What is the recommended treatment algorithm for an adult patient with opioid use disorder who has no contraindication to buprenorphine‑naloxone (Suboxone)?

Treatment Algorithm for Opioid Use Disorder with Buprenorphine-Naloxone (Suboxone)

For adults with opioid use disorder and no contraindications to buprenorphine-naloxone, initiate treatment in the emergency department or outpatient setting using a standardized induction protocol, followed by maintenance therapy at 16 mg daily for indefinite duration—not short-term detoxification—because maintenance dramatically reduces relapse and mortality. 1, 2

Step 1: Pre-Induction Assessment

Confirm Clinical Diagnosis of Opioid Withdrawal

• Verify time elapsed since last opioid use to prevent precipitated withdrawal: 1, 2
  • Short-acting opioids (heroin, morphine IR, oxycodone IR, fentanyl): Wait >12 hours 1, 2
  • Extended-release formulations (OxyContin, MS Contin): Wait >24 hours 1, 2
  • Methadone maintenance patients: Wait >72 hours and strongly consider continuing methadone instead 1, 2

Measure Withdrawal Severity Using COWS

• Use the Clinical Opiate Withdrawal Scale to objectively confirm active withdrawal through 11 clinical signs: pulse rate, sweating, restlessness, pupil size, bone/joint aches, runny nose/tearing, GI upset, tremor, yawning, anxiety, and piloerection 2
• COWS interpretation: 2
  • <8 (mild): No buprenorphine indicated; reassess in 1-2 hours 1, 2
  • 8-12 (moderate): Safe to initiate buprenorphine 2
  • 13-24 (moderate): Initiate buprenorphine 2
  • 25-36 (moderately severe): Initiate buprenorphine 2
  • >36 (severe): Initiate buprenorphine 2

Screen for Contraindications

• Check for QT-prolonging medications (concomitant use is contraindicated) 2
• Identify high-risk benzodiazepine co-prescribing: The FDA black-box warning states that combining opioids with benzodiazepines markedly increases risk of respiratory depression and death 2
• Assess for complicating factors: viable pregnancy, chronic opioid therapy for pain, anticipated surgery, intoxication with alcohol/benzodiazepines/sedatives, post-overdose naloxone reversal, or serious acute medical illness 1

Step 2: Buprenorphine Induction Protocol

Day 1 Dosing (Emergency Department or Office)

• Initial dose: Give 4-8 mg sublingual buprenorphine-naloxone based on withdrawal severity (COWS >8) 1, 2
• Reassess after 30-60 minutes: Check COWS score and symptoms 1, 2
• Additional dosing: If withdrawal persists, give 2-4 mg every 2 hours as needed 2
• Target Day 1 total: 8 mg (range 4-8 mg depending on response) 2

Day 2 and Maintenance Dosing

• Standard maintenance dose: 16 mg sublingual daily (this is the target for most patients) 1, 2
• Dosing range: 4-24 mg daily, but 16 mg occupies approximately 95% of mu-opioid receptors and creates a ceiling effect 2
• Dosing schedule: Once daily is standard; twice-daily dosing (e.g., 8 mg BID) is acceptable but creates overlapping peak effects that increase respiratory risk when combined with benzodiazepines 2

Critical Safety Warning: Precipitated Withdrawal

• Buprenorphine's high binding affinity and partial agonist properties can displace full opioid agonists and precipitate severe withdrawal if administered too early, particularly in methadone-maintained patients 2
• If precipitated withdrawal occurs, give more buprenorphine (not less) as the primary treatment, supported by case reports and pharmacological rationale 2
• Add adjunctive symptomatic management: clonidine (0.1-0.2 mg every 6-8 hours) for autonomic symptoms, antiemetics (promethazine or ondansetron) for nausea, benzodiazepines for anxiety/muscle cramps, and loperamide for diarrhea 1, 2

Step 3: Discharge Planning and Prescribing

Prescribing Authority (Post-2023)

• The X-waiver requirement has been eliminated as of 2023, expanding prescribing access to all DEA-licensed providers 2
• Prescribe buprenorphine-naloxone 16 mg sublingual daily for 3-7 days or until follow-up appointment if known 1, 2
• Sample prescription: 1
  • Buprenorphine/naloxone 8 mg/2 mg sublingual tablet or film
  • Take 2 tablets/films once daily in AM
  • Dispense #6 (for 3-day supply) or #14 (for 7-day supply)
  • No refills

Non-Prescribing Providers

• Non-waivered providers can administer (but not prescribe) buprenorphine for up to 72 hours while arranging referral to addiction treatment 1, 2

Harm Reduction and Preventive Health

• Provide take-home naloxone kit and overdose prevention education (strongly recommended) 1, 2
• Offer hepatitis C and HIV screening 1, 2
• Consider reproductive health counseling 1, 2

Step 4: Long-Term Maintenance Strategy

Duration of Treatment

Buprenorphine should NOT be discontinued once started—discontinuation precipitates withdrawal and dramatically increases relapse risk to more dangerous opioids 2

• There is no maximum recommended duration of maintenance treatment; patients may require treatment indefinitely 2
• Medication-assisted treatment with buprenorphine demonstrates better short-term improvement in treatment outcomes and illicit opioid use rates compared to referral only or brief intervention 1
• Buprenorphine maintenance therapy is more effective than detoxification in preventing relapse among patients with opioid use disorder 2

