Sertindole causes distinct electrocardiographic T-wave morphology changes.
Sertindole's propensity to prolong the QT interval relates to blockade of the KCNH2 (HERG) encoded Ikr potassium channel, but there has been limited detailed data on T-wave morphology changes. Digital 12-lead ECG was recorded at baseline and at steady-state in 37 patients switched to sertindole. ECG was analyzed for quantitative T-wave morphology changes and Fridericia-corrected QT duration (QTcF). Prominent T-wave morphology changes occurred during sertindole treatment and in some cases without concomitant prolongation of the QTcF interval. Four patients developed notched T-waves during sertindole treatment. Mean QTc prolongation was 19 ms. The mean effect size was higher for T-wave morphology combination score (MCS) (ES=1.92; 95% CI: 1.35-2.49) compared to the mean effect size for QTcF (ES=0.88; 95% CI: 0.52-1.24). The use of T-wave morphology analysis may become clinically relevant, particularly if shown to be associated with drug-induced arrhythmia risk.
Nielsen
Jimmi
J
Unit for Psychiatric Research, Aalborg Psychiatric Hospital, Aarhus University Hospital, Mølleparkvej 10, PO Box 210, DK-9100 Aalborg, Denmark. jin@rn.dk
Graff
Claus
C
Hardahl
Thomas
T
Andersen
Mads P
MP
Kristoffersen
Jens
J
Struijk
Johannes J
JJ
Toft
Egon
E
Meyer
Jonathan M
JM
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D007211:Indoles / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D012559:Schizophrenia / Q000188:drug therapy
D014150:Antipsychotic Agents; D007093:Imidazoles; D007211:Indoles; C066304:sertindole