Wellbutrin (Bupropion) is Contraindicated in Patients with a History of Seizures
Bupropion should not be prescribed to patients with a history of seizure disorders, as it is explicitly contraindicated in this population due to dose-dependent seizure risk. 1, 2
Absolute Contraindication
Bupropion hydrochloride extended-release tablets are contraindicated in patients with a seizure disorder or conditions that increase the risk of seizure. 2
The FDA drug label explicitly lists seizure disorder as a contraindication, along with conditions such as severe head injury, arteriovenous malformation, CNS tumor or infection, severe stroke, anorexia nervosa, bulimia, and abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs. 2
Multiple clinical guidelines reinforce that bupropion should be avoided in patients with seizure disorders due to its ability to lower the seizure threshold. 1
Seizure Risk Data
The incidence of seizures with bupropion is dose-dependent, ranging from 0.35%-0.48% at doses ≤450 mg/day, but increases nearly tenfold at doses between 450-600 mg/day. 2, 3
In clinical trials with bupropion sustained-release formulations up to 300 mg per day, the seizure incidence was approximately 0.1% (1/1000 patients). 2
A large prospective study found seizure incidence of approximately 0.4% (13/3200) with immediate-release bupropion at doses of 300-450 mg/day. 2
Case reports document seizures occurring even at moderate doses (600 mg/day) and moderate blood levels (83 ng/ml) in patients without any premorbid history or predisposing factors to epilepsy. 4
Clinical Reasoning
The mechanism behind bupropion's seizure risk relates to its effects on dopamine and norepinephrine neurotransmission, which can lower the seizure threshold in susceptible individuals. 5 Unlike other antidepressants that primarily affect serotonin, bupropion's unique dopaminergic and noradrenergic activity creates a distinct seizure risk profile. 5
In patients with a history of seizures, predisposing factors were noted in over half of reported seizure cases with bupropion use. 3 This means that even patients with controlled seizure disorders on anticonvulsant medication remain at elevated risk.
Alternative Recommendations
For patients with depression and a history of seizures, consider:
SSRIs (selective serotonin reuptake inhibitors) as first-line alternatives, which do not carry the same seizure risk profile. 5
Mirtazapine, which has sedating properties and no significant seizure risk, may be particularly useful if insomnia is a comorbid concern. 5
Vortioxetine or vilazodone, newer antidepressants with different mechanisms that do not lower seizure threshold. 5
Critical Pitfall to Avoid
Do not attempt dose reduction strategies or "cautious use" of bupropion in patients with seizure history. The contraindication is absolute, not relative. Even at the lowest therapeutic doses, the risk-benefit ratio is unacceptable given the availability of equally effective alternatives without seizure risk. 1, 2