title: Corrected QT changes during antipsychotic treatment of children and adolescents: a systematic review and meta-analysis of clinical trials.
abstract: OBJECTIVE
  To evaluate the effect of antipsychotics on the corrected QT (QTc) interval in youth.
  
  
  METHODS
  We searched PubMed (http://www.ncbi.nlm.nih.gov/pubmed) for randomized or open clinical trials of antipsychotics in youth <18 years with QTc data, meta-analyzing the results. Meta-regression analyses evaluated the effect of age, sex, dose, and study duration on QTc. Incidences of study-defined QTc prolongation (>440-470 milliseconds), QTc >500 milliseconds, and QTc change >60 milliseconds were also evaluated.
  
  
  RESULTS
  A total of 55 studies were meta-analyzed, evaluating 108 treatment arms covering 9 antipsychotics and including 5,423 patients with QTc data (mean age = 12.8 ± 3.6 years, female = 32.1%). Treatments included aripiprazole: studies = 14; n = 814; haloperidol: studies = 1; n = 15; molindone: studies = 3; n = 125; olanzapine: studies = 5; n = 212; paliperidone: studies = 3; n = 177; pimozide: studies = 1; n = 25; quetiapine: studies = 5; n = 336; risperidone: studies = 23; n = 2,234; ziprasidone: studies = 10, n = 523; and placebo: studies = 19, n = 962. Within group, from baseline to endpoint, aripiprazole significantly decreased the QTc interval (-1.44 milliseconds, CI = -2.63 to -0.26, p = .017), whereas risperidone (+1.68, CI = +0.67 to +2.70, p = .001) and especially ziprasidone (+8.74, CI = +5.19 to +12.30, p < .001) significantly increased QTc. Compared to pooled placebo arms, aripiprazole decreased QTc (p = .007), whereas ziprasidone increased QTc (p < .001). Compared to placebo, none of the investigated antipsychotics caused a significant increase in the incidence of the 3 studied QTc prolongation measures, but there was significant reporting bias.
  
  
  CONCLUSIONS
  Based on these data, the risk of pathological QTc prolongation seems low during treatment with the 9 studied antipsychotics in otherwise healthy youth. Nevertheless, because individual risk factors interact with medication-related QTc effects, both medication and patient factors need to be considered when choosing antipsychotic treatment.
authors.affiliation: Child and Adolescent Mental Health Centre, Mental Health Services Capital Region and Faculty of Health Science, University of Copenhagen, Denmark. Electronic address: Karsten.Gjessing.Jensen@regionh.dk.
authors.forename: Karsten Gjessing
authors.initials: KG
authors.lastname: Jensen
authors.affiliation: Rigshospitalet University Hospital, Copenhagen.
authors.forename: Klaus
authors.initials: K
authors.lastname: Juul
authors.affiliation: Laboratory of Neuropsychiatry, University of Copenhagen and Psychiatric Centre Copenhagen, University Hospital Copenhagen.
authors.forename: Anders
authors.initials: A
authors.lastname: Fink-Jensen
authors.affiliation: Hofstra North Shore Long Island Jewish School of Medicine and the Recognition and Prevention Program, Zucker Hillside Hospital, Glen Oaks, NY.
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
authors.affiliation: Child and Adolescent Mental Health Centre, Mental Health Services Capital Region and Faculty of Health Science, University of Copenhagen, Denmark.
authors.forename: Anne Katrine
authors.initials: AK
authors.lastname: Pagsberg
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000009:adverse effects*; D002648:Child; D002986:Clinical Trials as Topic; D004562:Electrocardiography / Q000187:drug effects*; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced*
chemical_list: D014150:Antipsychotic Agents
keywords: ECG; QTc; adolescents; antipsychotics; children