Clozapine and Olanzapine Treatment of Aggression

• Psychiatric Symptoms [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  Psychiatric symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) weekly for the first 4 weeks and then bi-weekly for the remainder of the study
• Side effects of medications [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  The side effects of the medications were measured with the ESRS on a weekly basis for the duration of the study

This was a double-blind randomized study with three treatment arms: clozapine, olanzapine and haloperidol. We compared these three medications in the treatment of aggressive behavior over a 12 week period.

Objective: The purpose of our study was the investigation of the effect of atypical antipsychotic agents on interpersonal violence and aggression.

We compared the efficacy of two atypical antipsychotic agents, clozapine and olanzapine with one another and with haloperidol in the treatment of physical assaults and other assaultive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder.

Method: The subjects were 110 physically assaultive inpatients diagnosed with schizophrenia or schizoaffective disorder.

They were randomly assigned to treatment with clozapine (N=37), olanzapine (N=37) or haloperidol (N=36) in a 12-week, double-blind trial. Incidents of overt aggression were recorded and their severity was scored with the Modified Overt Aggression Scale (MOAS). Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS). We also assessed various side effects and monitored vital signs and drew bloods.

• Drug: Clozapine
  500 mg/day
  Other Name: clozaryl
• Drug: Olanzapine
  20 mg/day
  Other Name: zyprexa
• Drug: Haloperidol
  20 mg/day
  Other Name: Haldol

• Experimental: clozapine
  During the first 6 weeks clozapine was gradually increased to 500 mg/day and then continued. For the next period, it could vary from 200-800 mg/day;
  Intervention: Drug: Clozapine
• Experimental: Olanzapine
  During the first 6 weeks olanzapine was increased to 20 mg and remained fixed for until the end of six week. During the last 6 weeks olanzapine could vary from 10 to 30 mg/day
  Intervention: Drug: Olanzapine
• Active Comparator: Haloperidol
  During the first 6 weeks haloperidol was increased to 20 mg and remained fixed for until the end of six week. During the last 6 weeks the dose could vary from 10 to 30 mg/day
  Intervention: Drug: Haloperidol

• Krakowski MI, Czobor P, Citrome L, Bark N, Cooper TB. Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder. Arch Gen Psychiatry. 2006 Jun;63(6):622-9.
• Krakowski MI, Czobor P, Nolan KA. Atypical antipsychotics, neurocognitive deficits, and aggression in schizophrenic patients. J Clin Psychopharmacol. 2008 Oct;28(5):485-93.
• Krakowski MI, Czobor P. Executive function predicts response to antiaggression treatment in schizophrenia: a randomized controlled trial. J Clin Psychiatry. 2012 Jan;73(1):74-80. Epub 2011 Nov 29.

Inclusion Criteria:

• Age: 18 to 60 years.
• Diagnosis of schizophrenia or schizoaffective disorder.
• Aggression: One episode of physical assault directed at another person in the hospital and persistence of violence/hostility for two weeks, as evidenced by the presence of some other physical, verbal or property assault or hostility, which would result in a score of 4 or more on the Positive and Negative Syndrome Scale (PANSS) Hostility Item.

Exclusion Criteria:

• Patients who were hospitalized for more than a year
• Patients who had a history of nonresponse to clozapine, olanzapine or haloperidol (defined as a lack of improvement despite a contiguous adequate trial of medication)
• Patients who had a history of clozapine, olanzapine, or haloperidol intolerance
• Patients who had medical conditions that would be adversely affected by any of these three medications.
• Patients who received a depot antipsychotic within 30 days before randomization.