cont. from

Older Medication:

Perphenazine (Trilafon®)

Newer Medication:

Olanzapine (Zyprexa®)
Quetiapine (Seroquel®)
Risperidone (Risperdal®)
Ziprasidone (Geodon®)
(Aripiprazole [Abilify®] was not approved by the FDA in time to be included in this phase of the study.)

5. Why was perphenazine chosen as the older medication rather than haloperidol?

A: Haloperidol was one of the most widely prescribed of the older antipsychotics before the "atypical" newer antipsychotics became available in the 1990s. It remains the most frequently used comparison drug in industry-sponsored clinical trials. However, patients who take haloperidol experience high rates of movement side effects, called extrapyramidal side effects (EPS), such as rigidity and stiff movements, persistent muscle spasms, tremors, and uncontrollable restlessness. Because many individuals find EPS particularly difficult to tolerate, haloperidol is an unpopular treatment choice for many people with schizophrenia. Although EPS is associated to some degree with all the older "typical" antipsychotic medications, perphenazine is an effective older antipsychotic that is less likely to produce EPS. This made it a good choice to use as the representative of the older medications in this study.

6. How did researchers measure how well the medications worked?

A: For patients with schizophrenia, staying on medication is critical to controlling symptoms and preventing relapse. Previous studies have shown that antipsychotic treatment is far better than no treatment. Although the medications alone are not sufficient to cure the disorder, they are necessary to manage it. Thus, it is essential for doctors to find a medication that is both effective and tolerable for a patient. This is why the primary measure of treatment success in the CATIE study was how long a patient benefited from and thus stayed on a medication before they or their doctor decided that it had to be changed. Investigators also recorded why a patient stopped a medication: if the medication did not control symptoms, or if the side effects were not tolerable, or if the patient chose to stop treatment for some other reason. In addition to this primary outcome, the study also examined medication effects on the symptoms of schizophrenia, as well as other important outcomes such as overall level of function.

7. What are the most important results of the CATIE study?

A: Overall, the medications were comparably effective but were associated with high rates of discontinuation due to intolerable side effects or failure to adequately control symptoms. One new medication, olanzapine, was slightly better than the other drugs but also was associated with significant weight-gain as a side-effect. Surprisingly, the older, less expensive medication (perphenazine) used in the study generally performed as well as the four newer medications. The study supplies important new information that will help doctors and patients choose the most appropriate medication according to the patients' individual needs.

At the beginning of the study, patients were randomly assigned to receive one of the five medications. Almost three quarters of patients switched from their first medication to a different medication. The patients started on olanzapine were less likely to be hospitalized for a psychotic relapse and tended to stay on the medication longer than patients taking other medications. However, patients on olanzapine also experienced substantially more weight gain and metabolic changes associated with an increased risk of diabetes than those participants taking the other drugs.

Perphenazine (the older medication) equally as effective as the other three newer medications (risperidone, quetiapine, and ziprasidone) and was as well tolerated as the newer drugs. The three newer medications performed similarly to one another.

Contrary to expectations, movement side effects (rigidity, stiff movements, tremor, and muscle restlessness) primarily associated with the older medications were not seen more frequently with perphenazine than with the newer drugs. The advantages of olanzapine — in symptom reduction and duration of treatment — over perphenazine were modest and must be weighed against the increased side effects of olanzapine.

Several factors, such as adequacy of symptom relief, tolerability of side effects, and treatment cost, influence a person's willingness and ability to stay on medication. Patients and doctors must carefully evaluate the trade off between effectiveness, side effects, and cost in choosing an appropriate medication. Doctors must carefully monitor the physical health of their patients as well as the symptoms of psychosis.

continue: Results of CATIE Study

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Reviewed: 03/2006