A RANDOMIZED, CONTROLLED, DOSE-RANGING TRIAL OF SERTINDOLE IN PATIENTS WITH SCHIZOPHRENIA

Sertindole is a novel antipsychotic agent with high selectivity for th e mesolimbic dopaminergic pathway and nanomolar affinities for dopamin e D-2 serotonin 5-HT2 and norepinephrine NE(alpha 1) receptors. This 4 0-day randomized, placebo-controlled, dose-ranging multicenter study w as designed to assess the effect of sertindole on previously neurolept ic-responsive, hospitalized schizophrenic patients (n=205). Sertindole doses began at 4 mg/day and were increased to 8, 12 or 20 mg/day. dep ending on randomization. Efficacy measures included the Positive and N egative Syndrome Scale (PANSS). Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression (CGI). Extrapyramidal symptoms (EPS) w ere assessed by movement rating scales, EPS-related adverse events, an d use of anti-EPS medications. A dose-related improvement was observed for PANSS, BPRS, and CGI, with statistically significant mean differe nces (P<0.05) between placebo and 20-mg/day sertindole (decreases from baseline of -5.8 versus -16.9 for PANSS, -4.8 versus -10.4 for BPRS, respectively). The differences in CGI final improvement score between placebo and 20-mg/day sertindole were 3.8 versus 2.9, respectively. EP S-related events were comparable in the placebo and sertindole groups. In conclusion, sertindole 20 mg/day was effective, well tolerated, an d not associated with significant motor system abnormalities.