A prospective cohort study on orally administered heroin substitution for severely addicted opioid users

AIMS: To assess the efficacy and safety of orally administered heroin [diacetylmorphine (DAM)] tablets in substitution treatment of severely addicted opioid users. DESIGN: An open-label, prospective cohort study with two non-randomly assigned treatment arms and historical controls: DAM tablets only versus DAM tablets combined with injected DAM and/or other opioids, with an observation period of 1 year. SETTING: Twenty-one out-patient treatment centres of the Swiss heroin-assisted treatment programme. PARTICIPANTS: A total of 128 patients received DAM tablets only, and 237 patients received a combination of orally and intravenously applied DAM and other opioids. MEASUREMENTS: Retention rate after 1 year; number of serious adverse events; dosage of DAM over time; subjective tolerance of study medication. FINDINGS: In the intention-to-treat analysis, 1-year retention rates after 1 year in the DAM tablets-only group [0.804, 95% confidence interval (CI) = 0.735-0.873] as well as in the subgroup combining oral application of DAM with intravenous application or other opioids (0.843, 95% CI = 0.797-0.889) were higher compared to historical controls (Swiss cohort of patients who had been substituted intravenously with DAM; 1-year retention rate = 0.70). Rates of serious adverse events under study medication (tablets only = 0.038 per application year; tablets in combination = 0.028 per application year) were comparable to the historical rate of the Swiss heroin-assisted treatment (0.043). CONCLUSIONS: DAM tablets seem to be an effective and safe application mode of heroin-assisted substitution treatment. Randomized clinical trials to compare its relative efficacy to other substances are necessary.