What precautions should be taken for a patient with a history of seizures who is taking Wellbutrin (bupropion)?

Wellbutrin (Bupropion) is Contraindicated in Patients with Seizure Disorders

Bupropion should not be used in patients with a history of seizures, as it lowers the seizure threshold and is explicitly contraindicated in this population. 1, 2

Absolute Contraindication

• Seizure disorder is an absolute contraindication to bupropion use, whether prescribed as Wellbutrin for depression, Zyban for smoking cessation, or in combination formulations like naltrexone-bupropion ER (Contrave) for obesity. 1, 2

• The FDA drug label explicitly lists seizure disorder as a contraindication, and this applies to all formulations (immediate-release, sustained-release, and extended-release). 2

Seizure Risk Profile

• The incidence of seizures with bupropion at recommended doses (≤450 mg/day) ranges from 0.35-0.48%, which is approximately 1 in 200-300 patients. 3, 4

• At the commonly prescribed dose of 300 mg/day for smoking cessation, the seizure incidence is approximately 1 in 1,000 patients. 5

• Seizure risk increases substantially with doses above 450 mg/day, and predisposing factors were present in over half of reported seizure cases. 4

• Seizures can occur even in patients without prior seizure history, at therapeutic doses, and at moderate blood levels. 6, 7

Clinical Presentation

• Bupropion-induced seizures typically present as generalized tonic-clonic seizures with loss of consciousness and postictal confusion. 5, 6

• Seizures can occur within days of initiating treatment or after dose escalation. 5, 6, 7

• In one reported case, a seizure occurred just 4 days after starting bupropion in a patient with no personal or family history of seizures. 7

Additional Risk Factors to Consider

If a patient with seizure history is mistakenly prescribed bupropion, the following factors further increase seizure risk:

• Concomitant benzodiazepine withdrawal (e.g., recent discontinuation of alprazolam) can compound the seizure risk. 7

• Doses exceeding 450 mg/day dramatically increase seizure incidence. 4

• Rapid dose escalation without gradual titration increases risk. 2

• Concurrent use of other medications that lower seizure threshold should be avoided. 2

Management Algorithm

If a patient with known seizure disorder is currently taking bupropion:

1. Discontinue bupropion immediately and do not restart. 1, 2

2. Taper the dose if the patient is on 300 mg/day (reduce to 150 mg once daily before complete discontinuation to minimize withdrawal symptoms). 2

3. Consider alternative treatments: For depression, use SSRIs (sertraline, citalopram), mirtazapine, or nortriptyline; for smoking cessation, use nicotine replacement therapy or varenicline; for obesity, use GLP-1 agonists (semaglutide, liraglutide) or other agents without seizure risk. 1

4. Monitor for at least 14 days after discontinuation if switching to an MAOI antidepressant. 2

Critical Pitfalls to Avoid

• Do not use combination products containing bupropion (naltrexone-bupropion ER) in patients with seizure disorders, even if the primary indication is obesity or smoking cessation rather than depression. 1

• Do not assume safety based on low doses—seizures have been reported at therapeutic doses and moderate blood levels in patients without predisposing factors. 6

• Do not overlook family history—patients with family history of seizures may have undiagnosed photosensitivity or juvenile myoclonic epilepsy that becomes apparent only after bupropion exposure. 5

• Educate patients that bupropion is marketed under multiple brand names (Wellbutrin, Zyban, Aplenzin, Contrave) and they should not take any bupropion-containing product if they have a seizure history. 2