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Psychiatry Board Review Manual
Statement of
Editorial Purpose
The Hospital Physician Psychiatry Board Review
Manual is a study guide for residents and prac­
ticing physicians preparing for board exami­
nations in psychiatry. Each manual reviews
a topic essential to the current practice of
psychiatry.
PUBLISHING STAFF
PRESIDENT, Group PUBLISHER
Bruce M. White
editorial director
Debra Dreger
SENIOR EDITOR
Bobbie Lewis
Intermittent Explosive
Disorder
Editor:
Jerald Kay, MD
Professor and Chair, Department of Psychiatry, Wright State University
School of Medicine, Dayton, OH
Contributor:
Kelly Blankenship, DO
Psychiatry Resident, Department of Psychiatry, Wright State University
School of Medicine, Dayton, OH
EDITOR
Tricia Faggioli
assistant EDITOR
Farrawh Charles
executive vice president
Barbara T. White
executive director
of operations
Table of Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
Diagnostic and Associated Features. . . . . . . . . . . 2
Jean M. Gaul
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
PRODUCTION Director
Etiology and Pathophysiology. . . . . . . . . . . . . . . . 3
Suzanne S. Banish
PRODUCTION assistant
Nadja V. Frist
ADVERTISING/PROJECT Director
Differential Diagnosis. . . . . . . . . . . . . . . . . . . . . . 4
Comorbidity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Patricia Payne Castle
Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
sales & marketing manager
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Deborah D. Chavis
NOTE FROM THE PUBLISHER:
This publication has been developed with­
out involvement of or review by the Amer­
ican Board of Psychiatry and Neurology.
Summary Points . . . . . . . . . . . . . . . . . . . . . . . . . . 8
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Cover Illustration by Kathryn K . Johnson
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Psychiatry Volume 11, Part 5 Psychiatry Board Review Manual
Intermittent Explosive Disorder
Kelly Blankenship, DO
INTRODUCTION
Intermittent explosive disorder (IED) was once considered a rare disorder; however, recent studies have
indicated that IED is much more prevalent than previously thought.1 IED is associated with a high degree
of social impairment. In a study of 253 individuals in
a community sample diagnosed with IED, 81.3% reported psychosocial difficulties, 50% admitted to difficulties within their life due to their behavior, and 62.5%
noted significant difficulties with relationships.2 IED
may lessen in intensity as individuals become older.3
Diagnosis is difficult, in part due to the vagueness of the
DSM diagnostic criteria.4 Further, the paucity of IED
studies makes identifying and treating IED a challenge.
Despite these limitations, physicians must assess these
impulsive and aggressive patients and be aware of available treatment options for these individuals.5
DIAGNOSTIC AND ASSOCIATED FEATURES
IED is characterized by short-lived episodes of impulsive aggression that are substantially out of proportion to
the inciting stressor, resulting in destruction of property
or serious assaultive acts.6 IED is currently listed in the
DSM-IV under impulse-control disorders not elsewhere
classified.6 Diagnostic criteria and the name of the disorder have changed over time. In DSM-I, IED was referred
to as passive-aggressive personality, aggressive type, and
in DSM-II, IED was termed explosive personality disorder. It was not until DSM-III that the term IED was used;
however, the DSM-III criteria excluded patients with
antisocial personality disorder7 and generalized aggression or impulsivity,1 and in the DSM-III-R, patients with
borderline personality disorder were excluded. The
DSM-IV criteria for diagnosing IED no longer excludes
patients with impulsivity or generalized aggression7 but
includes the criterion that another mental disorder,
substance abuse, or general medical condition must not
better account for the aggressive acts (Table 1).6 Impulsive aggression is not unique to IED and can be seen in
multiple psychiatric and medical conditions. Thus, IED
Hospital Physician Board Review Manual
is a diagnosis of exclusion.3 Of note, some studies use
terms such as “episodic dyscontrol” or “rage attacks” to
describe aggression, making it difficult to pinpoint how
many patients meet the criteria for IED.4 In addition,
some doubt that IED is an actual diagnosis and believe
that impulsive aggression is a symptom that can be experienced in multiple diseases.8
The aggressive episodes are often described by patients as “spells” or “attacks,” and the symptoms often
appear and resolve in minutes to hours. Symptoms
have been described as an “adrenaline rush” or “seeing
red.”1 As with other impulse-control disorders, there is
often a feeling of release of tension after the episode.
