title: Risk factors for neutropenia in clozapine-treated children and adolescents with childhood-onset schizophrenia.
abstract: OBJECTIVE
  The purpose of this study was to retrospectively analyze rates of neutropenia and risk factors for neutropenia in hospitalized children and adolescents treated with clozapine.
  
  
  METHODS
  A retrospective chart review was conducted for all patients who received clozapine at any time during a hospitalization at the National Institute of Mental Health (NIMH) between 1990 and 2011. All patients satisfied screening criteria for the NIMH childhood-onset schizophrenia study, including onset of psychosis before the age of 13 years. Absolute neutrophil count (ANC) values recorded during inpatient hospitalization were extracted for 87 eligible patients with a mean age of 13.35±2.46 years at hospitalization and a mean length of stay of 117±43 days.
  
  
  RESULTS
  Mild neutropenia only (lowest ANC<2000/mm3 but>1500/mm3) was observed in 27 (31%) patients and moderate neutropenia (any ANC<1500/mm3) was observed in 17 (20%) patients. There were no cases of agranulocytosis or severe infection. Significant risk factors for mild neutropenia compared with no hematologic adverse effects (HAEs) were male gender (p=0.012) and younger age (p<0.001). Male gender was also a significant risk factor for moderate neutropenia compared with no HAEs (p=0.003). If a child of African American ethnicity developed neutropenia during hospitalization at all that child was significantly more likely to develop moderate neutropenia than mild neutropenia only (p=0.017). African American boys had the highest rate of moderate neutropenia at 47%. Sixteen of the 17 patients exhibiting moderate neutropenia were successfully treated with clozapine by the time of discharge; 8 of these 16 required adjunctive lithium carbonate administration to maintain ANC>2000/mm3.
  
  
  CONCLUSIONS
  Our study shows that the rates of neutropenia in clozapine-treated children and adolescents are considerably higher than in the adult population. Younger age, African American ethnicity, and male gender were significant risk factors. These are also risk factors for benign neutropenia in healthy children and adolescents. Despite these high rates of neutropenia, all but one of the patients with neutropenia during hospitalization were successfully discharged on clozapine.
authors.affiliation: Child Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892, USA.
authors.forename: Kristin N
authors.initials: KN
authors.lastname: Maher
authors.forename: Marcus
authors.initials: M
authors.lastname: Tan
authors.forename: Julia W
authors.initials: JW
authors.lastname: Tossell
authors.forename: Brian
authors.initials: B
authors.lastname: Weisinger
authors.forename: Peter
authors.initials: P
authors.lastname: Gochman
authors.forename: Rachel
authors.initials: R
authors.lastname: Miller
authors.forename: Deanna
authors.initials: D
authors.lastname: Greenstein
authors.forename: Gerald P
authors.initials: GP
authors.lastname: Overman
authors.forename: Judith L
authors.initials: JL
authors.lastname: Rapoport
authors.forename: Nitin
authors.initials: N
authors.lastname: Gogtay
mesh_terms: D000293:Adolescent; D001741:Black or African American / Q000706:statistics & numerical data; D000367:Age Factors; D017668:Age of Onset; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006760:Hospitalization; D006801:Humans; D007902:Length of Stay; D007958:Leukocyte Count; D008297:Male; D009315:National Institute of Mental Health (U.S.); D009503:Neutropenia / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D012189:Retrospective Studies; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index; D012737:Sex Factors; D014481:United States
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine