What to Make of CATIE: Are We Better Off With Atypical Antipsychotics?

 

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Educational Objectives

After reading this article, you will be familiar with:

• The different arms of the CATIE study
• The use of number needed to treat and number needed to harm in appraising the clinical relevance of study results
• CATIE efficacy, tolerability, and safety results for the atypical antipsychotics as well as the representative typical antipsychotic, perphenazine
• The advantages/disadvantages of one antipsychotic over another

Who will benefit from reading this article?
Psychiatrists, child and adolescent psychiatrists, psychologists, primary care physicians, nurse practitioners, and other health care professionals. To determine whether this article meets the continuing education requirements of your specialty, please contact your state licensing and certification boards.

Efficacy variations among the atypical and typical antipsychotics result in overlaps between the 2 groups.¹ Adverse-effect profiles differ as well. In general, typical antipsychotics have a greater propensity to cause extrapyramidal side effects, tardive dyskinesia, and prolactin elevations than do atypical anti-psychotics. The adverse effects associated with some atypical antipsychotics are more weight gain and greater disturbances in lipid and glucose regulation than are associated with typical antipsychotics. However, there is considerable heterogeneity among the individual agents in both classes and overlapping adverse effects.

According to Sackett and colleagues,² the philosophy of evidence-based medicine requires the thoughtful clinician to incorporate the best available research findings into an individualized treatment plan, and to take into account clinical experience and patient preferences. When selecting antipsychotics for patients with schizophrenia, the prescribing physician can approach this decision-making process using these principles of evidence-based medicine.

On the basis of the results from the NIMH-funded Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), this article reviews the principles of antipsychotic therapy selection based on individual patient profiles as it pertains to perphenazine (the representative typical anti-psychotic in the CATIE study), olanzapine, risperidone, quetiapine, ziprasidone, and clozapine. Using a basic tool of evidence-based medicine-effect size as measured by number needed to treat-demonstrates that we are better off having choices.

CASE VIGNETTE

Simone is a 45-year-old African American woman whose schizophrenia was diagnosed when she was 22 years old. She has had about 5 brief hospitalizations for exacerbations of her symptoms, usually precipitated by nonadherence when her medications were changed to something she did not agree with. She lives in a basement apartment owned by her family and attends a day treatment program 3 times a week. Simone smokes about 10 cigarettes a day when she is able to afford them. She does not use street drugs or alcohol. Simone has a fraternal twin, Sabella, who also has schizophrenia.

Simone responds reasonably well to quetiapine or risperidone, but not to haloperidol, and she objects to extrapyramidal side effects, particularly akathisia. Simone’s mother and all of her maternal aunts have type 2 diabetes mellitus. Her body mass index is 29 kg/m², and she eats high-fat foods and does not exercise. She is willing to take either quetiapine or risperidone and her clinician prescribes generic risperidone.

Simone presents with a number of conflicting issues, and the best medication option for Simone at this juncture is difficult to immediately ascertain. Fortunately, there are clinical trials that can help inform the clinician in making thoughtful individualized treatment decisions about antipsychotic medication switches. Simone is representative of ambulatory patients with schizophrenia who have been ill for a decade or more. Thus, she resembles the patients enrolled in the CATIE schizophrenia studies.^3-6

Approximately 1500 patients participated in at least one part of CATIE, and the study remains the largest randomized pragmatic clinical trial to date that compares the overall relative effectiveness of several of the atypical antipsychotics with each other as well as with a representative typical antipsychotic (perphenazine). Time to all-cause discontinuation was the primary outcome measure and represents the “real-world” usefulness of a medication. The assumption is that a patient will continue to use a medication (and a clinician will continue to prescribe it) if the medication is considered by all parties to be effective, safe, and tolerable.

Number needed to treat

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