Lamotrigine (Lamictal) 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 titration based on the indication (target 200 mg/day for bipolar disorder, 100-500 mg/day for epilepsy) and concurrent medications—strict adherence to this slow titration schedule is the single most critical factor in preventing serious rash including Stevens-Johnson syndrome. 1, 2
Standard Initial Titration Protocol
The American College of Neurology establishes the following escalation schedule 2:
- Weeks 1-2: 25 mg once daily 1, 2
- Weeks 3-4: 50 mg once daily (increase from 25 mg) 1
- Subsequent titration: Gradual escalation to target dose based on indication and concurrent medications 1, 2
Never exceed recommended dose escalation rates—this is the primary strategy to prevent serious rash, which occurs in 0.1% of patients. 2
Target Maintenance Doses
- Bipolar disorder: 200 mg/day 1, 2
- Epilepsy: 100-500 mg/day 1, 2
- Elderly patients: Mean effective dose is approximately 72 mg/day, with 52% of patients maintaining seizure control on just 50 mg/day 3
Critical Dosing Adjustments for Drug Interactions
Lamotrigine dosing must be modified based on enzyme-inducing or enzyme-inhibiting comedications 2:
- With valproate (enzyme inhibitor): Lamotrigine half-life increases to 48-59 hours, requiring dose reduction and slower titration 4
- With carbamazepine, phenytoin, or phenobarbital (enzyme inducers): Lamotrigine half-life decreases to 13.5-15 hours, requiring higher doses 4
- With desvenlafaxine: No dose adjustment needed—no significant cytochrome P450 interactions occur 2
Special Loading Dose Protocol (Limited Use Only)
A loading dose of 6.5 mg/kg can be considered only in patients who 5:
- Were previously on lamotrigine for >6 months
- Have been off lamotrigine for <5 days
- Have no history of rash or intolerance
This loading strategy should never be used in lamotrigine-naive patients or those with prior rash history due to severe rash risk. 5
Restarting After Discontinuation
If lamotrigine has been discontinued, do not restart at the full dose—instead, re-titrate from the beginning using the standard slow titration schedule. 1
Therapeutic Monitoring
Monitor lamotrigine plasma levels in the following situations 1, 2:
- Known or suspected malabsorption
- Poor treatment response
- Significant drug interactions
- Therapeutic range: 1-4 mg/L 1, 2, 4
Critical Safety Warnings
Educate all patients to report any rash immediately. 2 The risk of serious rash, including Stevens-Johnson syndrome, is minimized through low, slow dosage titration. 2, 5 Patients with a history of allergy are more likely to discontinue treatment early due to adverse effects. 6
Long-Term Tolerability
Long-term use of lamotrigine is very well tolerated, even at high maintenance doses (>200 mg/day), with only 2% of patients discontinuing after 6 months due to adverse effects. 6 Most adverse effects occur during the early titration phase, and if patients tolerate the first 6 months, long-term continuation is typically safe. 6