TY - JOUR
T1 - The suitability of oral diacetylmorphine in treatment-refractory patients with heroin dependence: A scoping review
AU - F. Martins, Margarida L.
AU - Wilthagen, Erica A.
AU - Oviedo-Joekes, Eugenia
AU - Beijnen, Jos H.
AU - de Grave, Nelda
AU - Uchtenhagen, Ambros
AU - Beck, Thilo
AU - van den Brink, Wim
AU - Schinkel, Alfred H.
N1 - Funding Information: This review has been made possible in part through a financial contribution from DiAcetylM BV (The Netherlands). DiAcetylM BV does not produce diacetylmorphine intended for oral administration. A representative of DiAcetylM BV (J.H.B) did contribute to the study design and interpretation of the data as well as to the writing of the manuscript and the decision to submit for publication. Publisher Copyright: © 2021 Elsevier B.V.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - Objective: To review the scientific literature on the pharmacokinetics, pharmacodynamics and clinical efficacy and safety of (supervised) oral diacetylmorphine for patients with severe heroin dependence. Methods: 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. Results: 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. Conclusions: 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.
AB - Objective: To review the scientific literature on the pharmacokinetics, pharmacodynamics and clinical efficacy and safety of (supervised) oral diacetylmorphine for patients with severe heroin dependence. Methods: 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. Results: 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. Conclusions: 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.
KW - Diacetylmorphine
KW - Heroin
KW - Heroin-assisted treatment
KW - Opioid dependence
KW - Oral administration
KW - Scoping review
UR - http://www.scopus.com/inward/record.url?scp=85114333875&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.drugalcdep.2021.108984
DO - https://doi.org/10.1016/j.drugalcdep.2021.108984
M3 - Review article
C2 - 34482044
SN - 0376-8716
VL - 227
JO - Drug and alcohol dependence
JF - Drug and alcohol dependence
M1 - 108984
ER -