Hydromorphone Compared With Diacetylmorphine for Long-term Opioid Dependence

Prerana Patel, Mercer University College of Pharmacy


The American Society of Addiction Medicine (ASAM) states that nearly 23% of individuals who use heroin will develop an opioid addiction.  It is also stated that of the 21.5 million Americans who had a substance use disorder in 2014, 586,000 of those individuals abused heroin.   The death toll from drug abuse amongst women tripled from 2010 to 2013. [1]

Title: Hydromorphone Compared With Diacetylmorphine for Long-term Opioid Dependence [2]
Design Phase 3, double-blind, non-inferiority trial, N = 202
Objective To test if injectable hydromorphone hydrochloride is noninferior to injectable diacetylmorphine in reducing illicit heroin use for chronic injection opioid users after 6 months of intervention
Study Groups Hydromorphone (n = 100), diacetylmorphine (n = 102)
Methods Participants were randomly assigned to receive injectable diacetylmorphine or hydromorphone (up to three times daily) for 6 months under supervision.
Duration December 19, 2011 to December 18, 2013
Primary Outcome Measure Self-reported days of street heroin use
Baseline Characteristics   Hydromorphone Hydrochloride

(n = 100)

Diacetylmorphine Hydrochloride

(n = 102)

Age, mean (SD), y 45.17 (10.19) 43.50 (9.03)
Male, No. (%) 67 (67.0) 73 (71.6)
Female, No. (%) 33 (33.0) 29 (28.4)
Years injecting street heroin, mean (SD) 15.56 (9.45) 15.34 (9.29)
Days of illegal activities in the prior month, mean (SD) 12.78 (13.58) 15.50 (3.77)
Results   Hydromorphone Diacetylmorphine
Days of street heroin use in the prior month, no. of days
Intent to treat (ITT) 5.50 (3.81 to 7.34) 3.15 (1.82 to 4.67)
Per protocol (PP) 4.08 (2.42 to 5.81) 2.64 (1.36 to 3.95)
Days of street opioid use in the prior month, including heroin, no. of days
ITT 5.75 (4.07 to 7.62) 4.90 (3.34 to 6.79)
PP 4.34 (2.66 to 6.18) 4.20 (2.62 to 5.88)
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: Overdose: hydromorphone (1.49%), diacetylmorphine (5.45%); seizure: diacetylmorphine (1.98%)
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions This study provides evidence to suggest noninferiority of injectable hydromorphone relative to diacetylmorphine for long-term opioid dependence.  In jurisdictions where diacetylmorphine is currently not available or for patients in whom it is contraindicated or unsuccessful, hydromorphone could be offered as an alternative.

Heroin overdose and addiction is a serious problem in today’s society and treatment is not always simple.  Due to federal and state laws, the use of diacetylmorphine is not always allowed and this study helps give an alternative solution.  The study also shows that serious side effects with hydromorphone use are less when compared to diacetylmorphine further making hydromorphone a great alternative to use. In this study, there were less adverse effects associated with hydromorphone, which makes it an even more attractive alternative to diacetylmorphine.



[1] American Society of Addiction. Opioid Addiction 2016 Facts & Figures. Available at: http://www.asam.org/docs/default-source/advocacy/opioid-addiction-disease-facts-figures. Accessed November 10, 2015.

[2] Oviedo-joekes E, Guh D, Brissette S, et al. Hydromorphone Compared With Diacetylmorphine for Long-term Opioid Dependence: A Randomized Clinical Trial. JAMA Psychiatry. 2016


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