Effects of aripiprazole and risperidone on ventricular repolarization in children and adolescent.

Introduction: Atypical antipsychotics (AP) are increasingly beingused in children and adolescents for the treatment of psychiatricdisorders such as psychoses, autism, attention-deficit/hyperactivitydisorder (ADHD), and aggressive behavior. Atypical AP may cause QT prolongation on the electrocardiogram (ECG), which predisposes patients to an increased risk of developing threatening ventricular arrhythmias. Although this phenomenon has been exhaustively reported in adults, few studies investigated the safety of these drugs in pediatric patients. Patients (or Materials) and Methods: We performed an open-label, prospective study to assess the arrhythmic risk of aripiprazole and risperidone in pediatrics. A total of 60 patients (55 M/5 F; mean age, 11.8 [3.27] years; range, 3–17 years), receiving a new prescription of aripiprazole or risperidone in monotherapy underwent a standard ECG before and after 2 months from the beginning of antipsychotic treatment. Basal and posttreatment ECG parameters, including mean QT (QTc) and QT dispersion (QTd) interval duration, were compared within treatment groups. Results: Twenty-nine patients were treated with aripiprazole (mean dosage, 7.8 [3.2] mg/d) and 31 with risperidone (mean dosage, 1.7 [1.1] mg/d). Although no patients exhibited pathologic values of QTc or QTd, treatment with risperidone was associated with a significant increase of both QTc and QTd values (407.4 [11.9] ms vs 412.4 [10.3] ms, P = 0.03; and 40.0 [4.4] ms vs 44.7 [5.5] ms, P = 0.0001, respectively). Conversely, treatment with aripiprazole was associated with a statistically significant increase of QTd (40.6 [6.5] ms vs 46.3 [7.2] ms, P = 0.0001) in presence of an unmodified QTc. Moreover, in patients treated with aripiprazole, a significant decrease in heart rate was observed after treatment (90.0 [21.2] beats/min vs 79.8 [19.3] beats/min; P = 0.0003). Conclusion: The present study provided important advances in the assessment of the cardiologic safety of second-generation AP during the pediatric age. Indeed, the treatment with risperidone and aripiprazole was associated with modifications of the QT tract on ECG, thus indicating that these drugs can exert a substantial effect on the ventricular repolarization. Our study remarks the importance to perform an ECG examination in all patients undergoing AP therapy. Both QTc and QTd evaluation should be performed to warranty a reliable assessment of drug-induced QT prolongation. Caution should also be exercised in prescribing aripiprazole in patients at risk of bradycardia.