Injectable heroin or methadone for addiction treatment

by Charles Bankhead

Heroin addicts had almost a threefold increase in negative urine specimens when treated with supervised heroin injection rather than with oral methadone, data from a British study showed.

Overall, 72% of patients had negative specimens at least 50% of the time compared with 27% of patients assigned to oral methadone, according to the report published in the May 29 issue of The Lancet.

Treatment with injectable heroin almost doubled the success rate compared with injectable methadone, although the trial lacked statistical power for that comparison.

“We have shown that treatment with supervised injectable heroin leads to significantly lower use of street heroin than does supervised injectable methadone or optimized oral methadone,” John Strang, MD, of King’s College London, and co-authors wrote. “Furthermore, this difference was evident within the first six weeks of treatment.

At least 5% to 10% of heroin addicts do not benefit from conventional therapy. Whether the patients are untreatable or just difficult to treat is unclear, the authors wrote.

An evidence base has begun to emerge in support of carefully supervised medicinal heroin (diamorphine or diacetylmorphine) as second-line therapy for chronic heroin addiction, they continued, but its effectiveness has remained unclear.

The British government has allowed injectable heroin as an option for treating addiction, but injectable methadone has been used most often, the authors wrote. A 2002 update to England’s drug strategy set forth general principles for supervised heroin injection to ensure safety and prevent drug diversion. Following publication of the update, several medically supervised injection clinics opened in England.

A 2008 update opened the door for “rolling out the prescription of injectable heroin and methadone to clients who do not respond to other forms of treatment,” contingent on results of the randomized trial reported by Strang and colleagues.

For the study, the investigators enrolled 127 chronic heroin addicts who continued to inject street heroin on a regular basis, despite ongoing treatment with oral methadone. The participants were randomized to injectable methadone, injectable heroin, or optimized oral methadone treatment.

Injectable treatments were self-administered under direct nursing supervision at clinic sites. Participants assigned to injectable heroin went to the clinics twice a day to administer 450-mg doses. Injectable methadone was generally administered daily as a single 200-mg dose.

Randomized treatment continued for 26 weeks. The primary endpoint was the proportion of participants who tested negative for street heroin by urinalysis at least 50% of the time during weeks 14 through 26 (response).

The unadjusted intention-to-treat (ITT) analysis showed a response rate of 72% for injectable heroin, 39% for injectable methadone, and 27% for oral methadone. Injectable heroin achieved statistical superiority versus oral methadone (P<0.0001), but injectable methadone did not (P=0.264).

In an adjusted analysis, response rates were 66% for injectable heroin and 19% for oral methadone (P<0.0001). Injectable methadone had an adjusted response rate of 30%, also not significantly better than oral methadone.

The trial was not statistically powered to compare the two injectable treatments, nonetheless, injectable heroin demonstrated a significant advantage in the unadjusted (P=0.003) and adjusted (P=0.002) analyses.

Evidence of an advantage for injectable heroin emerged within the first six weeks.

“Treatment with supervised injectable heroin leads to significantly lower use of street heroin than does supervised injectable methadone or optimized oral methadone,” the authors wrote in conclusion. “U.K. government proposals should be rolled out to support the positive response that can be achieved with heroin maintenance treatment for previously unresponsive chronic heroin addicts.”

The results of the study reported by Strang and colleagues, combined with those from other studies, “should help to allay concerns about this approach, including methodological issues . . . safety, and cost,” Thomas Kerr, PhD, Julio S.G. Montaner, MD, and Evan Wood, MD, PhD, of the University of British Columbia in Vancouver, wrote in a commentary.

Nonetheless, implementation of supervised heroin injection has been delayed in several countries despite favorable results from clinical trials.

“History tells us that availability of heroin prescription can be dictated more by special interests and politics than evidence,” the commentators wrote.

“This state of affairs is sad because other medical specialties commonly embrace second-line therapies, even if only for a selected group who fail first-line treatments,” they continued.

“The existing interference and non-evidence-based opposition from politicians and care providers, who refuse to acknowledge the limitations of methadone maintenance and the superiority of prescribed heroin in selected populations, is arguably unethical,” the Canadian authors concluded.

“Denying effective second-line therapy to those in need ultimately serves to condemn many users of illicit heroin to the all too common outcomes of untreated heroin addition, including HIV infection or death from overdose.”

Charles Bankhead is a MedPage Today staff writer.

Originally published in MedPage Today. Visit for more addiction news.