A review of the efficacy, tolerability and safety of sertindole in clinical trials.
Sertindole is a non-sedating atypical antipsychotic agent with high selectivity for dopaminergic neurons in the mesolimbic system. In pivotal clinical trials, sertindole has demonstrated significantly greater efficacy than placebo against both the positive and negative symptoms of schizophrenia. In addition, sertindole has had at least similar efficacy to haloperidol and risperidone against positive symptoms, and significantly greater efficacy than haloperidol and risperidone against negative symptoms. The incidence of extrapyramidal symptom (EPS)-related adverse events and the rate of medication used to treat EPS in patients receiving clinically effective doses of sertindole in clinical trials were similar to those observed in placebo recipients and significantly less than those in haloperidol recipients. The incidence of QTc interval prolongation of 500 ms or greater with therapeutic dosages of sertindole has also been low. In general, sertindole has been well tolerated in clinical trials. Unlike other antipsychotic agents, sertindole has not been associated with cognitive impairment, and can actually improve cognitive function. Observational studies have shown that the efficacy and tolerability of sertindole observed in the clinical trial situation are emulated in a naturalistic setting. Large cohort analyses (N > 8000) have shown that all-cause and cardiovascular mortality is no greater with sertindole than with risperidone or olanzapine.
Psychiatric Center Amsterdam Valeriuskliniek, Amsterdam, the Netherlands.
Lowijs
L
Perquin
Tilman
T
Steinert
D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000209:etiology; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology; D002986:Clinical Trials as Topic; D003071:Cognition / Q000187:drug effects; D004361:Drug Tolerance; D004409:Dyskinesia, Drug-Induced / Q000209:etiology; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D012565:Schizophrenic Psychology; D013405:Suicide; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D007093:Imidazoles; D007211:Indoles; C066304:sertindole