A 7-day Opioid Withdrawal Management Protocol With Escalating Doses of Naltrexone Did Not Help With Transition to Long-acting Naltrexone

Long-acting injectable naltrexone (XR-NTX) has been shown to be an effective treatment for opioid use disorder, but transition to this treatment is complicated by the need to abstain from opioids prior to initiation. Researchers recruited adults with DSM-IV opioid dependence seeking treatment with XR-NTX and compared with placebo a protocol using gradually escalating doses of oral naltrexone (NTX), with and without a 3-day buprenorphine taper (BUP). Of 653 participants assessed, 378 were randomized to NTX/BUP, NTX/placebo BUP, or placebo NTX/placebo BUP. All received ancillary medications, including clonidine, trazodone, and clonazepam. The primary endpoint was initiation of XR-NTX.

• Transition to XR-NTX was achieved by 44% of participants and 18% received 3 monthly injections; there was no significant difference in either outcome between the 3 groups.
• Participants in the NTX/BUP group were significantly more likely to be abstinent during the 7-day transition period.

Comments: The difficulty with transitioning to treatment remains a major limitation of XR-NTX. For most individuals, agonist treatment with buprenorphine or methadone will remain the treatment of choice until better transition protocols can be found.

Darius A. Rastegar, MD

Reference: Bisaga A, Mannelli P, Yu M, et al. Outpatient transition to extended-release naltrexone for patients with opioid use disorder: a phase 3 randomized trial. Drug Alcohol Depend. 2018;187:171–178.