WEDNESDAY, Sept. 3, 2003 (HealthDayNews) -- A trial looking at new ways to combat opiate addiction was successful enough to be halted early, affording people in the placebo group a chance to benefit from the intervention.
The investigators looked at a new drug, buprenorphine, both alone and in combination with naloxone. Buprenorphine diminishes cravings for opiates such as heroin, while naloxone counters potential abuse of buprenorphine. The drugs were also administered in a new way: from the privacy of a doctor's office, rather than an open clinic setting.
Effective treatments for opiate addictions are few and far between. Methadone and levomethadyl acetate have been used as "substitution therapies" to block cravings, but the circumstances under which they are dispensed are strictly regulated and sometimes humiliating to the addicted person, who must report to a clinic every day to take his or her dose while being monitored. These therapies are also only available for people who have had long-term addictions. According to Dr. Paul Bridge, co-principal investigator of a study appearing in the Sept. 4 issue of the New England Journal of Medicine, some 90 percent of people who are opiate-dependent are not in treatment.
The U.S. Food and Drug Administration approved buprenorphine alone and in combination with naloxone last year. Thanks to the Drug Addiction Treatment Act of 2000, these medications can also now be dispensed from a physician's office.
While researchers had already seen the superiority of buprenorphine over a placebo, they did not know how well the combination worked, nor did they know how well buprenorphine worked on its own in an office setting. The investigators also wanted to look more closely at safety issues.
The initial study involved 326 people addicted to opiates who were randomly assigned to receive ether buprenorphine and naloxone, buprenorphine alone, or a placebo. Both the buprenorphine alone and in combination were found to be more effective than the placebo. In the combined group, 17.8 percent of urine samples were negative for opiates and in the buprenorphine group, 20.7 percent were negative. In the placebo group, only 5.8 percent tested negative. The active treatment groups also reported fewer cravings. The drug was administered daily in an office setting, while extra medication was provided for at-home use on weekends and holidays.
After this phase of the trial, an "open-label" phase continued in which 268 participants in the initial trial received the combination treatment. Here, the percentage of urine samples coming out negative for opiates ranged from 35.2 percent to 67.4 percent.
The need for new and different addiction treatments seems to have been confirmed by the speed at which subjects were recruited for the trial. "One site in New York completed recruitment in 48 hours," says Bridge, who, at the time of the study, was chief of the clinical trials branch of the National Institute on Drug Abuse. "There's a real demand for this."
Both the combination product and the buprenephrine alone each probably have a place in treatment, Bridge says.
"I'm excited not only from the standpoint of medication but from the point of view of the treatment paradigm," says study author Paul Fudala, a clinical toxicologist with the VA Medical Center in Philadelphia. "It's exciting to be able to offer this option to people, because treatment has shown to be more effective than incarceration or no treatment. So many pieces had to fall into place."
Those pieces included the science as well as the legislation. Other pieces are still finding their place. For the program to meet the need, physicians have to receive a waiver of the requirements to comply with the Controlled Substances Act from the government and receive training. According to an accompanying article, however, only 1,981 waiver applications have been received.
"For almost 80 years, it was illegal for physicians to prescribe narcotic medications to treat opioid dependence. It's going to take a while for physicians to make the transition. We need to change the culture," says Dr. H. Westley Clark, director of the Center for Substance Abuse Treatment, part of the Substance Abuse and Mental Health Services Administration, and author of an accompanying article. "We've got to help physicians make a transition into recognizing that they can now treat this problem in their office."
"Certainly there is a real transition from the research clinic to the everyday treatment clinic," Bridge adds. "The ultimate goal of this is to increase treatment capacity. That's going to be the defining test whether this is successful or not. All the hurdles that are there with regard to introducing a new medication are going to be amplified for this drug because it's a new medication and a new treatment setting. It has not been attempted previously."
More information
For more on buprenorphine, visit the Substance Abuse and Mental Health Services Administration. The National Alliance of Methadone Advocates has more on methadone.
