Executive Function Predicts Response to Antiaggression Treatment in Schizophrenia: A Randomized Controlled Trial

Objective: Despite extensive experience with antipsychotic medications, we have limited capacity to predict which patients will benefit from which medications and for what symptoms. Such prediction is of particular importance for the proper treatment of violence. Our goal was to determine whether executive function predicts outcome of treatment for aggressive behavior and whether such prediction varies across medication groups.

Method: Ninety-nine physically aggressive inpatients (aged 18-60 years) with schizophrenia or schizoaffective disorder (diagnosed according to DSM-IV) who completed tests of executive function were randomly assigned in a double-blind, parallel-group, 12-week trial to clozapine (n = 32), olanzapine (n = 32), or haloperidol (n = 35). The number and severity of aggressive events as measured by the Modified Overt Aggression Scale (MOAS) were the outcome measures. Psychopathology and medication side effects were also assessed. The study was conducted from 1999 to 2004.

Results: Poor executive function predicted higher levels of aggression, as measured by MOAS scores over the 12-week period, in all 3 medication groups (F1,98 = 222.2, P < .0001). There was, however, a significant interaction effect between medication grouping and executive function (F1,98 = 15.32, P < .001): clozapine exerted an antiaggression effect even in the presence of executive dysfunction.

Conclusions: Executive function was a strong predictor of response to antiaggression treatment in all medication groups, but clozapine still retained clinical efficacy in the presence of poor executive functioning. Olanzapine was particularly efficacious in the absence of executive dysfunction. These findings have important implications for a targeted approach to the treatment of aggression in patients with schizophrenia.

Trial Registration: clinicaltrials.gov Identifier: NCT01123408

J Clin Psychiatry 2012; 73(1):’ ‹81-86

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