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The introduction of the new generation of antipsychotic medications for the treatment of schizophrenia has been accompanied by a growing interest in the neurocognitive effects of these drugs. The present study compared the effects of risperidone and haloperidol on secondary memory in a group of treatment-resistant schizophrenia patients. The study design included a baseline phase and two double-blind phases in which patients were randomly assigned to medication under two different dose conditions (fixed dose and flexible dose). Secondary memory was assessed at baseline, fixed-dose, and flexible-dose phases, using the California Verbal Learning Test (CVLT). Six measures were selected, which formed three factors (general verbal learning ability, retention, and learning strategy). Risperidone-treated patients showed greater improvement than haloperidol-treated patients in general verbal learning ability, a finding characterized by significant treatment effects on CVLT measures of learning acquisition, recall consistency, and recognition memory. After controlling for benztropine status, differences on the measures of learning acquisition and recall consistency remained significant, and differences in recognition memory weakened slightly (p = 0.07). No significant treatment effects were noted on retention or learning strategy. These findings suggest that risperidone may exert a facilitating effect on the acquisition of new verbal information, an effect that does not appear to be due to the activation of semantic encoding strategies.

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In this article, data are presented from Parts A and B of the Trail Making Test, which examined the effects of haloperidol vs risperidone on cognitive function in treatment-resistant scxhizophrenic patients. This report focuses on findings from the Trail Making Test. Overall, risperidone had a positive effect on Trail Making Part B performance following 4 weeks of treatment. These effects were due, at least in part, to the direct effects of risperidone. The possibility that an antipsychotic agent can enhance executive functioning through direct mechanisms, perhaps mediated by frontal cortex neurochemistry, indicates that the evaluation of antipsychotic medications in the treatment of schizophrenia should be expanded to include cognition.