title: Clozapine use in childhood and adolescent schizophrenia: A nationwide population-based study.
abstract: Early onset schizophrenia (EOS) begins in childhood or adolescence. EOS is associated with poor treatment response and may benefit from timely use of clozapine. This study aimed to identify the predictors of clozapine use in EOS and characterize the clinical profile and outcome of clozapine-treated youths with schizophrenia. We conducted a nationwide population-based study using linked data from Danish medical registries. We examined all incident cases of EOS (i.e., cases diagnosed prior to their 18th birthday) between December 31st 1994 and December 31st 2006 and characterized their demographic, clinical and treatment profiles. We then used multivariable cox proportional hazard models to identify predictors of clozapine treatment in this patient population. We identified 662 EOS cases (1.9% of all schizophrenia cases), of whom 108 (17.6%) had commenced clozapine by December 31st 2008. Patients had on average 3 antipsychotic trials prior to clozapine initiation. The mean interval between first antipsychotic treatment and clozapine initiation was 3.2 (2.9) years. Older age at diagnosis of schizophrenia [HR=1.2, 95% CI (1.05-1.4), p=0.01], family history of schizophrenia [HR=2.1, 95% CI (1.1-3.04), p=0.02] and attempted suicide [HR=1.8, 95% CI (1.1-3.04), p=0.02] emerged as significant predictors of clozapine use. The majority of patients (n=96, 88.8%) prescribed clozapine appeared to have a favorable clinical response as indicated by continued prescription redemption and improved occupational outcomes. Our findings support current recommendations for the timely use of clozapine in EOS.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King׳s College London, UK.
authors.forename: Carolina
authors.initials: C
authors.lastname: Schneider
authors.affiliation: Department of Primary Care and Population Health, University College London, London, UK.
authors.forename: Efstathios
authors.initials: E
authors.lastname: Papachristou
authors.affiliation: Department of Economics and Business, Centre for Integrated Register-Based Research, and the Initiative for Integrative Psychiatric Research ( iPSYCH), Aarhus University, Denmark.
authors.forename: Theresa
authors.initials: T
authors.lastname: Wimberley
authors.affiliation: Department of Economics and Business, Centre for Integrated Register-Based Research, and the Initiative for Integrative Psychiatric Research ( iPSYCH), Aarhus University, Denmark.
authors.forename: Christiane
authors.initials: C
authors.lastname: Gasse
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Center, Institute of Psychiatry, Psychology and Neuroscience, King׳s College London, UK; Clinical Neuroscience Studies (CNS) Center, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, USA.
authors.forename: Danai
authors.initials: D
authors.lastname: Dima
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King׳s College London, UK.
authors.forename: James H
authors.initials: JH
authors.lastname: MacCabe
authors.affiliation: Department of Economics and Business, Centre for Integrated Register-Based Research, and the Initiative for Integrative Psychiatric Research ( iPSYCH), Aarhus University, Denmark.
authors.forename: Preben Bo
authors.initials: PB
authors.lastname: Mortensen
authors.affiliation: Clinical Neuroscience Studies (CNS) Center, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, USA. Electronic address: sophia.frangou@mssm.edu.
authors.forename: Sophia
authors.initials: S
authors.lastname: Frangou
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002648:Child; D003024:Clozapine / Q000627:therapeutic use*; D018672:Community Health Planning; D003718:Denmark / Q000453:epidemiology; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D012042:Registries; D012189:Retrospective Studies; D012559:Schizophrenia / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
keywords: Adolescents; Antipsychotic; Children; Clozapine; Denmark; Schizophrenia