Corrected QT Changes During Antipsychotic Treatment of Children and Adolescents: A Systematic Review and Meta-Analysis of Clinical Trials

Objective To evaluate the effect of antipsychotics on the corrected QT (QTc) interval in youth. Method We searched PubMed (http://www.ncbi.nlm.nih.gov/pubmed) for randomized or open clinical trials of antipsychotics in youth  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 p  = .007), whereas ziprasidone increased QTc ( p Conclusion 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.