirms the safety and efficacy of sodium oxybate in promoting and maintaining abstinence from alcohol in recently detoxified alcoholics, particularly, but not only, in Lesch Type II alcohol-dependent patients. In addition, we found no evidence of abuse, misuse or dependence for the drug in this large patient population. Funding: Laboratorio Farmaceutico CT S.r.l. # SAT2.3 PHARMACODYNAMIC INTERACTIONS OF A SOLID FORMULATION OF SODIUM OXYBATE AND ALCOHOL IN HEALTHY VOLUNTEERS {#article-title-4} Background. Sodium oxybate shares some pharmacological effects with alcohol, and has been approved for the treatment of alcohol dependence in Europe. This study evaluated the pharmacodynamic interactions of SMO.IR, a solid formulation of sodium oxybate and alcohol, to assess possible synergism, potentiation or antagonism of SMO.IR and alcohol. Methods. 24 healthy volunteers participated in a double-blind crossover trial. Study participants randomly received: SMO.IR alone, alcohol alone, SMO.IR + alcohol, and double placebo. Study endpoints were objective and subjective cognitive tests, adverse events, vital signs assessed before, and 15 and 165 minutes after study drug administration. Cognitive tests included: Body Sway Test, Saccadic Eye Movement, Choice Reaction Time, Critical Tracking Test, Digit Vigilance, Numeric and, Spatial Working Memory, Bond & Lader VAS, ARCI 49, and Biphasic Alcohol Effects Scale. Results. Alcohol produced a significant impairment in cognitive performance and subjective sedation at 15 min. SMO.IR-induced less pronounced objective and subjective sedation 165 min post dose. There was a significant interaction between SMO.IR and alcohol, at 15 min, with an increase in alertness and stimulation and a decrease in sedation. An isolated mild decrease in digit vigilance accuracy was observed at 165 minutes post dose with the combination. The combination increased the number of treatment-emergent adverse events: 46 vs 30 with SMO.IR and 34 with alcohol. No significant changes in vital signs, oxygen saturation, and laboratory tests were observed. Conclusion. SMO.IR and alcohol have a distinct pharmacodynamic profile. Sedative effects of SMO.IR are much less marked than those of alcohol and no reciprocal potentiation was observed. # SAT2.4 A RETROSPECTIVE STUDY ON THE USE OF SODIUM OXYBATE IN NORTHERN ITALY {#article-title-5} Background. The Sodium Oxybate is successfully used in Italy from ore than fifteen years for the treatment of both alcohol withdrawal and relapse prevention. The principal aim of this retrospective study, named GUM (GHB use and misuse), was to evaluate the effectiveness and the safety of Sodium Oxybate in the daily clinical practice. Method. The study analysed 485 individuals (604 treatment cycles), with a diagnosis of alcohol dependence according to DSM-IV criteria, treated with Sodium Oxybate at seven alcoholism rehabilitation centers in northern Italy in the years 2005–2007. The primary outcomes of the study were: the drug anti-withdrawal effects; the drug effects on relapse prevention, the treatment drop out rate; while the secondary outcomes were: the drug side effects and adverse reactions, the appetive behavour (“misuse”), the drug abuse and the overdose, intoxication and withdrawal episodes. Finally, the study evaluated, for the first time, in a large cohort of Italian alcoholics, the prevalence of both infection diseases (e.g. hepatitis C, HIV, ect.) and prevalent psychiatric illness (including personalities disorders). Findings. The study confirmed the effectiveness of Sodium Oxybate in suppressing withdrawal syndrome (81% of the subjects treated were successfully rehabilitated) and in maintaining abstinence (76% and 78% of patients were abstinent at six and twelve months after starting treatment). The study showed that the drug is also safe and manageable, especially if used in doses between 50 and 100 mg/kg/die (the average dose was between 78.11 + 22.30 mg/kg/die). Misuse and abuse were limited (12% of treatments), cases of intoxication an overdose extremely rare. For the first time in Italy, the study helped to identify the main demographics and clinical features of a significant sample of alcoholics subjects treated with Sodium Oxybate and the prevalence of prevalent infections diseases (31 % were HBcAb + HBsAg positive, 15% were HCV positive and 4% were HIV positive) and psychiatric illnesses (12% in Axis I and 4% in Axis II). Interpretation. The GUM study confirms the effectiveness and the safety of Sodium Oxybate in the treatment of subjects undergoing rehabilitation in Italian alcohol treatment centers. Funding: Laboratorio Farmaceutico CT S.r.l.