Early Initiation of Injectable Naltrexone After Low-Dose Naltrexone Titration May Lead to Improved Treatment Outcomes

Before starting long-acting injectable naltrexone (XR-naltrexone), a 7–10 day period of opioid abstinence is recommended for patients with opioid use disorder (OUD) to reduce the severity of precipitated withdrawal; this can be very difficult, especially for outpatients. Prior literature suggests that XR-naltrexone may be started earlier if preceded by low-dose oral naltrexone while managing withdrawal symptoms with non-opioid medication. Researchers randomly assigned 150 outpatient adults with OUD to either early oral naltrexone or standard buprenorphine-managed withdrawal. Patients in the early naltrexone group received buprenorphine on day 2 only, followed by ascending doses of oral naltrexone and non-opioid medications on days 3–7, and XR-naltrexone on day 8. Patients in the standard buprenorphine group received a 7-day buprenorphine taper, followed by 7 days of opioid abstinence, and XR-naltrexone on day 15. Primary outcomes were successful first and second XR-naltrexone injections.

• The buprenorphine group experienced a more rapid reduction in moderate-to-severe withdrawal symptoms compared with the early naltrexone group, but differences were not seen in the proportion of patients with at least mild withdrawal symptoms during the first week.
• 56% of participants in the early naltrexone group received a first XR-naltrexone injection, compared with 33% in the buprenorphine group.
• Half of the participants in the early naltrexone group received a second injection, compared with 27% in the buprenorphine group.
• People who used prescription opioids had 3.8 times greater odds of first naltrexone injection and 2.3 times greater odds of a second injection, compared with people who used heroin.

Comments: This study demonstrates that outpatients with OUD offered oral and then XR-naltrexone injection earlier during withdrawal managed medically with only one buprenorphine dose and other medications (day 8) are more likely to receive the injection than those offered buprenorphine followed by XR-naltrexone later (day 15). Generalizability of the findings may be limited because most participants (~4/5) did not inject opioids. Caution should be used in applying study findings to patients who use heroin, who were less successful in both treatment groups.

Jessica L. Taylor, MD^† and Alexander Y. Walley, MD, MSc

^† Contributing editorial intern and Assistant Professor of Medicine, Boston Medical Center

Reference: Sullivan M, Bisaga A, Pavlicova M, et al. Long-acting injectable naltrexone induction: A randomized trial of outpatient opioid detoxification with naltrexone versus buprenorphine. Am J Psychiatry. 2017;174(5):459–467.