Aggression related to IED is often ego-dystonic and
patients feel a sense of remorse and regret after the
aggressive act.3 In a study of 27 patients who met current or past DSM-IV criteria for IED, 33% complained
of physical autonomic symptoms such as palpitations,
tingling, and tremor prior to the episode, and 52%
complained of a change in their level of awareness.8
In a study of 443 violent men, those who met
DSM-III criteria for IED (n = 15) felt that an intimate
partner would most likely provoke them. Their attacks
usually occurred without warning, and all of the men
denied wanting the outburst to occur prior to the episode. Men often attempted to console their victim after
their rageful outburst.9
Impulsive aggression often has different motivations.
If motivation includes monetary gain, vengeance, selfdefense, social dominance, expressing a political statement, or when it occurs as a part of gang behavior, IED
should not be the diagnosis.3 The impulsive aggression
seen in IED is not the same as the willingly performed
and thought out aggression often seen in criminal behavior. Thus, when behavior is premeditated, individuals should not be diagnosed with IED.4
Because DSM-IV exclusion criteria created difficulties in diagnosing IED, integrated research criteria
(IED-IR) have been formed. A study that examined
the convergent and discriminate validity of the IED-IR
criteria found that IED-IR individuals who met DSM-IV
diagnostic criteria for IED were no more aggressive or
impaired than IED-IR individuals who did not meet
these criteria.4 In another attempt to clarify diagnostic
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Intermittent Explosive Disorder
criteria for IED, an interview module for IED (IED-M)
was studied. The IED-M required a minimum number
of aggressive acts (2 times/wk for 1 mo) and the events
must be spontaneous, excessive, and have associated
anguish.5 A pilot study was performed to evaluate the
validity of the IED-M in detecting IED in children.10
Olvera et al10 provided preliminary data that the IED-M
is useful for detecting IED in teenagers.
EPIDEMIOLOGY
As formulated in the DSM-IV-TR, IED is probably a
rare disorder3; however, recent data have indicated that
this may not be true. In a chart review of 830 patients
in 1983, only 1.1% were found to meet DSM-III criteria
for IED.11 In a second report of 433 aggressive participants, 1.8% qualified for a diagnosis of IED by DSM-III
standards.7 A 2005 study of 1300 patients seeking mental health care found that 6.3% met DSM-IV criteria for
lifetime IED and 3.1% met criteria for a current diagnosis of IED.7 A face-to-face household survey of 9282
individuals found a lifetime and 12-month incidence of
IED of 7.3% and 3.9%, respectively.1
Most studies indicate onset of IED in adolescence.
McElroy et al8 found an average age of onset of 14 years,
with the disease lasting an average of 20 years. Seventyfour percent of the participants were male. Kessler et al1
also found the average disease onset of age 14 years as
well as an average of 43 attacks over an individual’s life
with an average cost of $1359 for damaged objects per
lifetime. In the study, injuries related to the disorder
occurred 180 times for every 100 lifetime cases. Risk
factors included male sex, young age, lower level of
education, being married, employment, and having
decreased revenue within the home.1 Another study
found that IED showed a linear pattern of occurrence
from young to old and lower to higher education.7
Individuals who completed a college degree or beyond
were 2 times less likely to meet criteria for IED than
those who had a high school diploma and/or some
college. Further, high school graduates were 2 times
less likely to meet criteria for IED as those who did not
graduate high school. IED was less common in whites
as compared with nonwhites.7
ETIOLOGY AND PATHOPHYSIOLOGY
At one time, theories regarding impulsive aggression
included possession by spirits, humeral imbalances, and
moral weakness. As psychiatry advanced, so did its theo-
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Table 1. DSM-IV-TR Diagnostic Criteria for Intermittent
Explosive Disorder
A. Several discrete episodes of failure to resist aggressive impulses
that result in serious assaultive acts or destruction of property
B. The degree of aggressiveness expressed during the episodes
is grossly out of proportion to any precipitating psychosocial
stressors
C. The aggressive episodes are not better accounted for by another
mental disorder (eg, antisocial personality disorder, borderline
personality disorder, psychotic disorder, manic episode, conduct
disorder, attention-deficit/hyperactivity disorder) and are not
due to the direct physiologic effects of a substance (eg, a drug
of abuse, a medication) or a general medical condition (eg, head
trauma, Alzheimer’s disease)
Adapted with permission from American Psychiatric Association. Diag­
nostic and statistical manual of mental disorders. 4th ed., text revision.
