Disulfiram -- One Tool of Recovery

At "Parents' Weekend" at a major university, I was informed, "Every year, universities are graduating more alcoholics than M.D.s and Ph.D.s combined!" Might our medical judgment render disulfiram (Antabuse) a reasonable medical consideration as one tool of recovery in the recovery program of an otherwise healthy alcohol-dependent university graduate?

The ideal candidate for disulfiram might well be physiologically young and vigorous; be on no other medications; have no evidence of cardiovascular, cardiopulmonary, hepatobiliary, renal or neurologic disorders or comorbid psychosis; have fully accepted the neuropsychiatric diagnosis of alcohol dependency with ongoing 12-step sponsorship and step work; have a caring significant other working a 12-step program of recovery to witness and affirm the disulfiram oral pharmacotherapy; and not be looking for a quick fix.

Pharmaceutical Promotion

At the outset, it is fair and reasonable to endorse and accept that, at a nickel per tablet, there really is no money in disulfiram. I have personally spoken to the pharmaceutical company that manufactures disulfiram, and I have been informed that historically there has been little interest in promoting disulfiram since, from the pharmaceutical company's point of view, there is no money in the drug. From personal communications with my colleagues in the pharmaceutical industry, I am persuaded that over $300 million is spent to bring each new pharmaceutical from the research and development level to clinical use. Disulfiram is a quasi-historic, inexpensive pharmaceutical that may be better known and respected in our judicial system than in our health care delivery system.

Patient Education

I inform my alcohol-dependent patients that disulfiram has been in use prior to World War II. I inform my alcohol-dependent patients that disulfiram, at a nickel per pill, may be viewed as inexpensive. I inform my alcohol-dependent patients that drinking while on disulfiram may be fatal.

First and foremost, let me state that I personally adjust the dose of disulfiram for each patient. In general, given a patient who is chronologically and physiologically young with adequate nutrition, a reasonable dose may be one 250 mg tablet by mouth daily. For more senior patients with less than optimal nutrition, a reasonable dose may be 125 mg by mouth daily.

I provide a tablet splitter, along with patient education on the use of the tablet splitter, to my patients willing to take disulfiram. I recognize and inform my alcohol-dependent patients that liver failure has been described, albeit rarely, following the administration of disulfiram.

Side Effects

To reduce the severity of the expected side effects and the percent probability of a fatality from drinking while on disulfiram, I do not provide the "pre-World War II" 500 mg daily disulfiram dose and loading doses. Should my patients choose to drink alcohol after taking disulfiram, I do not want them to suffer nausea, vomiting, diarrhea, hypotension, chest pain, flushing and shock, which may occur and which may be fatal pursuant to drinking on disulfiram. Instead, I would hope that, at most, they experience only mild to moderate retching. I inform my alcohol-dependent patients and their families and/or significant others of this, and they accept and appreciate my empowering and considerate treatment and care.

Drug Interactions

According to the 1999 Physicians' Desk Reference and other sources (Barker et al., 1995; Carey et al., 1998), certain pharmaceuticals cannot and should not be taken with disulfiram:

• Metronidazole (Metrolotion), which may produce an adverse reaction similar to alcohol and disulfiram;
• Phenytoin (Dilantin), which may elevate the blood level of phenytoin toxicity; and
• Warfarin (Coumadin), which may elevate the International Normalized Ratio/Prothrombin Time and produce bleeding.

I hesitate to provide disulfiram to my senior alcohol-dependent patients since 1) renal function decreases with age; 2) cardiovascular disorders increase with chronologic age; and 3) the risk of a fatal drinking-on-disulfiram reaction may be reasonably anticipated to increase with chronologic age (Dambro, 2000; Rowland, 1984).

I am cautious with disulfiram. If a 55-year-old patient states, "I have been on 250 mg disulfiram per day for a decade," I just might consider advising a reduction in dosage to 125 mg/day. I would rather not provide disulfiram to alcohol-dependent patients with comorbid psychosis, since mania has been described pursuant to the administration of disulfiram (Nasrallah, 2000).

• Ethical Issues

I do not require my alcohol-dependent patients to take disulfiram; however, I have provided care for alcohol-dependent patients who said, "Doctor, I wish your program would just make me take it!"

I discourage -- strongly discourage -- family members of alcohol-dependent patients who want to sneak disulfiram into the soup or stew of the alcohol-dependent member of their family, even though I have been privileged to provide health care to recovering alcohol-dependent patients who were in strong favor of doing just that. Of course, ethically, I forbid such shenanigans, and instead, I encourage Alcoholics Anonymous (AA) for the actively drinking alcoholic and Al-Anon and Alateen for the family members and significant others. Their daily meetings, sponsorship and step work help them to develop and use the tools of recovery (AA World Service Office, 1986).

• Compliance Issues

Compliance, with the notable exception of court-ordered disulfiram, may be suboptimal (Martin et al., 2000).

