Disulfiram continues to be prescribed as part of alcohol treatment programs and is being more widely studied for other drugs of abuse. Disulfiram toxicity associated with acute overdose, chronic therapy, and from disulfiram—ethanol reactions continues to be reported worldwide. Most of the adverse effects are from case reports and case series which are difficult to interpret because of complications and comorbidities associated with alcohol use and alcoholism, the potential effects of polypharmacy, use of other drugs of abuse, and difficulty in relating specific adverse effects to disulfiram, alcohol or a disulfiram—ethanol reaction. Although serious and life-threatening effects associated with disulfiram are rare, clinicians and toxicologists must remain vigilant in diagnosing and appropriately managing patients with disulfiram associated toxicity.
For over 200 years disulfiram (tetraethylthiuram disulfide) and related chemicals have been used in the rubber industry as catalytic accelerators for the vulcanization (stabilization) of rubber by the addition of sulfur.117 In the early 1900s, workers exposed to disulfiram were observed to develop adverse reactions when exposed to ethanol. Williams, an American physician, suggested that disulfiram might be a useful adjunct in the treatment of alcoholism.127 In the 1940s, two Danish physicians, Hald and Jacobsen, became ill after consuming alcohol while using disulfiram as an antihelmintic.42 Subsequently, disulfiram was approved by the FDA for the the treatment for alcoholism in 1951. Although data supporting the benefit of using disulfiram in a comprehensive alcohol treatment program have been questioned, other pharmacologic therapies such as naltrexone and acamprosate have been approved for the treatment of alcohol dependence, and the potential benefits of disulfiram therapy continue to be evaluated in clinical trials disulfiram is still widely prescribed today.38,47,70,95,115 Although the use of disulfiram for treating alcoholism is decreasing, its use in the management of addictions to other drugs of abuse such as cocaine is increasing.92 Specific epidemiologic information about the three different forms of disulfiram toxicity is difficult to elucidate, even from an analysis of the American Association of Poison Control Centers (AAPCC) (Chap. 135).
Data from the AAPCC from 2003 to 2007 confirms that each year US poison centers are notified of between three and four hundred disulfiram exposures. Major adverse outcomes are rare. Since 1982 only 14 deaths associated with disulfiram have been reported to the AAPCC, most reported to involve a disulfiram-ethanol reaction.
Unlike many xenobiotics reported to the AAPCC, the majority of the disulfiram exposures were in adults. Serious adverse effects reported in the literature associated with both therapeutic use of disulfiram and with disulfiram overdose continue to be reported mostly in the form of case reports and case series. As such, these reports are difficult to interpret because of complications and comorbidities associated with alcohol use and alcoholism, the potential effects of polypharmacy, and the difficulty in relating the adverse effect to disulfiram, alcohol or a disulfiram—ethanol reaction.