Seizure Risk: Wellbutrin XL vs Wellbutrin SR
The seizure risk is equivalent between Wellbutrin XL and Wellbutrin SR when used at recommended doses, as both formulations are bioequivalent in terms of systemic exposure to bupropion and its active metabolites. 1, 2
Formulation Equivalence and Seizure Risk
Both SR (sustained-release) and XL (extended-release) formulations carry the same seizure risk of approximately 0.35-0.44% at doses ≤450 mg/day. 3, 4
The three bupropion formulations (IR, SR, and XL) are bioequivalent in terms of systemic exposure to bupropion, meaning they deliver the same amount of active drug to the body despite different release profiles. 1, 2
The primary difference lies in dosing frequency: SR is administered twice daily (typically 150 mg BID) while XL is given once daily (typically 300 mg QD), but this does not alter the overall seizure risk. 5, 2
Dose-Dependent Seizure Risk
The cumulative 2-year seizure risk at the maximum recommended dose of 450 mg/day or less is 0.48%, regardless of formulation. 3
Seizure risk increases substantially above 450 mg/day, making adherence to maximum dosing critical for both formulations. 5, 3
The maximum dose for SR is 400 mg/day (though some sources cite 450 mg/day), while XL has a maximum of 450 mg/day. 5
Key Clinical Considerations
Both formulations should be avoided entirely in patients with seizure disorders, as bupropion lowers the seizure threshold. 6, 5, 1
Predisposing factors were present in over half of reported seizure cases, including history of head trauma, structural brain lesions, alcohol abuse, eating disorders (bulimia/anorexia), and concomitant medications that lower seizure threshold. 6, 3
The seizure risk with newer antidepressants including bupropion (0.0-0.4%) is not substantially different from the incidence of first seizure in the general population (0.07-0.09%). 4
Formulation-Specific Pharmacokinetics
XL has a prolonged absorption with Tmax of approximately 5 hours compared to SR's Tmax of approximately 3 hours, but this does not translate to differential seizure risk. 1
Both formulations produce the same active metabolites (hydroxybupropion, threohydrobupropion, erythrohydrobupropion) at similar steady-state concentrations. 1
Common Pitfalls to Avoid
Do not exceed 450 mg/day total daily dose with either formulation to minimize seizure risk. 5, 3
Screen all patients for seizure predisposition before initiating either formulation, including history of eating disorders, head trauma, CNS tumors, and concurrent medications. 6, 3
Be cautious when combining with other agents that lower seizure threshold or are metabolized by CYP2B6. 1
For patients with moderate to severe hepatic impairment, limit total daily dose to 150 mg regardless of formulation. 5
For moderate to severe renal impairment, reduce the total daily dose by half for either formulation. 5