The atypical
antipsychotic sertindole is a phenylindole-derived compound that has affinity for and functions as an antagonist at a number of receptor systems, including
dopamine D2 receptors, 5-HT(2A) and 5-HT(2C) receptors, and α-1-noradrenergic receptors. Although previous data suggested that
sertindole was well tolerated and had good efficacy against both positive and negative
symptom clusters, reports of QT prolongation with
sertindole prompted its voluntary removal from the market in 1998. After further safety analyses, it recently regained approval and was reintroduced to the European market for the treatment of
schizophrenia, where its role in
therapy among available atypicals remains unclear. This article evaluates the preclinical and clinical data regarding
sertindole's effectiveness and concludes that
sertindole continues to demonstrate a number of strengths, including effective management of both positive and negative symptoms, well-tolerated side effects (including little or no sedation,
weight gain, and extrapyramidal side effects), and a superior procognitive profile that is unique among atypical
antipsychotics. However, minor concerns regarding its sexual side effects and the major consideration of QT prolongation suggest that additional comparative effectiveness studies are needed to determine the superiority of
sertindole vs other atypical
antipsychotics recently introduced.