Clinical trial NCT01123408: Clozapine and Olanzapine Treatment of Aggression
Official title: Clozapine and Olanzapine in the Treatment of Violence in Schizophrenic Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Keywords: schizophrenia
aggression
clozapine
olanzapine
Lead sponsor: Nathan Kline Institute for Psychiatric Research
Sponsor class: OTHER
First posted: 2010-05-14
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of aggressive incidents
timeFrame: 12 weeks
Secondary outcomes:
measure: Psychiatric Symptoms
timeFrame: 12 weeks
measure: Side effects of medications
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Orangeburg
country: United States
facility: Nathan Kline Institute
state: New York
Study officials:
affiliation: Nathan Kline Institute
name: Bennett L Leventhal, MD
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.