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Research Summary

Injectable Diacetylmorphine for Second-Line Treatment of Opioid Addiction

Opioid agonist therapy (OAT) is the most effective treatment for opioid addiction, but some patients continue using illicit opioids even during treatment with optimal doses of oral methadone. In a randomized trial, UK investigators compared open-label treatment with supervised titrated doses of oral methadone, daily injected methadone, or twice-daily injected diacetylmorphine (heroin) among 127 patients receiving OAT who continued to use illicit opioids. The injectable treatments were supplemented with oral methadone when patients were unable to come to a participating clinic for injections.

  • At 26 weeks, 80% of subjects remained on their assigned treatments.
  • The primary outcome was 50% or more urine specimens negative for opioids and impurities associated with street heroin. More patients assigned to diacetylmorphine achieved this outcome (72%) than did those receiving injectable methadone (39%) or oral methadone (27%).
  • Abstinence or near abstinence (2 or fewer positive urine tests in 12 weeks) was also more common in the diacetylmorphine group.


To interpret these results without distraction, it may be useful to call the medication used a “novel pharmacotherapy,” which significantly reduced illicit heroin use among opioid-addicted patients who continued to inject heroin despite receiving OAT. A major study limitation, aside from the open-label design, is the lack of outcome measures beyond drug use; a short-acting agonist may not be the best treatment for patients with opioid addiction because of the need for frequent administration and the physiologic effects of fluctuating serum opioid levels. Even so, the treatment described here would likely improve outcomes among those for whom current best treatments are inadequate. The likelihood of even supervised heroin treatment of opioid addiction being allowed in the US, however, seems low. What happens clinically in countries where such trials have taken place (e.g., the UK, the Netherlands, Spain, Switzerland, Canada, and Germany) should be of great interest. Richard Saitz MD, MPH


Strang J, Metrebian N, Lintzeris N, et al. Supervised injectable heroin or injectable methadone versus optimised oral methadone as treatment for chronic heroin addicts in England after persistent failure in orthodox treatment (RIOTT): a randomised trial. Lancet. 2010;375(9729):1885–95.