Sertindole in schizophrenia: efficacy and safety issues

INTRODUCTION: Despite substantial progress in the pharmacological treatment of schizophrenia, antipsychotic drugs are associated with insufficient effects on negative and cognitive symptoms, adverse events, poor compliance and drug discontinuation. Sertindole , first withdrawn from the market for cardiovascular safety concerns, is currently available in many countries. It has high affinity for dopamine D2, serotonin 5-HT2A, 5-HT2C and a1-adrenergic receptors, and a low potential for extrapyramidal symptoms. AREAS COVERED: The pharmacodynamics, pharmacokinetics, clinical efficacy, safety and tolerability, and cost-effectiveness of sertindole are covered in this article, based on a literature review (PubMed) from 1990 to 2014. EXPERT OPINION: The reviewed studies suggest a beneficial effect of sertindole on positive, negative and cognitive symptoms, and on relapse prevention. Although generally well tolerated, sertindole is associated with a dose-related QT-interval prolongation; thus, its administration requires electrocardiogram screening and monitoring. The presence of congenital long QT syndrome, prolongated QTc at baseline, cardiac disease and drug interactions should be carefully considered before prescribing sertindole. Further direct 'head-to-head' comparisons with other second-generation antipsychotics (SGAs), trials on special populations and further clarification on cardiac safety are needed to better define the role of sertindole in the treatment of schizophrenia.