The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) was an important study in mental health, focusing on the treatment of schizophrenia. This large-scale, nationwide clinical trial aimed to provide comprehensive data on antipsychotic medications. It represented an effort to understand the real-world effectiveness of treatments for a complex mental health condition.
Understanding the CATIE Trial
The CATIE trial emerged from a need for comparative effectiveness research concerning antipsychotic medications. Before this study, much of the available information on newer antipsychotics came from trials primarily sponsored by drug manufacturers.
The trial’s main goal was to compare the effectiveness and side effects of different antipsychotic drugs used for schizophrenia. The National Institute of Mental Health (NIMH) provided funding for this extensive public health-focused clinical trial.
Trial Design and Medications Studied
The CATIE trial employed a multi-phase, randomized, controlled, and double-blind design across 57 clinical sites in the United States. This rigorous methodology helped ensure objective results by preventing both patients and researchers from knowing which medication was being administered. The study enrolled 1,460 patients, aged 18 to 65, who had a diagnosis of schizophrenia and were able to take oral antipsychotic medication.
In its first phase, participants were randomly assigned to one of five treatment groups. These included four newer, second-generation antipsychotics: olanzapine, quetiapine, risperidone, and ziprasidone. The trial also included an older, first-generation antipsychotic, perphenazine. Patients with tardive dyskinesia, a movement disorder, were excluded from receiving perphenazine in phase 1A.
The study defined “effectiveness” broadly, encompassing not only a reduction in symptoms but also patient tolerability and continuation in treatment. Patients were followed for up to 18 months, or until they discontinued treatment for any reason. This long follow-up period aimed to capture real-world outcomes, including reasons for stopping medication such as lack of effectiveness or intolerable side effects.
Key Findings and Clinical Implications
The CATIE trial yielded several findings, challenging some prevailing assumptions about antipsychotic medications. For many patients, there was no significant difference in overall effectiveness among most of the second-generation antipsychotics and the first-generation antipsychotic perphenazine in Phase 1. Olanzapine, however, showed a longer time to treatment discontinuation compared to quetiapine and risperidone, with similar trends against perphenazine and ziprasidone, though these latter comparisons did not meet strict statistical significance after adjustment.
While overall effectiveness was similar for many drugs, distinct differences emerged in side effect profiles. Olanzapine, despite its longer time to discontinuation, was associated with significant metabolic concerns, including weight gain, hyperlipidemia, and hyperglycemia. Conversely, ziprasidone was linked to weight loss and improvements in lipid and blood glucose levels. Perphenazine, a first-generation drug, exhibited comparable overall effectiveness to quetiapine, risperidone, and ziprasidone, and was found to be the most cost-effective option.
A high rate of “all-cause discontinuation” was found, with approximately 74% of patients stopping their assigned medication before completing 18 months, and a median discontinuation time of about six months. This measure combined both efficacy and tolerability into a single indicator of overall effectiveness, reflecting real-world patient and clinician decisions to switch medications. Discontinuation due to intolerability was relatively rare, occurring in about 7% of cases overall.
The trial’s findings have had a lasting impact on clinical practice, emphasizing the importance of individualized treatment. Clinicians now consider not only the effectiveness of a drug in managing symptoms but also its specific side effect profile and patient preferences. For instance, clozapine was confirmed as the most effective option for individuals whose symptoms did not respond to other antipsychotic trials, despite its troublesome adverse effects. The results underscore that a “one-size-fits-all” approach to schizophrenia treatment is not appropriate, highlighting that patient characteristics and clinical circumstances play a role in drug effectiveness.