Review of: Sullivan MA et al, Am J Psychiatry 2017;174(5):459–467

Extended-release (XR) naltrexone (Vivitrol) is FDA approved for opioid use disorder and has shown efficacy in several trials. It works best for patients who have already successfully detoxed from opioids and who are highly motivated to abstain. But what about oral naltrexone? While it is effective for alcohol use disorder, studies for opioid use disorder have shown limited utility. The reason is obvious—patients who are craving a fix can simply skip a dose of the naltrexone pill in order to achieve an opioid high, whereas the XR formulation forces a long delay, during which patients might reconsider their decision to use. Oddly enough, though, no study has been done comparing oral to XR naltrexone, until now.

Researchers randomized 60 adults with opioid use disorder (DSM-IV opioid dependence) to either oral or XR naltrexone. The study was a 6-month open-label trial, excluding people with unstable medical or psychiatric disorders, physical dependence on alcohol or sedative-hypnotics, treatment with opioids or psychotropic medications, and history of opioid overdose in the prior 3 years. The primary outcome measure was retention in treatment.

The study didn’t quite mimic real-world treatment, as study participants in both groups were asked to attend behavioral therapy sessions twice weekly, and those randomized to oral naltrexone either had to have a responsible adult as an involved medication monitor at home or go to the clinic 3 times weekly to have it administered. Vouchers were used to reinforce attendance. Participants were mostly white (63.3%), male (83.3%), and in their late 30s (mean age 39.5, SD = 11.1).

At the end of 6 months, the retention rate in the XR naltrexone group was significantly higher than the oral naltrexone group (57.1% and 28.1%, respectively). There was no significant difference in the percentage of ­opioid-positive urine tests between the groups, though that was not the primary outcome, and missed urine tests were not counted as positive.

Overall, the treatment was well tolerated, and most adverse events reflected opioid withdrawal and gradually improved.

CATR’s Take
The results confirm that XR naltrexone is more effective than oral naltrexone, even when rigorous strategies are used to ensure adherence with the oral formulation. We still recommend reserving XR naltrexone for patients who cannot be on buprenorphine or methadone—medications for which we have even more robust data.