Management of Seizure in a Patient on Bupropion and Rexulti

Immediate Actions

• Discontinue bupropion immediately and permanently as it is contraindicated after a seizure has occurred, due to its significant lowering of the seizure threshold, with a dose-dependent risk of approximately 0.1% at doses up to 300 mg/day 1, 2
• Stop bupropion at once, as it is absolutely contraindicated in patients with seizure disorders or a history of seizures, with the seizure risk being dose-dependent 1, 2, 3

Antiepileptic Therapy Decision

• The American College of Physicians recommends selecting second-generation antidepressants based on adverse effect profiles, cost, and patient preferences, as efficacy does not differ significantly among agents, which can guide the choice of alternative antidepressants after bupropion discontinuation 4

Alternative Antidepressant Selection

• Switch to an SSRI (sertraline, fluoxetine, escitalopram) or another second-generation antidepressant without significant seizure risk, as recommended by the American College of Physicians 4
• Consider mirtazapine or vortioxetine as alternatives if the patient was benefiting from bupropion's activating properties or lower sexual side effect profile 4

Monitoring Plan

• Monitor for seizure recurrence weekly for the first month after bupropion discontinuation, and assess for worsening depression, suicidal ideation, or behavioral changes with medication transition 4
• Continue regular psychiatric follow-up to assess therapeutic response and adverse effects of the new antidepressant regimen, and modify treatment if no response after 6-8 weeks on adequate dosing of the new agent 4

Critical Pitfalls to Avoid

• Never restart bupropion in this patient—a history of seizure is an absolute contraindication, as documented by the Journal of the National Comprehensive Cancer Network and other sources 1, 2, 3