Objective:

To evaluate the risks associated with delayed withdrawal symptoms following the use of long-acting injectable buprenorphine (LAIB) as a tapering strategy.

Approach:

• Case Presentation: A 45-year-old man with opioid use disorder (OUD) in sustained remission transitioned to LAIB for tapering after years of stability on sublingual buprenorphine and developed withdrawal symptoms four months post-injection.
• Symptom Monitoring: Symptoms included gastrointestinal upset, fatigue, mood-related issues, and sleep disturbances, which were attributed to delayed withdrawal.
• Pharmacokinetic Analysis: Buprenorphine and norbuprenorphine levels were monitored, showing a decline in buprenorphine levels that coincided with the onset of symptoms.
• Management: Transdermal buprenorphine was used as rescue therapy, and naltrexone administration confirmed ongoing μ-opioid receptor occupancy.

Key Findings:

• Delayed withdrawal symptoms can occur months after LAIB administration.
• Loss of kappa opioid receptor antagonism may contribute to mood-related symptoms.
• Naltrexone administration precipitated worsening withdrawal, indicating ongoing receptor occupancy.

Interpretation:

The case highlights the under-recognized risks of delayed withdrawal during LAIB tapering and the potential for misattribution of symptoms to primary psychiatric disorders.

Limitations:

• The single case study limits the generalizability of the findings.
• There is a lack of comprehensive tapering protocols and monitoring guidelines.

Conclusion:

Comprehensive tapering protocols and extended monitoring are essential when using LAIB for buprenorphine discontinuation.