Method: The model involved a simulation of diabetes, primary CHD, and secondary CHD events in men and women having the baseline characteristics of patients enrolled in the CATIE randomized double-blinded effectiveness trial of olanzapine, risperidone, quetiapine, and ziprasidone. The simulation and all statistical analyses were written in the R-statistical programming language. Annual, 1-way transition probabilities for primary and secondary CHD events were estimated from the Framingham Heart Study risk equations and that for diabetes from the National Nurse Health study. Change in metabolic parameters (LDL, HDL, Triglycerides, Systolic Blood Pressure, and BMI) was set equal to the mean, exposure adjusted change observed in CATIE and was simulated with 10,000 replications from multivariate log-normal distributions. Risks for each atypical antipsychotic included in CATIE were quantified using relative risk (RR) and number needed to harm (NNH). The reference group for relative risk was ziprasidone, the lowest risk atypical.
Results: Olanzapine substantially elevated risk for diabetes among men (RR=1.26, NNH=24) and women (RR = 1.09, NNH=62). Olanzapine also increased risk for CHD in men (RR = 1.08, NNH=144) and women (RR=1.12, NNH=257). Quetiapine increased risk for diabetes in men (RR=1.09, NNH=93) and women (RR=1.03, NNH=224) and CHD in men (RR =1.06,NNH=197) and women (RR=1.09, NNH=442). Risperidone increased risk moderately for diabetes and CHD although only for men. Ziprasidone did not increase risk for diabetes or CHD.
Relative risk for myocardial infarction (MI) within 10-years was elevated for olanzapine (RR=1.26-1.33), quetiapine (RR=1.14-1.26), and risperidone in men (RR=1.07) but not for ziprasidone (RR=.95-.87).
Conclusions: Metabolic changes observed in the CATIE study following atypical antipsychotric treatment are sufficiently large to have patient safety implications. Results are consistent with the ADA/APA consensus statement regarding the safety profiles of atypical antipsychotics and are consistent with a previously published study using baseline CATIE study metabolic parameters to predict CHD risk.1
1. Goff DC, Sullivan LM, McEvoy JP, et al. A comparison of ten-year cardiac risk estimates in schizophrenia patients from the CATIE study and matched controls. Schizophr Res 2005 Dec 1;80(1):45-53.