Expert opinion on drug safety

Drug safety and efficacy evaluation of sertindole for schizophrenia.

PMID 22992213


Despite the progress in antipsychotic treatment, modern antipsychotic medication is still associated with side effects, reduced compliance, drug discontinuation and insufficient effects on negative and cognitive symptoms. Sertindole is an antipsychotic compound, with high affinity for dopamine D(2), serotonin 5-HT(2A), 5-HT(2C) and α(1)-adrenergic receptors, which has been reintroduced in the market after extended re-evaluation of its safety and risk-benefit profile. Sertindole's pharmacological profile, pharmacokinetics, neuophysiological properties, efficacy on positive, negative and cognitive symptoms and safety issues are covered in this article, based on a literature review from 1990 to 2012. Based on five double-blind, randomized, placebo-, haloperidol- or risperidone-controlled studies in patients with schizophrenia, sertindole shows a comparable efficacy with haloperidol and risperidone on positive symptoms, while the effect on negative symptoms seems to be superior. Sertindole is generally well tolerated, but is associated with a dose-related QTc interval prolongation (+22 ms). Risk factors for drug-induced arrhythmia, such as cardiac diseases, congenital long QT syndrome, prolongated QTc at baseline, etc. and drug interactions should be considered before prescribing sertindole. To minimize cardiovascular risk, regular ECG recording is required. Sertindole can be an important second-line option for the treatment of schizophrenia for patients intolerant to at least one other antipsychotic. Further comparison with other SGAs and investigations on subgroups (e.g., children, elderly, first-episode, treatment-refractory patients, etc.) are still needed for a precise understanding of the therapeutic benefits and its role in schizophrenia therapy.