Risk Factors for Neutropenia in Clozapine-Treated Children and Adolescents with Childhood-Onset Schizophrenia

Maher, Kristin N.; Tan, Marcus; Tossell, Julia W.; Weisinger, Brian; Gochman, Peter; Miller, Rachel; Greenstein, Deanna; Overman, Gerald P.; Rapoport, Judith L.; Gogtay, Nitin

doi:10.1089/cap.2011.0136

Cited by 28 publications

(14 citation statements)

References 41 publications

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“…Therefore, p53 expression after melphalan exposure is a potential biomarker corresponding to clinical response to melphalan, which is in agreement with our modeling results. Furthermore, previous articles reported gender and ethnicity as risk factors for neutropenia after other chemotherapies. Our model also indicates that gender and race could explain portions of IIV for SLOPE and MTT, respectively.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic‐Pharmacodynamic Model of Neutropenia in Patients With Myeloma Receiving High‐Dose Melphalan for Autologous Stem Cell Transplant

Cho

Irby

Sborov

et al. 2018

CPT Pharmacom & Syst Pharma

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High‐dose melphalan (HDM) is part of the conditioning regimen in patients with multiple myeloma (MM) receiving autologous stem cell transplantation (ASCT). However, individual sensitivity to melphalan varies, and many patients experience severe toxicities. Prolonged severe neutropenia is one of the most severe toxicities and contributes to potentially life‐threatening infections and failure of ASCT. Granulocyte‐colony stimulating factor (G‐CSF) is given to stimulate neutrophil proliferation after melphalan administration. The aim of this study was to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model capable of predicting neutrophil kinetics in individual patients with MM undergoing ASCT with high‐dose melphalan and G‐CSF administration. The extended PK/PD model incorporated several covariates, including G‐CSF regimen, stem cell dose, hematocrit, sex, creatinine clearance, p53 fold change, and race. The resulting model explained portions of interindividual variability in melphalan exposure, therapeutic effect, and feedback regulation of G‐CSF on neutrophils, thus enabling simulation of various doses and prediction of neutropenia duration.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic‐Pharmacodynamic Model of Neutropenia in Patients With Myeloma Receiving High‐Dose Melphalan for Autologous Stem Cell Transplant

Cho

Irby

Sborov

et al. 2018

CPT Pharmacom & Syst Pharma

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“…Hematologic abnormalities induced by antipsychotics may be life-threatening in some patients. Several studies revealed the association between clozapine and leukopenia in children, and clozapine is generally recommended for drug-resistant cases 26 - 28 . In addition, Etain et al reported that leukopenia was induced by risperidone 29 .…”

Section: Discussionmentioning

confidence: 99%

Antipsychotics-Associated Serious Adverse Events in Children: An Analysis of the FAERS Database

Kimura¹,

Kadoyama²,

Brown³

et al. 2015

Int. J. Med. Sci.

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Objective: The reports submitted to the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from 1997 to 2011 were reviewed to assess serious adverse events induced by the administration of antipsychotics to children.Methods: Following pre-processing of FAERS data by elimination of duplicated records as well as adjustments to standardize drug names, reports involving haloperidol, olanzapine, quetiapine, clozapine, ziprasidone, risperidone, and aripiprazole were analyzed in children (age 0-12). Signals in the data that signified a drug-associated adverse event were detected via quantitative data mining algorithms. The algorithms applied to this study include the empirical Bayes geometric mean, the reporting odds ratio, the proportional reporting ratio, and the information component of a Bayesian confidence propagation neural network. Neuroleptic malignant syndrome (NMS), QT prolongation, leukopenia, and suicide attempt were focused on as serious adverse events.Results: In regard to NMS, the signal scores for haloperidol and aripiprazole were greater than for other antipsychotics. Significant signals of the QT prolongation adverse event were detected only for ziprasidone and risperidone. With respect to leukopenia, the association with clozapine was noteworthy. In the case of suicide attempt, signals for haloperidol, olanzapine, quetiapine, risperidone, and aripiprazole were detected.Conclusions: It was suggested that there is a level of diversity in the strength of the association between various first- and second-generation antipsychotics with associated serious adverse events, which possibly lead to fatal outcomes. We recommend that research be continued in order to gather a large variety and quantity of related information, and that both available and newly reported data be placed in the context of multiple medical viewpoints in order to lead to improved levels of care.

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“…Among a sample of 87 children and adolescents being treated with Clozapine, approximately half of them displayed mild to moderate neutropenia, which is much higher than the risk of neutropenia among adults. There appears to be certain risk factors that can increase the likelihood of developing this complication, including younger age, being male and being an African-American (Maher et al, 2013 ). There continues to be disagreement around the efficacy of typical versus atypical antipsychotic medication in the treatment of schizophrenia.…”

Section: Treatmentmentioning

confidence: 99%

Childhood-onset schizophrenia: what do we really know?

Bartlett

2014

Health Psychology and Behavioral Medicine

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Childhood-onset schizophrenia (COS) is a rare, chronic mental illness that is diagnosed in children prior to the age of 13. COS is a controversial diagnosis among clinicians and can be very difficult to diagnose for a number of reasons. Schizophrenia is a psychotic disorder characterized by hallucinations, delusions, flat affect, limited motivation and anhedonia. The psychotic nature of this disorder is quite disruptive to the child's emotional regulation, behavioural control and can reduce the child's ability to perform daily tasks that are crucial to adaptive functioning. Prior to the onset of schizophrenia, children often develop premorbid abnormalities, which are disturbances to a child's functioning that may serve as warning signs. These disturbances can manifest in a variety of behavioural ways and may include introversion, depression, aggression, suicidal ideation and manic-like behaviours. This article will review the clinical presentation of schizophrenia in children and examine the existing knowledge around aetiology, treatment approaches, assessment techniques and differential diagnostic considerations. Gaps in the literature are identified and directions for future research are discussed.

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Risk Factors for Neutropenia in Clozapine-Treated Children and Adolescents with Childhood-Onset Schizophrenia

Cited by 28 publications

References 41 publications

Pharmacokinetic‐Pharmacodynamic Model of Neutropenia in Patients With Myeloma Receiving High‐Dose Melphalan for Autologous Stem Cell Transplant

Pharmacokinetic‐Pharmacodynamic Model of Neutropenia in Patients With Myeloma Receiving High‐Dose Melphalan for Autologous Stem Cell Transplant

Antipsychotics-Associated Serious Adverse Events in Children: An Analysis of the FAERS Database

Childhood-onset schizophrenia: what do we really know?

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