Is it safe to prescribe Wellbutrin (bupropion) to a patient with a history of seizure 40 years ago?

Bupropion is Contraindicated for Patients with a History of Seizures

Bupropion (Wellbutrin) should not be prescribed to a patient with a history of seizures, even if the seizure occurred 40 years ago. 1, 2

Rationale for Contraindication

Bupropion lowers the seizure threshold, which significantly increases the risk of recurrent seizures in patients with a prior seizure history. This contraindication is clearly stated in multiple clinical guidelines:

• The FDA drug label explicitly lists seizure disorder as a contraindication for bupropion, with no time-based exceptions for remote seizures 1
• NCCN guidelines specifically state that "bupropion is contraindicated for patients with seizure risks" 2
• Obesity management guidelines similarly identify seizure disorder as a contraindication for naltrexone-bupropion therapy 2

Seizure Risk with Bupropion

The risk of seizures with bupropion is dose-related but present even at therapeutic doses:

• The incidence of seizures with bupropion SR at therapeutic doses is approximately 0.1% (1/1000 patients) 1, 3
• The risk increases almost tenfold at higher doses (between 450-600 mg/day) 1
• Seizures can occur even in patients without predisposing factors 4, 5

Alternative Medications to Consider

For patients with a history of seizures who need treatment for:

1. Depression:

   • SSRIs (fluoxetine, sertraline, etc.)
   • SNRIs (venlafaxine, duloxetine)
   • Mirtazapine

2. Smoking cessation:

   • Nicotine replacement therapy
   • Varenicline (Chantix)

3. Weight management:

   • GLP-1 receptor agonists (semaglutide, liraglutide)
   • Phentermine-topiramate (with appropriate monitoring)
   • Orlistat

Important Clinical Considerations

• The time since the last seizure (40 years ago) does not eliminate the contraindication
• Even with anticonvulsant co-therapy, bupropion remains contraindicated in patients with seizure history 6
• Case reports document seizures occurring in patients without other risk factors when taking bupropion 4, 5
• The risk of mortality and morbidity from a seizure outweighs the potential benefits of bupropion in patients with seizure history

Common Pitfalls to Avoid

1. Assuming remote seizures pose no risk: The contraindication applies regardless of how long ago the seizure occurred

2. Relying on anticonvulsants for protection: Even patients on anticonvulsant medications have experienced seizures while taking bupropion 6

3. Underestimating seizure risk: Even at therapeutic doses, bupropion carries a seizure risk that is significantly higher in those with prior seizures

4. Overlooking alternative medications: Several effective alternatives exist for the conditions bupropion treats

In conclusion, based on the most recent and authoritative guidelines, bupropion should not be prescribed to patients with any history of seizures, regardless of how remote that history may be.