Improvement in cognition associated with novel antipsychotic drugs: A direct drug effect or reduction of EPS?

Background: Administration of novel, versus classic, antipsychotic agents to patients suffering from psychosis is associated both with moderately better scores on cognitive tests, and with fewer extrapyramidal symptoms (EPS). Because improved motor functioning may enable better performance on some components of cognitive test batteries, and because the advantages of the novel antipsychotics on cognitive performance are not very large, it is sometimes difficult to discern if improvement in a given cognitive task is due to a direct effect of the novel antipsychotic drug, or is secondary to the novel drug's decreased propensity to induce EPS. In an attempt to distinguish between these two possibilities, the present study examined the ability of patients suffering from schizophrenia receiving classic, versus novel antipsychotics, to perform a computerized visuo-motor test (VMT). VMT assesses planning capabilities, attention and executive functions known to be impaired in schizophrenia, which are suggested to be affected by novel antipsychotics. Methods: Seventy-six patients suffering from schizophrenia or schizophreniform disorder, receiving haloperidol (23 patients, mean dose 10.01±6.1mg/day), olanzapine (26 patients, mean dose 10.56±4.9mg/day) or risperidone (27 patients, mean dose 4.35±1.7mg/day) were assessed for EPS using the parkinsonian subscale of the Extrapyramidal Symptom Rating Subscale (ESRS), and with the VMT. Results: Cognitive functioning as measured by the VMT was better for patients receiving risperidone or olanzapine, compared with those receiving haloperidol (F=6.636, df=2,67, P=0.002), while the patients receiving haloperidol or risperidone suffered from more severe EPS compared with the patients receiving olanzapine (F=3.996, df=2,71, P=0.023). Discussion: Although the patients receiving risperidone suffered from EPS similar in severity to the EPS of the patients receiving haloperidol, their performance on a task involving visuo-motor and attentional skills was similar to that of the patients receiving olanzapine. This finding implies that there is a dissociation between the antipsychotic drug's ability to affect cognitive functioning, and EPS. This dissociation indirectly suggests that the advantages offered by novel antipsychotics on cognitive performance are a direct effect, rather than being entirely mediated by improved movement abilities. Copyright (C) 2000 Elsevier Science B.V.