Treatment with injectable diacetylmorphine, the active ingredient in heroin, compared favorably with methadone treatment in a phase III clinical trial reported in the the New England Journal of Medicine.
Patients who received diacetylmorphine through the North American Opiate Medication Initiative were more likely to stay in treatment, reduce their use of illegal drugs, and scale back other illegal activities than were those given methadone. They also showed greater improvements in medical, psychiatric, and economic status, and in their family and social relationships, which “suggests a positive treatment effect beyond reduction in illicit-drug use or other illegal activities,” said Eugenia Oviedo-Joekes, Ph.D., of the University of British Columbia, Vancouver, and her associates (N. Engl. J. Med. 2009;361:777-86).
“Methadone, provided according to best-practice guidelines, should remain the treatment of choice for the majority of patients. However, there will continue to be a subgroup of patients who will not benefit even from optimized methadone maintenance.
Prescribed, supervised use of diacetylmorphine appears to be a safe and effective adjunctive treatment for this severely affected population of patients who would otherwise remain outside the health care system,” the investigators said.
Injectable diacetylmorphine has been used in several European countries for many years. To assess its performance in a North American population, Dr. Oviedo-Joekes and her colleagues performed an open-label, randomized, controlled trial in Montreal and Vancouver.
A total of 115 patients were randomly assigned to receive diacetylmorphine, 111 to receive standard oral methadone, and 25 to receive injectable hydromorphone for validation of the self-reported use of illicit heroin by means of urine testing. All the study subjects had long histories of injectable drug use and extensive involvement in criminal activity, and all had undergone multiple attempts at treatment.
The medications were administered daily and under supervision in clinics, and patients were allowed to switch, partially or totally, to oral methadone if they wished. Twenty-three of the diacetylmorphine patients switched to methadone.
To ensure safety, all study subjects who received injectable medications were observed for 30 minutes after each injection.
After 1 year of follow-up, 67% of the diacetylmorphine group improved in illicit drug use and other illegal activities, compared with 48% of the methadone group. Scores improved on more subscales on a measure of this outcome, and they improved to a greater degree, with acetylmorphine than with methadone.
The rate of retention in treatment also was better with diacetylmorphine (88%) than with methadone (54%). Rates of response and retention with hydromorphone were 64% and 88%, respectively.
The mean number of days of illicit heroin use during the preceding month declined from 27 to 5 with diacetylmorphine and from 27 to 12 with methadone. At baseline, both groups had spent a median of $1,200 (U.S.) per month on illicit drugs, which was reduced to $320 with diacetylmorphine and to $400 with methadone.
A total of 54 patients reported 79 serious adverse events–18 with methadone, 51 with diacetylmorphine, and 10 with hydromorphone. Overdoses and seizures were the most common serious adverse events associated with diacetylmorphine.
“Sixteen of the 115 patients randomly assigned to receive diacetylmorphine had a life-threatening overdose or seizure during the study. Because the study included close medical supervision, these serious adverse events were promptly treated, and all patients recovered,” the investigators noted.
No potential conflicts of interest were reported.