Bupropion Remains Absolutely Contraindicated in Seizure Disorders Regardless of Lamotrigine Use
Bupropion is absolutely contraindicated in patients with any seizure disorder, and concurrent lamotrigine therapy does not eliminate this contraindication. The FDA drug label explicitly states that bupropion is contraindicated in patients with seizure disorder, without exception for concurrent antiepileptic drug use 1. This absolute contraindication exists because bupropion independently lowers the seizure threshold through its own pharmacologic mechanisms 2, 1.
Why Lamotrigine Does Not Override the Contraindication
Lamotrigine cannot reliably protect against bupropion-induced seizures because bupropion acts through distinct mechanisms that lower seizure threshold independent of the protective effects of antiepileptic drugs. Multiple case reports document seizures occurring in patients taking bupropion alongside antiepileptic medications:
- A 27-year-old woman experienced grand mal seizures while taking bupropion ER in combination with both clonazepam and lamotrigine, demonstrating that dual anticonvulsant therapy failed to prevent bupropion-induced seizures 3
- Patients without any seizure history have developed new-onset seizures on bupropion at standard doses (300 mg/day), with seizure risk estimated at 0.1% (1 in 1,000) even in previously healthy individuals 2, 4
- One case involved a patient who developed seizures at a modest blood level of 83 ng/mL on 600 mg/day, despite having no predisposing factors 5
The Mechanism Behind the Absolute Contraindication
Bupropion lowers seizure threshold through noradrenergic and dopaminergic mechanisms that are not adequately blocked by standard antiepileptic drugs like lamotrigine. The FDA explicitly lists "abrupt discontinuation of antiepileptic drugs" as an absolute contraindication, implying that even stable antiepileptic therapy does not provide sufficient protection to justify bupropion use in patients with underlying seizure disorders 1.
Clinical Evidence of Risk Even With Anticonvulsant Coverage
The case literature reveals a concerning pattern:
- Two patients on clozapine (which also lowers seizure threshold) developed seizures after bupropion was added, despite one being on divalproex for seizure prophylaxis 6
- The seizure risk appears additive or potentially synergistic when bupropion is combined with other seizure-threshold-lowering agents, even in the presence of anticonvulsants 6
- In the patient taking lamotrigine and clonazepam concurrently, bupropion ER still induced grand mal seizures after 6 months of therapy, requiring emergency department treatment for two seizures within 8 hours 3
What This Means for Your Patient
If your patient has a documented seizure disorder and is on lamotrigine, bupropion should not be prescribed under any circumstances. Alternative antidepressants that do not lower seizure threshold should be selected:
- For depression: Consider SSRIs (sertraline 50-200 mg daily, escitalopram 10-20 mg daily) or mirtazapine, which have favorable safety profiles in seizure disorders 2
- For smoking cessation: Use nicotine replacement therapy (patches, gum, lozenges) or varenicline instead of bupropion 2
- For depression with low energy/motivation: Consider augmenting an SSRI with aripiprazole rather than using bupropion 2
Critical Safety Pitfall to Avoid
Do not rationalize bupropion use in a patient with seizure disorder by assuming that "well-controlled" epilepsy on lamotrigine provides adequate protection. The FDA contraindication makes no distinction between controlled versus uncontrolled seizure disorders 1. The case of the patient on dual anticonvulsants (lamotrigine + clonazepam) who still seized on bupropion ER demonstrates that even aggressive anticonvulsant therapy cannot reliably prevent bupropion-induced seizures 3.
The absolute nature of this contraindication reflects the unpredictable and potentially life-threatening risk of seizures, which can occur even at therapeutic doses in patients without traditional risk factors 5, 7, 4.