Lamotrigine Dosing for Epilepsy and Bipolar Disorder
Lamotrigine must be titrated slowly over 6 weeks to a target dose of 200 mg/day to minimize the risk of serious rash, with dose adjustments required based on concomitant medications. 1, 2
Standard Dosing Regimen
For Bipolar Disorder Maintenance
- The FDA-approved target dose is 200 mg/day for maintenance therapy in adults with bipolar disorder. 3
- The 6-week titration schedule is mandatory to reduce the incidence of serious rash, which occurs in approximately 0.1% of patients and can include Stevens-Johnson syndrome. 1, 2
- Therapeutic serum concentrations for bipolar disorder are substantially lower than those used in epilepsy, with effective concentrations averaging 3,341 ng/ml (range 177-11,871 ng/ml), well below the epilepsy therapeutic range of 3,000-14,000 ng/ml. 4
For Epilepsy Treatment
- Monotherapy doses range from 100-300 mg/day for partial onset seizures and generalized tonic-clonic seizures in adults with newly diagnosed epilepsy. 5
- As adjunctive therapy, effective doses range from 50-500 mg/day for refractory partial epilepsy. 5
- In children with refractory seizures, doses up to 15 mg/kg/day (maximum 400 mg/day) have proven effective. 5
Critical Dose Adjustments Based on Concomitant Medications
- When coadministered with valproate, both initial and target doses must be reduced due to valproate's inhibition of lamotrigine metabolism. 1, 2
- When coadministered with carbamazepine, doses require upward adjustment due to enzyme induction that increases lamotrigine clearance. 1, 2
Restarting After Discontinuation
The approach to restarting lamotrigine depends critically on the duration of discontinuation and prior tolerance:
- If off lamotrigine for less than 5 days AND previously on medication for more than 6 months without rash: A single loading dose of 6.5 mg/kg may be considered. 3, 6
- If off lamotrigine for more than 5 days OR any history of rash: The full 6-week titration must be restarted from the beginning. 6
- Never load a patient who has not previously tolerated lamotrigine. 6
Key Safety Considerations
- Rash is the most common cause of treatment discontinuation (occurring in approximately 10% of patients), and the slow titration schedule is specifically designed to minimize this risk. 1, 2, 5
- Serious rash incidence is 0.1% when proper titration is followed. 1, 2
- Unlike lithium, lamotrigine does not require routine serum level monitoring in most cases and does not cause weight gain. 1, 2
Special Population: Women with Epilepsy
- Monotherapy at the minimum effective dose is preferred for women with epilepsy. 3
- Valproic acid should be avoided if possible in this population. 3
- Folic acid supplementation should be routinely prescribed for women with epilepsy on antiepileptic drugs. 3
Common Pitfall to Avoid
The most critical error is rushing the titration schedule or restarting at full dose after a brief interruption beyond 5 days, which dramatically increases the risk of serious dermatologic reactions including Stevens-Johnson syndrome. 6, 1, 2