A randomized double-blind comparison of ziprasidone vs. clozapine for cognition in patients with schizophrenia selected for resistance or intolerance to previous treatment

Background: Recent data have suggested few differences in the cognitive effects of antipsychotic medications. However, assessment of such effects can be complex, due to a number of factors. Clozapine has previously shown greater clinical and lesser cognitive benefits than other atypicals. This study compared the cognitive benefits of clozapine and ziprasidone in schizophrenia patients (n = 130) with a history of either failure to respond to or intolerance of previous adequate antipsychotic treatments. Methods: Patients were randomized (double-blind) to either clozapine or ziprasidone in a single country (Italy), multi-site trial. The cognitive assessments examined episodic memory (RAVLT), executive functioning (Stroop test), and processing speed (Trail-making test (TMT) Parts A and B). Results: Analyses found statistically significant within-group improvements for ziprasidone in learning and delayed recall on the RAVLT and on TMT Parts A and B. Clozapine-treated patients improved on the RAVLT, but not on the TMT. A composite cognitive score improved from baseline in both groups, but the improvements were significantly larger in the ziprasidone group (p = .029). Implications: These results indicated that cognitive functioning improved following treatment with ziprasidone in patients with a history of either treatment resistance or intolerance, and that the effects are comparable or greater than those observed with clozapine. One interpretation of these findings is that clozapine treatment interferes with the performance benefits associated with practice.