Ultra-Low Dose Naltrexone for Suboxone (Buprenorphine/Naloxone) Tapering
The recommended ultra-low dose naltrexone (ULDN) dosage for tapering off Suboxone is between 0.25 mg to 1 mg daily, with a starting dose of 0.25 mg that can be gradually increased while simultaneously decreasing buprenorphine doses. 1
Understanding ULDN for Buprenorphine Tapering
- Ultra-low dose naltrexone (ULDN) is considered to be in the dosage range of less than 1 μg per day, while very low-dose naltrexone (VLDN) ranges between 1 μg and 1 mg 2
- VLDN has primarily been used as an experimental adjunct treatment to boost tolerability during opioid-weaning methadone taper 2
- Low-dose naltrexone (LDN), in the range of 1-5 mg daily, works by modulating Toll-like receptor 4 signaling and upregulating endogenous opioid signaling through transient opioid-receptor blockade 2
Recommended Protocol for Suboxone Tapering with ULDN
- Begin with 0.25 mg naltrexone while simultaneously reducing buprenorphine dose (e.g., starting at 4 mg buprenorphine) 1
- Gradually increase naltrexone dose while decreasing buprenorphine over approximately 7 days 1
- Monitor for withdrawal symptoms, craving, and adverse events daily during the induction procedure 1
- This approach has been shown to be safe, well-tolerated, and successfully completed by most participants in clinical studies 1
Important Considerations and Precautions
- 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 3
- Starting naltrexone too soon after buprenorphine discontinuation can lead to severe withdrawal symptoms 3
- Full antagonist effects of naltrexone may persist for 2-3 days after discontinuation due to the accumulation of its metabolite 3
- Patients with opioid use disorder who are tapered from buprenorphine often relapse to more dangerous opioids 3
Alternative Approaches for Managing Withdrawal
Several medications can help mitigate withdrawal symptoms during opioid tapering 3:
- α2-agonists (clonidine, tizanidine)
- Lofexidine
- Short-term use of trazodone, tricyclic antidepressants, gabapentin, and mirtazapine
Incorporating psychosocial treatments has been shown to reduce dropouts and opioid use during treatment 3
Addressing depression, anxiety, and insomnia before and during reduction is important for successful tapering 3
Common Pitfalls to Avoid
- Tapering too quickly can lead to withdrawal symptoms, increased pain sensitivity, and risk of relapse 3
- Failing to assess for opioid use disorder before initiating a taper 3
- Using standard doses of naltrexone without adequate time after buprenorphine discontinuation (naltrexone should be avoided for at least 2-3 days after stopping opioids at standard doses) 3
Evidence for ULDN in Buprenorphine Discontinuation
- In one feasibility trial, naltrexone facilitated buprenorphine discontinuation in stable individuals who had tolerated a taper to 2mg or less but were unable to terminate entirely 4
- The procedure included supervised buprenorphine discontinuation and oral naltrexone titration with a starting dose of 6.25mg 4
- Participants did not experience an increase in withdrawal symptoms after the first oral dose of naltrexone compared to 24 hours after the last dose of buprenorphine 4
- All participants in this trial were able to discontinue buprenorphine and remain opioid-free during the trial and at follow-up 4
Long-term Considerations
- Studies indicate that most opioid agonist-using patients are not able to successfully complete tapering attempts without support 5
- For patients who cannot complete tapering, switching to buprenorphine/naloxone maintenance or naltrexone maintenance may be viable alternatives 5
- Close monitoring for signs of instability during tapering is essential 5