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Background: Difficulties with affect regulation and impulse control have a strong influence on violence. The objective of this study was to determine whether baseline depression and impulsivity predict aggression and whether they predict differential response to antiaggressive treatment. This is important, as we lack knowledge as to the selection of antipsychotics for the treatment of aggression., Methods: Physically aggressive inpatients with schizophrenia who received an evaluation of depression and impulsivity at baseline were randomly assigned in a double-blind, parallel group, 12-week trial to clozapine, olanzapine, or haloperidol. Trait impulsivity was measured by the Barratt Impulsiveness Scale; depression by the Positive and Negative Syndrome Scale Depression factor. The number and severity of aggressive events, as measured by the Modified Overt Aggression Scale (MOAS), were the outcome measures., Results: Baseline depression and impulsivity predicted higher levels of aggression, as measured by the MOAS total score, over the 12-week treatment period across all 3 medication groups. In addition, there was a strong interaction effect between baseline depression/impulsivity and medication grouping in predicting MOAS score. In particular, when higher depression and impulsivity were present at baseline, patients on haloperidol presented with more aggression than patients on the other 3 medications., Conclusions: Depression and impulsivity are important predictors of aggression and of differential response to antiaggressive treatment. This is most likely due to the medications' dissimilar neurotransmitter profiles. By identifying patients who will respond better to a given medication, we will be able to develop individualized strategies for the treatment of violent behavior., (© The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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 (F(1,98) = 222.2, P < .0001). There was, however, a significant interaction effect between medication grouping and executive function (F(1,98) = 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., (© Copyright 2012 Physicians Postgraduate Press, Inc.)

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.

Context: Violent behavior of patients with schizophrenia prolongs hospital stay and interferes with their integration into the community. Finding appropriate treatment of violent behaviors is of primary importance., Objective: To compare the efficacy of 2 atypical antipsychotic agents, clozapine and olanzapine, with one another and with haloperidol in the treatment of physical assaults and other aggressive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder., Design and Setting: Randomized, double-blind, parallel-group, 12-week trial. Physically assaultive subjects with schizophrenia or schizoaffective disorder who were inpatients in state psychiatric facilities were randomly assigned to treatment with clozapine (n = 37), olanzapine (n = 37), or haloperidol (n = 36)., Main Outcome Measures: Number and severity of physical assaults as measured by the Modified Overt Aggression Scale (MOAS) physical aggression score and the number and severity of all aggressive events as measured by the MOAS overall score. Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS)., Results: Clozapine was superior to both olanzapine and haloperidol in reducing the number and severity of physical assaults as assessed by the MOAS physical aggression score and in reducing overall aggression as measured by the MOAS total score. Olanzapine was superior to haloperidol in reducing the number and severity of aggressive incidents on these 2 MOAS measures. There were no significant differences among the 3 medication groups in improvement of psychiatric symptoms as measured by the PANSS total score and the 3 PANSS subscales., Conclusions: Clozapine shows greater efficacy than olanzapine and olanzapine greater efficacy than haloperidol in reducing aggressive behavior. This antiaggressive effect appears to be separate from the antipsychotic and sedative action of these medications.

Objective: High doses of neuroleptic medication are still administered to many patients, although many studies have shown the effectiveness of low-dose strategies. The purposes of the study were to determine whether and in what ways high-dose patients differed from patients on regular dosages and whether the higher dosages were more effective., Methods: In a case-control study at two large state hospitals, 38 high-dose patients were compared with 29 regular-dose patients., Results: The high-dose patients had a persistent course of illness, with severe chronic symptoms resulting in hospitalizations of much longer duration than those of the regular-dose patients. The high-dose patients evidenced more regressed functioning and were more violent. To control these behaviors, clinicians increased neuroleptic dosages., Conclusions: The high-dose patients represented a subgroup of chronic regressed and violent patients. Clinicians prescribed high dosages and continued to use them despite a lack of clear evidence that such treatment is effective.