What are the recommended starting dose and titration schedule for lamotrigine in an adult with newly diagnosed focal or generalized epilepsy (without enzyme‑inducing drugs) and for bipolar disorder maintenance, including adjustments for enzyme inducers and safety monitoring?

Lamotrigine Dosing and Titration in Epilepsy and Bipolar Disorder

Standard Dosing for Bipolar Disorder Maintenance (Without Enzyme-Inducing Drugs)

For adults with bipolar disorder not taking enzyme-inducing drugs or valproate, start lamotrigine at 25 mg daily for weeks 1–2, increase to 50 mg daily for weeks 3–4, then increase to 100 mg daily for week 5, and reach the target maintenance dose of 200 mg daily by week 6. 1, 2

Detailed Titration Schedule

• Weeks 1–2: 25 mg once daily 1, 2
• Weeks 3–4: 50 mg once daily 1, 2
• Week 5: 100 mg once daily 1, 2
• Week 6 onward: 200 mg once daily (standard maintenance dose) 3, 1, 2

Adjustments for Concomitant Medications

When lamotrigine is combined with valproate, reduce the target dose to 100 mg daily and slow the titration: start at 25 mg every other day for weeks 1–2, then 25 mg daily for weeks 3–4, then 50 mg daily for week 5, reaching 100 mg daily by week 6. 3, 1

When lamotrigine is combined with enzyme-inducing drugs (carbamazepine, phenytoin, phenobarbital, rifampin), increase the target dose to 400 mg daily and accelerate titration: start at 50 mg daily for weeks 1–2, increase to 100 mg daily (divided twice daily) for weeks 3–4, then 200 mg daily for week 5, reaching 400 mg daily by week 6. 3, 1

Critical Safety Monitoring

Slow titration is mandatory to minimize the risk of Stevens-Johnson syndrome and serious rash, which occurs in approximately 0.1% of adults when proper titration is followed. 1, 2, 4

Monitor weekly for any signs of rash during the first 8 weeks of titration, and instruct patients to immediately discontinue lamotrigine and seek medical attention if any rash develops. 5

If lamotrigine is discontinued for more than 5 days, restart with the full initial titration schedule rather than resuming the previous dose to minimize rash risk. 5

Efficacy Profile in Bipolar Disorder

Lamotrigine significantly delays time to intervention for depressive episodes in bipolar I disorder, making it particularly effective for preventing depressive recurrence rather than treating acute mania. 1, 2, 4

Lamotrigine has not demonstrated efficacy in treating acute mania and should not be used as monotherapy for manic episodes. 1, 2

In patients with a history of severe and repeated manic episodes, combine lamotrigine with an antimanic agent (lithium or a second-generation antipsychotic) even during the maintenance phase. 3

Maintenance Therapy Duration

Continue lamotrigine maintenance therapy for at least 12–24 months after achieving mood stabilization, with some patients requiring lifelong treatment. 5

Lamotrigine does not require routine serum level monitoring, unlike lithium, and does not cause weight gain. 1, 2

Common Adverse Effects

The most common adverse events with lamotrigine are headache, nausea, infection, and insomnia, with significantly lower rates of diarrhea and tremor compared to lithium. 1, 2

Special Populations

Lamotrigine can be used during pregnancy and breastfeeding following a risk-benefit assessment, and in patients with hepatic or renal impairment with appropriate dose adjustments. 3

Pitfalls to Avoid

Never rapid-load lamotrigine, as this dramatically increases the risk of Stevens-Johnson syndrome, which can be fatal. 5

Do not use lamotrigine as monotherapy for acute mania, as it lacks efficacy for this indication. 1, 2

Avoid premature discontinuation; an adequate trial requires reaching 200 mg daily for at least 6–8 weeks before concluding ineffectiveness. 5