Antipsychotic Medications for Schizophrenia on Equal Footing in Improving Patients’ Thinking Skills

June 4, 2007 • Science Update

Patients with schizophrenia taking antipsychotic medications experience a small improvement in thinking and reasoning skills (neurocognition), but no one medication appears to be better than the others in improving these skills during the first two crucial months of treatment, according to the latest results from the NIMH-funded Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE). The study was published in the June 2007 issue of the Archives of General Psychiatry.

Neurocognitive impairment is often a central feature of schizophrenia, and one of the disease’s most troublesome and difficult-to-treat symptoms. However, medications for schizophrenia currently do not target neurocognitive symptoms specifically.

In the CATIE trial, patients were randomly assigned to take either perphenazine—an older, first-generation antipsychotic medication—or one of several newer, second-generation medications (olanzapine, quetiapine, risperidone, or ziprazidone). Richard Keefe, PhD of Duke University, and colleagues evaluated the neurocognitive skills of 817 CATIE participants who completed an initial evaluation before the study began and, after being on the same medication for two months, underwent a second evaluation. Keefe and colleagues measured any neurocognitive change by comparing pre- and post-test results from 11 examinations designed to test an individual’s thinking, memory, reasoning and problem-solving abilities. They found a small rate of improvement among all the treatment groups, but no treatment group appeared to benefit more than the others.

The results run contrary to previous studies, and the widely held belief, that the newer, second-generation antipsychotics are better than the older medications in improving schizophrenia patients’ cognitive skills.

The researchers also retested participants remaining in the trial after six months and after 18 months. After six months, no differences among the medication groups emerged in the 523 remaining participants. After 18 months, 303 participants remained; those who had taken the older antipsychotic perphenazine for the duration of the study showed slightly more neurocognitive improvement than those taking the newer, second-generation medications. However, because so few participants remained at this point, the researchers could not conclude that perphenazine had any advantage over the other medications.

The overall neurocognitive improvement remained small among all treatment groups, and most of the improvement occurred in the early stages of treatment. “What happens during the first few months of treatment is the most important indicator of success,” said Dr. Keefe. “But the neurocognitive benefits over the long term were limited. We clearly need new treatments that will improve schizophrenia patients’ cognitive skills.”