Lamotrigine (Lamictal) Dosage and Usage for Epilepsy and Bipolar Disorder
For optimal outcomes in terms of morbidity and mortality, lamotrigine dosing must follow specific titration schedules based on concurrent medications, with different protocols for epilepsy versus bipolar disorder. 1
Dosing for Epilepsy
Initial Titration and Maintenance Dosing
Monotherapy for adults with epilepsy:
- Start with 25 mg daily for 2 weeks
- Increase to 50 mg daily for weeks 3-4
- Increase to 100 mg daily for week 5
- Increase to 150-200 mg daily (target maintenance dose)
- Maximum dose: 500 mg/day in divided doses
For patients taking valproate concurrently:
- Start with lower doses (12.5-25 mg every other day)
- Slower titration due to decreased lamotrigine clearance
- Lower target maintenance dose (100-150 mg/day)
For patients taking enzyme-inducing AEDs (carbamazepine, phenytoin, phenobarbital, primidone):
- Start with higher doses (50 mg daily)
- Faster titration due to increased lamotrigine clearance
- Higher target maintenance dose (300-500 mg/day in divided doses)
Special Populations
Women with epilepsy: 2
- Use monotherapy at minimum effective dose
- Avoid polytherapy with other antiepileptic drugs
- Folic acid supplementation required
- Valproic acid should be avoided if possible
Patients with intellectual disability and epilepsy: 2
- Consider valproic acid or carbamazepine instead of phenytoin or phenobarbital due to lower risk of behavioral adverse effects
- Individualize based on seizure type
Dosing for Bipolar Disorder
Initial Titration and Maintenance Dosing 1
For patients NOT taking valproate or enzyme-inducing medications:
- Weeks 1-2: 25 mg daily
- Weeks 3-4: 50 mg daily
- Week 5: 100 mg daily
- Week 6: 200 mg daily (target maintenance dose)
For patients taking valproate:
- Weeks 1-2: 25 mg every other day
- Weeks 3-4: 25 mg daily
- Week 5: 50 mg daily
- Week 6: 100 mg daily (target maintenance dose)
For patients taking enzyme-inducing medications:
- Weeks 1-2: 50 mg daily
- Weeks 3-4: 100 mg daily in divided doses
- Week 5: 200 mg daily in divided doses
- Week 6: 300 mg daily in divided doses
- Week 7: Up to 400 mg daily in divided doses
Maintenance Treatment for Bipolar Disorder
- Standard maintenance dose: 200 mg daily 1
- Duration: At least 2 years after the last episode 2
- Continuation beyond 2 years: Should be evaluated by a mental health specialist 2
Critical Safety Considerations
Rash Risk Minimization
- Never exceed recommended initial doses or escalation rates 1
- Serious rash risk is increased with:
- Coadministration with valproate
- Exceeding recommended initial dose
- Exceeding recommended dose escalation rate
Drug Interactions Requiring Dose Adjustments
Women taking estrogen-containing oral contraceptives:
- May need up to 2-fold increase in maintenance dose 1
- Adjust dose when starting or stopping contraceptives
When discontinuing concurrent medications: 1
- After stopping valproate: Double lamotrigine dose over 2 weeks
- After stopping enzyme inducers: Reduce lamotrigine dose by half over 2 weeks
Clinical Efficacy
- For bipolar disorder: Most effective for preventing depressive episodes rather than manic episodes 3
- For epilepsy: Effective for both partial and generalized seizures 4
Common Adverse Effects
- Headache, nausea, infection, insomnia 3
- Lower incidence of diarrhea and tremor compared to lithium 3
- No significant weight gain 3
- Risk of serious rash (0.1% in bipolar studies) 3
Important Monitoring
- No routine blood level monitoring required (unlike lithium) 3
- Clinical response should guide dosing rather than target plasma levels 1