Which agent is known to significantly increase levels of lamotrigine in patients?

Lamotrigine is primarily metabolized in the liver by UDP-glucuronosyltransferases, and certain medications can either increase or decrease its levels in the bloodstream. Valproate is particularly significant in this context because it inhibits the metabolism of lamotrigine, leading to an increase in lamotrigine levels. This interaction can result in an increased risk of adverse effects, including the potential for serious rashes such as Stevens-Johnson syndrome.

Phenytoin, diazepam, and phenobarbital, on the other hand, are known to either induce liver enzymes or have minimal impact on lamotrigine metabolism. Phenytoin and phenobarbital are enzyme inducers and would typically decrease the levels of lamotrigine. Diazepam does not have a significant interaction with lamotrigine metabolism.

Understanding the role of enzyme induction and inhibition is crucial for managing polypharmacy in patients, especially those on antiepileptic medications like lamotrigine. Thus, recognizing that valproate significantly increases lamotrigine levels is essential for safe and effective treatment planning.