What is the recommended dosage of ultra-low dose naltrexone (NLX) for tapering off Suboxone (buprenorphine/naloxone)?

Ultra-Low Dose Naltrexone Dosage for Suboxone (Buprenorphine/Naloxone) Tapering

For tapering off Suboxone (buprenorphine/naloxone), ultra-low dose naltrexone should be initiated at 0.25 mg and gradually titrated upward while simultaneously decreasing the buprenorphine dose. This approach has been shown to facilitate successful discontinuation of buprenorphine while minimizing withdrawal symptoms.

Dosing Protocol for Ultra-Low Dose Naltrexone (ULDN) with Buprenorphine Taper

• Start with naltrexone 0.25 mg while simultaneously reducing buprenorphine from a stable dose (typically when patient has already tapered to 2 mg or less) 1
• Gradually increase naltrexone dose over approximately 7 days while decreasing buprenorphine 1
• The naltrexone dose can be titrated upward from 0.25 mg to around 1-5 mg during the transition period 2, 1
• Buprenorphine should be simultaneously tapered downward from the starting dose (e.g., from 4 mg to complete discontinuation) 1

Evidence for Effectiveness

• Studies have demonstrated that this approach allows most patients to successfully discontinue buprenorphine and transition either to complete abstinence or to extended-release naltrexone maintenance 1
• The combination of very low dose naltrexone with tapering buprenorphine has been shown to reduce withdrawal symptoms, cravings, and opioid use compared to baseline 1
• In one study, 14 out of 20 participants (70%) successfully completed the transition from buprenorphine to naltrexone using this protocol 1

Mechanism of Action

• Ultra-low dose naltrexone (doses below 1 μg per day) works by acting on filamin A, a scaffolding protein involved in μ-opioid receptor signaling 2
• Very low-dose naltrexone (1 μg to 1 mg) has been used experimentally to improve tolerability during opioid tapering 2
• Low-dose naltrexone (1-5 mg daily) reduces glial inflammatory response and systemically upregulates endogenous opioid signaling through transient opioid-receptor blockade 2

Important Considerations and Precautions

• This approach should be medically supervised, as improper timing or dosing can precipitate withdrawal 1, 3
• Patients who fail initial attempts at discontinuation may benefit from a more structured approach using buprenorphine stabilization followed by a cross-taper with naltrexone 3
• For patients who cannot tolerate outpatient transition, inpatient protocols exist that can facilitate the transition in 5-7 days using low-dose oral naltrexone and non-opioid medications 4
• Regular monitoring for withdrawal symptoms using validated tools like the Subjective Opioid Withdrawal Scale (SOWS) is recommended 5
• Patients should be informed that this approach represents a relatively new protocol with limited but promising evidence 5, 1

Alternative Approaches

• For patients who cannot tolerate the ULDN approach, standard naltrexone induction typically requires 7-10 days of complete opioid abstinence 4
• Some patients may benefit from transitioning to extended-release naltrexone (XR-NTX) after successful discontinuation of buprenorphine 5, 1
• If withdrawal symptoms become intolerable during the transition, resuming buprenorphine maintenance may be appropriate 3

This protocol offers a promising approach to facilitate the challenging transition from buprenorphine maintenance to either complete abstinence or naltrexone maintenance, with evidence suggesting it can be successful in outpatient settings when properly supervised.