Two case reports of oral ulcers with lamotrigine several weeks after oxcarbazepine withdrawal

Objective: To report two cases of mouth ulcers in lamotrigine patients after oxcarbazepine withdrawal. Patients and methods: The first patient was a 35-year-old woman with bipolar disorder II (BD II) started on lamotrigine and tapered off oxcarbazepine while an inpatient. The second patient was a 36-year-old man with BD II. He was discharged on lamotrigine and oxcarbazepine with the recommendation of a slow withdrawal of oxcarbazepine. Results: Many weeks after hospital discharge and after a stable lamotrigine dose had been established, both patients developed painful mouth ulcers that were diagnosed during outpatient visits. The first patient developed ulcers 39days after oxcarbazepine was stopped and the ulcers resolved 4days after lamotrigine discontinuation. The second patient was taking 1200mg/day of oxcarbazepine and after leaving hospital decreased this to 600mg/day. Twenty-two days after the oxcarbazepine decrease, he developed oral ulcers that resolved with oxcarbazepine and lamotrigine discontinuation. Conclusions: Lamotrigine is mainly metabolized by glucuronidation, specifically by the uridine 5′-diphosphate glucuronosyltransferases 1A4 (UGT1A4). Carbamazepine is a UGT1A4 inducer. These two cases suggest that oxcarbazepine may also induce lamotrigine metabolism. The discontinuation or dosage decrease of carbamazepine or oxcarbazepine may be associated with a slow increase of lamotrigine levels over several weeks and thus increase risk of lamotrigine toxicity that may manifest as oral ulcers. Hospital psychiatrists need to be aware that discontinuation of inducers may take several weeks to manifest as side effects.