Is it safe to combine Wellbutrin (bupropion) and propranolol in a patient with a history of depression and anxiety?

Combining Wellbutrin (Bupropion) and Propranolol: Safety and Clinical Considerations

The combination of bupropion and propranolol is generally safe and can be used together in patients with depression and anxiety, with no documented contraindications or significant drug interactions between these agents. 1

Evidence for Safety

• No documented drug interactions exist between bupropion and propranolol in the medical literature or FDA guidance 1
• The PDR does not warn against interactions between bupropion and beta-blockers 1
• No case reports of adverse effects have been documented when these agents are combined 1

Clinical Rationale for Combination

This combination can be particularly advantageous for patients with comorbid depression and anxiety:

Bupropion's Role

• Bupropion is activating and works through dopamine/norepinephrine reuptake inhibition 1
• Effective for depression, particularly in patients with low energy and apathy 1
• Lower rates of sexual dysfunction compared to SSRIs (fluoxetine, sertraline, paroxetine) 1
• Should be dosed with the second dose before 3 PM to minimize insomnia risk 1
• Typical dosing: start 37.5 mg every morning, increase by 37.5 mg every 3 days to maximum 150 mg twice daily 1

Propranolol's Role

• Propranolol is effective for anxiety symptoms, particularly panic disorder and performance anxiety 1
• Nonselective beta-blocker that reduces physical manifestations of anxiety (tremor, tachycardia, nervousness) 1, 2
• Can be combined with cognitive behavioral therapy and/or antidepressants for panic disorder 1

Important Clinical Caveats

Bupropion Precautions

• Avoid in patients with seizure disorders or conditions that lower seizure threshold 1
• Should not be used in agitated patients due to its activating properties 1
• Monitor blood pressure, as bupropion can increase BP in some patients 1
• Contraindicated with MAO inhibitors (within 14 days) 1

Propranolol Precautions

• Monitor for bradycardia and hypotension, especially in elderly patients 1
• Take full medical history for sudden death, repeated fainting, or arrhythmias in first-degree family members before initiating 1
• Can mask hypoglycemia symptoms in diabetic patients 1
• May worsen depression in some patients (though this is more theoretical than evidence-based) 1

Monitoring Strategy

• Begin monitoring within 1-2 weeks of initiating either medication 1
• Assess for worsening depression, suicidal ideation, agitation, or unusual behavioral changes 1
• Monitor heart rate and blood pressure regularly when using propranolol 1
• Evaluate therapeutic response at 4-8 weeks for bupropion's antidepressant effects 1
• Watch for insomnia with bupropion; adjust timing of second dose if needed 1

When This Combination is Particularly Useful

• Patients with depression plus performance anxiety or panic symptoms benefit from bupropion's antidepressant effects and propranolol's anxiolytic properties 1, 2
• Patients who experienced sexual dysfunction on SSRIs can switch to bupropion while managing anxiety with propranolol 1, 3
• Patients with comorbid migraine headaches may benefit from propranolol's migraine prophylaxis while treating depression with bupropion 1