Washington (DC): The Association; 2000:667. Copyright 2000, Ameri­
can Psychiatric Association.
ries on impulsive aggression. In the latter part of the
19th century, 2 main theories evolved: (1) impulsive aggression was, at least in part, due to events experienced
in youth and (2) impulsive aggression was the result of
differences in brain chemistry and makeup.3
In studies involving rhesus monkeys, researchers
found that disrupting early attachment to parental
figures was a risk factor for becoming aggressive at
improper times.12 In a human study that measured
gender differences in proactive and reactive aggression, proactive aggression was associated with poor
parenting in both sexes, and reactive aggression was
associated with traumatic experiences at a young age in
females.13 In monkey studies, female monkeys isolated
from their mother immediately and other monkeys
for the initial 18 months of their life showed deficits in
childrearing, being more indifferent and angry toward
their offspring.12 From a social learning perspective,
there is an expectation that children learn to parent
from interactions with their own parents. In a study
designed to examine the continuities in aggressive
parenting and behavior in their offspring, persons ex­
posed to aggressive parenting as children were likely
to parent aggressively as adults. It was also found that
childrearing also had a direct impact on behavior and
relationships experienced as young adults and teenagers.14 Evidence has suggested that IED is familial and
individuals with a family history of IED have an elevated
risk for the disorder.15
Decreased levels of serotonin activity, as measured by cerebrospinal fluid (CSF) concentrations of
5-hydroxyindoleacetic acid (5-HIAA), have been observed in studies of both humans and monkeys with
Psychiatry Volume 11, Part 5 Intermittent Explosive Disorder
Table 2. Psychiatric Disorders That Present with Impulsive Aggression
Mental Disorder
Features
Antisocial personality disorder
Pervasive pattern of disregard for and violation of the rights of others; symptoms may include irritability
and aggressiveness (eg, repeated physical fights and assaults)6
Borderline personality disorder
Pervasive pattern of instability of relationships, self-image, and affects, and marked impulsivity; symptoms
may include inappropriate, intense anger or difficulty controlling anger (eg, frequent displays of temper,
constant anger, recurrent physical fights)6
Conduct disorder
Repetitive and persistent pattern of behavior in which basic rights of others or societal norms and rules
are violated; symptoms may include aggression towards people and animals (eg, bullies/threatens oth­
ers, initiates physical fights) or destruction of property6
Dementia with behavioral disturbance
Aggression is a common behavioral symptom of dementia. Patients with dementia can become
combative with staff or loved ones who attempt to help them with their personal care19
Personality change caused by a general
medical condition, aggressive type6
Aggression can be caused by multiple neurologic conditions
Posttraumatic stress disorder (PTSD)
Although aggression is not included in the diagnostic criteria for PTSD, it is a recognized characteristic20
impulsive aggression. It has been suggested that decreased serotonin in CSF concentrations can lead to the
inability to constrain the impulse that causes “offensive
aggression.” This is supported by studies in which monkeys with decreased CSF serotonin exhibit “risky” behavior.12 Adolescent male rhesus macaques with low CSF
concentrations showed high levels of aggression and
were at greater risk of death at a young age due to aggression.16 In rodent studies, there was a noted increase
in aggression with decreased brain serotonin as well as
increased killing among the rodents with low serotonin.
