A direct comparison of typical and atypical antipsychotic agents shows that the drugs are comparably effective but associated with high discontinuation rates due to side effects or failure to adequately control symptoms, according to an article in the September 22 issue of the New England Journal of Medicine.

The atypical agent olanzapine was slightly more effective than the other drugs but also was associated with significant weight gain and metabolic changes. Surprisingly, the older, less expensive typical psychotic perphenazine generally performed as well as the newer agents. The study included more than 1,400 patients.

"The study has vital public health implications because it provides doctors and patients with much-needed information comparing medication treatment options," said NIMH Director Thomas R. Insel, M.D. "It is the largest, longest, and most comprehensive independent trial ever done to examine existing therapies for this disease [schizophrenia]."

The CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness)
trial directly compared perphenazine with four newer medications (olanzapine,
quetiapine, risperidone, and ziprasidone). The purpose of the study was to learn whether there are differences among the newer medications and whether the newer medications hold significant advantages over older drugs; atypical antipsychotics, cost roughly 10 times as much as the older medications.

The size and scope of the trial, with more than 1,400 participants at 57 sites around the country, its 18-month duration, and its inclusion of a wide range of patients in a variety of treatment settings ensured that the findings are reliable and relevant to the 3.2 million Americans suffering from schizophrenia.

At study onset, patients were randomized to one of the five medications. Almost 75 percent of patients switched from their first drug to a different one. The patients started on olanzapine were less likely to be hospitalized for a psychotic relapse and tended to stay on 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 study participants taking other drugs.

Contrary to expectations, movement side effects primarily associated with the older medications were not seen more frequently with perphenazine than with newer drugs. Perphenazine was as well tolerated as the newer drugs and was equally effective as all except olanzapine. 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.

Taken as a whole, the newer atypical antipsychotics have no substantial advantage
over the typical antipsychotic used in this study. An important issue still to be
considered is individual differences in patient response to these drugs.

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.

"There is considerable variation in the therapeutic and side effects of
antipsychotic medications. Doctors and patients must carefully evaluate the
tradeoffs between efficacy and side effects in choosing an appropriate
medication. What works for one person may not work for another," said
Jeffrey Lieberman, MD, CATIE's Principal Investigator and Chair of The
Department of Psychiatry, Columbia University and Director of the New York
State Psychiatric Institute.