SchizophreniaNCT01123408
Clozapine and Olanzapine Treatment of Aggression
A study testing Clozapine, Olanzapine and Haloperidol in people with Schizophrenia, run by Nathan Kline Institute for Psychiatric Research at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Clozapine, Olanzapine and Haloperidol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 1999to Jul 2004
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clozapine and Olanzapine in the Treatment of Violence in Schizophrenic Patients
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.
Read the 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.
- Conditions
- Schizophrenia
- Being tested
- Clozapine, Olanzapine, Haloperidol
- Keywords
- schizophrenia, aggression, clozapine, olanzapine
- Medical subject headings
- Schizophrenia, Aggression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClozapineDrug
Also called clozaryl
500 mg/day
OlanzapineDrug
Also called zyprexa
20 mg/day
HaloperidolDrug
Also called Haldol
20 mg/day
| Study group | Role | What they receive |
|---|---|---|
| clozapine | Experimental | 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; Receives: Drug: Clozapine |
| Olanzapine | Experimental | 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 Receives: Drug: Olanzapine |
| Haloperidol | Active comparator | 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 Receives: Drug: Haloperidol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 weeks
Secondary outcomes (2)
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
Measured: 12 weeks
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
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2010 (estimated)
- Study startJun 1999
- Primary completionJul 2004
- Study completionJul 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nathan Kline Institute for Psychiatric Research
- Sponsor type
- University, hospital or other
- Investigators
- Bennett L Leventhal, MD, Study director, Nathan Kline Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01123408
- Sponsor's protocol ID
- 2244
- Status last verified
- May 2010
- First submitted
- 12 May 2010
- Last updated
- 14 May 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 16754835Krakowski 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.
PubMed 18794642Ibragimov K, Keane GP, Carreno Glaria C, Cheng J, Llosa AE. Haloperidol (oral) versus olanzapine (oral) for people with schizophrenia and schizophrenia-spectrum disorders. Cochrane Database Syst Rev. 2024 Jul 3;7(7):CD013425. doi: 10.1002/14651858.CD013425.pub2.
PubMed 38958149Krakowski 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.
PubMed 33472389Krakowski 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.
PubMed 22152404
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clozapine and Olanzapine in the Treatment of Violence in Schizophrenic Patients
- ClinicalTrials.gov ID
- NCT01123408
- Acronym / sponsor ID
- 2244
- Conditions
- Schizophrenia
- Keywords
- schizophrenia, aggression, clozapine, olanzapine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Nathan Kline Institute for Psychiatric ResearchUniversity, hospital or other
- Study start
- Jun 1999
- Primary completion
- Jul 2004 (actual)
- Study completion
- Jul 2004 (actual)
- First posted
- 14 May 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| clozapine | Experimental | Drug: ClozapineDuring 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; |
| Olanzapine | Experimental | Drug: OlanzapineDuring 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 |
| Haloperidol | Active comparator | Drug: HaloperidolDuring 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 |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClozapineAlso: clozaryl500 mg/day | Drug | clozapine |
| OlanzapineAlso: zyprexa20 mg/day | Drug | Olanzapine |
| HaloperidolAlso: Haldol20 mg/day | Drug | Haloperidol |
Primary outcome
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
2 secondary outcomes
Psychiatric Symptoms
Time frame: 12 weeks
Side effects of medications
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2010.
- Results publication: PubMed 16754835Krakowski 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 publication: PubMed 18794642Krakowski 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.
- Derived from this study: PubMed 38958149Ibragimov K, Keane GP, Carreno Glaria C, Cheng J, Llosa AE. Haloperidol (oral) versus olanzapine (oral) for people with schizophrenia and schizophrenia-spectrum disorders. Cochrane Database Syst Rev. 2024 Jul 3;7(7):CD013425. doi: 10.1002/14651858.CD013425.pub2.
- Derived from this study: PubMed 33472389Krakowski 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.
- Derived from this study: PubMed 22152404Krakowski 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bennett L Leventhal, MD study director
Nathan Kline Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Clozapine, Olanzapine and Haloperidol in people with Schizophrenia, run by Nathan Kline Institute for Psychiatric Research at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 May 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of aggressive incidents (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01123408, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2010.