TY - JOUR
T1 - Cardiac effects of sertindole and quetiapine
T2 - Analysis of ECGs from a randomized double-blind study in patients with schizophrenia
AU - Nielsen, Jimmi
AU - Matz, Jørgen
AU - Mittoux, Aurelia
AU - Polcwiartek, Christoffer
AU - Struijk, Johannes J.
AU - Toft, Egon
AU - Kanters, Jørgen K.
AU - Graff, Claus
N1 - Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - The QT interval is the most widely used surrogate marker for predicting TdP; however, several alternative surrogate markers, such as Tpeak-Tend (TpTe) and a quantitative T-wave morphology combination score (MCS) have emerged. This study investigated the cardiac effects of sertindole and quetiapine using the QTc interval and newer surrogate markers. Data were derived from a 12 week randomized double-blind study comparing flexible dosage of sertindole 12-20. mg and quetiapine 400-600. mg in patients with schizophrenia. ECGs were recorded digitally at baseline and after 3, 6 and 12 weeks. Between group effects were compared by using a mixed effect model, whereas assessment within group was compared by using a paired t-test. Treatment with sertindole was associated with QTcF and QTcB interval prolongation and an increase in MCS, T-wave asymmetry, T-wave flatness and TpTe. The mean increase in QTcF from baseline to last observation was 12.1. ms for sertindole (p<0.001) and -0.5. ms for quetiapine (p=0.8). Quetiapine caused no increase in MCS, T-wave asymmetry, T-wave flatness or TpTe compared to baseline. In the categorical analysis, there were 11 patients (9.6%) receiving quetiapine who experienced more than 20. ms QTcF prolongation compared with 36 patients (33.3%) in the sertindole group. Sertindole (12-20. mg) was associated with moderate QTc prolongation and worsening of T-wave morphology in a study population of patients with schizophrenia. Although, quetiapine (400-600. mg) did not show worsening of repolarization measures some individual patients did experience significant worsening of repolarization. Clinical Trials NCT00654706.
AB - The QT interval is the most widely used surrogate marker for predicting TdP; however, several alternative surrogate markers, such as Tpeak-Tend (TpTe) and a quantitative T-wave morphology combination score (MCS) have emerged. This study investigated the cardiac effects of sertindole and quetiapine using the QTc interval and newer surrogate markers. Data were derived from a 12 week randomized double-blind study comparing flexible dosage of sertindole 12-20. mg and quetiapine 400-600. mg in patients with schizophrenia. ECGs were recorded digitally at baseline and after 3, 6 and 12 weeks. Between group effects were compared by using a mixed effect model, whereas assessment within group was compared by using a paired t-test. Treatment with sertindole was associated with QTcF and QTcB interval prolongation and an increase in MCS, T-wave asymmetry, T-wave flatness and TpTe. The mean increase in QTcF from baseline to last observation was 12.1. ms for sertindole (p<0.001) and -0.5. ms for quetiapine (p=0.8). Quetiapine caused no increase in MCS, T-wave asymmetry, T-wave flatness or TpTe compared to baseline. In the categorical analysis, there were 11 patients (9.6%) receiving quetiapine who experienced more than 20. ms QTcF prolongation compared with 36 patients (33.3%) in the sertindole group. Sertindole (12-20. mg) was associated with moderate QTc prolongation and worsening of T-wave morphology in a study population of patients with schizophrenia. Although, quetiapine (400-600. mg) did not show worsening of repolarization measures some individual patients did experience significant worsening of repolarization. Clinical Trials NCT00654706.
U2 - 10.1016/j.euroneuro.2014.12.005
DO - 10.1016/j.euroneuro.2014.12.005
M3 - Journal article
C2 - 25583364
SN - 0924-977X
VL - 25
SP - 303
EP - 311
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
IS - 3
ER -