Risperidone-Induced Morning Pseudoneutropenia

Ms. A, a 33-year-old Caucasian woman with paranoid schizophrenia, was given risperidone (1 mg/day titrated to 4 mg/day within 4 weeks). After 6 weeks of outpatient treatment, partial improvement in her symptoms led to hospitalization. On admission (at 8:00 a.m.), her total WBC count and absolute neutrophil count were 3240/mm³ and 1560/mm³, respectively. The next morning (at 8:00 a.m.), her WBC count and absolute neutrophil count had further declined to 2910/mm³ and 1310/mm³, showing leucopenia (WBC count <3000/mm³) and neutropenia (a neutrophil count <1500/mm³). A second blood sample taken at 2:00 p.m. the same day showed that her WBC count and absolute neutrophil count had returned to normal values (4910/mm³ and 3290/mm³, respectively).

During the subsequent 8 weeks, risperidone treatment was continued and titrated up to 12 mg/day, leading to a satisfactory improvement in Ms. A’s symptoms. Blood tests were performed at 8:00 a.m. and at 2:00 p.m. twice a week and showed persistent morning pseudoneutropenia. Ms. A’s absolute neutrophil counts were consistently between 1310/mm³ and 1850/mm³ at 8:00 a.m. (her WBC counts were between 2910/mm³ and 3620/mm³) and between 3120/mm³ and 3570/mm³ at 2:00 p.m. (her WBC counts were between 4450/mm³ and 4910/mm³), i.e., in the normal range.

No concomitant medication was administered. A physical examination, a medical history, and baseline laboratory investigations did not indicate chronic or acute inflammation or infection or autoimmunological or hematological disease. During Ms. A’s previous hospitalization (15 months earlier), while she was receiving haloperidol, her WBC count and absolute neutrophil count were measured once at 8:00 a.m. and were in the normal range (5770/mm³ and 3230/mm³, respectively). Other laboratory tests, including a serum protein immunoelectrophoresis, immunophenotyping of serum lymphocytes, and an antipolynuclear neutrophil alloantibodies assay, did not show any abnormalities. We considered the risk of Ms. A developing agranulocytosis was low because her absolute neutrophil counts were in the normal range at 2:00 p.m. Efficacious risperidone treatment was therefore not interrupted.