Acute agranulocytosis when switching from risperidone to paliperidone

To the Editor

Agranulocytosis and neutropenia are hematological complications known to occur with many antipsychotics. Paliperidone is a second-generation antipsychotic drug and is also reported to induce neutropenia (Kim et al., 2010). Paliperidone has a similar pharmacological action and pharmacodynamic profile to risperidone. Here, we report a patient with schizophrenia who developed acute agranulocytosis when switching from risperidone to paliperidone.

A 46-year-old man had been living with schizophrenia for more than 5 years but had no other significant medical history. He was treated with blonanserin 24 mg/day, following which his auditory hallucinations gradually dissipated, although his suspiciousness and irritability continued. For the subsequent 4 years, his psychiatric symptoms stabilized with outpatient treatment of blonanserin 24 mg/day plus risperidone 4 mg/day. He had no significant abnormality in hematological parameters including white blood cell (WBC) and other blood cell counts.

Subsequently, the patient experienced worsened suspiciousness and irritability. It was decided to switch from risperidone to paliperidone and, therefore, risperidone was decreased to 2 mg/day and paliperidone 6 mg/day was started. Thirteen days after treatment with paliperidone began, the patient was suddenly unable to walk and his family brought him to our emergency department.

Upon admission, physical examination revealed tachycardia (160 bpm), hypotension (81/39 mm Hg) and increased body temperature (40.5°C). Laboratory tests showed elevated C-reactive protein (CRP: 4.79 mg/mL) with agranulocytosis (WBC: 0.3 × 10⁹/L). Chest computed tomography revealed bilateral pulmonary infection. The patient was suspected to have paliperidone-induced agranulocytosis and was hospitalized. All psychotropics were immediately ceased and granulocyte-colony stimulating factor (G-CSF) 75 µg/day was administered for 3 consecutive days. Furthermore, doripenem (a parenteral carbapenem with broad-spectrum antibacterial activity) 3 mg/day was administered. Two days later, the patient’s WBC count was elevated at 4.95 × 10⁹/L. Ten days later, his bilateral pulmonary infection was cured and he was discharged without sequela. After discharge, he was treated with aripiprazole instead of paliperidone/risperidone without further hematological complications.

One previous paper has reported a similar case to ours, with combined use of paliperidone depot/risperidone resulting in neutropenia while risperidone alone did not (Raj et al., 2013). Combined use of paliperidone/risperidone might increase toxic effects in the bone marrow possibly leading to agranulocytosis. This is likely because the major mechanism underlying drug-induced agranulocytosis is toxicity, which is determined by the dosage of medication (Flanagan and Dunk, 2008). Our case suggests that physicians should consider possible occurrence of hematological complications and monitor WBC counts when administering both paliperidone and risperidone.