Comparative mortality associated with ziprasidone and olanzapine in real-world use among 18,154 patients with schizophrenia: The Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC).
OBJECTIVE
The authors compared 1-year mortality rates associated with ziprasidone and olanzapine in real-world use.


METHODS
The Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC) was an open-label, randomized, postmarketing large simple trial that enrolled patients with schizophrenia (N=18,154) in naturalistic practice in 18 countries. The primary outcome measure was nonsuicide mortality in the year after initiation of assigned treatment. Patients were randomly assigned to receive treatment with either ziprasidone or olanzapine and followed for 1 year by unblinded investigators providing usual care. A physician-administered questionnaire was used to collect baseline demographic information, medical and psychiatric history, and concomitant medication use. Follow-up information on hospitalizations and emergency department visits, patients' vital status, and current antipsychotic drug status was collected and reported by treating psychiatrists. Post hoc analyses of sudden death, a secondary endpoint, were also conducted.


RESULTS
The incidence of nonsuicide mortality within 1 year of initiating pharmacotherapy was 0.91 for ziprasidone (N=9,077) and 0.90 for olanzapine (N=9,077). The relative risk was 1.02 (95% CI=0.76-1.39). This finding was confirmed in numerous secondary and sensitivity analyses.


CONCLUSIONS
Despite the known risk of QTc prolongation with ziprasidone treatment, the findings of this study failed to show that ziprasidone is associated with an elevated risk of nonsuicidal mortality relative to olanzapine in real-world use; the study excludes a relative risk larger than 1.39 with a high probability. However, the study was neither powered nor designed to examine the risk of rare events like torsade de pointes.
Department of Biostatistics and Epidemiology, the Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, 19104-6021, USA. bstrom@mail.med.upenn.edu
Brian L
BL
Strom
Sybil M
SM
Eng
Gerald
G
Faich
Robert F
RF
Reynolds
Ralph B
RB
D'Agostino
Jeremy
J
Ruskin
John M
JM
Kane
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use / Q000633:toxicity*; D001569:Benzodiazepines / Q000627:therapeutic use / Q000633:toxicity*; D002423:Cause of Death; D003430:Cross-Sectional Studies; D016757:Death, Sudden, Cardiac / Q000453:epidemiology* / Q000209:etiology*; D016883:Diabetic Ketoacidosis / Q000139:chemically induced / Q000401:mortality; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000401:mortality*; D000077152:Olanzapine; D010879:Piperazines / Q000627:therapeutic use / Q000633:toxicity*; D011358:Product Surveillance, Postmarketing; D011446:Prospective Studies; D012306:Risk; D012559:Schizophrenia / Q000188:drug therapy* / Q000401:mortality*; D013405:Suicide / Q000706:statistics & numerical data; D013844:Thiazoles / Q000627:therapeutic use / Q000633:toxicity*
D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; D001569:Benzodiazepines; C092292:ziprasidone; D000077152:Olanzapine