Efficacy and tolerability of ziprasidone versus risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder: an 8-week, double-blind, multicenter trial.

BACKGROUND: More head-to-head comparisons of antipsychotics are needed to discern the relative efficacy and safety profiles of these compounds. Thus, we compared ziprasidone and risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder.

METHOD: Patients with DSM-III-R acute exacerbation of schizophrenia or schizoaffective disorder were randomly assigned to double-blind ziprasidone 40 to 80 mg b.i.d. (N = 149) or risperidone 3 to 5 mg b.i.d (N = 147) for 8 weeks. Primary efficacy measures included Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions-Severity of Illness scale (CGI-S) score; secondary measures included scores on the PANSS negative sub-scale, CGI-Improvement scale (CGI-I), and PANSS-derived Brief Psychiatric Rating Scale (BPRSd) total and core items. Safety assessments included movement disorder evaluations, laboratory tests, electrocardiography, vital signs, and body weight. Efficacy analyses employed a prospectively defined Evaluable Patients cohort. Treatment equivalence was conferred if the lower limit of the 95% confidence interval of the ziprasidone/risperidone ratio of least-squares mean change from baseline was > 0.60. Data were gathered from August 1995 to January 1997.

RESULTS: Equivalence was demonstrated in PANSS total scores, CGI-S scores, PANSS negative subscale scores, BPRSd total and core item scores, and PANSS total and CGI-I responder rates. Both agents were well tolerated. Risperidone exhibited a significantly higher Movement Disorder Burden (MDB) score (p < .05) and higher incidences of prolactin elevation and clinically relevant weight gain. However, compared with current recommendations, study dosing may have been high for some risperidone-treated patients (mean dose = 7.4 mg/day) and low for some ziprasidone-treated patients (mean dose = 114.2 mg/day).

CONCLUSION: Both agents equally improved psychotic symptoms, and both were generally well tolerated, with ziprasidone demonstrating a lower MDB score and less effect on prolactin and weight than risperidone.