Fred C. had tried all the standard cures. Seven-and-a-half years in and out of Alcoholics Anonymous, Ontario’s Addiction Research Foundation and psychiatric care. Nothing offered permanent release from his suicidal attachment to alcohol. Then, three years ago. Fred became one of the first Canadians to receive a new—and controversial—treatment for alcholics. Every six months, 10 tablets of the drug disulfiram are implanted underneath the skin of his lower abdomen. Except for one slip, he hasn’t had a drink since.
Taken orally in pill or liquid form, disulfiram (marketed under the brand name Antabuse) is probably the most potent anti-alcoholic drug available. Alcoholics fear it. Drinking even less than an ounce of liquor within 12 hours of swallowing a disulfiram pill produces violent reactions— nausea and vomiting, throbbing headache, wild heart palpitation, and hyperventilation. But even on oral disulfiram it is possible to cheat. “When my wife or secretary gave me the pill. I’d sneeze it out,” says one. “When they gave it to me in liquid form. I’d force myself to throw up.”
To treat these chronic alcoholics. Dr. Edward Kingstone and Dr. Stephen Kline pioneered North America disulfiram implants at Toronto’s Sunnybrook Medical Centre three years ago. “Oral disulfiram is probably the safest and easiest way of producing a deterrent effect,” says Kingstone. “It works for a large number of patients. So we don’t give an implant to anyone who hasn’t tried it orally. But many alcoholics who take the oral regularly constantly ruminate about the day they will stop tak-
ing it. Inside they know, as long as it’s within their control, that at some point they’ll stop taking it and start drinking again.” Explains one implant patient, dry for two years: “I’ve made a decision to take the decision away from myself. On the oral, I knew I was going to stop. With the implant that decision is taken away from me. I decide once every six months instead of every day.”
The implant works much like a 12-hour cold capsule. Eight or 10 100-milligram tablets of disulfiram are placed subcutaneously in the lower left or right-hand side of the abdomen, above the hip (the site offers a good blood supply and less chance of the tablets being damaged by accidental bumping). The drug is absorbed into the bloodstream over a period of six to 18 months, depending on individual metabolism. And the adverse reaction to alcohol is dramatically different—slower, less severe. but longer lasting (two or three days). Since the implant dose is smaller (oral doses range from 250 to 1.000 milligrams per day), the drug’s side effects—tiredness, temporary impotence, irregular heart beat, bad breath and body odor—are also substantially reduced.
At least in theory. But Kingstone and Kline aren’t sure the theory applies. One patient who received seven implants over 2Vi years never suffered a reaction. For the moment, that catch will force the disulfiram implant to remain experimental. Some people suffer reactions, others report side effects but no reaction; others have neither. “There’s no way we can prove that if you have an implant and have a drink, you'll have a reaction.” says Kingstone. “The implant is probably absorbed into the bloodstream, but not in sufficient quantities to produce a strong enough reaction to deter most patients. There’s probably just enough present to produce some side effects.” Still, among 63 alcoholics who received the implant in their pilot study, 60% stayed on the wagon for six to 20 months. “Now that might not look like much,” says Kline, “but this group was in dire straits.” Regardless of its pharmacological reliability, “an implant operation is better than no operation at all.”
More optimistic is Dr. Alan Wilson, associate professor and coordinator of psychiatric research at the University of Manitoba. “Our results have been very positive indeed.” he says. Wilson's double-blind controlled studies—“the only way you can determine whether there’s any pharmacological component to a medication”— involve three groups: controls who don’t get an implant, a second group that gets a sham implant and a third that gets the real implant. Neither implant group, nor the therapists working with them, know who has the real or the sham, until the studv is over. Predictably, the controls stay dry for only a few days. A large number of sham
implants stay dry, confirming the psychological benefit of the implant. Eventually, recipients of both sham and real implants begin to test the implant, but only after staying dry four times as long as the controls. The shams who drink return to their old drinking patterns, while the real implants who drink have a mild or severe reaction, “at least severe enough to return to their therapist. Most stop drinking from that point on.”
Wilson insists that the severity of the reaction doesn’t matter, as long as there is one. He’s put implants in more than 160 chronic skid row alcoholics; after 18 months 70% are still dry. Like Kingstone and Kline. Wilson has some disulfiram implants who suffer no reaction at all. But he blames surgical technique—not the drug. “The slicker you get at putting the tablets in, the better the results you get. When they don’t have a reaction, we tend to see things we don’t see in the others. The tablets become engulfed in scar tissue and aren’t absorbed into the blood.”
In the meantime, psychiatrists Kingstone and Kline have reached an impasse. “We’re operating under a dichotomy.” Kingstone says. “As physicians we feel an obligation to continue using the implant. There’s nothing to lose in treating chronic cases. A lot of them do extremely well. But as scientists, we're very concerned, because we know the drug doesn’t have the deterrent effects we’d like it to have.” Already, their Sunnybrook Hospital program has slowed considerably. New implant patients are discouraged. “We’re disillusioned with the drug, not the implants. We’d like to see a different formulation of disulfiram or a completely new drug.” Wilson agrees: “There’s got to be a better drug, one whose absorption characteristics can be more carefully documented and made more predictable.” But he has no intentions of curbing his Winnipeg program and is putting all his energies into perfecting the disulfiram implant. “If in the long run it’s not effective, then we’ll look for something else. But so far our results have been better than any other available treatment and at 1.000 times less the cost. These skid row alcoholics are really hard core. Their prognosis through other treatments is less than 20%.”
Ultimately, whatever drugs are developed. the solution will probably have to come from the alcoholic himself. Three months ago. Peter S. had a drinking bout that brought him close to death. He vomited with dry heaves for two days and atrophic gastritis finally surfaced. Fifteen minutes after being rushed to hospital, his stomach began to hemorrhage. “1 finally hit that rock bottom point when you decide you don’t want to drink. 1 haven’t had a drink since then. I'm not on oral disulfiram and I won't have another implant. All my previous treatment was under pressure—I was forced to take it. Now I’m free. I’ve made my own decision and that just might be my salvation.” PETER DE VRIES
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