CompletedNCT00078754Updated Apr 27, 2021Results posted

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

A Phase 2 interventional study of Fluoxetine and Divalproex in Intermittent Explosive Disorder, sponsored by University of Chicago. Completed at 1 site in United States. Open to participants aged 21 Years to 55 Years. Per ClinicalTrials.gov, last updated 2021-04-27.

Sponsored by University of Chicago · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 90
Allocation: Randomized
Ages: 21 Years to 55 Years
Sex: All

Study 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).

Read the 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.

Conditions studied

Intermittent Explosive Disorder

Browse trials for

Disruptive, Impulse Control, and Conduct Disorders 47

In context

Disruptive, Impulse Control, and Conduct Disorders

47 studies on the registry are indexed under Disruptive, Impulse Control, and Conduct Disorders; 18 are open to participants now.

This study's enrollment of 90 is above the median of 45 across 39 interventional studies indexed under Disruptive, Impulse Control, and Conduct Disorders.

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Lead sponsor

University of Chicago is the lead sponsor of 907 studies on the registry; 182 are open to participants now.

Of its 99 completed or terminated interventional studies of FDA-regulated products, 68 (69%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 21 Years to 55 Years
Sexes eligible: 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

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 design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 90 participants (actual)

Study arms

Experimental
A
Participants will to receive treatment with fluoxetine for 12 weeks
Drug: Fluoxetine
Experimental
B
Participants will to receive treatment with divalproex for 12 weeks
Drug: Divalproex
Placebo comparator
C
Participants will to receive treatment with placebo for 12 weeks
Drug: Placebo

Interventions

DrugFluoxetine
Fluoxetine capsules by mouth, up to 60 mg daily
DrugDivalproex
Divalproex ER capsules by mouth, up to 3000 mg daily
DrugPlacebo
Placebo capsules by mouth, up to 8 capsules daily

What researchers measure

Primary outcomes

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.
Time frame: Measured at Week 12

Secondary outcomes

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

Results

Posted Dec 31, 2014

Limitations and caveats

Most participants did not have stable OAS-M Aggression scores from screening to randomization. Note that this was not a requirement for this study; only that OAS-Aggression scores were 15 or higher at screening.

Participant flow

Participant flow — Overall Study
Milestone	Group A - Fluoxetine Drug	Group B - Divalproex Drug	Group C - Placebo
Started	29	30	31
Completed	14	11	16
Not completed	15	19	15

Outcome measures

PrimaryOvert 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.

Time frame:: Measured at Week 12
Reported as:: Mean · units on a scale

Overt Aggression Scale-Modified for Outpatient Use (OAS-M)
units on a scale	Group A - Fluoxetine Drug	Group B - Divalproex Drug	Group C - Placebo
Overt Aggression Scale-Modified for Outpatient Use (OAS-M)	7.86 ± 4.11	15.73 ± 10.15	8.88 ± 3.51

Statistical analysis

Group A - Fluoxetine Drug vs Group B - Divalproex Drug vs Group C - Placebo · ANCOVA · p = 0.622

SecondaryOAS-M

Overt Aggression Scale Modified for Outpatient Use. Minimum value = 0 Maximum value = Infinity. Higher scores means worse outcome.

Time frame:: Measured at Week 12
Reported as:: Mean · score on a scale

OAS-M
score on a scale	Fluoxetine	Divalproex	Placebo
High Aggression Group	13.2 ± 5.0	13.7 ± 4.8	19.5 ± 5.1
Medium Aggression Group	25.1 ± 7.6	29.6 ± 8.0	26.9 ± 7.1

Statistical analysis

Fluoxetine · ANCOVA · p = 0.029 (LHA score main effect.)The LHA Score F\[1,83\] = 4.91, p = 0.029; Condition F\[2,83\] = 0.20, p = 0.815; Condition x LHA Score F\[2,83\] = 0.255, p = 0.799.
Fluoxetine vs Divalproex · ANCOVA · p = 0.80 · Mean difference (final values): 19.0Baseline OAS-M Aggression score as covariate.

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Group A - Fluoxetine Drug	—	1/29 (3.4%)	23/29 (79.3%)
Group B - Divalproex Drug	—	0/30 (0%)	23/30 (76.7%)
Group C - Placebo	—	0/31 (0%)	24/31 (77.4%)

Most frequent serious events

Most frequent serious events
Event	Group A - Fluoxetine Drug	Group B - Divalproex Drug	Group C - Placebo
hyponatremia/hypokalemiaBlood and lymphatic system disorders	1/29	0/30	0/31

Most frequent other events

Showing 10 of 22

Most frequent other events
Event	Group A - Fluoxetine Drug	Group B - Divalproex Drug	Group C - Placebo
Soreness in your muscle, back, jointsInvestigations	13/29	17/30	16/31
Feeling tense or keyed upInvestigations	14/29	11/30	14/31
DrowsinessInvestigations	8/29	12/30	10/31
Trouble remembering thingsInvestigations	9/29	6/30	7/31
Nausea or upset stomachInvestigations	5/29	9/30	9/31
Dry mouthInvestigations	5/29	9/30	4/31
SweatingInvestigations	6/29	9/30	4/31
HeadachesInvestigations	7/29	6/30	8/31
Nervousness or shakiness insideInvestigations	6/29	6/30	4/31
Heart pounding or racingInvestigations	6/29	6/30	5/31

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Group A - Fluoxetine Drug	Group B - Divalproex Drug	Group C - Placebo	Total
<=18 years	0	0	0	0
Between 18 and 65 years	29	30	31	90
>=65 years	0	0	0	0

Sex: Female, Male
Sex: Female, Male(Participants)	Group A - Fluoxetine Drug	Group B - Divalproex Drug	Group C - Placebo	Total
Female	14	10	16	40
Male	15	20	15	50

overt aggression scale-modified (OAS-M).
overt aggression scale-modified (OAS-M).(units on a scale)	Group A - Fluoxetine Drug	Group B - Divalproex Drug	Group C - Placebo	Total
Mean	36.75 ± 46.88	36.96 ± 26.42	66.08 ± 77.99	47.30 ± 56.68

Study locations

1 site

The University of Chicago
Chicago, Illinois 60637, United States

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 27, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00078754
Lead sponsor: University of Chicago
Collaborators: National Institute of Mental Health (NIMH)
Responsible party: Sponsor
First posted: Mar 8, 2004
Start date: May 2003
Primary completion: Oct 2008
Completion: Oct 2008
Results posted: Dec 31, 2014
Last update: Apr 27, 2021

Study contacts

Emil F. Coccaro, MD

principal investigator · University of Chicago

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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