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A Comparison of Fluoxetine and Divalproex for the Treatment of Intermittent Explosive Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00078754
Recruitment Status : Completed
First Posted : March 8, 2004
Results First Posted : December 31, 2014
Last Update Posted : May 16, 2018
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
University of Chicago

Brief Summary:
This study will compare the medications fluoxetine (Prozac®) and divalproex (Depakote®) for the treatment of aggressive behavior in individuals with Intermittent Explosive Disorder (IED).

Condition or disease Intervention/treatment Phase
Intermittent Explosive Disorder Drug: Fluoxetine Drug: Divalproex Drug: Placebo Phase 2

Detailed Description:

IED is a condition characterized by a failure to resist aggressive impulses. IED is a behavioral defined condition for which effective treatments have not been identified. Research suggests that serotonin (5-HT), a chemical that helps regulate mood and emotions, may play a role in the response to pharmacological IED treatments. This study will examine the relationship between 5-HT receptors and response to treatment with fluoxetine or divalproex. In addition, this study will examine people with IED and those without the condition to determine whether there are differences in their 5-HT receptor and transporter systems.

Participants in this study will be randomly assigned to receive either fluoxetine, divalproex, or placebo for 12 weeks. Scale ratings will be used to assess the aggression levels of participants. Biologic evaluations of the 5-HT system will be conducted throughout the study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Fluoxetine and Divalproex: Treatment Correlates in IED
Study Start Date : May 2003
Actual Primary Completion Date : October 2008
Actual Study Completion Date : October 2008

Resource links provided by the National Library of Medicine

Drug Information available for: Fluoxetine

Arm Intervention/treatment
Experimental: A
Participants will to receive treatment with fluoxetine for 12 weeks
Drug: Fluoxetine
Fluoxetine capsules by mouth, up to 60 mg daily

Experimental: B
Participants will to receive treatment with divalproex for 12 weeks
Drug: Divalproex
Divalproex ER capsules by mouth, up to 3000 mg daily

Placebo Comparator: C
Participants will to receive treatment with placebo for 12 weeks
Drug: Placebo
Placebo capsules by mouth, up to 8 capsules daily

Primary Outcome Measures :
  1. Overt Aggression Scale-Modified (OAS-M) [ Time Frame: Measured at Week 12 ]
    OAS-M is a validated instrument that measures aggression. Anti-aggressive effect of the drug/placebo was measured by the aggression score from OAS-M. Possible scores for aggression range from 0 (no aggression) to infinity (because the score is calculated by the number of times an aggressive behavior occurred, which theoretically has no possible maximum). Therefore the bigger number, the worse anti-aggression effect, thus the worse outcome. In each weekly visit, OAS-M score was calculated for the past week.

Secondary Outcome Measures :
  1. Treatment Response, Assessed as a Function of the Severity of Lifetime Aggressiveness of the Participant and as a Function of the Pretreatment Status of the Central 5-HT Receptor System [ Time Frame: Measured at Week 12 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of Intermittent Explosive Disorder (IED)
  • In good physical health
  • Overt Aggression Scale-Modified (OAS-M) score of 15 or higher at screening
  • Willing and able to comply with the study requirements

Exclusion Criteria:

  • Life history of bipolar disorder, schizophrenia, organic mental syndrome, or mental retardation
  • Current major depressive disorder, with a Hamilton Depression (HAM-D) Scale score higher than 18
  • Current alcohol or drug abuse or dependence
  • Active medical conditions that will interfere with the study
  • Thymoleptic or neuroleptic treatments
  • Presence of the following serious and active medical conditions: demyelinating or progressive degenerative disorders; central nervous system infection; progressive degenerative neurological disorder; ischemic heart disease; respiratory, renal, or liver disease; Type I diabetes; malignant neoplasm; hyper- or hypo-coagulopathy; Acquired Immune Deficiency Syndrome (AIDS); or seizure disorder. Participants with a history of more than two febrile seizures prior to 1 year of age are eligible.
  • Chronic, ongoing treatment with the following classes of medications: antidepressants, neuroleptics, mood stabilizers, antianxiety agents, hypnotics, narcotics or synthetic narcotics, barbiturates, stimulants, anti-migraine agents, anti-epileptics, non-beta-blocking or Ca-channel blocking anti-arrhythmic agents prescribed to treat cardiac arrhythmia, anticoagulants, immunomodulators, anti-neoplastic agents, or HIV antiviral agents
  • Ongoing psychotherapeutic treatment for the treatment of IED or anger that was started less than 3 months before study entry
  • Hypersensitivity to fluoxetine or divalproex
  • Pregnancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00078754

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United States, Illinois
The University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
University of Chicago
National Institute of Mental Health (NIMH)
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Principal Investigator: Emil F. Coccaro, MD University of Chicago

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Responsible Party: University of Chicago Identifier: NCT00078754     History of Changes
Other Study ID Numbers: R01MH066984 ( U.S. NIH Grant/Contract )
R01MH066984 ( U.S. NIH Grant/Contract )
First Posted: March 8, 2004    Key Record Dates
Results First Posted: December 31, 2014
Last Update Posted: May 16, 2018
Last Verified: May 2018
Additional relevant MeSH terms:
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Disruptive, Impulse Control, and Conduct Disorders
Mental Disorders
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors