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Diss Factsheets

Administrative data

Description of key information

Disulfiram was widely used (approx. since 1950) as a drug for treatment of alcoholismis, usually administered p.o. in daily doses of 100 - 400 mg. It causes a blockade of the enzyme aldehyde dehydrogenase with consequently increasing levels of acetaldehyde upon ethanol consumption. The unpleasant clinical signs are known as Disulfiram-ethanol reaction (DER). Disulfiram also blocks the enzymatic degradation of dopamine by inhibition of dopamine b-hydroxylase (DBH). This effect might be used in the pharmacotherapy for the treatment of cocaine dependence.

Additional information

Adverse effects of disulfiram as well as contraindications are well investigated, as disulfiram was used for decades as a therapeutic drug against alcoholism. In recent publications (reviewed by Kampman, 2009) the pharmacological safety of disulfiram was evaluated again, as it was shown to have the potential to treat cocaine dependence. Whereas aldehyde dehydrogenase is the primary target in treating alcoholism, human laboratory, genetic, and preclinical animal studies indicate that its beneficial effects on cocaine use result from the inhibition of dopamine b-hydroxylase (Gaval-Cruz, 2009).

Peachey (1981) summarized four areas of concern associated with repeated disulfiram application:

Medical complications during disulfiram-ethanol reaction (DER)

Myocardial infarction, shock, and death can occur during the DER. Cerebrovascular haemorrhage and infarction, causing loss of consciousness during the DER followed by death after several days, are also reported. Although most fatal DERs have been associated with excessive dosages of disulfiram (> 1500 mg daily) followed by consumption of large amounts of ethanol, deaths have also been reported with therapeutic disulfiram dosages and relatively small amounts of ethanol. Reversible electrocardiographic changes are recorded during the DER. 

Toxicity associated with disulfiram administration in humans

Disulfiram and its metabolite diethyldithiocarbamate (DDC) inhibit dopamine-b-hydroxylase (DBH) causing increased dopamine levels and decreased norepinephrine levels in the brain and other tissues. Drowsiness, lethargy, disturbed sexual function, and neuropsychological dysfunction occur as a result of the DBH inhibition. More serious behavioural changes include psychosis and acute encephalopathy which occur particularly in individuals with low cerebral spinal fluid DBH activity or low pretreatment levels of platelet monoamine oxidase and amine oxidase and high levels of red cell catechol-O-methyltransferase. Patients with a diagnosis of depression or borderline schizophrenia may manifest more psychopathology while taking disulfiram. The development of neuropathy, muscle weakness, and motor incoordination are the result of CS2-induced toxicity during disulfiram treatment. In addition, disulfiram may cause hepatotoxicity, atherosclerosis, and increased blood pressure. Limb anomalies have been reported in infants born on disulfiram-treated alcoholic mothers.

Drug-drug interactions

Disulfiram inhibits the metabolism of other drugs including antipyrine, phenytoin, warfarin, isoniazid, rifampin, diazepam, and chlordiazepoxide causing increased blood levels of these drugs. It is noteworthy that a similar reaction does not occur with short- and intermediate acting benzodiazepines. The simultaneous administration of disulfiram with warfarin may result in prolongation of the prothrombin time with subsequent haemorrhage. Similarly, cumulative toxicity to phenytoin has been reported in alcoholics receiving disulfiram. On the other hand, with cessation of disulfiram administration, dosages of the other drugs may need to be adjusted downward. Diazepam induces the intensity of the DER, while amitriptyline enhances DER.

Toxicity due to acetaldehyde

Blood acetaldehyde levels are raised appreciably in disulfiram-treated alcoholics following the ingestion of relatively small amounts of ethanol. It is possible that alcoholics who receive disulfiram and who continue to drink may experience some degree of acetaldehyde-induced cardiotoxicity and/or hepatotoxicity.


Clinical cases are published, where delirium-associated neurotoxic effects are described. However, neurotoxic effects occurred upon combined exposure to disulfiram and ethanol (Mirsal, 2005).