The more aggressive impulses were also seen when serotonergic neurons were depleted. However, when serotonin in the brain was replaced, aggression remitted. In
a study comparing murderers with suicide attempters,
suicide attempters had decreased levels of CSF 5-HIAA,
whereas the murderers did not.16 However, murderers
who killed their sexual partners had extreme low levels
of CSF 5-HIAA. The authors assumed the murders were
performed during times of high affective response and
concluded that serotonin abnormalities are seen in
violence “in states of emotional turmoil.”16 Aggression
in adults and adolescents after puberty has been seen in
individuals with increased testosterone levels.5
Specific areas of the brain, including the prefrontal
cortex and the amygdala, have been suspected to be associated with impulsive aggression.5 Increased aggressive
behavior has been seen in individuals with lesions in the
frontal or temporal lobes.17 Impulsivity can be seen in
damage to the frontal lobe. In a study using functional
magnetic resonance imaging to examine response inhibition, more impulsive individuals activated paralimbic areas, particularly the right inferior frontal gyrus
extending to the posterior lateral orbitofrontal cortex
and anterior insula, whereas less impulsive individuals
Hospital Physician Board Review Manual
activated higher order association areas when inhibiting
a prepotent response.18 Other studies have shown that
areas of the prefrontal cortex can be involved in impulsive aggression, and brain positron emission tomography
has demonstrated a decreased glucose metabolism in
prefrontal and frontal cortex in these patients.3
DIFFERENTIAL DIAGNOSIS
A medical work-up should be performed before a
diagnosis of IED is given. If the patient has a history
of memory loss, head trauma, or seizures, a neurology consult may be considered. Imaging studies and
electroencephalography (EEG) may also be helpful.5
There are many neurologic disorders that can cause aggressiveness, including brain abscesses, dementia, partial complex seizures, encephalitis, frontal focal lesions,
and cerebrovascular accident. In these neurologic conditions, personality change due to a general medical
condition, aggressive type is the correct diagnosis.3
In patients with IED, physical examination may re­
veal nonspecific soft neurologic signs, such as minor
difficulties in hand-eye coordination or small reflex
asymmetries.3 There may also be hypersensitivity to sensory stimuli or abnormalities on EEG.11 In individuals
with anger that occurs suddenly, slowing may be seen
throughout the EEG.3
IED is a diagnosis of exclusion, and, as such, other
psychiatric diagnoses must first be ruled out (Table 2). Because many psychiatric disorders can present with a history of impulsive aggression, distinguishing IED from other
psychiatric disorders can be difficult. Antisocial personality
disorder, borderline personality disorder, conduct disorder, dementia with behavioral disturbance, oppositional
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Intermittent Explosive Disorder
Table 3. Lifetime Intermittent Explosive Disorder (IED) Diagnosis and Other Comorbid Axis I Diagnoses
Patients with IED
and Other ImpulseControl Disorders, %
Patients with IED
and ≥ 1 DSM-IV
Axis I Diagnosis, %
Patients with
IED and Anxiety
Disorder, %
Patients with
IED and Mood
Disorder, %
Patients with IED
and Substance Use
Disorder, %
Kessler et al1*
44.9
81.8
58.1
37.4
35.1
Coccaro et al7
7.3
—
78
75.6
59.8
McElroy et al8
44
96
48
93
48
Study
*Statistics used were for broadly defined lifetime IED.
defiant disorder, personality change caused by a general
medical condition, aggressive type, and posttraumatic
stress disorder (PTSD) all involve aggression.5 A diagnosis
of IED should be considered only after other diagnoses
for impulsive aggression have been invalidated.3
When distinguishing IED from personality disorders,
it is often helpful to consider baseline behavior. Aggressive behavior demonstrated on a normal daily basis is
in stark contrast to the discrete episodes of impulsive
aggressiveness seen in IED.3 In children, symptoms of
bipolar disorder and IED can be similar.21
The inappropriate expression of anger is a key feature in borderline personality disorder.22 Patients with
borderline personality disorder or antisocial personality
disorder often describe a history of lifetime of continuance impulsive aggression instead of discrete episodes
of aggression.3 Aggression (physical, verbal, or sexual)
is commonly seen in older individuals with dementia.
