Risperidone-Induced Morning Pseudoneutropenia
To the Editor: Pronounced diurnal variations in the number of circulating neutrophils, i.e., “morning pseudoneutropenia,” have been previously described during clozapine treatment only (1, 2). To our knowledge, we report the first case of 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.
In healthy subjects, circulating blood cells are known to show circadian rhythms. However, little is known about the mechanisms involved in these variations (3). In the case of morning pseudoneutropenia, it has been hypothesized that clozapine may amplify the diurnal variations in circulating neutrophils by means of an effect on the endogenous production of hematopoietic cytokines (2). This explanation may also apply to risperidone and probably to other antipsychotic drugs.
Because morning pseudoneutropenia does not systematically predispose one to agranulocytosis (1, 2), these patients may not unnecessarily be denied effective treatment. In conclusion, before interrupting risperidone treatment, we recommend that leukocyte counts be repeated systematically at 2:00 p.m., when absolute neutrophil counts and/or WBC counts are below the normal range at 8:00 a.m.
1. Ahokas A, Elonen E: Circadian rhythm of white blood cells during clozapine treatment. Psychopharmacology (Berl) 1999; 144:301–302Crossref, Medline, Google Scholar
2. Esposito D, Aouillé J, Rouillon F, Limosin F: Morning pseudoneutropenia during clozapine treatment. World J Biol Psychiatry 2003; 4:192–194Crossref, Medline, Google Scholar
3. Jilma B, Hergovich N, Stohlawetz P, Eichler HG, Bauer P, Wagner OF: Circadian variation of granulocyte colony stimulating factor levels in man. Br J Haematol 1999; 106:368–370Crossref, Medline, Google Scholar
