BioWorld International Correspondent

LONDON - A drug that has been considered as an alternative to methadone can safely and successfully treat people addicted to heroin, a joint Swedish-American study has shown.

All patients taking part in the trial were treated with either a placebo or the drug, buprenorphine, and all received intensive counseling and attended therapy sessions to identify ways of coping with the craving for heroin.

The trial found that 75 percent of patients in the buprenorphine group stayed in treatment for one year, and none died, compared to a 100 percent dropout rate and a 25 percent mortality rate in the placebo group. Urine tests for use of other drugs were negative 75 percent of the time in the buprenorphine group.

A report of the trial's results appears in an article in the Feb. 22, 2003, issue of The Lancet titled "1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden: a randomised, placebo-controlled trial."

Markus Heilig, associate professor at the Karolinska Institute in Stockholm, Sweden, and one of the authors of the paper, told BioWorld International, "We interpret this study as showing how the pharmacological treatment can set the scene and make it possible to deliver the modern evidence-based psychological treatment. Normally, people are fighting about whether you should do one or the other, but this trial shows what you can achieve if you get the two to work together."

Heilig said the trial documented how people in the treatment group had not only stopped taking drugs, but had begun to get their lives back together as demonstrated by their return to paid employment, their improved housing and a reduction in measures of criminality to almost zero.

Commenting on the paper in the same issue, Fergus Law and David Nutt of the Psychopharmacology Unit at the University of Bristol, UK, say the trial is likely to become "a classic." They write, "The results have far-reaching implications for the treatment of opioid dependence in general, and the role of psychological treatments and buprenorphine in particular."

They warn, however, that although the results for treatment with buprenorphine were "remarkably good," it is unlikely that treatment with this drug will produce such good outcomes outside the setting of a clinical trial.

Buprenorphine is a partial opiate-receptor agonist, unlike methadone, which is a full agonist of the brain's opiate receptors. "Because of this characteristic, buprenorphine activates the opiate receptors sufficiently to reduce the craving for heroin," Heilig said, "but there is a plateau for this effect, which means that you get virtually no toxicity - unlike with methadone where you can get respiratory depression in overdose. The reduced craving therefore helps to prevent relapse but, in addition, if someone samples the drug as a result of old habits, the partial agonist becomes a functional antagonist, so preventing heroin-induced euphoria."

For the trial, Heilig and his colleagues recruited 40 people older than 20 who were dependent on opiates but did not fulfill the Swedish legal criteria for treatment with methadone. They were allocated at random either to a dose of 16 milligrams of buprenorphine sublingually for 12 months (supervised daily for six months with the possibility of being able to self-administer the drug at home after that), or a six-day regimen of buprenorphine in a dose tapering to nothing, followed by placebo.

All patients had regular group therapy to help them avoid relapse, individual counseling sessions once a week and had to provide urine samples three times a week, which were tested for illicit drug use. All 20 patients in the placebo group dropped out of treatment, and in each case this followed positive urine tests for drugs. Only five of the 20 patients in the treatment group dropped out, again following positive urine tests.

Statistical analysis of the addiction severity index scores of the treatment group showed a highly statistically significant reduction in score.

Survival of the placebo group was significantly lower than the buprenorphine group: four of the 20 people who dropped out of the placebo group died during the treatment period, whereas none of the buprenorphine-treated group died.

Heilig says he would now like to compare the success of the buprenorphine treatment he and his colleagues studied with that of optimally delivered methadone treatment. He also wants to investigate whether it may be possible to discontinue treatment with buprenorphine after some years of maintenance, something that is possible to achieve without relapse in only 10 percent to 15 percent of people on methadone.