No family member or significant other of an alcohol-dependent patient should ever have to beg the patient to take disulfiram. If, and only if, the alcohol-dependent patient is ready, willing and eager to take the medically prescribed and provided disulfiram, then it may be reasonable for the parent, spouse, adult child or significant other to witness, affirm and validate the compliance by saying, "Thank you for taking your daily medication." In turn, the alcohol-dependent patient can choose to say, "Thank you for watching me take my daily medication." I was informed by one of my patients, "My wife places my disulfiram on the kitchen counter, and then she watches me take my disulfiram with my morning orange juice. Then I thank her for watching me take my medication." Another told me, "My wife stuffs my disulfiram all the way down my throat every night, and then she pours a big glass of water down my throat every night. I thank her."

• Lack of Evidence

Through personal communications with respected, reasonable addiction medicine provider teams, I have been informed that disulfiram may be a reasonable adjunct to an alcohol-dependent patient's recovery. These dedicated health care providers acknowledge that when it is used alone -- without 12-step work, addiction therapy group work or spiritual support -- disulfiram may be of no value toward a sustained recovery program. An analogy to antibiotics may be useful here. Given a college football player with fever, chills, rusty sputum, and imaging evidence on chest X-ray of pneumonia proven by gram stain to be pneumococcal and by culture to be sensitive to antibiotics, then the prescribed antibiotics would need to be accompanied by increased fluid intake and rest in order to be reasonably effective toward resolving the bacterial pneumonia and returning the student to pre-pneumonia level of college studies and football activities. Unlike antibiotics, there is currently no parenteral disulfiram yet!

Hard evidence for the efficacy of disulfiram is lacking. Nevertheless, in selected, motivated, alcohol-dependent patients who are working a program of recovery in AA and whose family and/or significant others are also working a program of recovery in Al-Anon or Alateen, disulfiram may be a reasonable tool of recovery. Respected addiction medicine providers liken disulfiram to both a cast on a fracture and a crutch to reduce weight-bearing on a fracture. A crutch and/or a cast, like disulfiram, provides one, and only one, tool of recovery; the alcohol-dependent patient and their family and/or significant others have to develop and use all of their tools of recovery.

• Risk Management

There can and will be no broad recommendation of any new pharmacotherapy or new application of previous pharmacotherapy without more in the way of hard evidence than we currently appear to have when focusing on disulfiram. Nevertheless, the increased awareness of the impact of alcohol dependency on the lives of our patients, which may include some of our alcohol-dependent colleagues; the varying health care expectations of ethnic groups; the documentation of the effects of alcohol on the incidence of disorders, including cancer; the increased awareness of self-help groups; and the growing awareness of the role of spirituality in the lives of our alcohol-dependent patients may support a reasonable judgment in favor of a focused health care provision of disulfiram in selected recovering alcohol-dependent patients. Just as the digitalis preparations are used in selected patients with cardiovascular disorders and chemotherapeutic agents are used in selected patients with malignant disorders, disulfiram may have a place in the recovery of selected alcohol-dependent patients.

The risk of providing the digitalis preparations and chemotherapeutic agents needs to be balanced against the risk of not providing them. Likewise, the risk of providing disulfiram needs to be balanced against the risk of not providing it. A vast number of studies have shown, in carefully selected alcohol-dependent patients, providing disulfiram would appear to reasonably outweigh the risks involved (Granfield and Cloud, 1996; Sobell et al., 1996).

References:

• References 1. Alcoholics Anonymous World Service Office (1986), Alcoholics Anonymous. Center City, Minn.: Hazelden Publishing and Educational Services.
  2. Barker LR, Burton JR, Zieve PD, eds. (1995), Principles of Ambulatory Medicine, 4th ed. Baltimore: Williams & Wilkins.
  3. Carey CF, Lee HH, Woeltje KF et al., eds. (1998), The Washington Manual of Medical Therapeutics, 29th ed. St. Louis: Lippincott-Raven.
  4. Dambro MR (2000), Griffith's 5-Minute Consult. Baltimore: Williams and Wilkins.
  5. Granfield R, Cloud W (1996), The elephant that no one sees: natural recovery among middle-class addicts. Journal of Drug Issues. 26(1):45-61.
  6. Martin BK, Clapp L, Bridgeford DC et al. (2000), Compliance with court-ordered versus voluntary disulfiram therapy. NR583. Presented at the 153rd Annual Meeting of the American Psychiatric Association. Chicago; May 17.
  7. Nasrallah HA (2000), Psychosis genotypes and phenotypes, diagnosis and treatment. No.29A. Presented at the 153rd Annual Meeting of the American Psychiatric Association. Chicago; May 16.
  8. Rowland LP (1984), Merritt's Textbook of Neurology, 7th ed. Philadelphia: Lea & Febiger.
  9. Sobell LC, Cunningham JA, Sobell MB (1996), Recovery from alcohol problems with and without treatment: prevalence in two population surveys. Am J Public Health 86(7):966-972.