Randomized, controlled, double-blind multicenter comparison of the efficacy and tolerability of ziprasidone and olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder.
OBJECTIVE
Limited randomized, controlled trial data exist on possible differences between atypical antipsychotics in efficacy, overall tolerability, and important indices of health status. The authors compared the efficacy and tolerability of ziprasidone and olanzapine in the treatment of acutely ill inpatients with schizophrenia or schizoaffective disorder.


METHODS
In this 6-week, multicenter, double-blind, parallel-design, flexible-dose trial, patients were randomly assigned to receive ziprasidone (N=136) or olanzapine (N=133). Primary efficacy measures were improvement in Brief Psychiatric Rating Scale and Clinical Global Impression (CGI) severity scale scores; secondary measures were scores on the CGI improvement scale, Positive and Negative Syndrome Scale, and Calgary Depression Scale for Schizophrenia. Tolerability assessments included fasting lipid profiles, fasting glucose and insulin measurements, electrocardiography, and monitoring of vital signs and body weight.


RESULTS
The overall mean daily doses were 129.9 mg (SD=27.3) for ziprasidone and 11.3 mg (SD=2.8) for olanzapine. Both antipsychotics were efficacious in improving symptoms and global illness severity. The two treatment groups did not differ significantly in primary or secondary efficacy measures at endpoint or in by-visit analysis. Both agents were well tolerated. Body weight, total cholesterol, triglycerides, and low-density lipoprotein cholesterol significantly increased with olanzapine but not with ziprasidone; all between-group comparisons of these variables were significant and favored ziprasidone. Olanzapine, but not ziprasidone, was associated with significant increases in fasting insulin level. No patient in either group exhibited a corrected QT interval >/=500 msec.


CONCLUSIONS
During 6 weeks' treatment, ziprasidone and olanzapine demonstrated comparable antipsychotic efficacy. Differences favoring ziprasidone were observed in metabolic parameters.
Department of Psychiatry and the Behavioral Sciences, LAC + USC Medical Center, IRD RM 204, Psychiatric Outpatient Clinic, 2020 Zonal Ave., Los Angeles, CA 90033, USA. gsimpson@hsc.usc.edu.
George M
GM
Simpson
Ira D
ID
Glick
Peter J
PJ
Weiden
Steven J
SJ
Romano
Cynthia O
CO
Siu
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008140:Lorazepam / Q000627:therapeutic use; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced; D008875:Middle Aged; D000077152:Olanzapine; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D015430:Weight Gain
D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; D001569:Benzodiazepines; C092292:ziprasidone; D000077152:Olanzapine; D008140:Lorazepam