The suitability of oral diacetylmorphine in treatment-refractory patients with heroin dependence: A scoping review

•Oral diacetylmorphine (DAM) is unlikely to produce a (substantial) opioid-‘rush’.•Oral DAM and oral morphine/methadone are equally effective in preventing opioid withdrawal.•Opioid dependent patients with low need of opioid-‘rush’ may benefit from oral DAM treatment.•Oral DAM can be suitable for opioid dependent patients with venosclerosis.•Take-home DAM dosages should be considered for stabilized opioid dependent patients. To review the scientific literature on the pharmacokinetics, pharmacodynamics and clinical efficacy and safety of (supervised) oral diacetylmorphine for patients with severe heroin dependence. The PubMed, Embase, Web of Science and PsycINFO databases were searched. Eleven published studies were identified and selected based on defined eligibility and exclusion criteria. Four pharmacokinetic studies reported negligible plasma concentrations of diacetylmorphine and its active metabolite 6-monacetylmorphine. Among six pharmacodynamic studies, three trials showed that oral diacetylmorphine reduced opioid withdrawal symptoms, one open-label pilot study reported that two patients experienced a modest ‘rush’ after oral diacetylmorphine and two studies found that patients could not distinguish between oral diacetylmorphine, methadone, or morphine. Regarding the clinical studies, a Swiss prospective cohort study in patients with heroin dependence showed high retention rates of oral diacetylmorphine treatment with few serious adverse events, whereas in the Canadian SALOME trial, oral diacetylmorphine treatment was prematurely discontinued because treatment retention of oral diacetylmorphine was lower than injectable diacetylmorphine maintenance treatment. Finally, two case studies illustrate the limitations and potential problems of oral diacetylmorphine in the treatment of treatment-refractory heroin dependent patients. Based on all published data, it is unlikely that oral diacetylmorphine produces a substantial ‘rush’. Prescription of oral diacetylmorphine might therefore be effective only for treatment-refractory patients with heroin dependence (i) as maintenance treatment for those who never injected or inhaled opioids; (ii) as maintenance treatment for those who want to switch from injection to oral administration of diacetylmorphine; and/or (iii) to reduce opioid withdrawal symptoms.