The physical aggression seen in this disease process
is often the prompt that leads to nursing home placement.19 Aggression may also be seen if individuals are
under the influence or withdrawing from a substance.
IED would not be diagnosed in either circumstance.23
A study addressing anger and aggression in outpatient psychiatric patients found that generalized anxiety
disorder and drug abuse/dependence were linked to
higher rates of aggression. IED, bipolar I disorder, and
PTSD were most likely to be linked with current aggressive behavior.24 Although aggression is not officially
recognized as a characteristic of PTSD, new evidence
is emerging to support that aggression does occur in
PTSD. Fifty couples in which the male was a Vietnam
veteran were questioned. All of the men exhibited
PTSD symptoms. The survey found that 100% of these
men participated in psychological aggression against
their mate, 92% engaged in verbal aggression, and 34%
had 1 or more episodes of physical aggression.20
Another type of aggression, anger attacks, may be
seen in depressed patients and usually occur when a
person feels emotionally trapped and experiences outbursts of anger. These attacks may include irritability,
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autonomic symptoms, and exaggerated reaction to a
small irritant with rage. Three studies indicated that in
patients with major depression, anger attacks were seen
between 38% and 44% of the time. Studies indicate
that 30% to 40% of patients with any type of depression
have anger attacks.25
COMORBIDITY
Studies have indicated that most individuals with
IED have a least 1 other lifetime DSM-IV diagnosis
(Table 3).1,7,8 In a report of 27 cases of IED, 26 (96%)
met requirements for at least 1 other DSM-IV Axis I diagnosis, and 19 (70%) patients met criteria for 3 or more
diagnoses.8 Of the 27 patients, 25 (93%) met criteria for
a mood disorder during their lifetime, and 14 (52%)
met lifetime criteria for bipolar disorder. Thirteen patients were diagnosed with a type of anxiety disorder,
13 were diagnosed with a substance abuse/dependence
disorder, 6 were diagnosed with eating disorders, and
12 had other impulse-control disorders.8 Five patients
reported a diagnosis of attention-deficit/hyperactivity
disorder as a child. Some participants with mood and
substance use disorders reported changes in their IED
symptoms with changes in mood or substance use. Six
participants noted worsening IED symptoms during
depression, while 5 noted a worsening of IED during
mania. Of the 7 women included in the study, 5 noted
that IED worsened during their premenstrual period.
All individuals with substance use disorders reported
differences in IED symptomatology with substance use;
7 patients noted an increase in IED symptoms with alcohol use whereas 2 noted a decrease, and 5 individuals
stated that marijuana decreased their IED symptoms.
Incidence of headache in the sample was high, with 12
of the participants reporting migraines.8
Coccaro et al7 studied 1300 patients requesting outpatient treatment and found that in addition to meeting criteria for IED, 75.6 % also met criteria for a lifetime mood disorder, 32.7% met criteria for personality
Psychiatry Volume 11, Part 5 Intermittent Explosive Disorder
disorders, 59.8% met criteria for a substance use disorder, and 78% met criteria for anxiety disorders. The
National Comorbidity Survey Replication found that
81.8% of individuals with lifetime broad IED also had
at least 1 or more other lifetime DSM-IV diagnosis.1 In
this study, the odds ratios of IED with impulse-control
and substance use disorders were not higher than those
with mood and anxiety disorders. Based on these data,
the author proposed that IED may be as much related
to affective instability and dysregulation as to problems
with impulse control. This study also found that IED
had an earlier age of onset than most comorbidities,
suggesting that IED could be a “risk factor” for diseases
such as major depression, generalized anxiety disorder,
panic disorder, and substance abuse disorders. However, there are no published data to confirm this suspicion.1 There is also some speculation that IED is also
associated with bipolar disorder, as many individuals
who meet criteria for IED also have a lifetime diagnosis
of bipolar disorder.4
TREATMENT
There are few studies evaluating treatment for IED.5
Further, the U.S. Food and Drug Administration has
not approved any medications for the treatment of aggression.24 The National Comorbidity Survey Replication indicated that individuals who sought treatment
for IED often waited until well after their first episode,
and when they did seek treatment, it was commonly for
another comorbid condition.1 Many people with IED
will eventually seek mental health treatment but not
for their anger episodes. It could be that many patients
may not feel that anger is a reason to seek psychiatric
treatment.1 One study found that only 20% of individuals with IED who sought treatment described IED as the
reason for mental health treatment.7
PHARMACOLOGIC THERAPY
Although there is a paucity of studies defining
treat­ment for IED, McElroy26 published an algorithm
for treating angry or combative individuals (Figure).
