What supplements are contraindicated with lamotrigine (antiepileptic medication)?

Supplements to Avoid with Lamotrigine

Ginseng should not be taken with lamotrigine as it can inhibit lamotrigine metabolism, potentially increasing blood levels and risk of serious adverse effects including DRESS syndrome. 1

Mechanism of Supplement Interactions with Lamotrigine

Lamotrigine is primarily metabolized through glucuronidation by the enzyme uridine diphosphate glucuronosyltransferase (UDPGT), particularly the UGT2B7 isoform. Supplements that inhibit this pathway can increase lamotrigine levels, while those that induce it can decrease levels.

Known Supplement Interactions:

1. Ginseng

   • Inhibits UGT2B7 enzyme (similar to valproic acid's mechanism)
   • Can significantly increase lamotrigine blood levels
   • Associated with increased risk of DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) 1
   • DRESS syndrome has a 10-40% mortality rate

2. St. John's Wort

   • Acts as an enzyme inducer similar to carbamazepine and phenytoin
   • Can decrease lamotrigine levels, potentially reducing seizure control 2, 3

Other Potential Interactions to Consider

While not explicitly documented in the evidence provided, based on known pharmacokinetic principles of lamotrigine:

• Supplements with enzyme-inducing properties may decrease lamotrigine levels:

  • Echinacea
  • Milk thistle (in high doses)
  • Licorice (mentioned as interacting with other medications) 2

• Supplements with enzyme-inhibiting properties may increase lamotrigine levels:

  • Berberine-containing supplements
  • Goldenseal
  • Kava

Monitoring Recommendations

If a patient is taking lamotrigine with any supplement:

• Monitor for signs of lamotrigine toxicity: dizziness, double vision, headache, ataxia, nausea, and rash
• Be particularly vigilant for rash development, which can progress to serious conditions like Stevens-Johnson syndrome or DRESS syndrome
• Consider lamotrigine level monitoring 1-2 weeks after starting or stopping any supplement 3

Special Considerations

• Vitamin B6 (Pyridoxine): While not contraindicated, be aware that enzyme-inducing antiepileptic drugs can cause B6 deficiency. Lamotrigine itself is not a strong enzyme inducer, but patients switching from enzyme-inducing AEDs to lamotrigine may have pre-existing B6 deficiency that should be addressed 4

• Oral contraceptives: While not supplements, it's worth noting that oral contraceptives can decrease lamotrigine levels 3

Clinical Approach to Supplements with Lamotrigine

1. Avoid ginseng completely - documented serious interaction
2. Avoid St. John's Wort - can reduce lamotrigine efficacy
3. For other supplements:
   • Discuss with healthcare provider before starting
   • Start at low doses
   • Monitor for changes in seizure frequency or side effects
   • Consider lamotrigine level testing when adding or removing supplements

Key Pitfalls to Avoid

• Assuming natural supplements are always safe with prescription medications
• Starting multiple supplements simultaneously, making it difficult to identify which one might be causing an interaction
• Failing to inform healthcare providers about supplement use
• Ignoring early signs of rash or other adverse effects that could indicate toxicity

Remember that supplement quality and content can vary significantly between manufacturers, potentially leading to unpredictable interactions with medications like lamotrigine.