The effects of olanzapine on neurocognitive functioning in medication-refractory schizophrenia

Neurocognitive deficits are an enduring characteristic of schizophrenia, an d remain prominent in patients whose positive symptoms have decreased after treatment with typical neuroleptics. Recent research has reported that ola nzapine improves cognitive functioning in relapsing schizophrenia followed in an outpatient setting. Whether olanzapine will have an effect on improvi ng cognitive function in chronic schizophrenics who have been hospitalized for long periods of time, and have shown a poor response to other conventio nal and atypical neuroleptics, has not been established. This study investi gated cognitive function in chronic medication refractory schizophrenics wh o were treated with olanzapine or haloperidol in a double-blind study for 8 wk, and followed in an open olanzapine study for several additional months . Patients were evaluated with psychopathology rating scales and a battery of neuropsychological tests at baseline, end of double-blind and end of ope n-label phases of the study. At the end of the double-blind phase there wer e no significant differences between olanzapine and haloperidol, except for a trend for improvement on the Wisconsin Card Sort Test on olanzapine, whi ch was significant at traditional but not corrected significance levels. Af ter an additional 3 months of treatment with olanzapine doses of 20-40 mg/d , our statistical analysis showed significant improvement on overall neurop sychological test performance and specific cognitive tasks assessing verbal memory. However, these open-label results are difficult to interpret defin itively because of the lack of a comparison drug group and the olanzapine d ose escalation over time. Neurocognitive changes were not correlated with c hanges in psychopathology as assessed by PANSS or SANS scores.