According to this algorithm, patients with unipolar depression should be started on a serotonin reuptake inhibitor, other antidepressants, or lamotrigine, whereas
those with bipolar depression with a history of mania
or mixed episodes should be treated with a mood
stabilizer, antipsychotics, other antiepileptics, or antiandrogens. If there is no affective component, it should
be determined whether the individual presented with
compulsive or impulsive primary symptomatology. If
Hospital Physician Board Review Manual
the patient complains of compulsivity, selective serotonin reuptake inhibitors (SSRIs) or other serotonin
agents are used. If the patient complains of impulsivity,
SSRIs, other antidepressants, mood stabilizers, antiepileptics, β blockers, stimulants, or antiandrogens should
be prescribed.26 In a study of 27 patients with IED, 20
re­ceived treatment with either a mood stabilizer or
SSRI. At least a moderate response to medication was
described by 60% of the individuals.8
Lithium has been found to be effective in decreasing
aggression in several studies in differing patient populations. In a study involving 66 young nonpsychotic adult
and adolescent prisoners (age range, 16–24 yr), lithium
was superior to placebo in demonstrating reduced aggressive episodes.27 In a 6-week, double-blind, placebocontrolled study of adolescents with conduct disorder,
patients taking lithium demonstrated reduced aggression compared with those taking placebo.28
Improvements in aggression have been seen in
adolescent males with the addition of valproic acid. In
a placebo-crossover, double-blind, parallel-group study
of 20 teens diagnosed with oppositional defiant disorder or conduct disorder and problematic temper and
mood liability, valproic acid was superior to placebo in
demonstrating reduced aggression.29
Several studies have shown that carbamazepine lessens
aggression in multiple psychiatric disorders. Two open
studies performed by Mattes30 and Mattes et al31 found
that carbamazepine lessened aggression in rageful patients. Both studies included patients with multiple diagnoses; 12 of 28 and 19 of 34 patients, respectively, had
been diagnosed with IED. In a randomized, double-blind
study by Neppe,32 aggression was 1.5 times less common
when treated with carbamazepine compared with placebo. These individuals were chronic psychiatric hospitalized inpatients who did not have epilepsy but had abnormal temporal lobe findings on EEG.32 Phenytoin has
also been shown to decrease impulsive aggression. In a
double-blind, placebo-controlled, crossover study performed on 60 inmates, the inmates with impulsive aggression had reductions in aggressive behavior.33
In a study of impulsive aggression in 40 patients with
a personality disorder, patients treated with fluoxetine
showed a significant reduction in aggressive symptoms
compared with the placebo group, as measured by the
Overt Aggression Scale Modified for Outpatients.34 All
40 participants in this study were found to fulfill IED research criteria.15 SSRIs may take approximately 3 months
to reach full benefit in patients with IED; thus, a sufficient trial of an SSRI should include at least 3 months.
