Is success higher when using adjunct ultra-low dose naltrexone during a Suboxone (buprenorphine) taper?

Using Ultra-Low Dose Naltrexone During Suboxone Taper

Ultra-low dose naltrexone may improve success rates during buprenorphine tapering by modulating opioid receptor function and reducing withdrawal symptoms, though evidence specifically for this application is limited.

Understanding Ultra-Low Dose Naltrexone (ULDN)

• Ultra-low dose naltrexone (ULDN), defined as less than 1 μg per day, works by acting on filamin A, a scaffolding protein involved in μ-opioid receptor signaling 1
• This differs from low-dose naltrexone (LDN, 1-5 mg daily) and very low-dose naltrexone (VLDN, 1 μg to 1 mg), which have different mechanisms of action 1
• VLDN has primarily been used experimentally as an adjunct treatment for improving tolerability during methadone tapering 1

Evidence for Buprenorphine Tapering Approaches

• Current guidelines recommend individualized tapering plans for patients on buprenorphine, with rates ranging from 10% per month (or slower) to 10% per week until reaching 30% of the original dose, followed by 10% weekly reductions 2
• Slow tapers may require several months or years and are more appropriate for patients who have been on long-term opioid therapy 2
• The goal should be durability of reduction over time rather than rapidity, focusing on maintaining patient comfort and valued activities 2

Potential Benefits of ULDN in Buprenorphine Tapering

• ULDN has been shown to potentiate opioid analgesia while reducing the total amount of opioids needed, which could theoretically help during tapering 1
• In a small study using very low-dose naltrexone with buprenorphine for transitioning patients to extended-release naltrexone, 14 out of 20 participants successfully completed the transition 3
• This approach combined upward titration of very low-dose naltrexone with downward titration of low-dose buprenorphine and was reported as safe and well-tolerated 3

Pharmacological Adjuncts for Tapering

• Several medications can mitigate physical and psychological withdrawal symptoms during opioid tapering 2:
  • α2-Agonists like clonidine and tizanidine directly attenuate opioid withdrawal
  • Lofexidine is FDA-approved for control of opioid withdrawal symptoms
  • Short-term use of trazodone, tricyclic antidepressants, gabapentin, and mirtazapine may help with anxiety, insomnia, and irritability

Important Considerations and Cautions

• Buprenorphine has unique properties as a partial mu-agonist that create a plateau in respiratory-depressant effects, making it safer than full mu-agonists 2
• Patients with opioid use disorder (OUD) who are tapered from buprenorphine often relapse to more dangerous opioids 2
• Abrupt withdrawal or major dose reduction of buprenorphine is considered unacceptable medical care except in extreme cases 2
• Clinicians should avoid abandonment of patients during tapering and should offer a comfortable and safe tapering regimen 2

Recommendations for Practice

• Before initiating a buprenorphine taper, assess for OUD as patients with this condition are unlikely to tolerate abstinence and are at heightened risk for using hazardous substitutes 2
• For patients without OUD but with poor pain control or poor functioning, consider either treatment with buprenorphine/naloxone or a slow opioid dose taper that may take months or years 2
• Set patients up for success by communicating individualized goals, expectations, addressing patient fears, and developing contingency plans 2
• Incorporate psychosocial treatments as they have been shown to reduce dropouts and opioid use during treatment 2

Common Pitfalls to Avoid

• Tapering too quickly, which can lead to withdrawal symptoms, increased pain sensitivity, and risk of relapse 2
• Failing to address depression, anxiety, and insomnia before and during reduction 2
• Not providing adequate support and observation during the taper, which is critical to the process 2
• Assuming that the target dose must be zero, when some patients may benefit from stabilization at a lower dose 2

While ULDN shows promise as an adjunct during buprenorphine tapering, more research is needed to definitively establish its efficacy for this specific application.