Anticonvulsant Hypersensitivity Syndrome From Addition of Lamotrigine to Divalproex

Ms. A, a 50-year-old woman with bipolar depression who was admitted for worsening depression was taking 0.05 mg/day of clonidine, 1000 mg/day of divalproex, 450 mg/day of lithium, 50 mg of trazodone at bedtime, 150 mg b.i.d. of bupropion, 0.5 mg/day of clonazepam, and lamotrigine, which was started 2 weeks before at 25 mg/day, and was recently increased to twice daily. A baseline lithium level was not available.

Three days after admission, Ms. A developed a fever of 101°F, nausea, mild headache, and loose stools, and 2 days later, she had a generalized fine macular rash. A CBC, blood chemistries, a urinalysis and stool studies, a chest X-ray, computerized tomographies of her sinuses, and plain abdominal films were all normal. She developed pancytopenia with a WBC count of 5,500 with 16% segs, 43% bands, platelets of 81,000, mild eosinophilia at 5%, and an elevation of her alanine transaminase level at 186 units/liter (normal range=0–36) and her aspartate transaminase level at 82 units/liter (normal range=0–33) and normal alkaline phosphatase and bilirubin levels. Lamotrigine was discontinued when the rash developed, and divalproex was discontinued 2 days later. The rash began to decrease; the fever remitted; the headache, loose stools, and pancytopenia resolved; and the aspartate transaminase and alanine transaminase levels decreased. A lithium level obtained during hospitalization was subtherapeutic at 0.3 mmol/liter (therapeutic range=0.6–1.2 mmol/liter). The lithium dose was increased, and Ms. A was given hydroxyzine for anxiety resulting in effective control of her symptoms.