Symptoms also tend to reappear shortly after the medication is discontinued.15
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Intermittent Explosive Disorder
Depressive/unipolar
SRIs
Other antidepressants
Lamotrigine
Manic or mixed/bipolar
Mood stabilizers (eg, divalproex,
lithium, carbamazepine)
Antipsychotics (typical and atypical)
Other antiepileptics (eg, gabapentin,
phenytoin)
Antiandrogens
Combinations
Compulsive
SRIs
5-HT agents
Combinations
Impulsive
SRIs
Other antidepressants
Mood stabilizers
Antiepileptics
b Blockers
Stimulants
Antiandrogens
Combinations
Affective symptoms/
syndrome
Is there an affective
component?
No affective symptoms/
syndrome
Figure. Algorithm for treating agitation and violence. SRI = serotonin reuptake inhibitor. (Reprinted with permission from McElroy SL.
Recognition and treatment of DSM-IV intermittent explosive disorder. J Clin Psychiatry 1999;60 Suppl 15:12–6. Copyright © 1999, Physi­
cians Postgraduate Press.)
β Blockers may also be used to treat aggression in
some patients, but they have worrisome side effects,
such as bradycardia, dizziness, and hypotension, and the
appropriate dose is difficult to determine.15,35 Studies
evaluating pindolol in brain damaged patients showed a
lessening of aggression in these patients.5 Another study
demonstrated a lessening of aggression in adolescents
who were given α2 agonists.36 However, their use in this
setting has been questioned due to reports of sudden
death in young patients taking α2 agonists with other
drugs. The side effects include worsening depression,
sedation, and decreased blood pressure.5
Recent studies have shown atypical antipsychotics to
be effective in treating aggression.37,38 Atypical antipsychotics have a preferred side effect profile compared
with typical antipsychotics.5
NONPHARMACOLOGIC THERAPY
Cognitive behavioral therapy has been shown to de­­
crease anger and aggression in individuals with anger
problems. These trials were not specific to IED patients;
thus, more studies are needed to confirm the effective-
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ness of cognitive behavioral therapy in patients with
IED.15 In a small sample (n = 4) of patients who received
insight-oriented or supportive psychotherapy when exhibiting IED signs, 3 of 4 found that it was useful for
constraining their impulsive aggression. All 4 patients
receiving family, couples, or group therapy reported no
reduction in aggressive behavior with therapy.8
CONCLUSION
IED is characterized by impulsive aggression occurring in discrete episodes. Impulsive aggression is seen
in multiple conditions; thus, IED is a diagnosis of exclusion, and other conditions in which aggression is seen
should first be ruled out before IED is diagnosed. IED
also occurs in association with other psychiatric disorders, adding to the difficulty in making an appropriate
diagnosis. Although the etiology is uncertain, IED has
been hypothesized to originate as a result of either
childhood events or alterations in brain chemistry,
particularly alterations in serotonin.3 Age of onset is
Psychiatry Volume 11, Part 5 Intermittent Explosive Disorder
adolescence, and risk factors include male sex, young
age, being married, a decreased household income,
and a high degree of social impairment. Studies evaluating IED are sparse, and studies evaluating treatments
for IED are even more so. Currently, there are no drugs
approved for the treatment of aggression; however, studies have demonstrated decreased aggression in certain
populations with the use of pharmacologic agents, such
as lithium, atypical antipsychotics, valproic acid, phenytoin, SSRIs, and β blockers, and psychotherapy.
SUMMARY POINTS
• Recent studies have indicated that IED is much more
prevalent than previously thought; a recent study of
9282 individuals found an incidence of 7.3% for lifetime diagnosis of IED and 3.9% 12-month incidence
rate.
• Diagnosis of IED can be difficult due to vagueness of
the diagnostic criteria and the frequency of impulsive aggression seen in other illnesses.
• When diagnosing IED, it is important to remember
that the episodes of rage are short and substantially
out of proportion to the stressor causing the event,
and the episodes result in property damage or assault of individuals.
• IED is a diagnosis of exclusion; thus, all other causes
of rage and outbursts must be excluded before giving this diagnosis. Other diagnoses that can mimic
IED include neurologic disorders, antisocial personality disorder, borderline personality disorder,
conduct disorder, dementia with behavioral disturbance, oppositional defiant disorder, and PTSD.
