Disulfiram

Additional information

The risk of alcohol use according to the Global Burden of Disease Study 2010, was ranked as number three in men and number twelve in women. Disability-adjusted life years were three times higher in men than in women and alcohol related deaths were twice as common in men as in women [1].

In Sweden, hospital care due to alcohol related diagnoses were twice as common in men compared to women in 2012 and alcohol related deaths were more common in men than in women [2].

Pharmacokinetics and dosing

A laboratory study of disulfiram added to blood from alcoholic patients (n=26) and healthy controls (n=18) reported that the metabolism of the ethanol metabolite acetaldehyde was inhibited similarly in men and women [3]. No sex differentiation in dosing has been recommended by the manufacturer [4].

Effects

Alcohol dependenceIn an observational study, patients with alcohol dependence (176 men, 33 women) were prescribed disulfiram (82%), acamprosate (14%) or disulfiram + acamprosate (10%) in addition to supportive counseling during 6 months. It showed that absence of heavy relapse in drinking was higher in men than in women (56% vs. 36%) [5]. Similarly, a review of disulfiram treatment in alcoholism including data from two large trials in alcoholics (500 men, 60 women and also 1020 patients with unknown sex distribution) showed a better outcome in men than in women [6, 7].

Opioid dependenceA Cochrane report states that there is little evidence supporting the clinical use of disulfiram in the treatment of cocaine dependence [8]. Disulfiram is not approved for treatment of opioid dependence in Sweden or the US [4, 9].

Two pooled analyses of six randomized placebo-controlled trials of disulfiram and behavioral therapies during 8-12 weeks in cocaine dependent patients (324 men, 179 women, in all) showed a poorer outcome in women than in men [10, 11].

Adverse effects

No studies with a clinically relevant sex analysis regarding the adverse effects of disulfiram have been found.

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Other information

A retrospective cross-sectional study of patients with alcohol dependence (833 men, 218 women) treated with supportive counseling and disulfiram or naltrexone showed that the retention of treatment was similar in men and women [12].

A US study based on data from Veterans Health Administration (VHA) of treatment of alcohol misuse (270 774 men, 9 319 women) showed that women were more likely than men to receive a prescription of acamprosate (1% vs. 0.6%), naltrexone (2.9% vs. 1.6%), disulfiram (1.8% vs 1.1%), or any medication (5.2% vs. 3%). The odds ratio for receiving any of these medications was 1.58 in women compared to men [13].

Randomized studies of compliance to disulfiram treatment (291 men, 143 women) of cocaine dependence have shown no sex differences [10].