Cognitive Benefits Differ Among Newer Antipsychotics

Ziprasidone (Geodon) is the latest second-generation antipsychotic to be associated with differential cognitive benefits, according to new research.

The research is the latest addition to a growing evidence base that supports the widely held clinical observation that the six second-generation medications—clozapine (Clozaril), risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), aripiprazole (Abilify), and ziprasidone (Geodon) are quite different, in spite of being similar in many ways.

Olanzapine and risperidone were previously shown in studies sponsored by the National Institute of Mental Health to elicit drug-specific effects on different cognitive domains.

“The take-home message here is that although these drugs on average appear to be pretty much the same, if you have a patient who is not doing well on one drug, the current evidence suggests that the patient should be tried on another [second-generation] drug,” said Phillip Harvey, Ph.D., a professor of psychiatry at Mt. Sinai School of Medicine and the first author on the new report.

The study, funded by Pfizer (which markets the Geodon brand of ziprasidone), appeared in the February issue of Schizophrenia Research.

Harvey and his colleagues followed 270 stable outpatients who had schizophrenia or schizoaffective disorder and were switched to ziprasidone either from conventional antipsychotics (108), olanzapine (104), or risperidone (58) because of lack of response or intolerable side effects.

Patients were started on ziprasidone 40 mg twice a day for two days, then continued on flexible dosing between 20 mg and 80 mg twice a day for 40 days. Their previous antipsychotic medication was discontinued or tapered within seven days. Anticholinergics and benzodiazepines were allowed as needed; however, they were prohibited in the 12 hours prior to cognitive testing.

Cognitive functions were assessed at baseline, at week six (or at early termination), and at the end of the study. Patients were rated on the Positive and Negative Syndrome Scale weekly, and a battery of standardized assessments was used to evaluate cognitive functioning in five domains: learning and memory, attention and vigilance, visuomotor speed, executive function, and verbal fluency.

Impairment Differed by Drug

“If you look at the baseline assessments,” Harvey told Psychiatric News, “either in cognitive impairment or clinical symptoms, you can see that the risperidone and conventional-drug patients were much more clinically impaired at the time of the switch, compared to those switched from olanzapine.” Patients taking olanzapine at baseline, however, had significantly higher body weight and body-mass index.

“Patients switched from conventionals or risperidone were more likely to improve cognitively than the olanzapine patients were,” Harvey said. “And it was sort of predictable.” Patients switched from conventionals improved in motor speed, while those switched from risperidone or olanzapine to ziprasidone did not. Patients who switched from risperidone improved more cognitively than did those who were switched from olanzapine. However, Harvey noted, they were more impaired to begin with and they were more likely to be switched because they were not responding adequately to risperidone, rather than because of intolerable side effects.

Memory, Learning Improved

The largest improvements were seen in tests of secondary learning and memory, where all three groups switching to ziprasidone had clinically significant changes. Improvements of 16 percent, 19 percent, and 21 percent were seen in patients switched from conventional drugs, olanzapine, and risperidone, respectively.

Smaller improvements were seen in attention and vigilance testing in patients switched from conventional antipsychotics (8 percent improvement) and risperidone (6 percent) but not those switched from olanzapine. No significant improvements were seen in visuomotor speed in any of the three groups.

Harvey noted that the standard deviations on the change scores were nearly as large as the changes themselves. “So what that means is that for every patient who improved by 20 percent, there was another patient who improved by 40 percent,” Harvey explained. Some patients, of course, saw much smaller levels of improvement.

“So for some of the patients, that certainly is a substantial improvement and likely to be clinically meaningful,” he said. “You might suggest that patients who have a good clinical response also have a good cognitive response, even though the two are not necessarily correlated one to one with each other.”

Harvey agreed that the study adds to the evidence base showing significant differences between the second-generation antipsychotics, but noted that “the larger the study, the less likely it is that you will find an overall benefit of one drug versus another. However, that doesn’t bear on the fact that for each person, there might be a different best drug. Indeed, on average, there being no difference actually tells you that there can’t possibly be a best drug for everyone. That’s a very important point.”

An abstract of “Improvement in Cognitive Function Following a Switch to Ziprasidone From Conventional Antipsychotics, Olanzapine, or Risperidone in Outpatients With Schizophrenia,” is posted online under the February issue at www.sciencedirect.com/science/journal/09209964. ▪