The Central Committee on the Treatment of Heroin Addicts (CCBH), which was installed by the Netherlands Minister of Health, has recently completed a large-scale study, which focused on the effect of medical prescription of heroin to chronic, treatment-resistant heroin addicts.

These addicts are in bad physical and psychological health, and most of them are highly dysfunctional in spite of long-term treatment in a methadone maintenance program. The committee concludes that a 12-month treatment of these patients with a combination of heroin and methadone is more advantageous to their medical and social condition than a 12-month treatment with methadone alone.

These gains are lost very soon after discontinuation of the treatment with heroin. The committee, therefore, recommends the introduction under stringent conditions in the Netherlands of supervised medical prescription of methadone plus heroin to chronic, treatment-resistant heroin dependent patients as a last-resort pharmacotherapeutic option.

Out of the estimated 25,000 heroin addicts in the Netherlands, approximately 13,000 are treated in methadone maintenance programs. About 5,000 of them are doing well. They are not using illegal drugs any longer, are in good health, and are socially reintegrated. The remaining 8,000 methadone treated patients are not profiting sufficiently from this treatment. In spite of their participation in the methadone program, these patients continue to use illegal drugs, often engage in criminal activities, are in poor health, and lead a marginalised existence.

In 1996, the Netherlands Minister of Health commissioned the CCBH to conduct a study that would focus on the beneficial and adverse effects of supervised dispensation of heroin to chronic, treatment-resistant heroin addicts, who did not sufficiently profit from participation in a methadone maintenance program.

Between 1998 and 2001, 549 patients were included in one of two randomised controlled trials: 174 in a trial for patients who are predominantly injecting heroin and 375 patients in a trial for patients who are predominantly inhaling heroin. In these trials, patients who received heroin and methadone for 6 or 12 months were compared with patients who received methadone alone during the same period. In addition, the effect of discontinuation of heroin treatment after 6 or 12 month was investigated.

The results of the study indicate that treatment with heroin in combination with methadone is more effective than treatment with methadone alone. The proportion of patients with a favourable response in the group that received heroin was 20-25% higher than in the group that received methadone alone. A favourable response was defined as clinically relevant improvements in physical and psychological health as well as improvements in social functioning, including reductions in criminality. The medical co-prescription of heroin resulted in a modest decrease in the consumption of cocaine.

Two months after the discontinuation of the treatment with heroin, the condition of more than 80% of the patients had seriously deteriorated and health gains were lost entirely.

The study also showed that supervised medical co-prescription of heroin is safe and controllable and does not increase public order problems.

Based on these results, the CCBH recommends: (1) the introduction under stringent conditions in the Netherlands of supervised medical prescription of methadone plus heroin to treatment-resistant heroin addicts as a last-resort pharmacotherapeutic option; (2) the promotion of an application for registration of heroin as a medicinal product; and (3) the development of a quality assurance system for the medical prescription of heroin.

The report with the first results, conclusions and recommendations will be presented to the Netherlands Minister of Health on Monday 4 February 2002 at 10.30 a.m. in The Hague (Nieuwspoort).

Further information: CCBH Utrecht
Stratenum - 5e verdieping/5th floor
Universiteitsweg 1000
3584 CG Utrecht
The Netherlands
CCBH@med.uu.nl

Main result: "The main finding of the study is, that methadone plus heroin treatment was more effective than methadone alone treatment in a population of chronic, treatment-resistant heroin dependent patients treated with methadone, irrespective of route of administration, population in the analysis (intention-to-treat; treatment completers), outcome parameter 12 months after randomization (response on the multi-domain outcome index; sustained response on the multi-domain outcome index; no longer meeting inclusion thresholds for the trial), and study site. On the main outcome parameter, the effect size amounted to 25% difference in response between the experimental and control group among injectors (OR=2.99) and to 23% difference in response among inhalers (OR=2.77). In a population of chronic, treatment-resistant patients, a difference in treatment response of more than 20% is generally regarded as quite substantial."

Nature of improvements: "The results of both trials showed that the supervised co-prescription of heroin to chronic, treatment-resistant methadone patients lead to improvements in all health outcome domains: physical health, mental status and social functioning. The experimental treatment with methadone plus heroin did not only yield more responders than the control treatment with methadone alone, but also yielded more multi-domain responders, indicating a more comprehensive response in the experimental treatment groups. In addition, relatively high rates of multi-domain responders implies clinically relevant improvements in at least one medical outcome domain (physical health or mental status).

How quickly benefits became evident: "Both trials showed that treatment effects of the co-prescription of heroin seemed to occur very early in the treatment process, i.e. within the first two months of treatment. At the same time, the data showed an increase in the percentage of responders and in the comprehensiveness of the effect are observed until the end of the randomized treatment phase of the study. Injectors seemed to respond somewhat quicker than inhalers. Among the injectors, the maximum effect in terms of the percentage of responders was almost reached at two months, but the quality of the response (percentage multi-domain responders; and percentage responders no longer meeting any of the inclusion thresholds) further improved during the course of the 12 months treatment."

Effect of discontinuance: "The current study showed that the majority (81-87%) of the treatment responders in the experimental condition deteriorated substantially following discontinuation of the heroin prescription. The severity of this deterioration is illustrated by the fact that the mean scores two months after discontinuation of the co-prescribed heroin had returned to the dysfunctional levels just before the start of the intervention.

"Taken together, these findings suggest that the benefits of supervised co-prescription of heroin in chronic, treatment-resistant heroin dependent patients in the current study were linked to the continuation of treatment."