1 Department of Clinical Medicine, The Faculty of Medicine, Aalborg University2 The Faculty of Medicine, Aalborg University3 Aalborg University Hospital, The Faculty of Medicine, Aalborg University4 Psykiatrien, Aalborg University Hospital, The Faculty of Medicine, Aalborg University5 Medical Informatics Group, Department of Health Science and Technology, The Faculty of Medicine, Aalborg University6 Department of Health Science and Technology, The Faculty of Medicine, Aalborg University7 unknown8 Forskningscenter for etik i praksis, Department of Learning and Philosophy, The Faculty of Humanities, Aalborg University
analysis of ECGs from a randomized double-blind study in patients with schizophrenia
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 12-20mg and quetiapine 400-600mg 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 12.1ms for sertindole (p<0.001) and -0.5ms 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 20ms QTcF prolongation compared with 36 patients (33.3%) in the sertindole group. Sertindole (12-20mg) was associated with moderate QTc prolongation and worsening of T-wave morphology in a study population of patients with schizophrenia. Although, quetiapine (400-600mg) did not show worsening of repolarization measures some individual patients did experience significant worsening of repolarization. Clinical Trials NCT00654706.
European Neuropsychopharmacology, 2015, Vol 25, Issue 3, p. 303-311
Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't