title: Cardiac effects of sertindole and quetiapine: analysis of ECGs from a randomized double-blind study in patients with schizophrenia.
abstract: 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.
authors.affiliation: Aalborg University Hospital, Psychiatry, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. Electronic address: jin@rn.dk.
authors.forename: Jimmi
authors.initials: J
authors.lastname: Nielsen
authors.affiliation: H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Matz
authors.affiliation: H. Lundbeck A/S, Copenhagen, Denmark.
authors.forename: Aurelia
authors.initials: A
authors.lastname: Mittoux
authors.affiliation: Aalborg University Hospital, Psychiatry, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Polcwiartek
authors.affiliation: Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Struijk
authors.affiliation: Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
authors.forename: Egon
authors.initials: E
authors.lastname: Toft
authors.affiliation: Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark; Herlev & Gentofte University Hospitals, Department of Cardiology, Copenhagen, Denmark.
authors.forename: Jørgen K
authors.initials: JK
authors.lastname: Kanters
authors.affiliation: Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Graff
mesh_terms: D014150:Antipsychotic Agents / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects*; D007211:Indoles / Q000009:adverse effects*; D008133:Long QT Syndrome / Q000139:chemically induced*; D008297:Male; D025341:Principal Component Analysis; D000069348:Quetiapine Fumarate / Q000009:adverse effects*; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D007093:Imidazoles; D007211:Indoles; D000069348:Quetiapine Fumarate; C066304:sertindole
keywords: Morphology; QT; QTc; SCD; T-wave