How to restart Lamictal (lamotrigine) after a 3-week break?

Restarting Lamictal After a 3-Week Break

After a 3-week discontinuation of lamotrigine, you must restart with the initial low-dose titration schedule from the beginning—never resume at your previous maintenance dose—because the risk of serious rash returns to baseline after this duration off the medication. 1

Critical Safety Principle

The 5-day cutoff is the key threshold: lamotrigine can only be reloaded at 6.5 mg/kg as a single dose if the patient has been off the medication for less than 5 days, has been on lamotrigine for more than 6 months, and has no history of rash or intolerance. 2 Since you've been off for 3 weeks (21 days), this loading option is not available to you.

Why You Cannot Resume at Your Previous Dose

• The American College of Neurology explicitly states that after any period of discontinuation, re-titration from the beginning starting at a low dose is required to minimize the risk of serious rash. 1
• The half-life of lamotrigine ranges from 22.8 to 37.4 hours in patients on monotherapy, meaning the drug is essentially cleared from your system after 3 weeks. 3
• The risk of serious rash (including Stevens-Johnson syndrome) necessitates strict adherence to slow titration schedules both when starting and restarting the medication. 1

Standard Restart Protocol

Begin with the standard 6-week titration schedule to reach 200 mg/day: 4

Weeks 1-2:

• Start at 25 mg once daily 4

Weeks 3-4:

• Increase to 50 mg daily (can be divided into 25 mg twice daily) 4

Weeks 5-6:

• Increase to 100 mg daily 4

Week 7 and beyond:

• Increase to target dose of 200 mg daily 4
• Further adjustments can be made in 50-100 mg increments every 1-2 weeks as needed 4

Important Dosage Adjustments Based on Concomitant Medications

If you are taking valproate (Depakote):

• Start at 25 mg every other day for weeks 1-2 4
• The half-life of lamotrigine increases to 48.3-59 hours with valproic acid, requiring slower titration 3
• Target dose is typically 100 mg/day (half the usual dose) 4

If you are taking enzyme-inducing antiepileptic drugs (carbamazepine, phenytoin, phenobarbital):

• Start at 50 mg once daily 4
• The half-life decreases to 13.5-15 hours with these medications 3
• Target dose may need to be 300-400 mg/day 4

Monitoring During Restart

Watch for skin rash, which occurs in approximately 10% of patients and is the most common cause of treatment withdrawal: 5

• Rash typically appears as maculopapular or erythematous 5
• The incidence of serious rash is 0.1% in bipolar disorder studies 4
• The risk of rash can be minimized through adoption of a low, slow dosage titration schedule 5

Other adverse effects to monitor include: 4

• Headache
• Nausea
• Insomnia
• Dizziness

Common Pitfall to Avoid

Never attempt to "catch up" by increasing doses faster than the standard schedule, even if you were previously stable on a higher dose. The slow titration is not negotiable—it's a safety requirement to prevent potentially life-threatening skin reactions. 1, 5 The 3-week gap has reset your tolerance to the medication, and your body must be re-acclimated gradually.