USPSYCH: Newer Antipsychotics Not Always Better

NEW ORLEANS, Nov. 22 -- The newer atypical antipsychotic drugs may not always outperform the old ones in managing schizophrenia, investigators said here.

That's what the results of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study suggested, said Rajiv Tandon, M.D., of the University of Florida in Tallahassee.

Dr. Tandon discussed the CATIE trial and its results at a symposium held in conjunction with the U.S. Psychiatric & Mental Health Congress here. The symposium was sponsored by Janssen pharmaceuticals of Titusville, N.J.

In CATIE, nearly 1,500 patients with schizophrenia (ages 18 to 65) were recruited at 57 sites in the U.S. Participants were randomly assigned to Zyprexa (olanzapine) at 7.5 to 30 mg per day, Triavil (perphenazine) at 8 to 32 mg per day, Seroquel (quetiapine) at 200 to 800 mg per day, Risperdal (risperidone) at 1.5 to 6 mg per day, or Geodon (ziprasidone) at 40 to 160 mg per day.

Triavil is an older, typical antipsychotic developed in the mid-1950s. This class of drugs is associated with extrapyramidal side effects, Dr. Tandon noted.

Follow-up in CATIE was 18 months. Endpoints included time to discontinuation of a particular drug as well as efficacy measures. Discontinuation of antipsychotic medications is common because they don't work in all patients and because of adverse effects, including metabolic side effects, extrapyramidal side effects, and weight gain, Dr. Tandon said.

Overall, 74% of patients discontinued their study medication and switched to a new medication before 18 months, including:

•49% of those assigned to Zyprexa.
•55% of those assigned to Risperdal.
•65% of those assigned to Seroquel.
•70% of those assigned to Geodon and Triavil.

The time to discontinuation of treatment for any cause was significantly longer in the Zyprexa group than in the Seroquel (P<0.001) or Risperdal (P=0.002) group, but not in the Triavil (P=0.021) or Geodon (P=0.028) group.

The times to discontinuation because of intolerable side effects were similar among the groups. However, Zyprexa was associated with more discontinuation for weight gain or metabolic effects, and Triavil was associated with more discontinuation for extrapyramidal effects.

Zxprexa was the most effective drug in terms of the rates of discontinuation, but it was the "worst offender" in terms of metabolic side effects, Dr. Tandon said.

Furthermore, the efficacy of the typical antipsychotic Triavil appeared similar to that of Seroquel, Risperdal, and Geodon in patients at low risk for extrapyramidal side effects, he said.

The CATIE study suggests that in schizophrenic patients with a low risk for extrapyramidal side effects, typical antipsychotics may work as well as the atypical "if you can get the dosing just right," Dr. Tandon said.

Individual dosing is the key because there is considerable variation in how patients respond to differing doses of antipsychotic drugs and in patients' susceptibility to their side effects, Dr. Tandon said.

Successfully managing schizophrenia is crucial because the disease is such a heavy burden not only on individuals but on the healthcare system, said Jacqueline M. Feldman, M.D., of the University of Alabama at Birmingham, a second speaker at the symposium.

Half of all mental hospital beds are filled by patients with schizophrenia, Dr. Feldman said. And about 16% of all patients getting healthcare services have schizophrenia, she added.

Half of schizophrenia patients attempt suicide at some point during their lives, and 10% of them succeed. Finally, one-third to two-thirds of the homeless in the United States have schizophrenia, Dr. Feldman said.

Both Dr Tandon and Dr. Feldman are members of the speakers bureau for Janssen, the sponsor of the symposium, and have financial relationships with Pfizer, AstraZeneca, and Bristol-Meyers Squibb as well.