What is the recommended buprenorphine (opioid partial agonist) microdosing process for a patient with opioid use disorder or chronic pain?

Buprenorphine Microdosing Protocol

Buprenorphine microdosing allows transition from full opioid agonists (including methadone or illicit fentanyl) to buprenorphine without requiring opioid abstinence or precipitating withdrawal, by gradually titrating low-dose buprenorphine while continuing the full agonist, then discontinuing the full agonist once adequate buprenorphine receptor occupancy is achieved.

Core Principle

The fundamental advantage of microdosing is that it eliminates the traditional requirement for patients to enter withdrawal before buprenorphine initiation 1, 2. This approach gradually displaces full agonist opioids from μ-receptors over several days while maintaining patient comfort 3.

Standard 7-Day Microdosing Protocol

The most widely validated approach uses sublingual buprenorphine/naloxone tablets or films in the following schedule 2:

• Day 1: 0.5 mg once daily 2
• Day 2: 0.5 mg twice daily 2
• Day 3: 1 mg twice daily 2
• Day 4: 2 mg twice daily 2
• Day 5: 3 mg twice daily 2
• Day 6: 4 mg twice daily 2
• Day 7: 12 mg once daily 2

On day 7, all full opioid agonists (methadone, morphine, illicit fentanyl) are abruptly discontinued 1, 2. After day 7, titrate buprenorphine to a maintenance dose of 12-32 mg daily based on withdrawal symptoms and cravings 2.

Critical Implementation Details

During the Microdosing Week (Days 1-6)

• Continue the patient's full dose of methadone or other full agonist opioids without reduction 1, 2
• Administer buprenorphine doses concurrently with the full agonist 1
• Most protocols use divided doses from partial sublingual tablets or films (1/8 to 1/2 of a 2 mg product) 3
• Monitor for precipitated withdrawal, though this is rare with true microdosing 2

Transition Day (Day 7-8)

• Abruptly discontinue methadone or other full agonists on day 8 1
• Increase buprenorphine to 12 mg or higher 1, 2
• Further titrate based on Clinical Opiate Withdrawal Scale (COWS) scores and patient symptoms 1

Alternative Formulations and Routes

While sublingual tablets/films are most common, other approaches have been reported 3:

• Transdermal patches: Can be used for slower, more gradual inductions 3
• Intravenous buprenorphine: Successfully used in hospital settings for rapid transitions, particularly useful when sublingual products are unavailable 4
• Buccal formulations: Less commonly reported but feasible 3

Special Population: Methadone Patients

Transitioning from methadone requires particular attention 1:

• Successfully demonstrated with methadone doses ranging from 40-100 mg/day 1
• The 7-day protocol allows gradual displacement of methadone from receptors without precipitating withdrawal 1
• All three patients in one case series transitioned successfully from methadone to buprenorphine 12-16 mg/day with minimal withdrawal symptoms 1

Setting Considerations

Outpatient Setting

• The 7-day protocol has been successfully implemented in outpatient addiction clinics 2
• Patients can continue using prescribed or illicit opioids during the first 6 days 2

Emergency Department Setting

• ED-initiated take-home microdosing packages (6-day supply) are feasible 5
• Microdosing may have better acceptance than standard induction, as fear of precipitated withdrawal is a major barrier (5 of 26 patients who declined cited precipitated withdrawal as the reason) 5
• 30-day retention on opioid agonist therapy was 32% with microdosing versus 23.8% with standard dosing 5

Inpatient Hospital Setting

• Successfully implemented for hospitalized patients with opioid use disorder 1
• Particularly useful for patients requiring concurrent pain management 4

Critical Pitfalls to Avoid

• Do not reduce or discontinue full agonist opioids during days 1-6 — this defeats the purpose of microdosing and may precipitate withdrawal 1, 2
• Do not use mixed agonist-antagonists (pentazocine, nalbuphine, butorphanol) during the transition, as these will precipitate acute withdrawal 6
• Do not attempt standard buprenorphine induction protocols if the patient cannot tolerate withdrawal or is on high-dose methadone 1
• Avoid fixed-interval dosing until proper inter-dose intervals are established through clinical observation 7

Concurrent Pain Management

If the patient requires analgesia during or after microdosing 8:

• For chronic pain: Once stabilized on buprenorphine, increase to divided doses (every 8 hours) with total daily doses of 4-16 mg for analgesia 8
• For breakthrough pain: Add adjuvant therapy (NSAIDs, acetaminophen, gabapentin for neuropathic pain) rather than additional opioids initially 8
• If maximal buprenorphine is insufficient: Add high-potency full agonists (fentanyl, hydromorphone, morphine) at higher-than-usual doses due to buprenorphine's receptor occupancy 8

Monitoring Requirements

• Assess withdrawal symptoms using validated scales (COWS) throughout the process 1
• Monitor for signs of precipitated withdrawal, particularly in the first 48 hours 2
• Verify patient adherence and response before advancing to the next dose level 3
• Have naloxone available for respiratory depression, though buprenorphine has a ceiling effect on respiratory depression 9