QT Interval Duration and Dispersion in Children and Adolescents Treated With Ziprasidone

Objective: To assess the incidence of symptoms (palpitations, syncope) and electrocardiographic signs (increased QT duration and dispersion) of an increased risk of torsades de pointes in youth treated with ziprasidone.

Method: Data for this study were collected as part of a prospective, observational, mixed inpatient and outpatient cohort study of youth who were administered antipsychotic treatment for the first time. For this study, we focus on 29 patients (mean ± SD age 15.3 ± 2.9 years) receiving ziprasidone (112.8 ± 50.6 mg/d; range, 20-240) for 99.3 ± 108.7 days. All patients had normal electrocardiograms (ECGs) and no serious medical illness at baseline. Patients had a mean of 2.7 ± 1.3 (median = 3; range, 1-7; total = 49) follow-up ECGs performed monthly for 3 months and every 3 months thereafter, with concurrent blood ziprasidone level measurements. Heart rate-corrected QT interval (QTc) duration and dispersion were measured manually in ≥ 6 ECG leads. QTc > 450-millisecond or ≥ 60-millisecond increase and QTc dispersion > 100 milliseconds were considered abnormal. The study was conducted from December 2001 to September 2007.

Results: No patient reported syncope or symptomatic arrhythmias. Seven patients (24.1%) developed ECG abnormalities; 5 had peak QTc durations > 450 milliseconds, and 2 had peak QTc dispersion > 100 milliseconds. The baseline-to-peak QTc duration increased by 22.9 ± 21 milliseconds (P < .0001). The baseline-to-peak QTc dispersion increased by 6.1 ± 31.4 milliseconds (P = .30). The peak QTc duration and dispersion occurred after 47.6 ± 46.0 and 60.4 ± 73.2 treatment days, respectively. Baseline-to-peak QTc duration and dispersion changes were not correlated with ziprasidone dose (P = .65) or plasma levels (P = .50).

Conclusions: Ziprasidone was associated with a dose- and level-independent, significant prolongation of QTc duration in one-quarter of youth. However, prolongation of QTc dispersion was nonsignificant, and no patient experienced concomitant abnormal prolongation of both QTc duration and QTc dispersion. The dissociation between prolonged QTc duration and dispersion suggests low arrhythmogenic potential in youth with normal baseline ECGs.

J Clin Psychiatry

Submitted: January 20, 2010; accepted June 3, 2010.

Online ahead of print: March 8, 2011 (doi:10.4088/JCP.10m05990yel).

Corresponding author: Peter Manu, MD, Zucker Hillside Hospital, 75-59 263rd St, Glen Oaks, NY 11004 ([email protected]).