How to safely initiate bupropion (Wellbutrin) and discontinue sertraline in a patient currently taking buprenorphine/naloxone (Suboxone)?

Initiating Bupropion and Discontinuing Sertraline in a Patient on Suboxone

Start bupropion at 150 mg once daily in the morning while continuing sertraline, then taper sertraline slowly over 4-8 weeks after bupropion reaches therapeutic levels; bupropion monotherapy is safe with Suboxone, but avoid any naltrexone-bupropion combination products which are absolutely contraindicated with opioid therapy. 1, 2

Critical Safety Distinction

Bupropion monotherapy (Wellbutrin) does NOT interact with Suboxone and is safe to use. 1 The absolute contraindication only applies to naltrexone-bupropion combination products (like Contrave), where naltrexone will precipitate severe opioid withdrawal in patients on Suboxone. 1

Bupropion Initiation Strategy

Starting Dose and Titration

• Begin bupropion SR 150 mg once daily in the morning while continuing current sertraline dose. 1
• After 3 days, if tolerated, increase to 150 mg twice daily (300 mg total), with the second dose given before 3 PM to minimize insomnia risk. 1
• Allow 6-8 weeks at therapeutic dose before assessing full antidepressant response. 1

Timing Considerations

• The morning dosing leverages bupropion's activating properties, which can improve energy and reduce apathy. 1
• The second dose must be administered before 3 PM to prevent sleep disturbances. 1

Sertraline Discontinuation Protocol

When to Begin Tapering

• Wait 2-4 weeks after bupropion reaches therapeutic dose (300 mg/day) before initiating sertraline taper to ensure adequate antidepressant coverage. 3, 4

Tapering Schedule

• Taper sertraline slowly over 4-8 weeks minimum, reducing by approximately 10% of the current dose every 1-2 weeks. 3, 4
• Each new dose should be 90% of the previous dose, not a straight-line reduction. 5
• Tapers carried out over weeks to months have lower risk of discontinuation symptoms than rapid tapers. 3, 4

Example Taper for Sertraline 100 mg Daily

• Week 1-2: 75 mg daily
• Week 3-4: 50 mg daily
• Week 5-6: 25 mg daily
• Week 7-8: 12.5 mg daily (can split tablets or use liquid formulation)
• Then discontinue

Monitoring for Withdrawal Symptoms

Common Discontinuation Symptoms

Sertraline discontinuation commonly causes insomnia, flu-like symptoms, mood disturbances, dizziness, and paresthesias that can last days to months. 4 These symptoms can be confused with depression relapse. 3

Management of Withdrawal Symptoms

• If significant withdrawal symptoms emerge, slow the taper further or hold at current dose for 1-2 weeks before continuing. 4
• If severe symptoms occur, restart the previous sertraline dose and taper even more gradually. 4
• Symptomatic management with clonidine or other adjuvants may be needed for autonomic symptoms. 5

Serotonin Syndrome Risk

Monitoring During Overlap Period

While combining bupropion with sertraline, monitor for serotonin syndrome symptoms including mental status changes, autonomic instability, neuromuscular symptoms, and gastrointestinal symptoms. 2

Important caveat: Although rare case reports exist of serotonin syndrome with bupropion-SSRI combinations 6, and Suboxone has triggered serotonin syndrome when combined with tricyclic antidepressants 7, the risk with therapeutic doses of bupropion, sertraline, and Suboxone together appears very low. The mechanism likely involves bupropion's inhibition of CYP2D6, which can increase SSRI levels. 6

Risk Mitigation

• Use standard therapeutic doses without exceeding maximum recommendations (bupropion 300-400 mg/day, sertraline up to 200 mg/day). 1, 2
• Educate the patient about serotonin syndrome symptoms and instruct them to seek immediate care if symptoms develop. 2
• The concomitant use is clinically warranted for cross-tapering, but patients should be aware of the potential increased risk. 2

Additional Safety Considerations

Contraindications to Screen For

• Seizure disorders or conditions lowering seizure threshold are absolute contraindications to bupropion. 1
• Uncontrolled hypertension should preclude bupropion use. 1
• Current or recent MAOI use (within 14 days) is contraindicated. 1
• Monitor blood pressure and heart rate, especially in the first 12 weeks, as bupropion can elevate both. 1

Suicidal Ideation Monitoring

• Patients under 24 years require close monitoring for increased suicidal thoughts, particularly in the first 1-2 months of treatment. 1, 2
• Risk for suicide attempts is greatest during the first 1-2 months of any antidepressant treatment. 1

Clinical Advantages of This Approach

Cross-tapering (overlapping medications) is preferred over abrupt switching because it avoids discontinuation symptoms and maintains continuous antidepressant coverage. 5, 3 The combination addresses depression through complementary mechanisms—sertraline affects serotonin while bupropion works via noradrenergic/dopaminergic pathways. 1

Bupropion offers advantages including lower rates of sexual dysfunction compared to SSRIs and minimal weight gain or even weight loss. 1 This makes it particularly suitable for patients concerned about these side effects.

Depression and Pain Management on Suboxone

For patients on Suboxone with inadequate pain control or depression, addressing psychiatric comorbidity before and during treatment is essential. 5 Depression, anxiety, and insomnia should be treated as part of comprehensive care. 5