An Open Multicentric Study Evaluating 4-Hydroxybutyric Acid Sodium Salt in the Medium-Term Treatment of 179 Alcohol Dependent Subjects

Abstract

We report the results of an "open' multicentre study evaluating the use, tolerability and therapeutic efficacy of the sodium salt of 4-hydroxybutyric acid (GHB) for the medium-term treatment of withdrawal symptoms in 179 patients with alcohol dependence followed up as outpatients. The follow-up of patients was 6 and 12 months after drug discontinuation. Following a daily oral administration of 50 mg/kg for approximately 6 months, no serious systemic or single-organ consequences leading to drug discontinuation were reported, and tolerability was fair in all patients. Eleven subjects (10.1%) showed craving for the drug and voluntarily increased their doses (6-7 times the recommended levels). GHB led to complete abstinence during drug administration in 78.0% of the patients. A significant reduction of compulsive desire ("craving') was observed in parallel, as deduced from evaluation of a specific questionnaire, the Alcohol Craving Scale. At follow-up examination, 43 of the treated subjects remained abstinent at 6 months, and 30 subjects were abstinent for 1 year after drug discontinuation.

Relative Abuse Liability of GHB in Humans: A Comparison of Psychomotor, Subjective, and Cognitive Effects of Supratherapeutic Doses of Triazolam, Pentobarbital, and GHB

“…In one study in opioid-dependent patients, 30 mg/kg (2.1 g/70 kg) GHB was found to significantly increase subjective ratings of 'good mood,' 'spaced,' 'sluggish,' and 'carefree' without significantly affecting psychomotor performance or ratings of 'liking' (Rosen et al, 1997). In an unblinded outpatient study that evaluated the ability of a larger dose of GHB (50 mg/kg or 3.5 g/70 kg tid) given three times daily for 24 weeks to promote abstinence from alcohol in alcoholdependent patients, approximately 10% of the patients increased the dose of GHB by 6-7 times the therapeutic dose to 300-350 mg/kg tid (21-24.5 g/70 kg tid), suggesting that GHB was reinforcing in this subset of alcoholic patients (Addolorato et al, 1996).…”

Dopamine and Alcohol Relapse: D₁ and D₂ Antagonists Increase Relapse Rates in Animal Studies and in Clinical Trials

“…A large multicenter trial with a parenteral application of bromocriptine showed that this substance did not reduce relapse rates [41]. GHB was effective in reducing relapses [2,3,13,19]. In a randomized, double-blind, double-dummy study, performed in our center, 50 mg/kg GHB reduced craving during withdrawal effectively.…”

Pharmacological treatment options for alcohol use disorder

“…It is thought that sodium oxybate reacts like alcohol, reducing symptoms of craving and withdrawal (74). However, 30-40% of patients do not respond to GHB treatment (75).…”