Injectable diacetylmorphine was more effective than oral methadone. Because of a risk of overdoses and seizures, diacetylmorphine maintenance therapy should be delivered in settings where prompt medical intervention is available. (ClinicalTrials.gov number, NCT00175357.)

IMPORTANCE Diacetylmorphine hydrochloride (the active ingredient in heroin), delivered under supervision, is effective for the treatment of severe opioid use disorder. However, owing to political and regulatory barriers, it is not available in many settings around the world, which limits the options for many long-term street opioid injectors not attracted into or retained in available treatments. 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. DESIGN, SETTING, AND PARTICIPANTS The Study to Assess Longer-term Opioid Medication Effectiveness (SALOME) was a phase 3, double-blind, noninferiority trial. The study randomized 202 long-term street opioid injectors in Vancouver,

Most of the estimated 125,000 injection drug users (IDUs)

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Despite decades of experience treating heroin or prescription opioid dependence with methadone or buprenorphine— two forms of opioid substitution therapy—gaps remain between current practices and evidence-based standards in both Canada and the United States. This is largely because of regulatory constraints and pervasive suboptimal clinical practices. Less than 10 percent of all people dependent on opioids in the United States are receiving substitution treatment, although the proportion may increase with expanded health insurance coverage as a result of the Affordable Care Act. In light of the accumulated evidence, we recommend eliminating restrictions on office-based methadone prescribing in the United States; reducing financial barriers to treatment, such as varying levels of copayment in Canada and the United States; reducing reliance on less effective and potentially unsafe opioid detoxification; and evaluating and creating mechanisms to integrate emerging treatments. Taking these steps can greatly reduce the consequent harms of opioid dependence by maximizing the individual and public health benefits of treatment.

In patients with severe opioid use disorder enrolled into the SALOME trial, injectable hydromorphone provided similar outcomes to injectable diacetylmorphine. Modelling outcomes during a patient's life-time suggested that injectable hydromorphone might provide greater benefit than methadone alone and may be cost-saving, with drug costs being offset by costs saved from reduced involvement in criminal activity.

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