What is the dosing regimen for Lamictal (lamotrigine) in treating epilepsy and bipolar disorder?

From the Guidelines

Lamotrigine (Lamictal) should be initiated with a gradual titration to minimize the risk of serious rashes, and for patients who have been on lamotrigine for more than 6 months without a history of rash or intolerance, a loading dose of 6.5 mg/kg can be considered if the patient has been off lamotrigine for less than 5 days 1. When treating epilepsy and bipolar disorder with lamotrigine, it's crucial to consider the dosing regimen carefully to balance efficacy with the risk of adverse effects.

• For epilepsy in adults, the typical starting dose is 25 mg once daily for 2 weeks, then increased to 50 mg daily for 2 weeks, followed by 100 mg daily for 1 week, and then increased by 100 mg weekly until reaching the maintenance dose of 300-500 mg daily (divided into two doses) 1.
• For bipolar disorder maintenance, the target dose is typically 200 mg daily, following a similar slow titration schedule. Key considerations include:
• Patients taking valproate require lower lamotrigine doses (typically half) due to drug interactions that increase lamotrigine levels.
• Those on enzyme-inducing antiepileptics (like carbamazepine) may need higher doses.
• Dosing should be reduced in patients with significant hepatic or renal impairment. The importance of gradual titration cannot be overstated, as rapid dose escalation significantly increases the risk of severe skin reactions, particularly in the first 8 weeks of treatment 1. If lamotrigine is discontinued, it should be tapered gradually over at least 2 weeks to prevent seizure recurrence or mood destabilization. In the context of emergency department settings, the loading dose strategy for lamotrigine, as outlined, can be a valuable approach for quickly re-establishing therapeutic levels in patients who have been temporarily off their medication 1.

From the Research

Dosing Regimen for Lamictal (Lamotrigine)

The dosing regimen for Lamictal (lamotrigine) in treating epilepsy and bipolar disorder is as follows:

• The recommended lamotrigine maintenance dose for bipolar disorder is 200 mg/day 2, 3.
• The dosage of lamotrigine is titrated over a 6-week period to 200 mg/day to minimise the incidence of serious rash 2, 3.
• Adjustments to the initial and target dosages are required if coadministered with valproate semisodium or carbamazepine 2, 3.
• In patients with epilepsy, the accepted therapeutic reference range (TRR) of lamotrigine is 3 000-14 000 ng/ml 4.
• However, in bipolar disorder, lower lamotrigine serum concentrations may lead to therapeutic benefit, with a mean lamotrigine serum concentration of 3 341 ± 2 563 ng/ml detected in patients who benefitted from therapy 4.

Key Considerations

• The incidence of serious rash with lamotrigine treatment is 0.1% in all studies of bipolar disorder 2, 3.
• Lamotrigine is generally well tolerated, with common adverse events including headache, nausea, infection, and insomnia 2, 3.
• Slow dose escalation is recommended to reduce the probability of skin rash 5.
• Lamotrigine may be considered a first-line drug for bipolar disorder, except for acute manic episodes or where rapid symptom control is required 5.