Higher cardiovascular mortality with sertindole in ADROIT: a signal not confirmed

Data from the Adverse Drug Reactions On-line Information Tracking (ADROIT) database, which records spontaneously reported adverse drug reactions (ADRs), suggested that the atypical antipsychotic, sertindole, might cause serious cardiac ADRs and be associated with a higher mortality rate than other atypicals. As sertindole was known to have the potential to cause QT interval prolongation, it was assumed to be responsible for the cardiac ADRs and apparently high death rate. During the ensuing CPMP deliberations, Lundbeck decided to withdraw sertindole from the market in 1998, pending further safety analyses. The ADROIT database, by design, is only suited for alert generation and not for hypothesis testing. Therefore, post-marketing observational studies providing valuable information on the effects of new drugs in real-life clinical practice, as well as long-term tolerability data, are necessary to evaluate a signal from the ADROIT database. In the case of sertindole, such studies did not substantiate the decision to suspend the drug. Moreover, no difference in the mortality rates has been observed for low- and high-risk patients. In conclusion, appropriately used, sertindole will provide yet another treatment option for patients with schizophrenia.