Antipsychotic Trials of Intervention Effectiveness CATIE

CLINICAL ANTIPSYCHOTIC TRIALS OF INTERVENTION EFFECTIVENESS (CATIE) 

In 2005, an NIMH multisite study called CATIE compared the older neuroleptic perphenazine (Trilafon) and atypical neuroleptics olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), and zipra-sidone (Geodon Lieberman et al., 2005a see also Nasrallah, 2007 Rosenheck et al., 2006 Weiden, 2007a). Phase I involved 1,460 patients diagnosed with schizophrenia initially randomly assigned in a doubleblind study to one of the five neuroleptics. The study lasted 18 months, with safety and tolerability outcomes evaluated at 1, 3, 6, 9, 12, 15, and 18 months. 

Note that perphenazine (Trilafon) is in the middle of the pack there was no statistical difference between it and the leader, olanzapine (Zy-prexa). But Zyprexa had the worst adverse effect profile (see subsequent sections). 

The most poorly tolerated drug, quetiapine (Seroquel), is the most commonly used in the United States and brings in the greatest revenues. Its success is a marketing triumph, not a clinical one. 

Clozapine (Clozaril) was also studied, but because of the requirements for blood testing for agranulocytosis, it was not double blind. Once again demonstrating the power of clinical bias, as the only drug that was not blinded, clozapine demonstrated some greater efficacy than the others. 

---

Lieberman JA, Stroup TS, McEvoy JP, et al. Clinical antipsychotic trials of intervention effectiveness (CATIE) investigators. Effectiveness of antipsychotic drugs in people with chronic schizophrenia. N Engl J Med 2005 353 1209-1223. 

The African-American Heart Failure Trial showed that a large number of African Americans can be recruited in sufficient numbers with enough power to show efficacy in a clinical trial. In psychiatry the large START) study of depression was made up of 24% minorities (Trivedi etal, 2006). The recently completed Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) was able to recruit enough African Americans to make up about one third of its participants (Stroup et al, 2006). 

McEvoy JP, Meyer JM, Goff DC, et al. Prevalence of the metabolic syndrome in patients with schizophrenia baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophr Res 2005 80 19-32. 

Changes in the 10-year risk of coronary heart disease have been compared between treatment groups in 1125 patients followed for 18 months or until treatment discontinuation in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) in schizophrenia [22 ]. The mean change in 10-year coronary heart disease risk differed significantly between treatments. Olanzapine was associated with a 0.5% increase and quetiapine with a 0.3% increase, while the risk fell in patients who used perphenazine (-0.5%), risperidone (—0.6%), and ziprasidone (—0.6%). The difference in 10-year coronary heart disease risk between olanzapine and risperidone was statistically significant. 

Miller DD, Caroff SN, Davis SM, Rosenheck RA, McEvoy JP, Saltz BL, Riggio S, Chakos MH, Swartz MS, Keefe RS, Stroup TS, Lieberman JA. Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Extrapyramidal side-effects of antipsychotics in a randomised trial. Br J Psychiatry 2008 193(4) 279 8. 

CATIE Clinical antipsychotic trial of intervention effectiveness... 

The CATIE project will evaluate the clinical effectiveness of atypical antipsychotics in the treatment of schizophrenia and of Alzheimer s disease. Although antipsychotics were first introduced for the treatment of schizophrenia, they are now used for many other disorders. It is unclear how effective they are and, most important, in view of their rather high cost, how favorably they compare to the first generation of antipsychotics, all of which are available in generic (and thus much less expensive) forms. The CATIE (Clinical Antipsychotic Trials in Intervention Effectiveness) study has specific aims, including the determination of long-term effectiveness and tolerability of the atypical antipsychotics, compared to each and to a typical or classic antipsychotic. At this... 

---