Lamotrigine Dosing for Epilepsy and Bipolar Disorder
Lamotrigine is FDA-approved for maintenance therapy in adults with bipolar disorder (200 mg/day) and for epilepsy treatment, with dosing that should be carefully titrated over 6 weeks to minimize serious rash risk.
Bipolar Disorder Dosing
Adult Dosing
- Initial dose: Start at low dose and titrate slowly over 6 weeks to minimize rash risk 1
- Target maintenance dose: 200 mg/day 2
- Dose range: 50-300 mg/day (clinical practice range) 3
- Therapeutic serum concentration: Lower concentrations are often effective for bipolar disorder (mean 3,341±2,563 ng/ml) compared to epilepsy 2
Clinical Considerations
- Lamotrigine is approved for maintenance therapy in adults with bipolar disorder 4
- Particularly effective for:
- Not effective for acute mania 1
Epilepsy Dosing
Adult Dosing
- Monotherapy dose range: 100-300 mg/day 5
- Adjunctive therapy dose range: 50-500 mg/day 5
- Therapeutic reference range: 3,000-14,000 ng/ml (higher than bipolar disorder) 2
Pediatric Dosing
- Approved for children >2 years old with Lennox-Gastaut syndrome 6
- Adjunctive therapy: Up to 15 mg/kg/day (maximum 400 mg/day) 5
Titration Schedule
A slow titration schedule is critical to minimize the risk of serious rash:
- Initial 6-week titration period required 1
- Begin with low doses and gradually increase to target dose
- Slower titration significantly reduces risk of Stevens-Johnson syndrome 1
Dose Adjustments
Required dose adjustments with concomitant medications:
- With valproate: Reduce lamotrigine initial and target doses by 50% 1, 6
- With carbamazepine: Increase lamotrigine target dose 1
Monitoring
- Monitor for skin rash, particularly during first 8 weeks of treatment
- Serious rash incidence is approximately 0.1% in bipolar disorder studies 1
- Discontinue immediately if rash appears, as it can progress to Stevens-Johnson syndrome 1, 6
- No routine serum level monitoring required 1
Safety Considerations
- Generally well-tolerated compared to other mood stabilizers 3
- Most common side effects: headache, nausea, infection, and insomnia 1
- Does not cause weight gain (advantage over many alternatives) 1
- Lower incidence of diarrhea and tremor compared to lithium 1
- No QTc prolongation concerns (unlike many antipsychotics) 7
- Particularly beneficial for women and elderly patients with epilepsy 6
Clinical Pearls
- Lamotrigine shows superior efficacy for bipolar depression compared to mania prevention 1
- For epilepsy, more effective against generalized seizures (particularly absence, atonic) than partial seizures 5
- Maculopapular or erythematous skin rash occurs in approximately 10% of patients and is the most common cause of treatment discontinuation 5
- The risk of serious rash can be minimized through adoption of a low, slow dosage titration schedule 5