Bupropion Use in Patients with Seizure History: Contraindicated
Bupropion is absolutely contraindicated in patients with a history of seizures, regardless of current seizure control with lamotrigine or other antiepileptic medications. 1
FDA Contraindication
The FDA drug label explicitly states that bupropion hydrochloride extended-release tablets are contraindicated in patients with a seizure disorder. 1 This is a black-box level safety concern that supersedes potential benefits for managing SSRI-induced sexual dysfunction. 1
Seizure Risk Profile
Dose-related seizure risk: The incidence of seizures with bupropion is approximately 0.1% (1/1000 patients) at doses up to 300 mg/day, but increases nearly tenfold at higher doses. 1
Risk persists even at therapeutic doses: Multiple case reports document new-onset seizures in patients taking bupropion at standard therapeutic doses (300-450 mg/day) who had no prior seizure history. 2, 3, 4, 5
History of seizures dramatically amplifies risk: Patients with any seizure disorder history—even if well-controlled on antiepileptic drugs like lamotrigine—have fundamentally lowered seizure thresholds that make bupropion use unacceptably dangerous. 1
Bupropion accounts for 1.4% of all new-onset seizures presenting to emergency departments, making it the third leading cause of drug-related seizures after cocaine and benzodiazepine withdrawal. 6
Alternative Management Strategies for SSRI-Induced Sexual Dysfunction
Since bupropion is contraindicated, consider these evidence-based alternatives:
Switch to a Different Antidepressant
Mirtazapine has lower rates of sexual dysfunction than SSRIs, though it causes sedation and weight gain. 7 This may be the safest alternative in a patient with seizure history, as it does not lower seizure threshold. 7
Among SSRIs, escitalopram and fluvoxamine cause the lowest rates of sexual dysfunction if continuing SSRI therapy is necessary. 7
Augmentation Strategies
PDE5 inhibitors (sildenafil, tadalafil) can be added to the current SSRI regimen to specifically address erectile dysfunction without changing the antidepressant. 8 Sildenafil improves ability to achieve and maintain erections (MD 1.04,95% CI 0.65 to 1.44). 8
Buspirone has been studied as an off-label augmentation strategy for SSRI-induced sexual dysfunction, though evidence quality is limited. 8 It does not lower seizure threshold. 8
Dose Reduction
- Reducing the SSRI to the minimum effective dose for depression control is a primary management strategy, as sexual side effects are strongly dose-related. 7
Critical Clinical Caveat
SSRIs themselves should be used cautiously in patients with seizure history, as seizures have been observed in the context of SSRI use. 9 However, this represents a much lower risk compared to bupropion's absolute contraindication. 9 Close monitoring is warranted when combining any serotonergic agent with lamotrigine. 9
Recommended Approach
Do not prescribe bupropion given the absolute contraindication. 1
Consider switching to mirtazapine 15-30 mg/day as the safest alternative antidepressant with lower sexual dysfunction rates. 7
If erectile dysfunction is the primary concern, add a PDE5 inhibitor (sildenafil 25-100 mg as needed) to the current SSRI regimen. 8
Reduce SSRI dose to the minimum effective level if depression remains controlled. 7
Monitor closely for any changes in seizure frequency when making medication adjustments. 9