Long-term γ-hydroxybutyric acid (GHB) and disulfiram combination therapy in GHB treatment-resistant chronic alcoholics

Int J Environ Res Public Health. 2011 Jul;8(7):2816-27. doi: 10.3390/ijerph8072816. Epub 2011 Jul 6.


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.

Keywords: GHB-disulfiram combination; alcohol dependence; long-term treatment.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Alcohol Deterrents / therapeutic use*
  • Alcoholics
  • Alcoholism / drug therapy*
  • Disulfiram / therapeutic use*
  • Drug Therapy, Combination / methods*
  • Ethanol / adverse effects
  • Female
  • Humans
  • Hydroxybutyrates / therapeutic use*
  • Italy
  • Male
  • Retrospective Studies
  • Substance Withdrawal Syndrome / drug therapy*
  • Treatment Outcome


  • Alcohol Deterrents
  • Hydroxybutyrates
  • 4-hydroxybutyric acid
  • Ethanol
  • Disulfiram