Which patient is most suitable for buprenorphine (opioid partial agonist) low-dose overlap initiation (LDOI) in the outpatient setting for opioid use disorder management?

Buprenorphine Low-Dose Overlap Initiation for Opioid Use Disorder

The patient currently using illicit fentanyl for whom traditional buprenorphine initiation has failed is the most appropriate candidate for buprenorphine low-dose overlap initiation (LDOI) in the outpatient setting. 1, 2

Understanding Low-Dose Overlap Initiation (LDOI)

LDOI is an alternative method of initiating buprenorphine that:

• Uses very low starting doses gradually increased to therapeutic levels over days
• Takes advantage of slow displacement of full opioid agonists from mu-opioid receptors
• Avoids the need for patients to experience opioid withdrawal before starting buprenorphine
• Minimizes risk of precipitated withdrawal
• Allows continuation of full opioid agonists during initiation

Why Fentanyl Users Are Ideal Candidates

Patients using illicit fentanyl who have failed traditional buprenorphine initiation are ideal candidates for LDOI because:

• Fear and risk of precipitated withdrawal are significant barriers for initiating buprenorphine, particularly among fentanyl users 2
• Traditional initiation methods requiring withdrawal before starting buprenorphine are especially challenging with fentanyl due to its potency and pharmacokinetics
• Studies show high success rates (92% of patients using fentanyl were able to initiate buprenorphine using LDOI protocols) 2

Why Other Patients Are Less Appropriate

1. Patient using naltrexone long-acting injectable (last dose 1 week ago):

   • Naltrexone is an opioid antagonist that blocks opioid receptors
   • One week after injection, significant blockade remains, making buprenorphine ineffective
   • LDOI would not be appropriate as the patient needs complete clearance of naltrexone before any opioid agonist therapy

2. Patient with current opioid withdrawal symptoms with last heroin use within 24 hours:

   • This patient is already in withdrawal and can use traditional buprenorphine initiation
   • Standard protocols recommend starting buprenorphine when COWS score >8 3, 4
   • LDOI is unnecessary when traditional initiation is feasible

3. Patient with possible delirium from illicit fentanyl and benzodiazepine use:

   • This patient requires emergency department evaluation for safety
   • Outpatient management is inappropriate due to risk of respiratory depression
   • Guidelines specifically caution against buprenorphine initiation with concomitant sedative use 3

LDOI Protocol for Fentanyl Users

For patients using fentanyl with failed traditional initiation, implement this protocol:

1. Initial Assessment:

   • Confirm ongoing fentanyl use
   • Document previous failed traditional initiation attempts
   • Assess for contraindications (severe liver disease, pregnancy, acute intoxication)

2. Initiation Protocol:

   • Start with very low doses (0.5-1mg SL buprenorphine)
   • Use divided doses of sublingual buprenorphine tablets
   • Consider blister packaging for easier dosing 2
   • Patient can continue using fentanyl during initiation

3. Titration Schedule:

   • Day 1: 0.5mg SL twice daily
   • Day 2: 1mg SL twice daily
   • Day 3: 2mg SL twice daily
   • Day 4: 4mg SL twice daily
   • Continue increasing until reaching target dose of 16mg daily 2

4. Monitoring:

   • Schedule follow-up on day 4 of initiation
   • Monitor for withdrawal symptoms (pause or delay dose increases if withdrawal occurs)
   • Provide comfort medications as needed
   • Maintain frequent communication

5. Transition to Maintenance:

   • Once reaching 8-16mg daily, patient should discontinue fentanyl use
   • Continue regular follow-up to adjust dosing as needed

Important Considerations and Pitfalls

• Avoid administering buprenorphine too early before adequate transition with LDOI protocol
• Ensure adequate dosing for withdrawal symptom control
• Recognize that pain itself may be a withdrawal symptom requiring management
• Address drug interactions, particularly with benzodiazepines 4
• Provide overdose prevention education and take-home naloxone kit 3
• Screen for hepatitis C and HIV and offer reproductive health counseling 3

LDOI offers a safe alternative to traditional buprenorphine initiation for patients using fentanyl who have previously failed standard approaches, with studies showing promising retention rates and successful transition to maintenance therapy 1, 2.