Very Late-Onset Neutropenia in a Japanese Schizophrenia Patient Treated with Clozapine

Abstract

We here reported a chronic schizophrenia patient who occurred neutropenia 13 years after starting clozapine. Thus, once clozapine is administered, the lifelong regular monitoring of the patient's total WBC count should be done.Keywords: Clozapine; Neutropenia; Late-onset Case ReportThe patient was a 46-year-old Japanese man who had met the DSM-IV diagnosis of schizophrenia, disorganized-type, for the prior 30 years. He had been on antipsychotic regimens since being diagnosed when he was 16 years old. He had been treated with therapeutic doses of sulpiride, haloperidol, levomepromazine, risperidone, olanzapine, aripiprazole, or lithium on several occasions, after which the treatments were stopped due to inadequate treatment response. After that, clozapine was started during his eighth hospitalization in 33-year-old in which he was brought to the hospital for persistent auditory hallucinations, monologia, persecutory delusion aggressiveness, and psychomotor excitement.After this admission, the clozapine dosage was titrated gradually up to 600 mg/day. The patient's total leucocyte count at baseline was 10,000/mm 3 . After discharge from the hospital, he showed a prominent improvement in his clinical status, with no apparent psychotic symptoms, and he attended a day-care service. During the long follow-up period, his total leucocyte count range was between 5,380 and 11,290/mm 3 with a daily 600 mg clozapine dosage. Twelve years after the start of that clozapine treatment, the patient's total leucocyte count had gradually decreased to 2,255 mm 3 . We therefore added lithium carbonate (600 mg/day) to increase the leucocyte count. However, the total leucocyte count did not recover after the addition of lithium carbonate (2,460 mm 3 , 1,663 mm 3 , 1,584 mm 3 , 1,526 mm 3 ). In 46-year-old (13 years later), the patient's total leucocyte count had gradually declined to 1,330/ mm 3 , and the 600 mg/day clozapine was stopped at the same time. His auditory hallucination, persecutory delusion, irritability, psychomotor excitement were exacerbated after stopping clozapine. Olanzapine (20 mg/day) and levomepromazine (150 mg/day) were re-started; those symptoms were however not ameliorated. Physical symptoms associated with neutropenia including fever, anemia, bleeding, irritability, and hot flashes were not seen. Four weeks after the clozapine was discontinued, the patient's total leucocyte count had recovered to 8,915/mm 3 . Written informed consent to have his case published was obtained from the patient.