Hematological Adverse Events in Clozapine-Treated Children and Adolescents

Gerbino-Rosen, Ginny; Roofeh, David; Tompkins, D. Andrew; Feryo, Doug; Nusser, Laurie; Kranzler, Harvey N.; Napolitano, Barbara; Frederickson, Anne M.; Henderson, Inika; Rhinewine, Joe; Kumra, Sanjiv

doi:10.1097/01.chi.0000171904.23947.54

Cited by 77 publications

(70 citation statements)

References 15 publications

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“…We should emphasize, however, that our data differ from previous naturalistic observational data (e.g., Gerbino-Rosen et al 2005). Specifically, we recruited a diagnostically homogeneous group of patients who were prospectively administered laboratory assessments and standardized clinical ratings by a centralized team of raters and by the use of random assignment in the original study.…”

Section: Limitationsmentioning

confidence: 89%

Clozapine Versus “High-Dose” Olanzapine in Refractory Early-Onset Schizophrenia: An Open-Label Extension Study

Kumra

Kranzler

Gerbino-Rosen

et al. 2008

Journal of Child and Adolescent Psychopharmacology

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Objective: A recent 12-week controlled comparison demonstrated the superiority of clozapine to "high-dose" olanzapine in adolescents with treatment-refractory schizophrenia. In the present study, the authors conducted a 12-week, open-label, follow-up study to examine changes in lipid and glucose metabolism in youths maintained on clozapine and to determine whether patients who were previously randomized to high-dose olanzapine (up to 30 mg/day) responded to clozapine. Method: Thirty three (14 clozapine, 19 olanzapine) (85%) of 39 patients were available for the present 12-week, open-label extension study. Extended safety data using an intention-to-treat analysis from the 14 subjects treated with clozapine for a total of 24 weeks are presented. In addition, we report the clinical outcomes for 10 of 19 olanzapine-treated patients who were switched after 12 weeks to clozapine due to treatment nonresponse. Clinical response was defined as a decrease of 30% or more in total Brief Psychiatric Rating score from week 12 and a Clinical Global Impression-Improvement rating of 1 (very much improved) or 2 (much improved). Results: The incidence of hypertriglyceridemia (defined as fasting triglycerides Ͼ125 mg/dL) (10/14 ϭ 71%) and the incidence of "prediabetes" (defined as fasting blood glucose Ն100) (4/14 ϭ 29%) at week 24 in the clozapine-treated subjects were notable. Seven (70%) of 10 of young patients with schizophrenia who failed treatment with "high-dose" olanzapine were found to respond to a 12-week, open-label clozapine trial. Conclusions: Clinicians and caregivers need to be aware of potential metabolic adverse events of long-term clozapine treatment. Adolescents with a poor response to olanzapine may do better on clozapine. 307

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Section: Limitationsmentioning

confidence: 89%

Clozapine Versus “High-Dose” Olanzapine in Refractory Early-Onset Schizophrenia: An Open-Label Extension Study

Kumra

Kranzler

Gerbino-Rosen

et al. 2008

Journal of Child and Adolescent Psychopharmacology

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“…In the same study, the most common adverse events were weight gain and changes in lipid metabolism. 59 The safety of clozapine in relation to the levels of prolactin in children and adolescents was greater than that of other AAPs. A double-blind study with 35 children and adolescents with a diagnosis of schizophrenia compared clozapine with haloperidol and olanzapine and found that the three substances increased the levels of prolactin, but clozapine led to increases that were still within normal levels.…”

Section: Ziprasidonementioning

confidence: 99%

Atypical antipsychotics in the treatment of pathological aggression in children and adolescents: literature review and clinical recommendations

Teixeira

Jacintho

Celeri

et al. 2013

Trends Psychiatry Psychother.

