What are the precautions for using bupropion (Wellbutrin) in patients with a history of seizure or at increased risk for seizures?

Bupropion Should Be Avoided in Patients with Seizure Disorders and Used with Caution in Those at Risk for Seizures

Bupropion is contraindicated in patients with a history of seizure disorders and should be used with extreme caution in patients with factors that increase seizure risk due to its ability to lower the seizure threshold. 1, 2

Seizure Risk with Bupropion

Bupropion has a well-documented association with increased seizure risk:

• The medication lowers the seizure threshold, with seizure incidence of approximately 0.1% at therapeutic doses 1
• Seizure risk increases with higher doses, with rates of 0.35%-0.44% at doses ≤450 mg/day 3
• Seizures can occur even in patients without prior seizure history or risk factors 4, 5
• New-onset seizures can occur within days of starting the medication 4, 5

Absolute Contraindications

Bupropion should not be prescribed to patients with:

• Seizure disorder/epilepsy 1
• History of seizures 1
• Anorexia nervosa or bulimia (due to increased seizure risk) 1
• Current use of other medications that lower seizure threshold 1

Risk Factors Requiring Caution

Use bupropion with extreme caution in patients with:

• History of head trauma
• Central nervous system tumors
• Severe hepatic cirrhosis
• Excessive alcohol use or abrupt alcohol discontinuation
• Drug withdrawal states (especially benzodiazepines) 1, 6
• Sleep deprivation 6
• History of attention deficit disorder 6
• Medications that lower seizure threshold
• Use of stimulants or anorectic drugs
• Diabetes treated with hypoglycemic agents or insulin 1

Dosing Considerations for At-Risk Patients

When bupropion must be used in patients with risk factors:

• Start at lower doses and increase gradually 2
• Consider maximum dose of 150 mg daily in patients with risk factors
• For moderate to severe hepatic impairment, maximum dose is 150 mg every other day 2
• Consider dose reduction in renal impairment 2
• Never exceed recommended maximum doses
• Do not allow patients to take doses close together (risk of inadvertent overdose)
• Educate patients about the importance of strict adherence to prescribed dosing

Monitoring Recommendations

For patients on bupropion with any seizure risk factors:

• More frequent follow-up during dose titration
• Lower threshold for discontinuation if concerning symptoms develop
• Consider discontinuation if other seizure risk factors develop during treatment
• Educate patients and families about seizure warning signs
• Instruct to discontinue and seek medical attention if seizure occurs

Clinical Pearls and Pitfalls

• Bupropion-induced seizures can occur at therapeutic doses, even in patients without prior seizure history 4, 7
• Seizures may occur shortly after initiation or dose increases 4, 5
• The combination of bupropion with other medications that lower seizure threshold significantly increases risk
• Patients may not disclose all seizure risk factors (e.g., history of eating disorders, alcohol use)
• Bupropion is available under multiple brand names for different indications (depression, smoking cessation), increasing the risk of inadvertent duplicate therapy

While bupropion can be effective for depression and smoking cessation 1, the seizure risk must be carefully weighed against potential benefits, especially in patients with any seizure risk factors.