Risperidone-Associated Agranulocytosis

Ms. A was a 40-year-old woman who had met DSM-IV criteria for chronic schizophrenia, paranoid type, from the age of 22. She had had no episodes of neutropenia or leu~kopenia, and her WBC count was generally around 5,000/mm³. At admission, her WBC count was 5,600 mm³, and the neutrophil rate was 57%. She was initially treated with chlorpromazine, 300 mg/day, and carbamazepine, 800 mg/day (at therapeutic blood levels), for 6 weeks. Her WBC count gradually fell to 2,500/mm³ and the neutrophil rate to 30%, and treatment was immediately stopped. Her WBC count rose after 2 weeks (5,200/mm³, neutrophil rate=51.7%). Haloperidol (30 mg/day) and lithium (900 mg/day) were then given for 3 weeks. Her WBC count fell again (2,200/mm³, neutrophil rate=52%). Haloperidol was suspended, but lithium was continued for another 5 weeks, along with diazepam (30 mg/day) and trihexyphenidyl (5 mg/day) because of extrapyramidal syndrome, until her WBC count normalized (4,500/mm³, neutrophil rate=53%). Because of Ms. A's psychotic state, treatment with zuclopentixol was started and reached 50 mg/day in the second week; however, zuclopentixol was suspended because of severe extrapyramidal syndrome and a fall in WBC count (2,700/mm³, neutrophil rate=29%). Ms. A developed agitated catatonia, and one course of ECT was administered (three times a week for 2 months), with partial response. Three weeks after zuclopentixol was discontinued and during the course of ECT, her WBC count normalized (4,500/mm³, neutrophil rate=62%). Bone marrow analysis was performed but did not reveal any pathology. Because of her resistant psychotic state and the presence of extra~pyramidal syndrome, risperidone treatment was started 2 weeks afterward and was gradually increased to 4 mg/day in the second week. At that time a blood sample was drawn, and risperidone was discontinued because of the emergence of agranulocytosis (WBC count=2,400/mm³, neutrophil rate=32%).