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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Emil Coccaro, University of Chicago
ClinicalTrials.gov Identifier:
NCT00078754
First received: March 5, 2004
Last updated: January 31, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Intermittent Explosive Disorder
Drug: Fluoxetine
Drug: Divalproex
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Fluoxetine and Divalproex: Treatment Correlates in IED

Resource links provided by NLM:


Further study details as provided by University of Chicago:

Primary Outcome Measures:
  • Anti-aggressive effects [ Time Frame: Measured at Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 90
Study Start Date: May 2003
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

IED is a condition characterized by a failure to resist aggressive impulses. It is a vaguely 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.

  Eligibility

Ages Eligible for Study:   21 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00078754

Locations
United States, Illinois
The University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
University of Chicago
Investigators
Principal Investigator: Emil F. Coccaro, MD University of Chicago
  More Information

No publications provided

Responsible Party: Emil Coccaro, Professor, University of Chicago
ClinicalTrials.gov Identifier: NCT00078754     History of Changes
Other Study ID Numbers: R01 MH66984, R01MH066984, DATR A5-ETMA
Study First Received: March 5, 2004
Last Updated: January 31, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Impulse Control Disorders
Mental Disorders
Valproic Acid
Fluoxetine
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Serotonin Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents

ClinicalTrials.gov processed this record on April 16, 2014