Back to resultsClozapine and Olanzapine Treatment of Aggression
Primary Purpose
Schizophrenia
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Clozapine
Olanzapine
Haloperidol
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring schizophrenia, aggression, clozapine, olanzapine
Eligibility 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.
Sites / Locations
- Nathan Kline Institute
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
clozapine
Olanzapine
Haloperidol
Arm Description
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;
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
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
Outcomes
Primary Outcome Measures
Number of aggressive incidents
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
Psychiatric Symptoms
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
The side effects of the medications were measured with the ESRS on a weekly basis for the duration of the study
Full Information
NCT ID
NCT01123408
First Posted
May 12, 2010
Last Updated
May 13, 2010
Sponsor
Nathan Kline Institute for Psychiatric Research
1. Study Identification
Unique Protocol Identification Number
NCT01123408
Brief Title
Clozapine and Olanzapine Treatment of Aggression
Official Title
Clozapine and Olanzapine in the Treatment of Violence in Schizophrenic Patients
Study Type
Interventional
2. Study Status
Record Verification Date
May 2010
Overall Recruitment Status
Completed
Study Start Date
June 1999 (undefined)
Primary Completion Date
July 2004 (Actual)
Study Completion Date
July 2004 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Nathan Kline Institute for Psychiatric Research
4. Oversight
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
schizophrenia, aggression, clozapine, olanzapine
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
110 (Actual)
8. Arms, Groups, and Interventions
Arm Title
clozapine
Arm Type
Experimental
Arm Description
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;
Arm Title
Olanzapine
Arm Type
Experimental
Arm Description
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
Arm Title
Haloperidol
Arm Type
Active Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
Clozapine
Other Intervention Name(s)
clozaryl
Intervention Description
500 mg/day
Intervention Type
Drug
Intervention Name(s)
Olanzapine
Other Intervention Name(s)
zyprexa
Intervention Description
20 mg/day
Intervention Type
Drug
Intervention Name(s)
Haloperidol
Other Intervention Name(s)
Haldol
Intervention Description
20 mg/day
Primary Outcome Measure Information:
Title
Number of aggressive incidents
Description
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
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Psychiatric Symptoms
Description
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
Time Frame
12 weeks
Title
Side effects of medications
Description
The side effects of the medications were measured with the ESRS on a weekly basis for the duration of the study
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bennett L Leventhal, MD
Organizational Affiliation
Nathan Kline Institute
Official's Role
Study Director
Facility Information:
Facility Name
Nathan Kline Institute
City
Orangeburg
State/Province
New York
ZIP/Postal Code
10962
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
16754835
Citation
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.
Results Reference
result
PubMed Identifier
18794642
Citation
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.
Results Reference
result
PubMed Identifier
33472389
Citation
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.
Results Reference
derived
PubMed Identifier
22152404
Citation
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.
Results Reference
derived
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Clozapine and Olanzapine Treatment of Aggression
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