Lamotrigine toxicity secondary to sertraline

Blood level monitoring helps to determine the therapeutic and toxic ranges for anticonvulsants and antidepressants. We investigated initial drug-drug interactions between lamotrigine and sertraline. We report on case histories of two epileptic patients who were initially on lamotrigine and to whom sertraline was added to control psychiatric features. In case 1, a total daily dose of 25 mg sertraline, with nondetectable sertraline and desmethylsertraline blood levels, resulted in a doubling of the lamotrigine blood level with symptoms of toxicity. In case 2, a 25 mg reduction in the total daily dose of sertraline resulted in halving of the lamotrigine blood level even though the lamotrigine dosage was increased by 33%. This shows that sertraline has potent interactions with lamotrigine metabolism. The authors hypothesize that inhibition of glucuronidation is responsible. Clinicians are advised to observe for symptoms of toxicity and to do serial blood levels to monitor this interaction.