Lamotrigine is being added to valproate in a patient with bipolar disorder. Which prescribing principle is essential?

• A Slow titration with reduced target dose, because valproate raises lamotrigine levels and the risk of severe cutaneous reactions ✓
• B Valproate increases lamotrigine clearance, so the dose must be doubled
• C Rapid titration to 200 mg/day within one week to achieve early mood stabilization
• D No interaction exists, so standard monotherapy dosing applies

Explanation

Valproate inhibits glucuronidation of lamotrigine, roughly doubling its plasma concentration. Combination therapy therefore mandates slower titration and a lower target dose, primarily to reduce the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis, which are concentrated in the first 8 weeks and rise sharply with rapid escalation. Enzyme inducers such as carbamazepine do the opposite, increasing clearance. The interaction and the rash are the two facts examiners test together.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

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