Lamotrigine (Lamictal) Dosing
Start lamotrigine at 25 mg once daily for the first two weeks, then increase to 50 mg daily, with slow titration over 6 weeks to reach the target dose of 200 mg/day for bipolar disorder or 100-500 mg/day for epilepsy. 1
Standard Titration Protocol
Initial Dosing
- Begin with 25 mg once daily for weeks 1-2 1
- Increase to 50 mg daily after the first two weeks 1
- The 6-week titration period to reach 200 mg/day is critical to minimize serious rash risk 2
- In elderly patients (>65 years), maintain 25 mg/day for the first 15 days, then increase to 50 mg/day, with many patients (52%) remaining on 50 mg/day long-term 3
Target Maintenance Doses
- Bipolar disorder: 200 mg/day 1
- Epilepsy: 100-500 mg/day 1
- Elderly patients: Mean effective dose is approximately 72 mg/day, with 50 mg/day often sufficient 3
Critical Safety Considerations
Rash Prevention
- Strict adherence to slow titration is the primary strategy to prevent serious rash, including Stevens-Johnson syndrome 1, 4
- Never exceed recommended dose escalation rates 1
- The incidence of serious rash is 0.1% when proper titration is followed 2
- Patients with a history of allergy are at higher risk for early discontinuation due to adverse effects 5
- Educate patients to report any rash immediately 1
Dosage Adjustments Required
- Adjustments to initial and target dosages are required if coadministered with valproate or carbamazepine 2
- Patients with renal or hepatic impairment may require dose modifications
Special Populations and Situations
Restarting After Discontinuation
- If lamotrigine has been discontinued, re-titrate from the beginning rather than restarting at the full dose 1
- Exception: A loading dose of 6.5 mg/kg can be used in patients previously on lamotrigine for >6 months without rash history who have been off lamotrigine for <5 days 1, 4
- This loading strategy should never be used in lamotrigine-naive patients or those with prior rash history 4
Elderly Patients
- Lower doses are often effective and better tolerated 3
- Start with 25 mg/day for 15 days, then 50 mg/day 3
- Many elderly patients achieve seizure control on 50-72 mg/day 3
Therapeutic Monitoring
When to Monitor Plasma Levels
- Monitor lamotrigine plasma levels in cases of known or suspected malabsorption, poor treatment response, or significant drug interactions 1
- Putative therapeutic range: 1-4 mg/L 1
- Unlike lithium, lamotrigine generally does not require routine serum level monitoring 2
Long-Term Tolerability
Adverse Effects Profile
- Most common adverse events: headache, nausea, infection, and insomnia 2
- Lamotrigine does not cause weight gain 2
- Long-term use (beyond 6 months) is very well tolerated, even at high maintenance doses 5
- Most adverse effects occur during the early titration phase 5
- Only 2 of 54 patients who continued treatment beyond 6 months later discontinued due to adverse effects 5