title: Maximizing clozapine utilization while minimizing blood dyscrasias: evaluation of patient demographics and severity of events.
abstract: The aim of this study was to determine whether patient characteristics such as age, sex, race/ethnicity, and frequency of monitoring play a role in clozapine-related blood dyscrasias. This study examined all neutropenic events to identify any potential demographic qualities that may pose increased risk to individuals receiving clozapine treatment in accordance with the FDA guidelines released in 2005. These guidelines required the addition of absolute neutrophil count (ANC) tests in addition to white blood cell (WBC) counts to regular monitoring and a reduction in the frequency of testing to once monthly after 1 year of satisfactory WBC counts and ANCs. The previous schedule neither included ANC testing nor allowed for further reductions in the frequency of testing after 1 year, with patients continuing to be tested every 2 weeks indefinitely. This is a retrospective, closed chart review of all patients who received clozapine at the State Psychiatric Center and experienced a leukopenic/neutropenic event and/or who had a substantial drop in WBC/ANC from January 2009 to December 2011. A subset of patients who were identified as achieving 'non-rechallengeable' status with either an ANC and/or WBC threshold value from 2001 to 2014 were also examined. This protocol was approved by the New York State Psychiatric Institute Institutional Review Board. A total of 193 patients were included in the study. Males experienced more total events at 6.4 events per person compared with 5.2 events per woman. White patients had 6.5 total events per person compared with 4.2 total events per Black patient; however, Black patients experienced more moderate leukopenia/granulocytopenia events compared with Whites. Regardless of race or ethnicity, patients in the 40-49-year age range had the most events at 8.1 events per person and also presented with the highest number of moderate leukopenia/granulocytopenia events as did those scheduled for weekly monitoring. Conversely, the majority of patients with no recorded events were female and either 20-29 or 60-69 years of age. In total, 16 patients were exclusively designated as non-rechallengeable from 2001 to 2014 and only had one single blood event prompting this clozapine monitoring status. Of these 16 patient events, seven were White males, eight were White females, and one was a Black female with roughly 40% of those patients in the 50-59-year age group. Currently published predictions on possible demographic risk groups may not reflect clinical experience and may pose unnecessary treatment barriers in the provision of clozapine. Although the healthcare team should be aware of the possible demographic predictors of blood dyscrasias when using clozapine, treatment goals and monitoring strategies must be individualized to ensure successful clozapine therapy.
authors.affiliation: aState University of New York at Buffalo, School of Pharmacy and Pharmaceutical Sciences bNew York State Office of Mental Health at the Buffalo Psychiatric Center, Buffalo cDepartment of Psychology, Long Island University, Brooklyn, New York, USA.
authors.forename: Tammie Lee
authors.initials: TL
authors.lastname: Demler
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Morabito
authors.forename: Charlene E
authors.initials: CE
authors.lastname: Meyer
authors.forename: Lewis
authors.initials: L
authors.lastname: Opler
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D003024:Clozapine / Q000008:administration & dosage / Q000009:adverse effects*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D007970:Leukopenia / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis / Q000208:ethnology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D011237:Predictive Value of Tests; D044469:Racial Groups; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine