A study of patients addicted to heroin shows that two medications other than the gold standard methadone are effective treatments, even for "hard core" users. Moreover, unlike methadone, the two therapeutic drugs needn't be taken daily, allowing patients a lifestyle far closer to non-addicts'.
The research, reported in last week's New England Journal of Medicine, is the first to compare methadone with LAAM, or levomethadyl acetate--a little-embraced treatment the FDA okayed in 1993--and with buprenorphine, or BUP, a therapy now under FDA review. (Legislation just approved by Congress makes BUP the first anti-addiction medication exempt from narcotic treatment regulations and available to patients outside traditional treatment programs.)
"The effects of the three medications differ somewhat," says Rolley E. Johnson, who led the research team, "but no single one dramatically overshadows the others. This study is important because it should increase treatment options. But even more useful, such work helps us, ultimately, to determine who'll do best under each drug therapy.
"We're beginning to look at opioid dependence like any chronic disease, like hypertension, for example. If you had only one drug to treat hypertension, a lot of people would be left out. The greater the variety of medications, the greater the likelihood you can help everyone, even with addictions."
The researchers recruited 220 heroin-addicted patients for the 17-week study. They placed all the patients on one of the three medications, tailoring the dose to an optimal effect for each patient. The exception was the control group, which took a lower, fixed dose of methadone. The methadone test group received daily treatment, while the LAAM and BUP test groups were treated three times a week.
"You measure how well patients do in addiction treatment in several ways," Johnson explains. "You ask them how they're doing, how they feel. You examine urine to see if they're still taking heroin. You see how long they're abstinent. You see if they stay in treatment. We did all of these in the study because no one measure is perfect.
"The results showed that all three medications were dramatically effective in reducing heroin use," Johnson says. "That included a 90 percent drop in use as reported by patients themselves and a 50 percent drop in urine tests positive for heroin. The medications were also effective in keeping patients off heroin," Johnson says. LAAM was the leader, keeping 36 percent of the patient group continuously "clean" for a month or longer. As for retaining patients in the study--a sign that treatment's working--high-dose methadone-takers were most successful, with an average of 105 out of 119 possible days in the study, but BUP patients weren't far behind. LAAM patients were somewhat more likely to drop out initially, but the patients who stayed, the researchers say, were abstinent longer.
"Studying why these differences occur will be crucial. It could one day let us fine-tune therapy for each patient, using these medications and others that come along," Johnson says. An addicted patient's individual response to treatment medication, he says, is complicated. It hinges not only on the genetic makeup of the nervous system, but on patients' metabolism, on how long they've taken drugs, on their behaviors in using them, on the patients' environment and on the biology of the therapeutic medication.
Methadone and LAAM, for example, attach to the opioid receptors on nerve cells, and are able to stimulate them completely. Further, when the body metabolizes LAAM, its by-products continue to stimulate the receptors. BUP, by contrast, only partially stimulates the receptors but takes longer to detach from them. This relatively longer "staying power" of BUP and LAAM, Johnson says, is why patients don't have to take the drugs daily.
"This study could be pivotal for less-than-daily dosing with buprenorphine," he adds. Other members of the research team are Mary Ann Chutuape, Eric C. Strain, Sharon L. Walsh, Maxine L. Stitzer and George E. Bigelow.
The research was funded by a grant from the National Institute on Drug Abuse.