Agranulocytosis Associated With Lamotrigine

Ms. A was a healthy, successful, 30-year-old woman with a psychiatric history of anorexia nervosa and past substance dependence and abuse of opiates, benzodiazepines, stimulants, and alcohol. She had a history of bipolar II disorder with refractory depression; she had experienced multiple ineffective trials of medication and ECT.

Four weeks after beginning treatment with lamotrigine Ms. A was receiving a dose of 100 mg/day. At bedtime we added a low dose of valproic acid, 125 mg/day, and slowly increased the dose to 250 mg/day. In the past a dose of 1250 mg at bedtime given to Ms. A had resulted in a blood level of 103 μg/ml of valproic acid. Her concurrent medications included 2 mg b.i.d. of clonazepam, 150 mg b.i.d. of sustained-release bupropion, and 5 mg of olanzapine at bedtime as needed. Ms. A was briefly hospitalized and was found to have a WBC count of 6,700 cells/mm³, 42% neutrophils, and an absolute neutrophil count of 2,814 cells/mm³.

Two weeks after the addition of valproic acid therapy Ms. A continued to fare poorly, and suicidal ideation led to another brief hospitalization. It was noted on admission that her WBC count was 3,200 and her absolute neutrophil count was 446. Two days later her WBC count was 2,600, and her absolute neutrophil count was 580. Lamotrigine therapy was discontinued at this point, and Ms. A was discharged. Two days after discharge her WBC count was 3,300, and her absolute neutrophil count was 1,386. Her mild leukopenia disappeared without further intervention while she was taking 750 mg of valproic acid at night.