How to start Wellbutrin (bupropion) in an adult patient with a history of opioid dependence and depression, currently taking Suboxone (buprenorphine and naloxone), while stopping another antidepressant medication at a dose of 150mg?

Starting Bupropion While Stopping Another Antidepressant at 150mg in a Patient on Suboxone

Bupropion monotherapy is safe to initiate in patients taking Suboxone (buprenorphine/naloxone), as the critical contraindication only applies to naltrexone-bupropion combination products, not bupropion alone. 1

Critical Safety Distinction

• Bupropion monotherapy does NOT interact with Suboxone and can be safely prescribed for depression or smoking cessation in patients on buprenorphine maintenance therapy 1
• The absolute contraindication exists only for naltrexone-bupropion combination products (like Contrave), which would precipitate severe opioid withdrawal 1
• Confirm the patient is NOT taking any naltrexone-containing medications before initiating bupropion 1

Discontinuing the Current 150mg Antidepressant

The approach depends on which antidepressant is being stopped:

If Stopping an SSRI/SNRI:

• Taper gradually over 2-4 weeks to minimize discontinuation syndrome, reducing by 25-50% every 1-2 weeks 2
• Common withdrawal symptoms include dizziness, flu-like symptoms, insomnia, and mood changes 2
• Do not stop abruptly, as this increases risk of discontinuation syndrome 2

If Stopping Another Medication at 150mg:

• Without knowing the specific medication, apply conservative tapering principles
• Monitor closely for withdrawal symptoms during the first 1-2 weeks 1

Initiating Bupropion: Step-by-Step Protocol

Week 1: Start Low

• Begin bupropion SR 37.5mg once daily in the morning 1
• This ultra-low starting dose minimizes adverse effects in patients on multiple medications 1
• Take the first dose in the morning to leverage activating properties 1

Week 1 (Days 4-7): First Titration

• Increase to 75mg once daily in the morning (increase by 37.5mg every 3 days as tolerated) 1

Week 2: Second Titration

• Increase to 112.5mg once daily in the morning 1

Week 2-3: Target Therapeutic Dose

• Increase to 150mg once daily in the morning 1
• After 3 days at 150mg once daily, if tolerated, advance to 150mg twice daily (300mg total) 1
• The second dose MUST be taken before 3 PM to prevent insomnia 1

Maximum Dose Considerations:

• Do not exceed 300mg/day total (150mg twice daily) for depression in this population 1, 3
• The maximum dose of 450mg/day applies only to XL formulation and should not be exceeded to maintain seizure risk at 0.1% 1, 3

Critical Pre-Treatment Screening

Before initiating bupropion, confirm the patient does NOT have:

• Active seizure disorder (absolute contraindication) 3
• Current or prior bulimia or anorexia nervosa (absolute contraindication) 3
• Uncontrolled hypertension (relative contraindication requiring BP control first) 1
• Recent abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs (absolute contraindication) 3
• Current MAOI use or use within 14 days (absolute contraindication) 3

Monitoring Requirements

First 1-2 Weeks:

• Monitor for worsening depression, suicidal ideation, or behavioral changes (highest risk period, especially in patients <24 years) 1, 3
• Assess for increased agitation, as bupropion is activating 1
• Check blood pressure and heart rate, as bupropion can elevate both 1

Weeks 2-8:

• Continue monitoring for neuropsychiatric adverse effects 1
• Assess therapeutic response at 6-8 weeks before considering treatment modification 1
• Monitor for common side effects: dry mouth, insomnia, agitation, tremor 3

Special Consideration for Opioid Dependence:

• Research suggests depression may be associated with earlier buprenorphine treatment dropout 4
• Treating depression adequately may improve buprenorphine retention 4
• One small study showed bupropion combined with buprenorphine had lower retention (58% vs 90%), though this was for concurrent tobacco cessation treatment 5

Timeline to Clinical Effect

• Energy and apathy may improve within 2 weeks 6
• Full antidepressant effect requires 6-8 weeks at therapeutic dose 1
• Do not discontinue prematurely before 6-8 weeks unless significant adverse effects occur 1

Common Pitfalls to Avoid

1. Never use naltrexone-bupropion combination products in patients on Suboxone—this will precipitate severe withdrawal 1
2. Never give the second dose after 3 PM—this causes insomnia 1
3. Never exceed 300mg/day total without careful consideration of seizure risk 1, 3
4. Never start at full therapeutic dose—gradual titration minimizes seizure risk 1, 3
5. Never abruptly stop the current antidepressant—taper to avoid discontinuation syndrome 2
6. Never assume generic formulations are equivalent—monitor closely if switching between formulations 1

Hepatic/Renal Impairment Adjustments

• Moderate to severe hepatic impairment: Maximum 150mg every other day 1, 3
• Moderate to severe renal impairment: Reduce total daily dose by 50% 1, 3
• Mild impairment: Consider reducing dose and/or frequency 3