What is the management plan for a patient with major depression on Rexulti (brexpiprazole) and bupropion who develops a seizure with normal electrolytes and a normal MRI brain?

Management of Seizure in a Patient on Bupropion and Rexulti

Discontinue bupropion immediately and permanently—it is contraindicated after a seizure has occurred. 1, 2

Immediate Actions

Discontinue the Offending Agent

• Stop bupropion at once as it significantly lowers the seizure threshold and is absolutely contraindicated in patients with seizure disorders or a history of seizures. 1, 2
• The seizure risk with bupropion is dose-dependent (approximately 0.1% at doses up to 300 mg/day), but any seizure occurrence makes continued use unacceptable. 2
• Multiple case reports document bupropion-induced seizures at therapeutic doses and blood levels, including generalized tonic-clonic seizures, status epilepticus, and recurrent seizures. 3, 4, 5, 6

Evaluate Rexulti (Brexpiprazole)

• Rexulti can be continued as it does not significantly lower seizure threshold and is not contraindicated after a single seizure in the context of a clear precipitant (bupropion). 1
• Monitor closely for any neuropsychiatric changes, as recommended for all antidepressant and antipsychotic therapy. 1

Antiepileptic Therapy Decision

Single Unprovoked Seizure Management

• Do not routinely start antiepileptic drugs (AEDs) after a single provoked seizure when the provoking factor (bupropion) has been removed. 3
• If seizures recur after bupropion discontinuation, initiate AED therapy with phenytoin or sodium valproate as documented effective in similar cases. 3
• Obtain neurology consultation if there is any uncertainty about seizure etiology or if seizures recur. 3, 4

Alternative Antidepressant Selection

Choose Based on Safety Profile

• Switch to an SSRI (sertraline, fluoxetine, escitalopram) or another second-generation antidepressant without significant seizure risk. 1
• 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. 1
• Avoid other medications that lower seizure threshold, including high-dose SSRIs, though their risk is substantially lower than bupropion. 3

Specific Considerations

• If the patient was benefiting from bupropion's activating properties or lower sexual side effect profile, consider mirtazapine or vortioxetine as alternatives. 1
• Assess response to the new antidepressant within 1-2 weeks and modify treatment if inadequate response after 6-8 weeks. 1

Monitoring Plan

Short-Term (First 2-4 Weeks)

• Monitor for seizure recurrence weekly for the first month after bupropion discontinuation. 1
• Assess for worsening depression, suicidal ideation, or behavioral changes with medication transition, particularly in the first 1-2 weeks. 1
• Monitor for antidepressant withdrawal symptoms if bupropion is stopped abruptly, though this is necessary given the seizure. 1

Long-Term

• Continue regular psychiatric follow-up to assess therapeutic response and adverse effects of the new antidepressant regimen. 1
• If no response after 6-8 weeks on adequate dosing of the new agent, modify treatment by switching medications, augmenting therapy, or considering psychotherapy. 1

Critical Pitfalls to Avoid

• Never restart bupropion in this patient—a history of seizure is an absolute contraindication. 1, 2
• Do not assume the seizure was idiopathic when a clear medication-related cause exists; bupropion is well-documented to cause seizures even at therapeutic doses in patients without predisposing factors. 5, 6
• Do not delay discontinuation of bupropion while awaiting further workup—the medication must be stopped immediately. 3, 4
• Avoid combining multiple medications that lower seizure threshold if future medication changes are needed. 3