Clozapine and Olanzapine Treatment of Aggression

• ClinicalTrials.gov Identifier: NCT01123408
• Recruitment Status: Completed
• First Posted: May 14, 2010
• Last Update Posted: May 14, 2010
• Sponsor: Nathan Kline Institute for Psychiatric Research
• Information provided by: Nathan Kline Institute for Psychiatric Research

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Schizophrenia	Drug: Clozapine; Drug: Olanzapine; Drug: Haloperidol	Not Applicable

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 110 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Clozapine and Olanzapine in the Treatment of Violence in Schizophrenic Patients
• Study Start Date: June 1999
• Actual Primary Completion Date: July 2004
• Actual Study Completion Date: July 2004

Arms and Interventions

Arm	Intervention/treatment
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;	Drug: Clozapine; 500 mg/day; Other Name: clozaryl
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	Drug: Olanzapine; 20 mg/day; Other Name: zyprexa
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	Drug: Haloperidol; 20 mg/day; Other Name: Haldol

Outcome Measures

Primary Outcome Measures :

1. Number of aggressive incidents [ Time Frame: 12 weeks ]
   The Modified Overt Aggression scale (MOAS) was used to record all aggressive incidents. The primary measure was the total score on the MOAS as well as the score on the MOAS physical aggression subscale

Secondary Outcome Measures :

1. Psychiatric Symptoms [ Time Frame: 12 weeks ]
   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
2. Side effects of medications [ Time Frame: 12 weeks ]
   The side effects of the medications were measured with the ESRS on a weekly basis for the duration of the study

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, New York

Nathan Kline Institute

Orangeburg, New York, United States, 10962

Sponsors and Collaborators

Nathan Kline Institute for Psychiatric Research

Investigators

• Study Director: Bennett L Leventhal, MD; Nathan Kline Institute

More Information

Publications of Results:

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. doi: 10.1001/archpsyc.63.6.622.

Krakowski MI, Czobor P, Nolan KA. Atypical antipsychotics, neurocognitive deficits, and aggression in schizophrenic patients. J Clin Psychopharmacol. 2008 Oct;28(5):485-93. doi: 10.1097/JCP.0b013e3181855cd6.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Krakowski M, Tural U, Czobor P. The Importance of Conduct Disorder in the Treatment of Violence in Schizophrenia: Efficacy of Clozapine Compared With Olanzapine and Haloperidol. Am J Psychiatry. 2021 Mar 1;178(3):266-274. doi: 10.1176/appi.ajp.2020.20010052. Epub 2021 Jan 21. Erratum In: Am J Psychiatry. 2021 Jul;178(7):671.

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. doi: 10.4088/JCP.11m07238. Epub 2011 Nov 29.

• Responsible Party: Krakowski, Menahem, Nathan Kline Institute
• ClinicalTrials.gov Identifier: NCT01123408
• Other Study ID Numbers: 2244
• First Posted: May 14, 2010
• Last Update Posted: May 14, 2010
• Last Verified: May 2010

Keywords provided by Nathan Kline Institute for Psychiatric Research:

schizophrenia; aggression; clozapine; olanzapine

Additional relevant MeSH terms:

Schizophrenia; Aggression; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Behavioral Symptoms; Haloperidol; Olanzapine; Haloperidol decanoate; Clozapine; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Dopamine Antagonists; Dopamine Agents; Anti-Dyskinesia Agents; Serotonin Antagonists; GABA Antagonists; GABA Agents