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Objective: To review the literature about the use of atypical antipsychotics in the treatment of pathological aggression in children and adolescents. Method: The databases MEDLINE, SciELO, and LILACS were searched for publications in Portuguese or English from 1992 to August 2011 using the following keywords: mental disease, child, adolescent, treatment, atypical antipsychotic, aggressive behavior, aggression, and violent behavior. Results: Sixty-seven studies of good methodological quality and clinical interest and relevance were identified. Studies including children and adolescents were relatively limited, because few atypical antipsychotics have been approved by the Food and Drug Administration (FDA). All the medications included in this review (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole and clozapine) have some effectiveness in treating aggression in children and adolescents, and choices should be based on clinical indications and side effects. Conclusions: There are few studies about the effectiveness and safety of atypical antipsychotics for the pediatric population, and further randomized controlled studies with larger groups of patients and more diagnostic categories, such as severe conduct disorder and oppositional defiant disorder, should be conducted to confirm the results reported up to date and to evaluate the impact of long-term use. Keywords: Aggression, violence, atypical antipsychotics, behavioral disorders, children, adolescents. ResumoObjetivo: Realizar uma revisão sistemática da literatura científica sobre o uso de antipsicóticos atípicos (APAs) no tratamento da agressividade patológica em crianças e adolescentes. Método: Foi realizada busca eletrônica nas bases de dados MEDLINE, SciELO e LILACS, de 1992 a agosto 2011, considerando artigos publicados em língua inglesa e portuguesa. Foram utilizadas associações das seguintes expressões: mental disease, child, adolescent, treatment, atypical antipsychotic, aggressive behaviour, aggression e violent behavior. Resultados: Foram identificados 67 artigos de boa qualidade metodológica, de relevância e interesse clínico para o tema em foco. De modo geral, os estudos são relativamente limitados para esta faixa etária, resultado do fato de poucos APAs terem sido aprovados pela Food and Drug Administration (FDA). Dentre as medicações consideradas nesta revisão (risperidona, olanzapina, quetiapina, ziprazidona, aripiprazol e clozapina), todas elas podem ter alguma efetividade no tratamento da agressividade em crianças e adolescentes, ficando a escolha baseada na indicação clínica e perfil de efeitos colaterais. Conclusão: O número ainda limitado de estudos acerca da efetividade e segurança na população pediátrica demanda pesquisas futuras com grupos maiores de pacientes e com mais categorias diagnósticas (como, por exemplo, as formas graves de transtorno de conduta e transtorno desafiador de oposição), desenhadas de forma randomizada e controlada. Assim poderão ser confirmados os achados até o momento e o impacto do uso em lo...

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“…But, 8-10% of neutropenia was reported for the NIMH cohort with VEOS (Gogtay and Rapoport, 2008;Sporn et al, 2007). Gerbino-Rosen et al (2005) reported 13% neutropenia and 0.6% agranulocytosis in 172 hospitalized children and adolescents treated with clozapine. However, little is known about the long-term use of clozapine in Asian children and adolescents suffering from EOS (Dean et al, 2006), despite evidences that interethnic differences exist in therapeutic dosage, clinical response, and side effects of clozapine (Matsuda et al, 1996;Subramaniam et al, 2007).…”

Section: Introductionmentioning

confidence: 94%

Long‐term sustained benefits of clozapine treatment in refractory early onset schizophrenia: A retrospective study in Korean children and adolescents

Kim

Cho

et al. 2008

Human Psychopharmacology

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Hematological Adverse Events in Clozapine-Treated Children and Adolescents

Cited by 77 publications

References 15 publications

Clozapine Versus “High-Dose” Olanzapine in Refractory Early-Onset Schizophrenia: An Open-Label Extension Study

Clozapine Versus “High-Dose” Olanzapine in Refractory Early-Onset Schizophrenia: An Open-Label Extension Study

Atypical antipsychotics in the treatment of pathological aggression in children and adolescents: literature review and clinical recommendations

Long‐term sustained benefits of clozapine treatment in refractory early onset schizophrenia: A retrospective study in Korean children and adolescents

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