Can a patient with a history of epilepsy or bipolar disorder, currently taking lamotrigine (lamotrigine) and Motegrity (prucalopride), start taking Wellbutrin (bupropion)?

Can a Patient on Lamotrigine with Motegrity Start Wellbutrin?

Yes, a patient taking lamotrigine and Motegrity (prucalopride) can start Wellbutrin (bupropion), but this requires careful consideration of seizure risk and close monitoring, particularly during the first 1-2 weeks of treatment.

Critical Safety Assessment Before Initiating Bupropion

Absolute Contraindications to Screen For

Before starting bupropion in this patient, you must rule out the following contraindications:

• Seizure disorder or epilepsy history - If the patient is taking lamotrigine for epilepsy rather than bipolar disorder, bupropion is absolutely contraindicated due to its seizure-lowering threshold 1
• Current or past eating disorder (anorexia nervosa or bulimia) - bupropion is contraindicated 1
• Recent alcohol cessation or abrupt discontinuation of benzodiazepines, barbiturates, or antiepileptic drugs - these dramatically increase seizure risk 1
• MAOI use within 14 days - absolute contraindication 1
• Uncontrolled hypertension - bupropion can elevate blood pressure and should be avoided 2, 1

Special Consideration for Lamotrigine Users

The key clinical question is WHY the patient is taking lamotrigine:

• If for bipolar disorder maintenance: Bupropion can be safely added with appropriate monitoring. Lamotrigine is used for prevention of depressive episodes in bipolar disorder 3, 4, and bupropion is a second-generation antidepressant appropriate for treating acute depressive episodes 5

• If for epilepsy/seizure disorder: Bupropion is absolutely contraindicated. The FDA label explicitly states patients with seizure disorders should not take bupropion 1, and the combination would create unacceptable seizure risk

Initiating Bupropion: Dosing Strategy

Starting Dose and Titration

Use a conservative, gradual titration approach to minimize seizure risk and assess tolerability 2:

• Days 1-3: Start with 37.5 mg once daily in the morning 2
• Increase by 37.5 mg every 3 days as tolerated 2
• Target dose: 150 mg twice daily (300 mg total daily) 2
• Maximum dose: Do not exceed 300 mg/day in this patient given the lamotrigine combination 2

Critical Timing Instructions

• First dose: Administer in the morning to leverage activating properties 2
• Second dose: Must be given before 3 PM to minimize insomnia risk 2

Monitoring Protocol

Initial Monitoring (Weeks 1-2)

Begin close monitoring within 1-2 weeks of initiation 5:

• Suicidal ideation and behavior - highest risk in first 1-2 months, especially if patient is under 24 years old 5
• Agitation, irritability, unusual behavioral changes - may indicate worsening depression 5
• Seizure activity - any seizure requires immediate discontinuation of bupropion 1
• Blood pressure and heart rate - monitor periodically, especially in first 12 weeks 2, 1

Ongoing Assessment

• Therapeutic response: Assess for adequate response at 6-8 weeks before considering treatment modification 5
• Manic symptoms: Monitor for activation of mania/hypomania (increased energy, decreased sleep, racing thoughts, reckless behavior) 1
• Dizziness: Common side effect that may require dose reduction if persistent 6

Drug Interaction Considerations

Lamotrigine-Bupropion Interaction

There is no significant pharmacokinetic interaction between lamotrigine and bupropion - they can be safely combined from a drug interaction standpoint. However, the cumulative effect on seizure threshold requires vigilance:

• Lamotrigine is an anticonvulsant that raises seizure threshold 3, 7
• Bupropion lowers seizure threshold 1
• The net effect depends on lamotrigine dosing adequacy and bupropion dose limitation

Motegrity (Prucalopride) Consideration

Prucalopride is a selective 5-HT4 receptor agonist used for chronic constipation. There are no known significant interactions between prucalopride and bupropion, and this combination does not create additional safety concerns beyond those already discussed.

Clinical Advantages of Bupropion in This Context

Bupropion may be particularly beneficial for this patient 5:

• Lower sexual dysfunction rates compared to SSRIs 5
• Minimal weight gain or potential weight loss 2
• Activating properties beneficial for depression with low energy, apathy, or hypersomnia 2
• No interference with lamotrigine's mood-stabilizing effects in bipolar disorder 5

When to Discontinue or Modify Treatment

Immediately discontinue bupropion and do not restart if 1:

• Any seizure occurs during treatment
• Severe allergic reaction (rash, hives, swelling, difficulty breathing)
• Severe hypertension develops
• Psychotic symptoms emerge (delusions, hallucinations, paranoia)

Consider dose reduction for 6:

• Persistent moderate dizziness
• Insomnia despite proper timing of doses
• Mild to moderate hypertension

Common Pitfalls to Avoid

• Do not exceed 300 mg/day total dose in patients on other medications that may affect seizure threshold 1
• Do not skip the gradual titration - rapid dose escalation increases seizure risk 2
• Do not administer second dose after 3 PM - this causes insomnia 2
• Do not assume lamotrigine indication - always confirm whether it's for epilepsy (contraindication) or bipolar disorder (acceptable) 1, 3
• Do not delay monitoring - begin assessment within 1-2 weeks, not at 6-8 weeks 5