To the Editor: Neutropenia is defined as an abnormal absolute neutrophil count (ANC) value, containing fewer than 1,500 cells per mm³ in the peripheral blood. Neutropenia had resulted from a range of antipsychotics and mood stabilizers, most notably as a result of treatment with clozapine.¹ Risperidone, an atypical antipsychotic, is widely used because of the tolerability, amelioration of negative symptoms, and reduced hematologic toxicity. We report the case of a patient who developed and was able to resolve neutropenia after administration of risperidone and then discontinuation.

A 55-year-old man had schizophrenia with acute exacerbation, without history of major surgery, hematologic disorder, or drug abuse. He was admitted for disorganized speech, auditory hallucinations, and persecutory delusions. Initial laboratory studies, including thyroid function test, and serum electrolyte, were within normal range. The white blood count (WBC) was 5,100 cells/mm³. Initially, quetiapine 1,200 mg was prescribed for 1 month. Because of inadequate control of symptoms and unacceptable sedative effect, quetiapine was tapered and stopped within 1 week, and risperidone 6 mg was added. One week later, all laboratory results were normal except the WBC and ANC. His WBC and ANC were 2,800 cells/mm³ and 1,400 cells/mm³, respectively, in the afternoon. Physical examination revealed no infectious signs. Risperidone-induced neutropenia was strongly suspected, and risperidone was tapered and stopped. Aripiprazole was cross-titrated to 15 mg per day for control of his psychotic symptoms. Two weeks later, the WBC was 4,600 cells/mm³, and the ANC was 3,420 cells/mm³; and 1 month later, the WBC was 8,200 cells/mm³, whereas the ANC was 5,000 cells/mm³.

The incidence rates of risperidone-associated neutropenia were poorly established and seemed to be very low. It is usually reversible with dose reduction or medication discontinuation. The pathophysiology was controversial. The common hypothesis was decreased marrow production, increased peripheral destruction, or a combination of these. Risk factors include preexisting low WBC and a history of drug-induced neutropenia. In our patient, it developed after risperidone administration and resolved with discontinued. The clinical characteristics suggested that the underlying pathophysiology might be drug-related. Despite this case report of neutropenia in association with risperidone, a larger study would be required to evaluate the incidence of neutropenia with risperidone. Careful monitoring and initial hematological assessment should be considered when the patients have previously had neutropenia with other antipsychotic treatment, particularly clozapine. If such a side effect was suspected, dose reduction or medication discontinuation should considered. This is a particular concern because this complication could be easily missed if there is no mandatory white cell-count monitoring as there is with clozapine treatment.