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Logo of mjafiGuide for AuthorsAbout this journalExplore this journalMedical Journal, Armed Forces India
 
Med J Armed Forces India. 2001 October; 57(4): 320–321.
Published online 2011 July 21. doi:  10.1016/S0377-1237(01)80013-7
PMCID: PMC4924115

CURRENT STATUS OF DISULFIRAM THERAPY

Abstract

The effectiveness of disulfiram is linked to the disulfiram-ethanol reaction in the treatment of Alcohol Dependence Syndrome. However disulfiram therapy is associated with various adverse effects and needs a structured and supervised after care program. Relapse rate is very high once disulfiram therapy is discontinued. Keeping these factors in mind disulfiram therapy is used less often today than previously.

KEY WORDS: Alcohol Dependence Syndrome (ADS), Adverse drug reaction (ADR), Disulfiram (Antabuse), Disulfiram-ethanol reaction (DER)

Disulfiram (antabuse) is used in alcohol rehabilitation because it inhibits aldehyde dehydrogenase and consequently causes the disulfiram-ethanol reaction (vomiting, vertigo, anxiety, cardiovascular effects) after ingestion of alcoholic beverges. However, adverse effects on the central nervous system (psychotic reaction, acute organic brain syndrome, catatonia) may appear as a direct result of the drug itself [1].

Although it has been suggested that the effectiveness of disulfiram is only as a placebo, there is evidence for the effectiveness being linked to the disulfiram ethanol reaction (DER) due to the pharmacological action and the operant conditioning model. Hepatitis following use of disulfiram has been reported in many studies. There is a close temporal relationship between the occurrence of symptoms and disulfiram intake. Fulminating hepatitis is a rare but potentially fatal adverse reaction that may occur after the use of disulfiram. Disulfiram toxicity may present different clinical aspects: (1) Cytolytic hepatitis with fatal ovulation in 30% of cases (fulminant hepatitis). (2) Severe optic neuritis. (3) Peripheral neuropathy. (4) Encephalitis [2].

Enghusen et al (1992) in their study of Adverse Drug Reaction (ADR) to disulfiram treatment have reported 1 per 2000 treatment year mainly of hepatic neurological, skin and psychiatric reaction in decreasing order of frequency and death 1 per 25000 treatment year [3]. Reports to the WHO collaborating center for Industrial Drug monitoring in Uppsala, Sweden, showed the same ADR profile, although with a higher rate of neurological and psychiatric and a lower rate of hepatic reaction. The latency time from the start of treatment to the manifestation of the ADR differed according to organ. Hepatitis occurred with a distinct peak after 2 months of treatment, skin reaction after 2 weeks and the rate of neurological ADR increased with duration of therapy. Obviously the use of disulfiram as therapeutic agent is not without danger, and it should be attempted only under careful medical supervision. Patient must be warned that as long as they are taking disulfiram, the ingestion of alcohol in any form will make them sick and may endanger their life. Patients must learn to avoid disguised forms of alcohol such as cough syrups, sauces, fermented vinegar and even after shave lotion and back rubs.

Murthy KK (1997) in his study of 52 patients of Alcohol Dependence Syndrome on 250 mg disulfiram twice daily after food showed 6 patients developed psychotic symptoms with mood disorder [4]. Psychiatric complications appear to be more common with the use of disulfiram in India than in Western Countries [5].

However, there are other studies that add weight to the evidence that disulfiram is not a drug with high incidence of adverse effects [6]. Larson FW et al (1992) reported that in treatment of alcohol dependence, disulfiram is most useful in conjuction with a structured, supervised, aftercare program [7]. The effectiveness of supervised disulfiram therapy was confirmed in a multicentric British study in which supervised disulfiram therapy was compared with vitamin ‘C’ in a sample of chronic alcoholics who had relapsed. The result clearly favoured the disulfiram group with significant reduction in several measures of drinking behaviour including the level of GGT in the disulfiram group compared to no reduction in these measures in the vitamin ‘C’ group. A review of controlled clinical trials with disulfiram concluded that there is unopposed evidence for its effectiveness [8].

Comments:

  • 1.
    Pharmacological benefits of disulfiram in the treatment of alcoholism have yet to be clearly demonstrated [9].
  • 2.
    Disulfiram is used in the treatment of alcohol dependence. Its main effect is to produce an unpleasant and potentially dangerous reaction in a person who ingests even a small amount of alcohol while taking disulfiram. However, because of the risk of severe and even fatal disulfiram - alcohol reaction, disulfiram therapy is used less often today than previously. Many clinicians have stopped routinely prescribing the agent, partly in recognition of the dangers associated with the drug itself: mood swings, rare instances of psychosis, the possibility of an increase in peripheral neuropathies and a potentially fatal hepatitis [10].
  • (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].
  • (5)
    Disulfiram is an aid in the management of selected chronic alcoholic patients who want to remain in a state of enforced sobriety so that supportive and psychotherapeutic treatment may be applied to best advantage.
  • 6.
    Disulfiram is not a cure for alcoholism. When used alone without proper motivation and supportive therapy, it is unlikely that it will have any substantive effect in the drinking pattern of the chronic alcoholic.

References

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2. Dupuy O, Flocard F, Vial C, Rode G, Charles N, Boison D, Flectaire A. Disulfiram Toxicity. Revue de Medicine Interne. 1995;16(1):67–72. [PubMed]
3. Poulsen H Enghusen, Loft S, Anderson JR, Anderson M. Disulfiram therapy — adverse drug reaction and interactions. Acta Psychiat Scand. 1992;369(Suppl):59–65. [PubMed]
4. Murthy KK. Psychosis during disulfiram therapy for alcoholism. Journal of the Indian Medical Association. 1997;95(3):80–81. [PubMed]
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8. Desai NG, Gupta DK, Khurshad KA. Substance use disorders. In: Vyas JN, Ahuja N, editors. Text Book of Postgraduate Psychiatry. 2nd ed. JP Brothers; New Delhi: 1999. pp. 76–139.
9. Allen RZ, Litten JP. Techniques to enhance compliance with disulfiram. Alcoholism: Clin Expt Res. 1992;16(6):35–41. [PubMed]
10. Schuchit MA. Alcohol Related Disorders. In: Sadock BJ, Sadock VA, editors. Comprehensive Text book of Psychiatry. 7th ed. Lippincott William & Wilkins; Philadelphia: 2000. pp. 953–971.
11. Helander A. Monitoring relapse drinking during disulfiram therapy by assay of urinary 5 hydroxytryptopiol. Alcoholism: Clin Expt Res. 1998;22(1):111–114. [PubMed]

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