Review of: Solli KK et al, Addiction 2018;113(10):1840-1849

Extended-release naltrexone (Vivitrol) has had some good data, yet getting patients on it remains a challenge, because an opioid-free period is required before starting it. Understandably, practitioners get nervous when patients stabilized on buprenorphine ask to be transitioned to extended-release (XR) naltrexone. But, if needed, can this switch be made safely and effectively?

To answer this question researchers in Norway conducted an open-label continuation of a previously-reported 3-month controlled trial. In the original study, 159 patients were randomized to up to 24 mg of buprenorphine/naloxone daily or 380 mg of extended-release (XR) naltrexone injection monthly. At the end of three months, participants were offered the option of continuing on XR naltrexone, switching from buprenorphine to XR naltrexone, or treatment with buprenorphine at a program outside the study. Of the 122 participants who completed the first phase, 117 chose XR naltrexone, and five chose buprenorphine outside of the study. XR naltrexone was not commercially available in Norway, which may account for the large number of people choosing it over buprenorphine. The switch was carefully made during a detox admission, where XR naltrexone was initiated after a test dose of naloxone and a minimum of 72 following any opioid intake (which is a lot shorter than the commonly recommended washout period), and adjunctive medications were available to help relieve withdrawal symptoms. Participants were followed for another 9 months, and the primary outcomes were continuation of treatment and abstinence rates for those who remained on XR naltrexone (n=54) compared with those who initiated XR naltrexone (n=63).

Participants were men and women ages 18-60 years with opioid use disorder (DSM-IV opioid dependence) and without alcohol dependence or serious somatic or psychiatric comorbidities. Pregnant and nursing women were excluded. The majority of participants were men (75%) and the mean age was 35.6 years.

9 months later there were no significant differences in outcomes between participants who continued XR naltrexone and those who switched to it from buprenorphine. Twenty-eight (51.9%) participants who were originally on XR naltrexone and 30 (47.6%) who newly started on it completed 9 months of follow-up. Complete abstinence from opioids was self-reported by 53.7% of participants continuing XR naltrexone and 44.4% of those newly started. Adverse events were generally related to withdrawal symptoms. Two patients discontinued XR naltrexone due to serious injection site reactions requiring surgery, after which they recovered completely.

CATR’s Take
The results of the study imply that switching from buprenorphine to XR naltrexone may work as well as starting XR naltrexone from scratch. The study was not perfect—the design was open-label, there was no objective confirmation of abstinence, and the switch was carefully done on an inpatient unit, limiting our confidence that it can be done as safely and effectively in outpatient settings. Nonetheless, the naturalistic setting is similar to clinical practice, and the 50% self-reported abstinence rate is encouraging. Switching from buprenorphine to XR naltrexone can be attempted in select patients, but we recommend approaching switch requests with great caution. We continue to think of XR naltrexone as a second-line option for patients who cannot be on agonist treatment.