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Risperidone- and aripiprazole-induced leukopenia: a case report.

Sir: Leukopenia and agranulocytosis are life-threatening side effects of antipsychotics, but routine white blood cell (WBC) count monitoring is not indicated, with the exception of clozapine. Studies have shown that < 3% of patients treated with clozapine develop granulocytopenia.1,2 Although several case reports have been published regarding leukopenia and/ or neutropenia associated with risperidone,3 olanzapine,4,5 quetiapine,6 and ziprasidone,7 data are still lacking. Lithium, on the other hand, has been used successfully to treat leukopenia associated with cancer chemotherapy,8 carbamazepine,9 and clozapine.2 
 
We report a case of risperidone- and aripiprazole-induced leukopenia successfully treated with lithium. We suggest careful monitoring of WBC counts in patients who have a history of antipsychotic-induced leukopenia, as they can be more prone to leukopenia with other antipsychotics. 
 
Case report. Mr. A, a 32-year-old African American man with a long history of schizophrenia, paranoid type (DSM-IV criteria), and no significant medical history, had been treated with risperidone 2 mg orally at night for a few years. He reported no side effects from his medication and continued to attend a vocational program and hold a summer job. Mr. A was followed at a community mental health clinic for medication management. 
 
On review of his annual physical examination and laboratory workup in September 2006, it was noted that his WBC count was 2.8 × 109, with an absolute neutrophil count (ANC) of 1.27 × 109. The other results of Mr. A's physical examination were normal, and he had no signs of any infection. Risperidone-induced leukopenia was suspected, but the patient refused to change his medication. He agreed to decrease the risperidone dose to 1 mg at night and repeat his bloodwork in a few weeks. His WBC count and ANC remained low, at 2.7 × 109 and 1.22 × 109, respectively, and finally risperidone was discontinued. The patient agreed to start treatment with aripiprazole 10 mg daily and undergo repeat laboratory testing in 6 months. He reported no side effects during this time and was evaluated at least every 4 weeks. 
 
Aripiprazole was discontinued after 6 months, as Mr. A's WBC count and ANC continued to decrease and were 2.4 × 109 and 0.85 × 109, respectively. The patient was referred for full hematologic workup and medical treatment. After 2 weeks with no antipsychotic medication, he decompensated and was hospitalized due to paranoid delusions, irritable mood, and auditory hallucinations. At the time of inpatient admission, his WBC count was found to be 6.4 × 109, and his ANC was 4.67 × 109. The patient was put back on treatment with aripiprazole 10 mg daily with good response and discharged from the hospital. 
 
Follow-up upon discharge at the mental health clinic showed that his WBC count and ANC had decreased again to 2.9 × 109 and 1.29 × 109, respectively. After extensive discussion with the treatment team and a review of the literature, aripiprazole was discontinued. It was decided to treat Mr. A with an antipsychotic along with lithium as it has been reported to correct leukopenia of various etiologies. The patient refused to try aripiprazole or risperidone again but agreed to treatment with paliperidone 6 mg and lithium 300 mg daily. He responded well to the medication change, and his WBC count increased to 3.3 × 109 and ANC increased to 1.42 × 109. 
 
The patient has refused to adjust medication dosages further but continues to attend a vocational program and keep his summer job. His hematologic workup is pending at this point. 
 
The exact pathophysiology of psychotropic-induced blood dyscrasias is still unclear, but direct toxic effect, immune reactions, and peripheral destruction of cells have all been implicated.10 Individual risk factors that have been suggested are being African Caribbean, being young, and having a low baseline WBC count, especially in cases of leukopenia associated with clozapine.2 Neutrophils can either circulate in the blood vessels or be marginalized alongside the vessel wall. African Caribbean individuals have apparently lower WBC counts due to increased margination.2,5 It has been proposed that lithium can cause leukocytosis and reverse leukopenia by direct stem cell stimulation,9 stimulation of granulocyte-macrophage colony-stimulating factor,11 stimulation of cytokines,12 and demargination.13 
 
It is an interesting finding that, as in our case, many patients who developed leukopenia as a result of one antipsychotic were also leukopenic after taking another antipsychotic.5–7 This might be due to some genetic vulnerability in these individuals. In the light of these data, we suggest careful monitoring of WBC count even while using newer antipsychotics, especially if the patient has a history of leukopenia associated with antipsychotic use. Lithium can improve the WBC count in some of these cases if used appropriately. 
 
 
Salah Uddin Qureshi, M.D. 
 
Eleonora Rubin, M.D. 
 
Department of Psychiatry, Jamaica Hospital Medical Center, Jamaica, New York