In a group of North American long-term opioid dependent patients, supervised injections of diamorphine gave better results over twelve months than oral methadone according to a controlled trial.

Clinical trials in Europe have shown that injectable diamorphine can be effective in the treatment of refractory opioid dependency, however there have been no major trials of this option in North America. This Canadian study compared injectable diacetylmorphine with oral methadone maintenance therapy in patients with opioid dependence that was refractory to treatment: eligible participants were long-term users of injectable heroin who had not benefited from at least two previous attempts at treatment for addiction (including at least one methadone treatment). They were randomised to treatment with oral methadone or supervised injections of diamorphine: a subgroup of the injection group was also randomised on a double-blind basis to injectable hydromorphone to allow determination of illicit diamorphine intake. All patients were offered primary care and psychosocial services according to Canadian best practice. Two primary outcomes were assessed, both after 12 months: retention in addiction treatment or confirmed drug-free status, and a 20% reduction in illicit-drug use or other illegal activity from baseline according to the European Addiction Severity Index. Participants who were lost to follow-up were considered to have not been retained in treatment nor to have had a response.

Screening identified a total of 581 potentially eligible patients, of whom 251 consented to treatment and were randomised: 111 to oral methadone, 115 to injectable diamorphine, and 25 to injectable hydromorphone. Twelve-month retention data were available for 245 participants and response data for 240. On the basis of an intention-to-treat analysis, retention rate in the diamorphine group was 87.8%, vs. 54.1% in the methadone group (rate ratio for retention, 1.62; 95% CI, 1.35 to 1.95; P<0.001). The reduction in rates of illicit-drug use or other illegal activity was 67.0% in the diamorphine group vs. 47.7% in the methadone group (rate ratio, 1.40; 95% CI, 1.11 to 1.77; P=0.004). Retention and response rates in the hydromorphone group was similar to that in the diamorphine group.

In both groups there was a significant reduction in expenditure on illicit drugs: both spent a median of $1,200 (U.S. dollars) on illicit drugs in the month before baseline; at 12 months, expenditure was $320 in the diacetylmorphine group and $400 in the methadone group.

During the course of the study, 79 serious events were reported in 54 patients, including one death in the methadone group ascribed to opioid overdose. Overdoses and seizures were the most frequent serious adverse events, all occurring in the injection drugs group and all were effectively treated without sequelae.

The authors conclude that in this population of dependent opioid users refractory to treatment, injectable diamorphine was better then oral methadone. They note that in this study, hydromorphone appeared to be as effective as diamorphine and indistinguishable from it by the participants, although the study was not powered to compare the two. They suggest that while optimised oral methadone should remain the first choice for most patients, their results indicate that in those for whom this is ineffective, supervised injectable treatment is safe and effective.

An accompanying editorial discusses the study.