Corrected QT changes during antipsychotic treatment of children and adolescents: a systematic review and meta-analysis of clinical trials

TY - JOUR

T1 - Corrected QT changes during antipsychotic treatment of children and adolescents

T2 - a systematic review and meta-analysis of clinical trials

AU - Jensen, Karsten Gjessing

AU - Juul, Klaus

AU - Fink-Jensen, Anders

AU - Correll, Christoph U

AU - Pagsberg, Anne Katrine

N1 - Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

PY - 2015/1

Y1 - 2015/1

N2 - 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 <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. 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.

AB - 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 <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. 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.

U2 - 10.1016/j.jaac.2014.10.002

DO - 10.1016/j.jaac.2014.10.002

M3 - Review

C2 - 25524787

SN - 0890-8567

VL - 54

SP - 25

EP - 36

JO - American Academy of Child and Adolescent Psychiatry. Journal

JF - American Academy of Child and Adolescent Psychiatry. Journal

IS - 1

ER -