Neuropsychological Normalization With Long-Term Atypical Antipsychotic Treatment: Results of a Six-Month Randomized, Double-Blind Comparison of Ziprasidone vs. Olanzapine

The authors examined cognitive changes associated with treatment with ziprasidone and olanzapine over a 6-month double-blind clinical trial, using normative standards for the cognitive measures. Sixty-two schizophrenia patients entered the study on ziprasidone treatment (39 completers), and 71 patients entered while receiving treatment with olanzapine (33 completers). From a larger set of cognitive domains assessed in the acute treatment study, we selected verbal learning, executive functioning, and verbal fluency for further analysis due to their functional relevance and extensive normative data. Standard scores were developed based on previously published age- and education-corrected norms. Baseline performance was impaired across all tests on average. The proportion of patients impaired on each of the tests at baseline ranged from 36% (letter fluency) to 89%. Performance was significantly improved by ziprasidone and olanzapine treatment for all cognitive variables and for the composite measure. A number of subjects met the a priori criteria for normalization in performance, ranging from 10% for Trail Making Test Part B to 37% for Word List Total Learning. There were no significant differences across medications in extent of change or likelihood of inducing normalization. Statistically significant improvements in cognitive performance over 6 months of treatment with atypical antipsychotic medications are associated with performance increasing into the normal range of cognitive functioning in a proportion of previously impaired patients.