Sertindole improves both the positive and negative symptoms of schizophrenia: Results of a phase III trial

OBJECTS: This large multicentre, double-blind, randomized study was designe d to evaluate four doses of sertindole and haloperidol 10 mg in the treatme nt of patients with DSR-I-III-R schizophrenia. METHOD: 617 patients were randomized, of whom 595 were included in an inten tion-to-treat analysis. 375 patients completed the study. Patients were ran domized to receive sertindole 8 mg/day, sertindole 16 mg/day, sertindole 20 mg/day, sertindole 24 mg/day or haloperidol 10 mg/day for 56 days. Efficac y was assessed through the changes in score on the Positive ann Negative Sy ndrome Scale (PANSS), and the Clinical Global Impressions (CGI) scale. Impr ovement in all end-points was observed for all treatment groups. RESULTS: Sertindole 16 mg showed significantly greater efficacy against neg ative symptoms than haloperidol 10 mg. The optimal nose of sertindole was 1 6 mg/day, Sertindole 8 mg appeared to be suboptimal with respect to efficac y, and increasing the nose of sertindole above 20 mg did not appear to offe r any additional benefit. Sertindole at all doses caused significantly fewe r extrapyramidal symptoms than haloperidol, CONCLUSION: Sertindole is effective against positive and negative symptoms of schizophrenia within the dose range 12-24 mg daily, with an optimal star ting nose of 16 mg daily. Efficacy is comparable to 10 mg of haloperidol wi th no difference in the time course of treatment response. The nose respons e relationship for efficacy with sertindole seems to plateau at about 16,ng daily with no demonstrable difference in increasing doses above this point .