Long-Term γ-Hydroxybutyric Acid (GHB) and Disulfiram Combination Therapy in GHB Treatment-Resistant Chronic Alcoholics

Abstract

Leading Italian studies support the use of γ-hydroxybutyric acid (GHB), not only in the treatment of the alcohol withdrawal syndrome, but also in maintaining alcohol abstinence. GHB gives a better result than naltrexone and disulfiram in maintaining abstinence, and it has a better effect on craving than placebo or disulfiram. The problem is that about 30–40% of alcoholics are non-responders to GHB therapy. In our clinical practice, we speculate that by combining disulfiram with GHB treatment we may be able to achieve a kind of ‘antagonist’ effect by using the ‘psychological threat’ of disulfiram (adversative effect) while taking advantage of the anticraving effect of GHB, despite the limitation of its ‘non-blockade’ effect on alcohol. In this context, to improve the outcome in GHB long-term treated alcoholics, we added disulfiram to GHB in the management of GHB treatment-resistant alcoholics. In this study we compared retention in treatment of 52 patients who were treated with the GHB-disulfiram combination for up to six months, with retention for the same subjects considering their most recent unsuccessful outpatient long-term treatment with GHB only. An additional comparison was carried out on the days of complete abstention from alcohol. Thirty four patients (65.4%) successfully completed the protocol and were considered to be responders; 18 (34.6%) left the programme, and were considered to be non-responders. Considering the days of complete abstinence from alcohol, 36 patients stayed in treatment longer with the GHB-Disulfiram combination, 12 stayed for a shorter time and four for the same time. The results of this study seem to indicate a higher efficacy of the GHB-disulfiram association compared with GHB alone. Randomized controlled trials are now needed to verify this hypothesis.

The neurobiology of alcohol consumption and alcoholism: An integrative history

“…In this regard, it is particularly interesting that γ-hydroxybutyric acid (GHB), which has been characterized as an agonist at GABA-B receptors (Andresen et al , 2011, Carai et al , 2008, Schep et al , 2012, Vienne et al , 2010), reduces alcohol consumption in animal models (Colombo et al , 2012), and is used to treat alcohol dependence and craving in Europe (Addolorato et al , 2011, Maremmani et al , 2011). Recently, GHB has been found to be a partial agonist at GABA-A receptors that contain α, β and δ (but not α, β and γ) subunits (Absalom et al , 2012).…”

Pharmacotherapy of alcoholic liver disease in clinical practice

“…In addition, a recent Cochrane meta‐analysis of 13 RCTs, confirming the favourable results of comparison with placebo, concluded that SO is more effective than NTX and DF in maintaining alcohol abstinence and reducing alcohol craving . Moreover, two studies have demonstrated that treatment with SO in combination with NTX or DF was significantly superior in maintaining complete abstinence from alcohol than monotherapy . SO, at the dosage of 50–100 mg/kg/day, is generally well tolerated, and the most common side effects are drowsiness, dizziness and asthenia, which do not require drug discontinuation, but disappear spontaneously.…”

Pharmacological treatment options for alcohol use disorder

“…However, 30-40% of patients do not respond to GHB treatment (75). For this reason, in one study GHB and disulfiram were used in combination, finding that the combination therapy increased the number of days staying in treatment and the number of days of abstinence compared to GHB therapy on its own (76). However, especially in patients with psychiatric comorbidities and other substance use disorders, sodium oxybate craving and sodium oxybate abuse were observed (77).…”