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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

Outcome Measures

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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

Results and Conclusions

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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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•PHASE 2

Outcome Measures

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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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•PHASE 2

Results and Conclusions

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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

Outcome Measures

17Phase 3

(Open- Label)

Primary: Time until discontinuation for any reason

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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.