Lamotrigine Initial Dosing
Start lamotrigine at 25 mg once daily for the first two weeks, then increase to 50 mg daily for weeks 3-4, with subsequent gradual titration to target doses of 200 mg/day for bipolar disorder or 100-500 mg/day for epilepsy. 1, 2
Standard Titration Schedule
The critical principle is slow, gradual dose escalation to minimize serious rash risk (0.1% incidence):
Weeks 1-2: 25 mg once daily 1, 2
Weeks 3-4: 50 mg once daily (or divided twice daily) 2
Week 5 onward: Increase by 25-50 mg every 1-2 weeks until reaching target dose 2
- Target maintenance dose: 200 mg/day for bipolar disorder; 100-500 mg/day for epilepsy 1, 2
- The 6-week titration period to 200 mg/day is standard practice to minimize rash risk 3
- Never exceed recommended dose escalation rates—this is the primary strategy to prevent serious rash 2
Critical Dosing Adjustments for Concomitant Medications
With enzyme-inducing drugs (phenytoin, carbamazepine, phenobarbital, rifampin):
- Double the standard doses and shorten titration intervals 4
- Target maintenance dose may need to increase to 400 mg/day 4
- These medications reduce lamotrigine half-life from 24-37 hours to 13-15 hours 5
With valproate:
- Halve all doses and extend titration intervals 2
- Valproate increases lamotrigine half-life to 48-59 hours, dramatically increasing rash risk 5
- This is the most dangerous drug interaction requiring dose reduction 3
Special Population Considerations
Elderly patients (>65 years):
- Start at 25 mg/day for 15 days, then increase to 50 mg/day 6
- Many elderly patients achieve seizure control at just 50-72 mg/day 6
- 52% of elderly patients maintained control on the initial 50 mg/day dose without further increases 6
Restarting After Discontinuation
If lamotrigine has been stopped:
- Re-titrate from the beginning using the full initial dosing schedule 1
- Do NOT restart at the previous maintenance dose 1
- Exception: If off for <5 days with no history of rash, a loading dose of 6.5 mg/kg may be considered in epilepsy patients 1
Monitoring and Safety
Therapeutic drug monitoring indications:
- Suspected malabsorption 1, 2
- Poor treatment response 1, 2
- Significant drug interactions 1, 2
- Putative therapeutic range: 1-4 mg/L 1, 2, 5
Critical patient education:
- Report any rash immediately—this is the most important safety measure 2
- Rash occurs in approximately 10% of patients but serious rash (including Stevens-Johnson syndrome) occurs in only 0.1% 2, 3
- The slow titration schedule is specifically designed to minimize this risk 7
Common Pitfalls to Avoid
- Never accelerate the titration schedule even if the patient is seizure-free or experiencing mood symptoms—this dramatically increases rash risk 2, 7
- Always adjust for valproate co-administration—failure to halve doses with valproate is a dangerous oversight 3, 5
- Don't assume elderly patients need standard doses—they often respond to much lower doses (50-72 mg/day) 6
- Remember that carbamazepine interactions are both pharmacokinetic and pharmacodynamic—lamotrigine increases carbamazepine-epoxide levels, potentially causing toxicity 5