A Comprehensive Monograph on Sertindole (DB06144): Efficacy, Cardiovascular Risk, and Regulatory Scrutiny

Executive Summary and Drug Identification

Overview

Sertindole is a second-generation, or atypical, antipsychotic agent developed by the Danish pharmaceutical company Lundbeck for the management of schizophrenia.[1] As a member of the phenylindole chemical class, its clinical profile is characterized by a significant and challenging dichotomy.[2] On one hand, Sertindole offers a favorable neurological side-effect profile, distinguished by a notably low incidence of extrapyramidal symptoms (EPSE) and minimal sedative properties when compared to many first- and second-generation antipsychotics.[4] This particular attribute makes it a potentially valuable therapeutic option for patients who are intolerant to the motor and cognitive side effects of other antipsychotic medications.

This therapeutic advantage, however, is critically counterbalanced by a substantial and well-documented risk of serious cardiovascular adverse effects. The primary concern is a dose-dependent prolongation of the QTc interval on the electrocardiogram, a phenomenon directly linked to an increased risk of life-threatening cardiac arrhythmias, including Torsades de Pointes and sudden cardiac death.[1] This significant safety liability led to a voluntary suspension of its marketing authorization in Europe in 1998, only two years after its initial launch.[2] Following extensive re-evaluation, it was reintroduced in some European markets under stringent restrictions, including mandatory cardiovascular monitoring and its designation as a second-line agent.[8] In contrast, these same safety concerns have prevented its approval by the U.S. Food and Drug Administration (FDA), where it remains an investigational agent.[1] Consequently, Sertindole occupies a highly specialized and restricted niche in the psychopharmacological armamentarium, reserved for specific patient pop