A new study analyzing the economic implications of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) concludes that the older (first generation) antipsychotic medication perphenazine was less expensive and no less effective than the newer (second generation) medications used in the trial during initial treatment, suggesting that older antipsychotics still have a role in treating schizophrenia. The study, published in the American Journal of Psychiatry on December 1, 2006, was funded by the National Institutes of Health’s National Institute of Mental Health (NIMH).

The $42.6 million CATIE trial aimed to help doctors and the 2.4 million Americans who suffer from chronic schizophrenia tailor treatments to individual needs. It is the first study to directly compare several second generation antipsychotic medications and a representative first generation antipsychotic medication.

“The results from CATIE should encourage doctors to reconsider the use of perphenazine as another choice for patients with schizophrenia,” said NIMH Director Thomas Insel, M.D.

More than 90 percent of antipsychotic prescriptions are written for second generation medications, despite the fact they are more expensive than the first generation agents used to treat schizophrenia. The majority of clinicians have traditionally believed that the newer antipsychotics are more effective and better tolerated than older agents, and many experts argued that these advantages justified the difference in cost.

Robert Rosenheck, M.D., of Yale University, and colleagues analyzed costs and quality-of-life factors associated with each of the five medications used in Phase 1 of the CATIE trial - olanzapine, quietapine, risperidone, ziprasidone, and perphenazine. They found that total monthly health costs, a figure that includes both average medication costs and inpatient and outpatient costs, were up to 30 percent lower for those taking the perphenazine than for those taking the second generation medications. In addition, the researchers found no statistically significant difference in overall effectiveness between perphenazine and the second generation antipsychotics, with regard to symptom relief and side effect burden.

The findings echo what was implied in the results of the first phase of CATIE, expanding the treatment options for patients with schizophrenia. It casts doubt on the notion that the second generation antipsychotics are better than the first generation antipsychotics, and suggests that perphenazine and other first generation antipsychotics may be just as beneficial for some patients.

Still, several conditions of CATIE limit any firm conclusions about perphenazine’s perceived advantages. Not all patients respond the same to different medications. In addition, the study lasted 18 months - long enough to determine how patients respond to and initially tolerate the drugs, but not long enough to consider some serious long-term side effects, such as development of the movement disorder tardive dyskinesia (TD), diabetes, cardiovascular problems, or other medical conditions that can develop even years after a patient with chronic schizophrenia starts taking an antipsychotic medication. Despite these caveats, the study results suggest new ways of thinking about medication treatments for schizophrenia.

“These results encourage doctors to revisit the older medication as an alternative, especially if a treatment change is warranted,” said Dr. Rosenheck. “By showing that perphenazine and possibly other older antipsychotics may be on equal footing with the second generation antipsychotics, CATIE has opened the door to more choice in treatment options.”

NIH/National Institute of Mental Health