REVIEW OF: Oviedo-Joekes E et al, JAMA Psychiatry 2016;73(5):447–455

We have effective FDA-approved medications for opioid use disorder (OUD): buprenorphine, methadone, and injectable naltrexone. Yet some patients with severe OUD decline these options. Many other countries offer a more controversial treatment—medically supervised IV administration of diacetylmorphine, the active ingredient in heroin. Six randomized trials have endorsed the effectiveness of this approach, but diacetylmorphine is not available in North America for regulatory/legal reasons. Investigators at Providence Health Care in Vancouver, BC, designed a study to determine if injectable hydromorphone (Dilaudid) may be as effective as diacetylmorphine in reducing illicit opioid use.

In a double-blind trial, investigators randomized participants who were injecting heroin illicitly (n = 202) to either hydromorphone or diacetylmorphine for 6 months of up to thrice-daily supervised treatment. The outcome measures were self-reported illicit heroin use, self-reported street opioid use, and urine toxicology.

The results suggested non-inferiority for hydromorphone in the per-protocol analysis. Individuals offered hydromorphone were just as unlikely to report street heroin use as those offered diacetylmorphine (odds ratio -1.44, 90% confidence interval [CI] -3.22–0.27), and the same was the case for report of any illicit opioid use (odds ratio -0.15, 90% CI -2.09–1.76). The study included two other hopeful findings. First, participants weren’t able to distinguish between hydromorphone and diacetylmorphine in terms of the high they felt, implying that hydromorphone may be a successful substitution for heroin. Second, hydromorphone was safer than diacetylmorphine, with only 5 severe adverse events (SAEs) and 3 overdoses for the former, versus 24 SAEs and 11 overdoses for the latter.

CATR’s TAKE
This study provides hopeful evidence of IV hydromorphone as a clinically comparable, perhaps safer alternative for those patients who do not succeed in or engage with other medications for OUD. It offers a new option for harm reduction in this difficult-to-treat population.