How to manage buprenorphine (Suboxone) withdrawal?

Management of Buprenorphine Withdrawal

For patients experiencing buprenorphine withdrawal, continue or increase buprenorphine dosing rather than stopping it, as buprenorphine itself is the most effective treatment for managing its own withdrawal symptoms. 1, 2

Understanding the Clinical Context

The question of "buprenorphine withdrawal" typically arises in two distinct scenarios that require different management approaches:

Scenario 1: Precipitated Withdrawal from Buprenorphine Induction

If a patient develops precipitated withdrawal after taking buprenorphine (acute worsening of symptoms immediately after buprenorphine administration), rapidly escalate the buprenorphine dose to saturate mu-opioid receptors. 1, 2

• Administer 2 mg buprenorphine every 1-2 hours until symptoms resolve 2
• Total doses of 16-20 mg within the first day have been shown to successfully reverse precipitated withdrawal 2
• This approach is safe and allows patients to continue on buprenorphine maintenance treatment rather than abandoning therapy 1
• Precipitated withdrawal occurs in approximately 8% of low-dose initiations with fentanyl users, but is rare (3%) when protocol instructions are followed correctly 3

Common pitfall: Providers often mistakenly discontinue buprenorphine when precipitated withdrawal occurs, but this worsens the situation. The correct approach is to push through with higher buprenorphine doses. 1, 2

Scenario 2: Withdrawal from Discontinuing Buprenorphine Maintenance

If the goal is to taper off buprenorphine maintenance therapy entirely, the evidence base is limited but suggests:

• Gradual dose reduction is preferable to abrupt discontinuation, though optimal taper rates remain uncertain 4
• The quality of evidence for different tapering strategies is very low, with divergent findings across studies 4
• Multiple factors affect response to dose taper, including whether transition to naltrexone is planned 4

Symptomatic Management of Withdrawal

For patients experiencing withdrawal symptoms during buprenorphine taper or discontinuation, use adjunctive medications to control specific symptoms rather than switching to alternative opioid agonists. 5

Adjunctive Medications for Symptom Control

• Clonidine for autonomic symptoms (sweating, tachycardia, hypertension) - average of 1.6 tablets needed per patient 5
• Antiemetics such as promethazine or ondansetron for nausea and vomiting 5
• Loperamide for diarrhea management 5
• Benzodiazepines to reduce catecholamine release and alleviate muscle cramps and anxiety 5

When Symptoms Are Severe

If withdrawal symptoms are severe despite adjunctive medications, consider transitioning to methadone 30-40 mg daily, which prevents acute withdrawal in most patients. 5

• Methadone provides superior pain control compared to partial agonists in opioid-tolerant individuals 5
• Alternatively, use scheduled full opioid agonists (morphine, hydromorphone, or oxycodone) at higher doses and shorter intervals than used for opioid-naïve patients 5
• Incorporate multimodal non-opioid interventions including NSAIDs, acetaminophen, and adjuvant analgesics to reduce total opioid requirements 5

Critical Drug Interactions to Avoid

Do not abruptly discontinue buprenorphine in patients taking CYP3A4 inhibitors or inducers, as this can precipitate severe withdrawal or cause respiratory depression. 6

• CYP3A4 inhibitors (macrolide antibiotics, azole antifungals, protease inhibitors) increase buprenorphine plasma concentrations 6
• CYP3A4 inducers (rifampin, carbamazepine, phenytoin) decrease buprenorphine concentrations and may precipitate withdrawal 6
• Avoid concomitant use with benzodiazepines or other CNS depressants due to risk of respiratory depression, profound sedation, and death 6
• Do not combine with opioid antagonists (naloxone, naltrexone) as this precipitates withdrawal 7

Perioperative Considerations

Continue buprenorphine perioperatively rather than holding it, as discontinuation risks withdrawal and relapse. 7

• The decision should reflect the prescribed daily dose, indication for treatment (pain vs dependency), risk of relapse, and expected level of postsurgical pain 7
• Multiple drug-drug interactions can cause QT-interval prolongation, serotonin syndrome, or reduced analgesic effect 7
• Concomitant use with QT-prolonging agents is contraindicated 7

Key Clinical Pearls

• Mild withdrawal symptoms occur in approximately 31% of patients during low-dose buprenorphine initiation, but most cases (21%) are mild 3
• Buprenorphine has similar capacity to methadone for ameliorating opioid withdrawal without clinically significant adverse effects 4
• Treatment completion rates are similar between buprenorphine and methadone (RR 1.04,95% CI 0.91 to 1.20) 4
• Counsel patients that mild withdrawal symptoms are likely during initiation, but severe precipitated withdrawal is rare when protocols are followed 3