Is very low dose naltrexone effective and safe for Suboxone (buprenorphine) tapering?

Very Low Dose Naltrexone for Buprenorphine Tapering

Very low dose naltrexone is not recommended for buprenorphine tapering as there is insufficient evidence supporting its safety and efficacy for this purpose, and it may precipitate withdrawal symptoms when used alongside buprenorphine. 1, 2

Understanding Naltrexone and Buprenorphine Interactions

• Naltrexone is a competitive opioid receptor antagonist with a plasma half-life of 4 hours, but its active metabolite (6-β-naltrexol) has a longer half-life of 13 hours and accumulates during therapy 3
• Full antagonist effects of naltrexone may persist for 2-3 days after discontinuation due to the accumulation of its metabolite 4, 3
• Buprenorphine is a partial mu opioid receptor agonist used in the treatment of opioid use disorder and pain 4
• When naltrexone and buprenorphine are used together, naltrexone can precipitate acute withdrawal symptoms in patients dependent on buprenorphine 5

Buprenorphine Tapering Recommendations

• The American Society of Addiction Medicine recommends individualized tapering plans for patients on buprenorphine, with rates ranging from 10% per month to 10% per week until reaching 30% of the original dose, followed by 10% weekly reductions 1
• Slow tapers are more appropriate for patients on long-term opioid therapy, focusing on maintaining patient comfort and valued activities 1
• Abrupt withdrawal or major dose reduction of buprenorphine is considered unacceptable medical care except in extreme cases 1

Evidence for Very Low Dose Naltrexone with Buprenorphine

• Limited research has examined very low dose naltrexone (starting at 0.25mg) combined with decreasing doses of buprenorphine for transitioning to extended-release naltrexone injection 6
• This approach was tested in a small study (n=20) for naltrexone induction, not specifically for buprenorphine tapering 6
• Low dose naltrexone (2.5-4.5mg) has been studied primarily for gastrointestinal disorders, with 61.2% of patients experiencing side effects, including neurological and gastrointestinal complaints 2

Potential Risks and Concerns

• Using naltrexone during buprenorphine treatment can precipitate withdrawal symptoms, as demonstrated in studies using naltrexone to induce withdrawal for rapid detoxification 7, 5
• Patients with opioid use disorder who are tapered from buprenorphine often relapse to more dangerous opioids 1
• Starting naltrexone too soon after buprenorphine discontinuation can lead to severe withdrawal symptoms 3

Alternative Approaches for Buprenorphine Tapering

• Several medications can help mitigate withdrawal symptoms during opioid tapering, including α2-agonists (clonidine, tizanidine), lofexidine, and short-term use of trazodone, tricyclic antidepressants, gabapentin, and mirtazapine 1, 4
• Incorporating psychosocial treatments has been shown to reduce dropouts and opioid use during treatment 1
• Addressing depression, anxiety, and insomnia before and during reduction is important for successful tapering 1

Common Pitfalls to Avoid

• Tapering too quickly can lead to withdrawal symptoms, increased pain sensitivity, and risk of relapse 1
• Failing to assess for opioid use disorder before initiating a taper, as patients with this condition are unlikely to tolerate abstinence 1
• Using naltrexone without adequate time after buprenorphine discontinuation (naltrexone should be avoided for at least 2-3 days after stopping opioids) 4, 3