Atypical antipsychotics, neurocognitive deficits, and aggression in schizophrenic patients

J Clin Psychopharmacol. 2008 Oct;28(5):485-93. doi: 10.1097/JCP.0b013e3181855cd6.


The purpose of this study was to compare the effects of olanzapine, clozapine, and haloperidol on neurocognitive function in schizophrenic patients who present with documented episodes of physical aggression and to determine whether change in cognitive function is related to aggression. One hundred physically aggressive schizophrenic inpatients were assigned to a randomized, double-blind, parallel-group, 12-week treatment, and received cognitive evaluations at baseline. There were 33, 34, and 33 subjects in the clozapine, olanzapine, and haloperidol groups, respectively. They were administered a battery of tests assessing psychomotor function, general executive function, visual and verbal memory, and visuospatial ability. A general cognitive index was derived from the above battery. The overall score on the Modified Overt Aggression Scale was used to measure the number and severity of the aggressive events. Psychiatric symptoms and side effects were also assessed. The improvement in the general cognitive index differed significantly among the 3 treatment groups, with olanzapine being superior to both haloperidol and clozapine. Further analyses revealed significantly greater improvement with olanzapine in several cognitive domains. Furthermore, improvement in the general cognitive index was significantly associated with a decrease in aggression in the olanzapine group but not in the other 2 medication groups. In violent schizophrenic patients, olanzapine treatment is associated with better cognitive functioning relative to haloperidol and clozapine. This improvement in neurocognitive function is associated with a decrease in aggressive behavior. As clozapine markedly reduced aggression, there may be different pathways for the antiaggressive effect of olanzapine and that of clozapine.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aggression / drug effects*
  • Aggression / psychology
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / pharmacology*
  • Antipsychotic Agents / therapeutic use
  • Benzodiazepines / adverse effects
  • Benzodiazepines / pharmacology
  • Benzodiazepines / therapeutic use
  • Clozapine / adverse effects
  • Clozapine / pharmacology
  • Clozapine / therapeutic use
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology
  • Double-Blind Method
  • Female
  • Haloperidol / adverse effects
  • Haloperidol / pharmacology
  • Haloperidol / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Olanzapine
  • Psychiatric Status Rating Scales
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology
  • Schizophrenic Psychology*
  • Severity of Illness Index
  • Violence / psychology


  • Antipsychotic Agents
  • Benzodiazepines
  • Clozapine
  • Haloperidol
  • Olanzapine