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Antipsychotics can differentially prolong the heart rate–corrected QT interval of the electrocardiogram (ECG), which may be associated with torsades de pointes, a potentially fatal arrhythmia (Blair et al. 2005). Even in adults, QTc prolongation is usually minimal compared to placebo, except for thioridazine. Among SGAs, ziprasidone has been associated with the greatest QTc prolongation (Glassman and Bigger 2001). QTc prolongation to >430 ms was described (Blair et al. 2005) in 3 of 20 youth treated prospectively with ziprasidone (mean peak QTc prolongation of 28 ± 26 ms, P <0.01), without relationship to ziprasidone dosage (mean: 30 ± 13 mg/day, range: 30–60 mg/day). In another study (N = 12), Malone et al. (2007) also reported a statistically significant increase in QTc (15 ± 21 ms, P = 0.04) at a mean ziprasidone dosage of 99 mg/day (range: 40–160 mg/day). However, QTc changes were nonsignificant in studies of 12 (McDougle et al. 2002), 16 (Sallee et al. 2000), and 21 (Biederman et al. 2007) patients at ziprasidone dosages of 57 mg/day (range: 20–120 mg/day), 28 mg/day (range: 5–40 mg/day), and 60 mg/day (range: 20–120 mg/day), respectively. Further, no patient in these studies reported cardiac side effects, such as dizziness, palpitations, or syncope. This indicates that the clinical relevance of this degree of QTc prolongation (not reaching the generally accepted pathological threshold of >500 ms or an increase in QTc over baseline of >60 ms [Glassman and Bigger 2001]) is unclear. Thus, theoretical concerns about QTc prolongation with ziprasidone need to be weighed against its more certain weight-related and metabolic benefits. However, ECGs may need to be obtained whenever there is a family history of early sudden death, prolonged QT syndrome, or a personal history of irregular heart beat, tachycardia at rest, shortness of breath, dizziness on exertion, or syncope. Only clozapine has been associated with a myocarditis risk that is greatest early in treatment. Clinical signs of acute myocarditis include palpitations, chest pain, shortness of breath, and syncope. Characteristic ECG changes include ectopic beats, atrioventricular block, atrial fibrillation or flutter, intraventricular conduction disturbance, ventricular tachycardia or fibrillation, and low QRS voltages. In youth, the incidence seems relatively low (Wehmeier et al. 2004).

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