title: Comparative study of mortality rates and cardiac dysrhythmias in post-marketing surveillance studies of sertindole and two other atypical antipsychotic drugs, risperidone and olanzapine.
abstract: Sertindole (Serdolect), an atypical antipsychotic, was voluntarily suspended 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 interval (QTc) and cardiac dysrhythmias in patients prescribed sertindole were compared with those for patients treated with two other atypical antipsychotics. All patients in England, prescribed atypical antipsychotics by general practitioners during each drug's immediate post-marketing period, were identified using an observational cohort technique, prescription-event monitoring. 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 cases 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 sertindole than the other antipsychotics. Six cases of prolongation of QTc interval were identified in 462 patients (1.3%, 95% CI 0.5-2.8) treated with sertindole 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 sertindole, the incidence of which was similar to that in clinical trials. Although no statistically significant difference was shown in mortality rates between sertindole and comparator cohort, the sertindole cohort was too small to rule out an association between the use of this drug and cardiovascular deaths.
authors.affiliation: Drug Safety Research Unit, Bursledon, Southampton, UK. lynda.wilton@dsru.org
authors.forename: L V
authors.initials: LV
authors.lastname: Wilton
authors.forename: E L
authors.initials: EL
authors.lastname: Heeley
authors.forename: R M
authors.initials: RM
authors.lastname: Pickering
authors.forename: S A
authors.initials: SA
authors.lastname: Shakir
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000453:epidemiology* / Q000401:mortality*; D001569:Benzodiazepines; D015331:Cohort Studies; D003645:Death, Sudden / Q000453:epidemiology; D004562:Electrocardiography / Q000187:drug effects; D005062:European Union; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects*; D007211:Indoles / Q000009:adverse effects*; D008133:Long QT Syndrome / Q000139:chemically induced / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects* / Q000031:analogs & derivatives*; D011358:Product Surveillance, Postmarketing; D018967:Risperidone / Q000009:adverse effects*; D012737:Sex Factors
chemical_list: D014150:Antipsychotic Agents; D007093:Imidazoles; D007211:Indoles; D001569:Benzodiazepines; D010890:Pirenzepine; C066304:sertindole; D018967:Risperidone; D000077152:Olanzapine