Monitoring and Follow-Up

• Schedule frequent follow-up visits (initially weekly) to monitor for adverse effects 2
• Document any relapses, reemergence of cravings or withdrawal, perform random urine drug testing, conduct pill/wrapper counts, and check state prescription drug database records 3
• Sporadic opioid use in the first few months is not uncommon and should be addressed by increased visit frequency and more intensive engagement with behavioral therapies 3

Step 5: Special Populations and Situations

Patients on Methadone Maintenance

• Wait >72 hours since last methadone dose before administering buprenorphine to avoid precipitating severe and prolonged withdrawal 1, 2
• Strongly consider continuing methadone instead, as it has similar effectiveness to buprenorphine for withdrawal management and may be safer for this population 2

Patients on High-Dose Opioids or Fentanyl

• Consider micro-dosing protocol: Start with very low doses (0.5 mg once daily on day 1, then 0.5 mg BID on day 2,1 mg BID on day 3,2 mg BID on day 4,3 mg BID on day 5,4 mg BID on day 6, and 12 mg once daily on day 7) while continuing full agonist opioids, then discontinue full agonists on day 7 2, 4
• This approach allows initiation without requiring withdrawal or discontinuation of the full opioid agonist, thereby avoiding precipitated withdrawal and improving tolerability 2

Patients Transitioning from Naltrexone

• Oral naltrexone: Wait 2-3 days after last dose before starting buprenorphine to allow antagonist effect to wear off 2
• Extended-release injectable naltrexone (Vivitrol): Wait 24-30 days after last injection before initiating buprenorphine due to depot release kinetics 2
• Premature buprenorphine induction before these waiting periods is ineffective and may precipitate severe withdrawal 2

Patients on Concurrent Benzodiazepines

This combination carries FDA black-box warning for fatal respiratory depression. 2

• Do NOT discontinue buprenorphine when this combination already exists; maintain the established dose to prevent opioid withdrawal and relapse 2
• Initiate gradual benzodiazepine taper rather than abrupt cessation to avoid withdrawal seizures 2
• Consider switching to longer-acting benzodiazepine (clonazepam or diazepam) before tapering 2
• Substitute non-benzodiazepine anxiolytics (SSRIs, SNRIs, buspirone, or gabapentin) 2
• If combination is unavoidable, obtain informed consent documenting discussion of respiratory depression and death risk, use lowest effective doses, and schedule frequent follow-up visits (initially weekly) 2

Step 6: If Taper Is Absolutely Necessary (Against Guideline Recommendations)

Maintenance therapy is substantially more effective than tapering for preventing relapse in stable adults. 2 However, if discontinuation is patient-desired despite counseling:

Recommended Taper Schedule

• Month 1: 7 mg daily (12.5% reduction from 8 mg) 2
• Month 2: 6 mg daily 2
• Month 3: 5 mg daily 2
• Month 4: 4 mg daily 2
• Month 5: 3 mg daily 2
• Month 6: 2 mg daily 2
• Month 7: 1 mg daily 2
• Month 8: 0.5 mg daily 2
• Month 9: 0.5 mg every other day 2
• Month 10: Discontinue 2

Taper Principles

• A ~10% dose reduction per month is generally better tolerated than faster tapers 2
• Tapers may be paused, restarted, or further slowed when patients reach lower doses or are not ready to continue 2
• When the smallest available dose is reached, extend the dosing interval rather than continue dose reductions 2
• Resume maintenance therapy if persistent withdrawal symptoms occur despite adjunctive medications 2

Adjunctive Medications During Taper

• Clonidine (0.1-0.2 mg every 6-8 hours) for autonomic withdrawal signs (sweating, tachycardia, hypertension, anxiety) 2
• Trazodone (50-100 mg at bedtime) or gabapentin (300-600 mg three times daily) for insomnia and anxiety 2
• Loperamide (2-4 mg as needed) for diarrhea 2
• Antiemetics (promethazine or ondansetron) for nausea 2

Post-Taper Monitoring

• Anticipate and treat protracted withdrawal symptoms (dysphoria, irritability, insomnia, anhedonia, vague malaise) that may persist for months after opioid elimination 2
• Abruptly returning to a previously prescribed higher buprenorphine dose after taper markedly increases overdose risk 2

Common Pitfalls to Avoid

1. Administering buprenorphine before adequate withdrawal onset (COWS <8) precipitates severe withdrawal 1, 2
2. Insufficient waiting time for methadone patients (<72 hours) causes prolonged precipitated withdrawal 1, 2
3. Using alpha-2 agonists (clonidine/lofexidine) as first-line therapy when buprenorphine is available represents suboptimal care; these agents are inferior with lower completion rates (NNT=4 favoring buprenorphine) 2
4. Tapering buprenorphine to comply with opioid dose guidelines—buprenorphine for OUD should not be reduced or discontinued due to its ceiling effect on respiratory depression 2
5. Prescribing inadequate discharge doses (<16 mg daily target) leads to persistent withdrawal and treatment failure 1, 2
6. Failing to address concurrent benzodiazepine use, which dramatically raises respiratory depression risk 2
7. Treating buprenorphine as short-term detoxification rather than indefinite maintenance therapy, which increases relapse and mortality 2