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

Condition(s) targeted: Intermittent Explosive Disorder

Intervention: Fluoxetine (Drug); Divalproex (Drug); Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: National Institute of Mental Health (NIMH)

Official(s) and/or principal investigator(s):
Emil F. Coccaro, MD, Principal Investigator, Affiliation: University of Chicago

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

Official title: Fluoxetine and Divalproex: Treatment Correlates in IED

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Anti-aggressive effects

Secondary outcome: 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

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.

Minimum age: 21 Years. Maximum age: 55 Years. Gender(s): Both.

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

The University of Chicago, Chicago, Illinois 60637, United States; Recruiting
Cynthia Bogue, RN, Phone: 773-834-8984, Email: cbogue@yoda.bsd.uchicago.edu
Royce Lee, MD, Phone: 773-834-5673, Email: rlee@yoda.bsd.uchicago.edu
Emil F. Coccaro, MD, Principal Investigator
Royce Lee, MD, Sub-Investigator

Starting date: May 2003
Ending date: April 2008
Last updated: February 12, 2008