Several studies have already examined the differential effects of first-generation agents (FGAs) and second-generation antipsychotic medications (SGAs) on employment. The data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial provided an opportunity to prospectively examine the differential effect of FGAs and SGAs on employment outcomes. This chapter describes the results from Phase 1 of CATIE that examined the relationship between assignment to five different antipsychotic medications and two outcomes: employment and participation in psychiatric rehabilitation. It examines participation in psychiatric or psychosocial rehabilitation (PSR), which includes participation in vocational rehabilitation. The chapter analyzes the bivariate and multivariate relationships between potential baseline predictors with both employment measures and participation in PSR. Employment in the competitive economy is a primary goal of recovery-oriented behavioral health services. The chapter suggests that SGAs are no more likely to facilitate achievement of that goal than FGAs.

This chapter reviews findings from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study as it compares the effects of olanzapine, perphenazine, quetiapine, risperidone, and ziprasidone on psychosocial functioning as measured on the Quality of Life Scale (QLS). In assessing psychosocial functioning, it was hypothesized that improvement would be different among treatments. The CATIE study was initiated by the National Institute of Mental Health (NIMH) to determine the effectiveness of antipsychotic drugs. For the Psychosocial Functioning Study presented in this chapter, we hypothesized that there would be differences among olanzapine, perphenazine, quetiapine, risperidone, and ziprasidone in improvement in psychosocial functioning as measured by the QLS total scale. The QLS is a clinician-rated scale of social functioning, interpersonal relationships, and psychological well-being, originally developed to measure schizophrenic deficit syndrome. Many diverse approaches to evaluate psychosocial functioning and quality of life for individuals with schizophrenia make comparisons across schizophrenia studies difficult.

This chapter summarizes the features of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial that are relevant to interpretation of extrapyramidal side effects (EPS) findings. CATIE was designed to address the overall effectiveness of second-generation antipsychotic (SGA) versus a mid-potency first-generation antipsychotic drugs (FGA), perphenazine, based on treatment discontinuation. Using measures of dystonia, Parkinsonism, akathisia, and tardive dyskinesia (TD), the analysis of incidence rates and continuous measures from CATIE shows no substantial or statistically significant differences between modest doses of the intermediate potency FGA perphenazine and four SGAs in patients with chronic schizophrenia requiring maintenance antipsychotic treatment. The conclusion that must be drawn from the CATIE study is that there were no significant differences in primary outcome measures of acute EPS and TD overall, while at the same time perphenazine was shown to be not different in overall effectiveness compared with olanzapine, risperidone, quetiapine, and ziprasidone.

This chapter describes the development of the study designed to assess the effectiveness of antipsychotic drugs for persons with chronic schizophrenia. The protocol was developed by a team of academic investigators through an inclusive, iterative, and systematic process. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) program was designed to address a discrepancy between research demonstrating the efficacy of antipsychotic drugs and disappointing findings regarding their effectiveness and the ostensible superiority of second-generation antipsychotic (SGA) medications relative to first-generation antipsychotic drugs (FGA) medications. Some of the key study design decisions made by the Schizophrenia Protocol Development Committee, with input from various stakeholder groups, and their rationales are reviewed in this chapter. The study design was that of a practical clinical trial intended to evaluate the effectiveness of treatments in everyday settings to generate results intended to inform clinicians, administrators, policy makers, and patients.

Multiple factors contribute to high levels of cardiovascular (CV) risk in schizophrenia patients including lifestyle habits. The additive CV effects of cigarette smoking, hypertension, total cholesterol, and high density lipoprotein (HDL) cholesterol have been found to predict the risk of major cardiac events over a 10 year period. These effects can be calculated with empirically derived CV risk algorithms. By the time the initial Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) analysis of metabolic syndrome prevalence was performed in 2005, there was already a signal that schizophrenia patients had 2-4 times higher prevalence than that expected from general population estimates. The CATIE schizophrenia trial data illustrate the possibility for improving metabolic health by switching patients from more offending medications, and for avoiding long-term CV consequences by preferential use of agents with metabolically benign profiles. Management of schizophrenia requires acknowledgment that CV disease remains a primary cause of excess mortality.

The CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) schizophrenia study sought to compare the effectiveness and cost-effectiveness of four second-generation antipsychotics and one first-generation antipsychotic in the treatment of schizophrenia. This study design posed several challenges for statistical analysis. The authors describe the stratified Phase 1/1A randomization, and explain the steps for comparing treatment groups within the stratified randomization structure. They describe strategies to perform treatment group comparisons that control the inflation of Type 1 error due to multiple pair-wise testing, and focus on the evaluation of multiple outcomes. The authors examine the advantages of using all-cause treatment discontinuation as the primary effectiveness outcome and the specific statistical issues for its analysis, and address the impact of missing data due to phase discontinuation on analysis of the secondary outcomes. The authors contrast the statistical methods employed to address this issue, and consider further methods.

Research has shown that up to 83% of friends and family members of people diagnosed with schizophrenia experience financial, emotional, and practical burdens. In their pioneering study of family psychoeducation, Falloon and colleagues found that reductions in family burden associated with family psychoeducation were associated with improvements in patient clinical status and reductions in relapse over time. The design of Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) permits investigation of the impact of random assignment to the first-generation antipsychotic perphenazine and four second-generation drugs on family outcomes over an 18-month study period. In addition, family members frequently take an active role in helping patients manage their medication and in other aspects of preventing relapse and promoting recovery. The findings of the CATIE study underscore the importance of involving family caregivers in treatment planning for their relatives with schizophrenia.