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Sertindole is an antipsychotic drug with a high affinity for D₂, 5HT_2A, 5HT_2C and α₁-adrenergic receptors. Preclinical studies have shown that it acts selectively on dopaminergic neurons in mesolimbic and mesocortical system and is effective at a low dopamine D₂ occupancy level.
The active substance has a long half-life, administration once daily yields stable plasma levels.
Clinical studies report that sertindole has similar efficacy to haloperidol with respect to positive symptoms and is significantly better than haloperidol and probably better than risperidone considering negative symptoms.
The effective dose is 12-20 mg/daily.
Sertindole is generally well tolerated, the most frequently reported adverse events are nasal congestion, decreased ejaculatory volume, orthostatic hypotention, small increase in weight . The frequency of extrapyramidal symptoms while using this drug is similar to placebo. Contrary to most antipsychotic drugs sertidole does not cause sedation,so it doesn’t worsen cognitive functioning.
Administration of sertindole is associated with greater prolongation of QTc compared with most other antipsychotic drugs. However, preclinical data suggest that this drug has also protective electrophysiological properties, and QTc prolongation is not associated with increased risk of arrhythmia. Large cohort analyses prove that cardiological and all-cause mortality rate is similar or lower than with other antipsychotic drugs.
Because of the QTc prolongation sertindole should not be used as a first-line treatment in the first psychotic episode. Nevertheless, its side-effect profile makes it an interesting alternative therapeutic option for patients, who didn’t respond well to the initially chosen antipsychotic drug.