Safety Issues Concerning the Use of Disulfiram in Treating Alcohol Dependence

Abstract

Disulfiram is known to cause hepatitis, which is sometimes fatal. The best estimate of the frequency of disulfiram-induced fatal hepatitis is 1 case in 30,000 patients treated/year. Its appears to be more common in patients given disulfiram for the treatment of nickel sensitivity. Frequent blood testing for liver function is probably not necessary, but patients taking disulfiram should be in regular contact with a physician. There are rare reports of psychosis and confusional states in conjunction with disulfiram treatment and peripheral neuropathy and optic neuritis have been reported; these effects are dose-related. Psychiatric complications appear to be more common with the use of disulfiram in India than in Western countries. Of the less serious adverse effects, tiredness, headache and sleepiness are the most common. Deaths from the disulfiram-alcohol (ethanol) interaction have not been reported in recent years, possibly because the dosages used are lower than those used 40 years ago, and patients with cardiac disease are now excluded from treatment. There is no evidence to suggest that disulfiram causes cancer. Of note, there are drug interactions with compounds that utilise the cytochrome P450 enzyme system. Disulfiram can be viewed as a drug with a moderate record of adverse effects. Alcohol dependence, for which it can be a helpful treatment, is associated with a high morbidity and mortality.

Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence

“…DARs were reported on 29 occasions [106] but none led to a dose reduction, and the authors concluded that disulfiram was well tolerated when given as part of a wider treatment programme. A small cohort study of more than 50 weeks duration (disulfiram cohort study in an Indian population (125mg/d) [111] showed an excess of skin rashes, supporting an earlier observation that there may be greater sensitivity to the adverse effects of disulfiram in Indian compared to Western patients [112]. A study in adolescents [113] found it to be well tolerated with no significant differences in reported adverse events between disulfiram (200mg/d) and placebo.…”

“…Early studies of disulfiram used much higher doses (1-3g daily) causing a higher burden of serious adverse effects and DAR, including death [112]. In one variable dose study, 500mg doses of disulfiram were much less tolerated than 250mg with all withdrawals due to adverse events in the 500mg group [114].…”

“…In patients with alcohol dependence especially, any medication to initiate abstinence or reduce drinking needs to have good evidence for the safety of the drug combined with alcohol, which seems well established for nalmefene [132] but less clearly for baclofen [146]. For medications that aim to promote abstinence from alcohol the safety profile needs to be weighed against the risks to the patient of relapse [112], but the prescriber also needs to take into consideration potential interactions with concomitantly prescribed medications in a patient group with considerable physical and psychiatric comorbidity. Baclofen is a good example of how the 'repurposing' of drugs in a different patient group may alter the safety profile, as was also seen in early reports of hepatotoxicity of naltrexone in non-alcohol dependent obese patients.…”

Current Status of Disulfiram Therapy

“…Psychiatric complications appear to be more common with the use of disulfiram in India than in Western Countries [5].…”

“…(3) Disulfiram can be viewed as a drug with a moderate record of adverse effects. Alcohol dependence, for which it can be helpful treatment, is associated with a high morbidity and mortality [5]. (4) Relapse rate is very high, Helander A (1998) reported 80% of his patients returned to drinking very soon on discontinuation of disulfiram therapy [11].…”