CATIE study

Three subfamilies of phenothiazines, based primarily on the side chain of the molecule, were once the most widely used of the antipsychotic agents. Aliphatic derivatives (eg, chlorpromazine ) and piperidine derivatives (eg, thioridazine ) are the least potent. These drugs produce more sedation and weight gain. Piperazine derivatives are more potent (effective in lower doses) but not necessarily more efficacious. Perphenazine, a piperazine derivative, was the typical antipsychotic drug used in the CATIE study described in the following text. The piperazine derivatives are also more selective in their pharmacologic effects (Table 29-1). 

As previously noted in chapter 2, the NIMH CATIE study summed up, There were no statistically significant differences between the rates of... 

Nowhere are these transitions more apparent than in the design of three important studies sponsored by the National Institute of Mental Health. One—the STAR D study—is discussed in detail in Chapter 3. The other two, the CATIE study and the STEP-BD study, are reviewed briefly here as an illustration of current trends in psychiatric research. These three studies break new ground in the sense that they go beyond the concept of efficacy that is established in the industry-sponsored studies The drug is shown to be efficacious for a certain disorder, but in the real world, will physicians prescribe it and will patients take it and stay on it The answer to these questions centers on the concept of effectiveness. An effective drug is one that not only has efficacy against a certain malady but also is accepted by patients because its safety, tolerability, mode and frequency of administration, price, taste, appearance, and so on. These issues are commonly left unexamined in the classic drug trials. 

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). 

Recently, a large study in the USA (CATIE) reported that perphenazine was as effective as atypical antipsychotic drugs, with the modest exception of olanzapine, and concluded that typical antipsychotic drugs are the treatment of choice for schizophrenia based on their lower cost. However, this study did not adequately consider the risk of tardivedyskinesia or the treatment history of patients in the design of this study. 

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. 

Schneider LS, Tariot PN, Dagerman KS, Davis SM, Hsiao JK, Ismail MS, Lebowitz BD, Lyketsos CG, Ryan JM, Stroup TS, Sultzer DL, Weintraub D, Lieberman JA, for the CATIE-AD Study Group. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer s disease. N Engl J Med 2006 355 1525-38. 

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... 

Tsai HT, Caroff SN, Miller DD, McEvoy J, Lieberman JA, North KE et al (2010) A candidate gene study of tardive dyskinesia in the CATIE schizophrenia trial. Am J Med Genet B Neuropsychiatr Genet 153B 336-340... 

Despite these limitations, the authors managed to establish some dialogue with Polish companies regarding the social capital of their supply chains. Questions regarding social capital were included in a questionnaire used in the second stage of the fundamental study -the final study (see Introduction). The questions regarding the supply chain s social capital were used both in the questionnaire drawn up for the purposes of the computer-assisted telephone interview (CATI) and in the questionnaire prepared for the face-to-face interview. 

Fournier, C., B. Hecquet, P. Bouffard, M. Vert, A. Caty, M. O. Vilain, L. Vanseymortier, S. Merle, A. Krikorian, J. L. Lefebvre and et al., 1991, Experimental studies and preliminary clinical trial of vinorelbine- loaded polymeric bioresorbable implants for the local treatment of solid tumors. Cancer Res 51 5384-5391. 

Daumit GL, Goff DC, Meyer JM, Davis VG, Nasrallah HA, McEvoy JP, Rosenheck R, Davis SM, Hsiao JK, Stroup TS, Lieberman JA. Antipsychotic effects on estimated 10-year coronary heart disease risk in the CATIE Schizophrenia Study. Schizophr Res 2008 105(1-3) 175-87. 

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