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1
AN OVERVIEW OF THE “CATIE” TRIAL
ALBREKA HUDSON, PHARMD CANDIDATE
PRECEPTOR: SOHEYLA MAHDAVIAN, PHARMD
The Clinical Antipsychotic Trials of Intervention
Effectiveness Trial
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The CATIE Trial
A nation-wide 3-phase clinical trial
Compared the effectiveness of older and newer antipsychotic medications used to treat schizophrenia
Funded by the National Institute of Mental Health (NIMH)
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Study Participants and Sites
1,460 participants
57 clinical sites across the U.S.
Between January 2001 and December 2004 (over a span of 18 months)
Largest, longest, and most comprehensive trial ever conducted to study pharmacotherapies for schizophrenia
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Objective
To compare the effectiveness of several newer (atypical)
antipsychotic drugs and one older (conventional/typical)
antipsychotic drug for schizophrenia in real-world settings
over 18 months.
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Demographics
Male 74%
Female 26%
Caucasian 60%
African American 35%
Spanish, Hispanic, Latino 12%
Asian 2%
American Indian or Alaska Native <1%
Native Hawaiian or other Pacific Islander
<1%
“Two or more races” 2%
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Co-Morbidities and Mental Health Conditions
Depression 28%
Anxiety 14%
Drug Dependence/Abuse
29%
Diabetes 11%
Hypertension 20%
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Phase 1
Primary: Rate of treatment discontinuation for any reason
Secondary: Measures for clinical and functional outcomes, safety
and neurocognition
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Phase 1
Olanzapine was the most effective in terms of rate of discontinuation
Disadvantages: Greater weight gain Increases in measures of glucose and lipid metabolism
Efficacy of the conventional antipsychotic perphenazine appeared similar to that of the atypical antipsychotics.
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Efficacy Tolerability
Primary: Time until
discontinuation for any reason
Secondary: Time to discontinuation
for inadequate therapeutic benefit, intolerable side effects, or patient decision.
Primary: Time until
discontinuation for any reason
Secondary: Reason for treatment
discontinuation
Phase 2
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Efficacy Tolerability
Treatment with clozapine was significantly more effective than switching to another of the newer atypicals.
Olanzapine and risperidone were more effective than quetiapine and ziprasidone* as reflected by longer time until discontinuation for any reason.
Olanzapine was the most
effective medication for those patients who discontinued their previous treatment due to inefficacy, although not for those who discontinued due to intolerability.
Phase 2
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•PHASE 3
Results and Conclusions
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Phase 3
All-cause discontinuation rate of 74% at 18 months.Olanzapine better efficacy than quetiapine,
risperidone and also with other medications. More individuals discontinued olanzapine
Weight gain Increase in hemoglobin Increase in cholesterol and triglyceride leading to metabolic
syndrome
Extrapyramidal symptoms were the most common reason for discontinuation with perphenazine.
No superior efficacy of atypical over conventional antipsychotic ( Ex. perphenazine)
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Phase 3
Clozapine was the most effective compound compared with all the other antipsychotics used in this study.
Irrespective of the class of antipsychotics, there was improvement in neuro-cognitive functioning. However this effect remained significant only for two months.
Ziprasiodone was most weight neutral and did not come up with any metabolic side-effects.
In the last phase which was open label, very few patients selected conventional antipsychotics.
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A REFLECTIVE REVIEW OF THE TRIAL
Journal Critique
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Pros Cons
Phase 1 & 2, double-blinded randomized
Broad inclusion and few exclusion criteria
“Real-world” efficacy trial
Phase 3, open-label Use of only ONE
first generation antipsychotic
All-cause treatment discontinuation
Critique
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Pros Cons
Broad inclusion and few exclusion criteria
Patients representative of the “real-world”
Counseling and patient education was offered to increase medication adherence
Suboptimal dosing for quetiapine, ziprasidone, and risperidone may have resulted in “better” outcomes for olanzapine which was more optimally dosed.
Inclusion of comorbid diseases and substance abuse
Details of randomization could not be evaluated
Treatment allocation based on patient choice
Critique
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Pros Cons
Use of Kaplan-Meier (KM) Curve
Patients had to have an adequate decisional capacity
Critique
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Clinical Pearls
All antipsychotic medications are effective but have substantial limitations reflected by high discontinuation rates.
Olanzapine and clozapine best efficacy but worst side effects.
Perphenazine is surprisingly comparable to atypicals in terms of efficacy and effectiveness.
Noted differences in types and severity of side effects.
Ziprasidone has least weight gain and metabolic side effects.
What drug you should switch to depends on what treatment you have received and why you stopped it.
•The superiority of the atypicals may be most evident in the refractory end of the schizophrenia spectrum.
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References
1. Davis JM, Chen N, Glick ID. A metaanalysis of the efficacy of second-generation antipsychotics. Arch Gen Psychiatry 2003; 60:553-64.
2. Ericksen, Jennifer, Sheri A. Strite, and Craig Stern. "CATIE Trial Review of Phases 1 and 2." EBM REVIEW. June 2008. Web. 18 Jan. 2013.
3. Stroup TS, McEvoy JP, Swartz MS, et al. Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia. N Engl J Med. 2005:353:1209-23.
4. Stroup, S., J. Lieberman, J. Mcevoy, M. Swartz, S. Davis, R. Rosenheck, and R. Keefe. "Findings Of Phase 3 Of The Catie Schizophrenia Trial."Schizophrenia Research 102.1-3 (2008): 34-35.
5. Stroup TS, McEvoy JP, Swartz MS, et al. The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project: schizophrenia trial design and protocol development. Schizophr Bull 2003;29:15-31.