n this issue of the Journal, the meta-regression analyses by Jensen et al. aim to quantify the effects of antipsychotic I drugs on cardiac QT prolongation in the setting of pediatric randomized or open clinical trials. The common prescription of atypical antipsychotic medication, the known metabolic burden of these agents, and the theoretical potential for related cardiovascular compromise have prompted significant clinical and public concerns regarding the safety of their use in children and adolescents. Of particular concern to prescribing clinicians is the potential effect that antipsychotic drugs have on prolonging the cardiac QT interval, which in turn is associated with torsade de pointes, a rare but potentially fatal cardiac arrhythmia. Repolarization reserve is a term used to describe the existence in normal ventricles and conducting systems of protective redundancy in the components of cardiac repolarization. Congenital (e.g., long QT syndrome) and acquired (e.g., atypical antipsychotic drugs) factors can affect and lessen a given patient’s repolarization reserve, resulting in QT prolongation. Additional acquired factors include overdose, medical conditions that result in hypokalemia, and concomitant therapy with agents that lengthen the QT interval. Risk of serious arrhythmias has been related to the heart rate-corrected QT (QTc) interval, with 480 ms a relatively accepted upper safety limit for most medications and longer than 500 ms a critical value. Lack of marked QTc prolongation alone does not preclude serious arrhythmias. The meta-analysis involved 5,423 medically screened, healthy participants with a mean age of 12.8 years. Participants were primarily boys treated for disruptive behavioral, psychotic, and bipolar spectrum disorders, with an average medication exposure of 16 weeks. Most patients were treated with risperidone (n 1⁄4 2,234; mean dose 2.1 mg/day) and aripiprazole (n 1⁄4 814; mean dose 14.0 mg/day). Restingstate electrocardiograms in the context of clinical trial participation provided the basis for the QT data, with only 4 studies explicitly examining cardiac conduction. Most studies did not report specific methods for correcting the QT interval according to heart rate. In this analysis, 1% to 3% of the sample developed a QTc interval longer than 440 to 470 ms during the course of antipsychotic treatment, whereas only 1 patient (on ziprasidone) had a QTc interval longer than 500 ms. Although the mean increase in QTc interval for the entire sample was modest at 1 to 2 ms, the mean increase for ziprasidone alone was 8.74 ms (CI þ5.19 to þ12.30 ms), which was significant compared with placebo. Of the antipsychotic drugs examined, only risperidone (þ1.68 ms) and ziprasidone were associated with a QTc change significantly different than 0.