https://immattersacp.org/weekly/archives/2017/11/21/2.htm

Extended-release naltrexone may be as effective as buprenorphine but more difficult to initiate

Buprenorphine might be a safer initial strategy for many patients because of the better chance of a quick, successful induction, a comment author noted.


In a recent open-label trial, extended-release naltrexone was as effective as buprenorphine-naloxone at preventing relapse in patients with opioid use disorder, although the opioid antagonist presented challenges with treatment initiation.

Between Jan. 30, 2014, and May 25, 2016, researchers randomized 570 participants at eight U.S. community-based inpatient services to receive either extended-release naltrexone (n=283) or buprenorphine-naloxone (n=287). Because buprenorphine-naloxone has opioid receptor agonist activity, induction requires only that an individual progresses to a mild state of opioid withdrawal before starting treatment. However, extended naltrexone is an opioid receptor antagonist and requires complete detoxification and an opioid washout period before initiating therapy.

Naltrexone was given as a monthly intramuscular injection, whereas buprenorphine was taken daily in sublingual form. Most participants were white men between the ages of 25 and 45 years who had been primarily using heroin by injection.

The primary outcome was relapse-free survival during 24 weeks of outpatient treatment, with the last follow-up visit occurring on Jan. 31, 2017. Secondary outcomes included adverse events and the proportion of participants successfully inducted with an initial medication dose.

Results were published online on Nov. 14 by The Lancet.

Fewer participants in the naltrexone group were successfully inducted into treatment compared to the buprenorphine group (72% [204 of 283 patients] vs. 94% [270 of 287 patients]; P<0.0001). Because nearly all of the naltrexone-induction failures resulted in early relapse (89% [70 of 79 patients]), the intention-to-treat analysis favored buprenorphine.

At the end of follow-up, overall relapse events were greater in the naltrexone group than the buprenorphine group (65% [185 of 283 patients] vs. 57% [163 of 287 patients]), for a hazard ratio of 1.44 (95% CI, 1.02 to 2.01; P=0.036). However, in the per protocol population (n=474), there was no significant difference in relapse events between groups (52% [106 of 204 patients] for naltrexone vs. 56% [150 of 270 patients] for buprenorphine), for a hazard ratio of 0.92 (95% CI, 0.71 to 1.18; P=0.49). Adverse events, including fatal and nonfatal overdoses, did not differ between groups, with the exception of mild-to-moderate naltrexone injection-site reactions. Overall, five fatal overdoses occurred (two in the naltrexone group and three in the buprenorphine group).

The authors noted limitations of the study, including differences in opioid detoxification protocols between sites and potential confounding in the per protocol analyses. Although many opioid-dependent patients choose naltrexone over buprenorphine for various reasons, the associated risks of induction failure and subsequent relapse “must be carefully considered, unless [patients] will be in a controlled setting long enough to withdraw completely from opioids before induction,” an accompanying comment noted. “[Buprenorphine] might be a safer initial strategy for many of these patients because of the better chance of a quick successful induction.”

A second comment, authored by the director of the National Institute on Drug Abuse (the trial's funding source), pointed out that the reach of effective treatments for opioid use disorder has been limited by structural and attitudinal barriers. “These barriers are holdovers from an era when drug addiction was still seen as a moral failing best addressed by the legal system, not a medical condition best addressed through treatment,” the commentator wrote.

The October issues of ACP Internist and ACP Hospitalist called attention to the burgeoning need to provide evidence-based treatment for patients with opioid use disorder. Read the cover stories to see which medications experts recommend in primary care and in the hospital.