Efficacy and tolerability of ziprasidone in patients with treatment-resistant schizophrenia.

This multicentre, parallel-group study compared the efficacy and tolerability of ziprasidone and chlorpromazine in treatment-resistant schizophrenia (at least three treatment periods of at least 6 weeks each with two or more antipsychotic agents during the past 5 years without significant response) that was unresponsive to 6 weeks of open-label haloperidol (</=30 mg/day). Haloperidol nonresponders were randomized to ziprasidone 80-160 mg/day (n=152) or chlorpromazine 200-1200 mg/day (n=154) for up to 12 weeks. The primary efficacy measures were the Brief Psychiatric Rating Scale (BPRSd) total score derived from the Positive and Negative Syndrome Scale (PANSS), BPRSd core psychotic symptoms, and Clinical Global Impression-Severity (CGI-S). Secondary efficacy variables included PANSS total score, PANSS Negative Subscale, and the Montgomery-Asberg Depression Rating Scale. Results were assessed at baseline and week 6 of haloperidol treatment (n=415) and at weeks 0, 3, 6, 9 and 12 of randomized treatment (n=306). Improvements in efficacy variables were greater with ziprasidone at weeks 3 and 6, reaching statistical significance versus chlorpromazine (P<0.05) at week 6 for CGI-S and week 12 for PANSS Negative Subscale. Improvements in BPRSd total and core items and PANSS total scores were comparable at weeks 9 and 12. Ziprasidone was associated with a greater decrease in median prolactin levels and a lower incidence of clinically significant weight change. Neither agent caused any clinically important changes in QTc interval.

RCT Entities:   Population Interventions Outcomes