Naltrexone implants shown to be more effective than oral form

October 2009, Archives of General Psychiatry

Context: Oral naltrexone hydrochloride effectively antagonizes heroin, but its utility is limited by patient noncompliance. Sustained-release preparations may overcome this limitation.

Naltrexone implants are more effective than oral naltrexone for helping heroin-dependent individuals stay off the drug, a small study in the Archives of General Psychiatry shows.

"Sustained-release naltrexone implants appear to provide a new treatment option for patients with heroin dependence, particularly for those seeking an alternative to opioid agonist maintenance," Dr. Gary K. Hulse of the University of Western Australia in Nedlands and his colleagues conclude.

While oral naltrexone has been approved in the US since 1984 for treating opiate dependence, patient compliance with daily dosing has hampered its efficacy, Dr. Hulse and his team note. Sustained-release formulations that are injected or surgically inserted have been shown to be safe and effective, but until now had never been compared with oral dosing, they add.

To do so, the researchers randomly assigned 70 heroin-dependent individuals to receive 50 mg daily of oral naltrexone for six months along with a placebo implant, or placebo tablets plus a 2.3-gram naltrexone implant.

One of the study's main outcome measures was maintenance of naltrexone blood levels above 2 ng/mL. According to their report, significantly more patients on oral naltrexone had drug blood levels below 2 ng/mL at one and two months compared to patients given implants, the researchers found.

Another main outcome was relapse to heroin use. By 6 months, the investigators report, significantly more patients in the oral treatment group had gone back to using heroin at least four times a week.

The average time to relapse was 115 days for patients given the pills, compared to 158 days for the implant users.

Five people in the oral group and four in the implant group were lost to follow-up and were regarded as having returned to regular heroin use. However, the researchers note, just two people in the implant group admitted to starting heroin again, at 152 and 159 days. "Clinically, these results are particularly impressive," they write.

Among male implant patients, mean naltrexone levels were maintained above 1 ng/mL for 101 days and above 2 ng/mL for 56 days. Among female patients, mean drug levels stayed above 1 ng/mL levels for 124 days and above 2 ng/mL for 43 days.

This duration of effectiveness is promising, given that heroin-dependent individuals may not return for monthly treatment, the researchers note. But implantation does require a "minor surgical procedure," they add, so injections "may be more acceptable to some patients and health care providers." The one serious adverse event seen in the study was a wound hematoma related to surgical implantation.

Nevertheless, "single or sequential applications of this type of treatment might significantly affect the long-term prognosis for heroin-dependent persons," the researchers write. "It is likely that the relapse rate for heroin dependence can be greatly reduced using this approach to treatment."

See more at Archives of General Psychiatry.