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

Fluoxetine and Divalproex: Treatment Correlates in IED

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

Study Overview

• Status: Completed
• Conditions: Intermittent Explosive Disorder
• Intervention / Treatment: Drug: Fluoxetine; Drug: Divalproex; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overt Aggression Scale-Modified for Outpatient Use (OAS-M)	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.	Measured at Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OAS-M	Overt Aggression Scale Modified for Outpatient Use. Minimum value = 0 Maximum value = Infinity. Higher scores means worse outcome.	Measured at Week 12

Collaborators and Investigators

• Sponsor: University of Chicago
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Emil F. Coccaro, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start: May 1, 2003
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: March 5, 2004
• First Submitted That Met QC Criteria: March 5, 2004
• First Posted (Estimate): March 8, 2004

Study Record Updates

• Last Update Posted (Actual): April 27, 2021
• Last Update Submitted That Met QC Criteria: April 26, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Disruptive, Impulse Control, and Conduct Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; GABA Agents; Cytochrome P-450 Enzyme Inhibitors; Anticonvulsants; Antidepressive Agents, Second-Generation; Antimanic Agents; Cytochrome P-450 CYP2D6 Inhibitors; Valproic Acid; Fluoxetine
• Other Study ID Numbers: R01MH066984 (U.S. NIH Grant/Contract); DATR A5-ETMA (Other Identifier: NIH)