Child and Adolescent Mental Health Centre, Mental Health Services Capital Region and Faculty of Health Science, University of Copenhagen, Denmark.
Rigshospitalet University Hospital, Copenhagen.
J Am Acad Child Adolesc Psychiatry. 2015 Jan;54(1):25-36. doi: 10.1016/j.jaac.2014.10.002. Epub 2014 Oct 16.
To evaluate the effect of antipsychotics on the corrected QT (QTc) interval in youth.
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.
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.
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.
评估抗精神病药对青少年校正 QT（QTc）间期的影响。
我们检索了 PubMed（http://www.ncbi.nlm.nih.gov/pubmed）中关于在<18 岁的青年中使用 QTc 数据的抗精神病药的随机或开放临床试验，对结果进行了荟萃分析。荟萃回归分析评估了年龄、性别、剂量和研究持续时间对 QTc 的影响。还评估了研究定义的 QTc 延长（>440-470 毫秒）、QTc>500 毫秒和 QTc 变化>60 毫秒的发生率。
共对 55 项研究进行了荟萃分析，评估了 108 个治疗臂，涉及 9 种抗精神病药，包括 5423 名有 QTc 数据的患者（平均年龄 12.8±3.6 岁，女性 32.1%）。治疗包括阿立哌唑：研究=14；n=814；氟哌啶醇：研究=1；n=15；莫利酮：研究=3；n=125；奥氮平：研究=5；n=212；帕利哌酮：研究=3；n=177；匹莫齐特：研究=1；n=25；喹硫平：研究=5；n=336；利培酮：研究=23；n=2234；齐拉西酮：研究=10；n=523；安慰剂：研究=19；n=962。在组内，从基线到终点，阿立哌唑显著降低 QTc 间期（-1.44 毫秒，CI=-2.63 至-0.26，p=0.017），而利培酮（+1.68，CI=+0.67 至+2.70，p=0.001）和特别是齐拉西酮（+8.74，CI=+5.19 至+12.30，p<0.001）显著增加了 QTc。与汇总安慰剂组相比，阿立哌唑降低了 QTc（p=0.007），而齐拉西酮增加了 QTc（p<0.001）。与安慰剂相比，研究中的任何一种抗精神病药都没有导致 3 项研究的 QTc 延长指标发生率显著增加，但存在显著的报告偏倚。
根据这些数据，在其他方面健康的青少年中使用研究中的 9 种抗精神病药治疗时，病理性 QTc 延长的风险似乎较低。然而，由于个体风险因素与药物相关的 QTc 效应相互作用，在选择抗精神病药治疗时，需要考虑药物和患者因素。
