Influence of atypical neuroleptics on executive functioning in patients with schizophrenia: a randomized, double-blind comparison of olanzapine vs. clozapine.

Accepted clinical evidence suggests superior efficacy of novel antipsychotics in the treatment of cognitive symptoms in schizophrenia. Whether this constitutes a primary drug effect or a secondary effect due to easing extrapyramidal side-effects or improving positive symptoms when converting from a first- to a second-generation neuroleptic is still open to debate. Long-term efficacy as well as differential drug effects on cognitive performance are also poorly documented. We therefore compared cognitive performance of olanzapine vs. clozapine treatment in a controlled, randomized, double-blind trial. Fifty-four patients were assessed following a 2- to 9-day washout and again after 4 and 26 wk of neuroleptic treatment. Patients were rated on the PANSS for psychopathological changes, extrapyramidal side-effects were assessed on the Simpson-Angus Scale, and cognitive performance was assessed with the Stroop, Wisconsin Card Sorting and the Tower of London tests. Schizophrenia symptoms, extrapyramidal side-effects and cognitive performance improved significantly in the course of either drug treatment. Stroop test performance and Tower of London planning time improved significantly over 26 wk compared to baseline and 4-wk follow-up assessment while Wisconsin Card Sorting and Tower of London execution time improved significantly after 4 wk with no further improvement after 26 wk. Improved executive function was not related to improving positive symptoms and easing extrapyramidal side-effects, thus indicative of a primary treatment effect of either antipsychotic. However, Stroop reaction time improved with olanzapine while clozapine had a stronger effect on improving negative symptoms, thus suggestive of a differential drug effect.