Can Wellbutrin (bupropion) and Lamictal (lamotrigine) be given together to a patient, especially those with a history of seizure disorders or bipolar disorder?

Can Wellbutrin and Lamictal Be Given Together?

Yes, Wellbutrin (bupropion) and Lamictal (lamotrigine) can be given together, but this combination requires careful monitoring in patients with seizure disorders, as bupropion lowers the seizure threshold and should be avoided in patients with epilepsy or conditions that increase seizure risk. 1

Key Contraindications and Warnings

Bupropion (Wellbutrin) - Seizure Risk

• Bupropion is absolutely contraindicated in patients with:

  • Current seizure disorder or epilepsy 1
  • History of seizures 2
  • Conditions that increase seizure risk including severe head injury, arteriovenous malformation, CNS tumor, CNS infection, severe stroke 1
  • Brain metastases 2

• The seizure risk with bupropion is dose-dependent, with an incidence of approximately 0.1% at doses up to 300 mg/day, increasing nearly tenfold at doses between 450-600 mg/day 1

• Additional factors that increase seizure risk when combined with bupropion include:

  • Concomitant medications that lower seizure threshold (including antiepileptic drugs if abruptly discontinued) 1
  • Metabolic disorders (hypoglycemia, hyponatremia, severe hepatic impairment) 1
  • Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1

Lamotrigine (Lamictal) - Seizure Considerations

• Lamotrigine is an antiepileptic drug that works by inhibiting voltage-sensitive sodium channels and stabilizing neuronal membranes 3, 4
• It is FDA-approved for maintenance treatment of bipolar I disorder and has demonstrated efficacy in preventing depressive episodes 3, 5
• Lamotrigine does not inherently increase seizure risk; rather, it is used to prevent seizures 6

Clinical Decision Algorithm

For Patients WITHOUT Seizure History:

• The combination is generally safe and can be used together for conditions like bipolar disorder with comorbid depression or ADHD 3, 7
• Monitor blood pressure, as bupropion can cause hypertension 1
• Watch for neuropsychiatric symptoms including mood changes, agitation, or suicidal ideation 1
• Titrate lamotrigine slowly over 6 weeks to 200 mg/day to minimize risk of serious rash (0.1% incidence) 3

For Patients WITH Seizure History or Risk Factors:

• Do not prescribe bupropion - this is an absolute contraindication 1
• Consider alternative antidepressants such as SSRIs, though these should be used cautiously in patients with seizure history 2
• Lamotrigine alone may be appropriate for bipolar depression without the seizure risk associated with bupropion 3, 4

For Patients WITH Bipolar Disorder:

• Bupropion should be avoided in patients with bipolar depression due to risk of precipitating mania 2
• Lamotrigine is specifically indicated for maintenance treatment of bipolar I disorder and prevention of depressive episodes 3, 5, 4
• Lamotrigine does not cause mood destabilization or precipitate mania, unlike traditional antidepressants 4

Important Drug Interaction Considerations

• Lamotrigine dosing requires adjustment when coadministered with valproate (decrease dose) or carbamazepine (increase dose) 3
• Bupropion inhibits CYP2D6 and may affect metabolism of other medications 7
• Neither medication requires combination with MAOIs (14-day washout period required for bupropion) 1

Monitoring Requirements

• Before initiating bupropion: Assess for seizure history, eating disorders, head injury, CNS tumors, and measure baseline blood pressure 1
• During treatment: Monitor blood pressure periodically, watch for neuropsychiatric symptoms, and observe for signs of serious rash with lamotrigine 1, 3
• If seizure occurs: Immediately discontinue bupropion and do not restart 1

Common Pitfalls to Avoid

• Never use bupropion in patients with any seizure history - this is frequently overlooked but represents an absolute contraindication 1
• Do not abruptly discontinue alcohol, benzodiazepines, or antiepileptic drugs in patients taking bupropion, as this dramatically increases seizure risk 1
• Avoid rapid titration of lamotrigine, as this increases the risk of serious rash including Stevens-Johnson syndrome 3
• Do not exceed bupropion dose of 450 mg/day (maximum 300 mg once daily for XL formulation) 1