Daniel Carlat, MDDr. Carlat has disclosed that he has no significant relationships with or financial interests in any commercial companies pertaining to this educational activity.
Guess what: Antabuse (disulfiram) is back in fashion, over a half century after its initial approval by the FDA. You have probably seen some of the infomercials funded by Odyssey Pharmaceuticals and published as supplements by the usual journals. Whether the renewed interest in Antabuse has been fueled by this advertising, or whether Odyssey is taking advantage of a spontaneous groundswell of clinical interest, is immaterial. The fact is, Antabuse is a very useful tool for a subsegment of your alcohol-using patients, and you'd do well to learn about it.
Its mechanism of action is infamous. It inhibits the metabolism of acetaldehyde, which is a metabolic byproduct of alcohol. High levels of acetaldehyde cause extreme discomfort, including nausea, vomiting, throbbing headache, dizziness, and flushing. While cardiovascular collapse and even death are theoretical results, I have yet to meet a clinician who has actually seen a patient become severely ill from an Antabuse reaction. An accurate way of describing the Antabuse reaction to a patient is: "You'll wish you were dead, but it won't kill you."
How does the drug help? Classified as an "aversive" treatment, Antabuse provides an extra layer of motivation to those of your patients who are already highly motivated to stop drinking. A good Antabuse candidate screening question is: "Are you able to make a commitment to me and to yourself right here and now that you are ready to say goodbye to alcohol forever?" A "yes" answer may or may not be sincere, but it's a good start. Patients who sort of grit their teeth and say "I don't know, forever's a long time" are much less likely to benefit from Antabuse. They will either not fill the prescription or they'll make a plan to stop taking it on a Monday in order to drink on a Friday.
The typical good Antabuse candidate is a sales rep with several one to two day relapses of alcohol use divided by long periods of sobriety. He knows if he relapses, he'll end up out of a job, but finds the temptation when he is on the road, away from his usual AA meetings, to be too great to deal with. Antabuse is a good check on his impulsivity.
Research-wise, few controlled trials have been done on Antabuse; the largest and most widely cited was published back in 1986 (JAMA 1986;256:1449). In this study of 605 alcoholic males in the VA system, the subjects were divided into three treatment arms: 202 patients were given Antabuse 250 mg QD, 204 were given Antabuse at only 1 mg QD, and 199 were given riboflavin. The patients in the Antabuse arms were all told that they were taking Antabuse, but were not told the dose. The riboflavin group was told they were taking vitamins.
Antabuse Dosing Guidelines Start at 125 mg QD X 1 week, then increase to 250 mg QD. Check baseline LFTs and periodically thereafter.
What was the point of the 1 mg arm of the study? To evaluate whether or not the active aspect of Antabuse treatment is merely the psychological threat of a reaction, in the absence of a possibility of an actual reaction.
After one year of treatment, there was good news and bad news. The bad news was that there was no difference in the percentage of men remaining abstinent. The good news was that in the subpopulation of men who attended all the scheduled followup research appointments, Antabuse 250 mg significantly decreased drinking days vs. Antabuse 1 mg and vitamin. The bottom- line: Those alcoholics who are most highly motivated will do the best on Antabuse.
Now, down to the nitty-gritty of dosing and side effects.
Since Antabuse can rarely cause liver toxicity, it's good to check LFTs (liver function tests) at baseline, and then periodically thereafter. "Periodically" may mean monthly initially then every 3 months for the more obsessive among us, and less frequently for others. A recent study of liver abnormalities in patients prescribed Antabuse was very reassuring, indicating that the drug rarely worsens liver problems even when baseline LFTs are elevated (J Clin Psychiatry 1998; 59: 313-316). Don't give Antabuse to patients on Flagyl or to patients with severe cardiac problems.
The common side effects are initial fatigue (so start it at bedtime), a metallic taste in the mouth, and GI side effects such as nausea or diarrhea. Tell patients not to drink Nyquil or other alcohol-based medicines. There is some lore that alcohol-based perfumes and aftershaves can seep into the blood and cause a reaction, but it’s likely quite rare.
Dosing is also a matter of clinician preference. The package insert recommends starting at a whopping 500 mg QD to get robust blood levels early on but nobody does this. A common strategy is to start at 125 mg QD (you have to split the pill in half) for a week and then increase to a maintenance dose of 250 mg QD. However, some keep it at 125 mg QD on the theory that this is enough to cause a reaction with drinking, but low enough to minimize the risk of hepatic toxicity. If a patient reports drinking on 250 with no reaction, bump it up to 500.