Is there a contraindication for using Wellbutrin (bupropion) and propranolol together?

No Absolute Contraindication, But Significant Cardiovascular Interaction Risk

There is no absolute contraindication for using bupropion (Wellbutrin) and propranolol together, but this combination requires careful monitoring due to documented pharmacokinetic interactions that can intensify beta-blocker effects, particularly bradycardia and hypotension. 1

Key Safety Concerns

Documented Interaction Profile

• Bupropion inhibits CYP2D6, which is the primary metabolic pathway for propranolol, leading to increased propranolol serum levels and enhanced beta-blockade effects 2, 3
• The most common adverse effect is bradycardia (37.9% of documented cases in one analysis), with intensified beta-blocker side effects including hypotension, dizziness, and fatigue 3
• One case report documented cardiac arrest when fluoxetine (another CYP2D6 inhibitor like bupropion) was combined with propranolol, highlighting the potential severity of this interaction 3

Monitoring Requirements

If this combination is necessary, implement the following safety thresholds:

• Hold propranolol if systolic blood pressure drops below 90 mmHg 1, 4
• Hold propranolol if heart rate falls below 55 beats per minute 1, 4
• Monitor vital signs closely during the first 2-3 weeks after initiating bupropion or adjusting doses 3
• Consider reducing propranolol dose by 25-50% when adding bupropion 3

Bupropion-Specific Contraindications (Unrelated to Propranolol)

Bupropion itself has absolute contraindications that must be ruled out:

• Seizure disorders or conditions that lower seizure threshold (including brain metastases) 1
• Concurrent use with MAO inhibitors (must allow ≥14 days between discontinuation) 1
• Uncontrolled hypertension 1
• Bulimia or anorexia nervosa (increased seizure risk) 1
• Abrupt discontinuation of alcohol or benzodiazepines (seizure risk) 1

Clinical Decision Algorithm

Step 1: Verify no absolute bupropion contraindications exist (seizure disorder, MAOIs, eating disorders) 1

Step 2: Assess baseline cardiovascular status - measure resting heart rate and blood pressure 1

Step 3: If heart rate is already <60 bpm or systolic BP <100 mmHg, consider alternative antidepressant without CYP2D6 inhibition 3

Step 4: If proceeding with combination, reduce propranolol dose prophylactically and monitor vital signs weekly for first month 3

Step 5: Educate patient on symptoms of excessive beta-blockade: severe fatigue, dizziness, syncope, shortness of breath 1

Alternative Considerations

• Mirtazapine or trazodone may be safer alternatives if antidepressant therapy is needed with propranolol, as they have minimal CYP2D6 interaction 3
• Sertraline has been successfully used with beta-blockers but still carries some interaction risk 3
• The combination is not contraindicated in clinical practice and has been used successfully with appropriate monitoring 5

Common Pitfall

The primary error is initiating this combination without dose adjustment or monitoring protocols, leading to symptomatic bradycardia or hypotension that could have been prevented with prophylactic propranolol dose reduction 3.