Disulfiram in the management of alcohol dependence: A comprehensive clinical review

Abstract

Disulfiram remains a viable option as a treatment for alcohol dependence and has been shown in recent studies to be successful in treating patients with alcohol dependence in a manner that is superior to both naltrexone and acamprosate. It is also useful in dual diagnosis patients and those with co-morbid cocaine and alcohol dependence. Although disulfiram's mechanism of action in alcohol dependence was long thought to be its effects as a psychological deterrent, more recent studies have uncovered potential anticraving effects as well. Recent reviews exhort to the importance of supervised disulfiram therapy in highlighting many of the potential and unique benefits of disulfiram. The present article will review the major clinical trials of disulfiram spanning nearly 60 years. It also discusses the usage of disulfiram across diverse populations along with monitoring for compliance and various adverse effects that may be encountered. The paper also reviews certain studies on long acting disulfiram therapy, recent comparative trials of disulfiram and its use in alcohol dependence. The review concludes with the role of disulfiram in the present day and long-term pharmacotherapy of alcohol dependence along with future research needs in this area.

Preoperative Interventions for Alcohol and Other Recreational Substance Use: A Systematic Review and Meta-Analysis

“…Disulfiram trials (Tønnesen et al, 1999; Tønnesen, 2002) were by far the most effective—both achieving complete abstinence prior to surgery, and benefits up to 1 month post-surgery. However, these trials were both small, and given dangerous side effects (e.g., neurotoxicity) and generally low compliance (e.g., Fuller et al, 1986; Pettinati et al, 2008; Kalra et al, 2014), disulfiram is a medication to be used with caution and only in a small population of highly motivated, alcohol dependent patients. There are however a number of other pharmaceutical protocols, shown useful in similar contexts, which may aid detoxification in the preoperative context, such as those involving pregabalin and clomethiazole (Di Nicola et al, 2010; e.g., Sychla et al, 2017).…”

Epidrug Repurposing: Discovering New Faces of Old Acquaintances in Cancer Therapy

“…Disulfiram is an alcohol aversive drug that has been approved by the FDA for more than 60 years for treating alcohol abuse. It allows acetaldehyde to accumulate in the blood by inhibiting ALDH (165). Disulfiram's anticancer activity is mediated by its ability to suppress DNMT1 and through the reactivation of epigenetically silenced genes such as APC and RARB in prostate cancer cell lines (70) ( Table 4, Section 1).…”

Contribution of Noradrenaline, Serotonin, and the Basolateral Amygdala to Alcohol Addiction: Implications for Novel Pharmacotherapies for AUDs

“…The anti-alcohol addiction properties of disulfiram were serendipitously discovered, when a Danish physician Jacobsen accidentally ingested alcohol over disulfiram and experienced its unpleasant and nauseous effects [38,39]. Disulfiram inhibits the enzyme aldehyde dehydrogenase (ALDH), which results in the accumulation of acetaldehyde on alcohol ingestion [40]. This toxic metabolite produces aversive symptoms, such as flushing, nausea, and vomiting, and a desire to avoid this reaction encourages abstinence [41].…”

“…Disulfiram also inhibits dopamine-β-hydroxylase (DBH), the enzyme required to synthesize noradrenaline (NE). It reduces NE concentrations and elevates dopamine (DA) concentrations to facilitate normal DA functioning [40,41], a pharmacotherapeutic feature of the drug that makes it an excellent treatment option even for cocaine addicts.…”