Study on choosing Ziprasidone or Clozapine for Treating Schizophrenia

A study called CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) was conducted by NIMH to find the affects of using ziprasidone or clozapine on patients of Schizophrenia. The study was conducted in two phases which are defined as below:

Two different treatment pathways were available to the participants who stopped medication for any reason during phase 1 yet wanted to continue with the study. Participants in phase 2 collaborated with their doctors to determine the pathway that was best for them.

The efficacy pathway was designed for participants who discontinued their phase 1 medication because of inadequate symptom control. This pathway examined the question: if a patient stops taking an atypical antipsychotic because it was not effective enough, what are the benefits of clozapine (Clozaril®) versus another atypical antipsychotic medication as the next treatment? The efficacy pathway compared clozapine to the other newer atypical antipsychotic medications. Participants who chose this pathway were randomly assigned to receive either clozapine or an atypical antipsychotic (olanzapine, risperidone, or quetiapine) different from the one they took in phase 1.
The tolerability pathway was designed for participants who discontinued their phase 1 medication because of side effects. This pathway examined the question: if a person with schizophrenia stops taking an atypical antipsychotic because of intolerable side effects, which medication is the best next choice? The tolerability pathway compared ziprasidone to the other atypical medications. Participants who chose this pathway were randomly assigned to receive either ziprasidone or an atypical medication different from their phase 1 medication.

Phase 1 of CATIE study

Phase 1 demonstrated that the atypical antipsychotic medicines for Schizophrenia differ considerably in their side effects. However, patients and doctors did not know whether a person who had intolerable side effects with one atypical medication might respond to and tolerate a different atypical antipsychotic medication. When the CATIE study began, ziprasidone was the newest antipsychotic and the least familiar to doctors. It was known that the side effects of ziprasidone were very different from the side effects of the other atypical antipsychotic mediations; in particular, ziprasidone was known not to cause weight gain. Therefore, it was important to test whether switching to ziprasidone versus switching to some other atypical antipsychotic medication would be beneficial to participants who stopped taking their first antipsychotic medication due to side effects.

Phase 2 - Participants assigned to the two treatment pathways

Participants who discontinued their first antipsychotic medication because of inadequate management of symptoms were encouraged to enter the efficacy (clozapine) pathway, while participants who discontinued their first treatment because of intolerable side effects were encouraged to enter the tolerability (ziprasidone) pathway. However, participants were free to choose either pathway regardless of the reason for discontinuing their initial treatment. This freedom to choose mimics real-world practice where patients might or might not accept a doctor's recommendation of one treatment over another.

Of the 1,052 participants who discontinued phase 1 treatment before 18 months, 509 left the study entirely, 99 participants entered the efficacy (clozapine) pathway, and 444 entered the tolerability pathway. Most of the 99 participants who entered the efficacy pathway (86 percent) had stopped their phase 1 medication because of inadequate symptom management; very few participants who stopped due to side effects chose the efficacy pathway.

There were 184 participants who stopped their phase 1 medication because of inadequate symptom control who did not enter the efficacy pathway but instead entered the tolerability pathway, presumably because they were reluctant to try clozapine. Thus, the 444 participants in the tolerability pathway included a mix of participants: 41 percent discontinued their first treatment due to lack of efficacy, 38 percent discontinued due to intolerable side effects, and 21 percent discontinued for other reasons.

Schizophrenia Treatment Study
Schizophrenia Treatment Study Results
Clozapin Side Effects