Naltrexone-Facilitated Buprenorphine Discontinuation: A Feasibility Trial

• Little is known about when or how to discontinue buprenorphine in maintained individuals who achieve sustained full remission.
• A rapid naltrexone induction procedure was found to facilitate successful discontinuation in individuals on stable long-term buprenorphine maintenance who had tolerated a taper to 2 mg or less, but who were previously unable to stop altogether due to withdrawal-related distress.
• Initiation of long-acting injectable naltrexone deserves further study as a strategy by which to transition buprenorphine-maintained individuals to abstinence or antagonist treatment.

RationaleBuprenorphine is an effective and popular treatment for opioid dependence. It remains unclear, however, when or how to transition stable buprenorphine-maintained individuals to complete abstinence. This trial investigates the feasibility of using naltrexone to facilitate buprenorphine discontinuation in stable individuals who had tolerated a taper to 2 mg or less but were unable to terminate entirely due to withdrawal-related distress.MethodsThe sample consisted of 6 buprenorphine-maintained individuals in sustained full remission, and who had tolerated a taper but were unable to discontinue altogether. A rapid induction procedure was performed, which included supervised buprenorphine discontinuation, oral naltrexone titration with a starting dose of 6.25 mg, and administration of long-acting injectable naltrexone. Participants were followed weekly for 5 weeks after the injection, with telephone follow-up occurring at 6 months.ResultsThe rapid induction procedure was well tolerated. There was no observed or reported clinical worsening over the course of study participation. Notably, no participants experienced an increase in Subjective Opioid Withdrawal Scale (SOWS) scores after the first oral dose of NTX as compared to day 1 (24 hours after last dose of buprenorphine); instead, SOWS scores decreased between days 1 and 7 (p = 0.043). All participants were able to discontinue buprenorphine and to remain opioid free during the trial and at follow-up.ConclusionsThis preliminary trial represented for all participants the first successful attempt at buprenorphine discontinuation. Further research is needed to better understand if naltrexone is effective at facilitating buprenorphine discontinuation, as well as the feasibility of a sequential approach (buprenorphine stabilization to naltrexone) for opioid use disorders.