Volume-1 Issue-3 September, 2011
Alcohol dependence or alcoholism is often a progressive chronic disorder which has significant adverse
implications on patients, their families, and the society. Treating alcoholism involves several stages. In the initial stage,
acute withdrawal is treated by detoxification with benzodiazepines especially Chlordiazepoxide. Later stages attempt to
maintain patients in abstinence or controlled drinking. This latter aspect of patient management traditionally involves
pharmacological modalities like Disulfiram for complete abstinence or psycho-social interventions including Motivational Interviewing, option of Alcoholics Anonymous and various counseling approaches or combinations of both. Drugs used to manage alcohol dependence includes Disulfiram, the opioid antagonists like Naltrexone & almefene, Acamprosate, various serotonergic agents (including SSRIs), Topiramate, Baclofen etc. Though many drugs are being marketed, Disulfiram is still a better option considering its efficacy & cost effectiveness.
Disulfiram (Tetraethylthiuram disulfide) is an aldehyde dehydrogenase inhibitor that interferes with the
metabolism of alcohol by producing a marked increase in blood acetaldehyde levels leading to unpleasant symptom
referred to as the disulfiram-ethanol reaction. Thus Disulfiram is used as an aversive conditioning agent. Either the fear
of having a Disulfiram-Ethanol Reaction or the memory of having had one is meant to condition the patient not to use
alcohol. Disulfiram has a half-life estimated at 60 to 120 hours because of which it may produce symptoms even 1 or 2
weeks after the last dose! Disulfiram-Ethanol Reaction can occur within 10 mins of taking alcohol & features can be
sweating, palpitation, facial flushing, throbbing headache, nausea, vomiting, chest pain, dyspnea, hyperventilation,
tachycardia, hypertension, syncope, marked uneasiness, vertigo, blurred vision, & confusion. In severe cases, there may
be respiratory depression, cardiovascular collapse, arrhythmias, myocardial infarction, acute congestive heart failure,
unconsciousness, convulsions, and even death. The intensity of the reaction may vary with each individual but is
generally proportional to the amount of Disulfiram and alcohol ingested. In severe reactions, supportive measures to
restore blood pressure & to treat shock should be instituted. Other measures such as the administration of oxygen,
massive intravenous doses of vitamin C (1 g), ephedrine sulfate or antihistamines might be helpful.
For reasons explained above every patient is educated about Disulfiram & written consent taken. Disulfiram like
reaction can occur in patients who are taking metronidazole, cephalosporins, sulphonylureas or griseofulvin when
alcohol is ingested. The patients on Disulfiram also need to be aware that alcohol-containing preparations i.e., in sauces, vinegars, cough & cold mixtures, and even aftershave lotions or liniments can also trigger off such reactions! Since Disulfiram-alcohol reactions could aggravate some medical conditions such as diabetes mellitus, hypothyroidism,
epilepsy, cerebral damage, chronic & acute nephritis, hepatic cirrhosis or hepatic insufficiency, they need to be warned.
Extreme care should be taken in such patients or avoid Disulfiram altogether. Disulfiram inhibits enzyme induction, thus
interfere with the metabolism of drugs & enhances the effects of Coumarin anticoagulants, diazepam, paraldehyde,
caffeine, tetrahydrocannabinol, barbiturates, isoniazid, tricyclic drugs & phenytoin. In a small number of patients, a
transient mild drowsiness, fatigue, impotence, headache, acneiform eruptions, allergic dermatitis, or a metallic or garliclike aftertaste may be experienced during the first 2 weeks of therapy. Disulfiram is supplied in tablets of 250 mg and 500 mg. Average maintenance dose is 125 to 250 mg / day but should not exceed 500 mg daily. Disulfiram does not produce tolerance. Daily uninterrupted administration continued until the patient has self-control. Although implants of disulfiram appear to be an attractive method to ensure compliance in future but has its own drawbacks.
Disulfiram is certainly an old drug in use and data available on it for more than 50 years now. Although many
individuals do achieve long-term sobriety, few others continue to relapse and deteriorate despite multiple courses of
treatment. However, with proper motivation and supportive therapy, Disulfiram is an old (in terms of years of use & data available) and beautiful Drug (in terms efficacy & cost effectiveness) which wins hands down.
HOD, Department of Psychiatry, K V G Medical College, Sullia
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