Comparative study of mortality rates and cardiac dysrhythmias in post-marketing surveillance studies of sertindole and two other atypical antipsychotic drugs, risperidone and olanzapine

Sertindole (Serdolect), an atypical antipsychotic, was voluntarily suspende d in the European Union in 1998 following regulatory concerns over reports of serious cardiac dysrhythmias and sudden unexpected deaths. The reported causes of death, their frequency, prolongation of the rate corrected QT int erval (QTc) and cardiac dysrhythmias in patients prescribed sertindole were compared with those for patients treated with two other atypical antipsych otics. All patients in England, prescribed atypical antipsychotics by gener al practitioners during each drug's immediate post-marketing period, were i dentified using an observational cohort technique, prescription-event monit oring. Mortality rates in the sertindole cohort were compared with those in a comparator cohort using standardized mortality ratios and incidence rate ratios. Cardiovascular events were reviewed and followed up to identify ca ses of prolongation of QTc interval. There was no statistically significant difference in mortality rates between sertindole and the comparator cohort , although confidence intervals (CI) were wide due to small numbers in the sertindole cohort. A much smaller number of patients were prescribed sertin dole than the other antipsychotics. Six cases of prolongation of QTc interv al were identified in 462 patients (1.3%, 95% CI 0.5-2.8) treated with sert indole and one with unspecified electrocardiogram changes in the comparator cohort of 16 542 patients. This study contributes to the understanding of the occurrence-of prolongation of QTc interval during clinical use of serti ndole, the incidence of which was similar to that in clinical trials. Altho ugh no statistically significant difference was shown in mortality rates be tween sertindole and comparator cohort, the sertindole cohort was too small to rule out an association between the use of this drug and cardiovascular deaths.