• Aggression of different forms is very common when
patients are withdrawing or under the influence of
different substances. These individuals should not
be diagnosed with IED.
• Patients with IED are at risk for high impairment in
multiple aspects of their life. Many report difficulties
psychosocially, and individuals with IED often have
difficulties with significant relationships throughout
their life.
• The intensity of IED tends to lessen as the patient
becomes older.
• IED-related behavior is not the same as well-planned
criminal behavior. If the behavior is premeditated,
individuals should not be given a diagnosis of IED.
• Although the average age of onset of IED appears
Hospital Physician Board Review Manual
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to be in adolescence, most patients do not seek
treatment until they are much older. The reason for
seeking treatment is most often another psychiatric
condition they have comorbidly.
Most patients with IED have at least 1 other lifetime
DSM-IV diagnosis. It is common for individuals with
this disorder to met criteria for 3 or more diagnoses.
Mood and anxiety disorders are often seen comorbidly in patients with IED.
Risk factors for IED include male sex, young age,
low level of education, marriage, employment, and
having decreased revenue in the home.
IED is thought to arise as a result of experiences
from youth and differences in brain chemistry. Early
disruption of attachment to a primary caregiver or
aggressive parenting has been shown to be risk factors for aggressive behaviors as adults. A decreased
level of serotonin activity in the CSF has been seen
in aggressive individuals.
Studies have indicated that certain areas of the
brain, including the prefrontal cortex and amygdala, are involved in aggression. Individuals with
lesions in the frontal or temporal lobe have been
shown to have increased aggression.
According to McElroy, violent individuals with unipolar depression should be started on a serotonin reuptake inhibitor, another antidepressant, or lamotrigine.
Individuals with bipolar depression and a history of
mania should be treated with a mood stabilizer, antipsychotics, other antiepileptics, or antiandrogens.
If no affective component is present, patients should
be evaluated for compulsive verses impulsive primary symptomatology. If the patient has compulsive symptoms, SSRIs or other sertonin agents are
indicated. If the patient has impulsivity symptoms,
SSRIs, other antidepressants, mood stabilizers, antiepileptics, β blockers, stimulants, or antiandrogens
are indicated.
In certain populations, studies have indicated that
pharmacologic treatments, such as lithium, valproic
acid, carbamazepine, phenytoin, fluoxetine, or atypical antipsychotics, are more effective than placebo
in treating aggression.
Nonpharmacologic therapy, such as cognitive behavioral therapy, can help decrease anger episodes
in patients with anger problems. A small study
indicated that insight-oriented and supportive psychotherapy was helpful in controlling aggression in
some patients when exhibiting signs of IED.
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Intermittent Explosive Disorder
REFERENCES
1. Kessler RC, Coccaro EF, Fava M, et al. The prevalence
and correlates of DSM-IV intermittent explosive disorder
in the National Comorbidity Survey Replication. Arch
Gen Psychiatry 2006;63:669–78.
2. Coccaro EF, Schmidt CA, Samuels JF, Nestadt G. Lifetime
and 1-month prevalence rates of intermittent explosive
disorder in a community sample. J Clin Psychiatry 2004;
65:820–4.
3. Tasman A, Kay J, Lieberman JA. Psychiatry. 2nd ed.
Hoboken (NJ): Wiley; 2003.
4. McCloskey MS, Berman ME, Noblett KL, Coccaro EF.
Intermittent explosive disorder-integrated research diagnostic criteria: convergent and discriminant validity.
J Psychiatr Res 2006;40:231–42.
5. Olvera RL. Intermittent explosive disorder: epidemiology, diagnosis and management. CNS Drugs 2002;16:
517–26.
6. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. 4th ed.,
text revision. Washington (DC): American Psychiatric
Association; 2000.
pulse control, affect regulation, and social functioning.
J Neuropsychiatry Clin Neurosci 2003;15:294–305.
17. Haller J, Kruk MR. Normal and abnormal aggression:
human disorders and novel laboratory models. Neurosci
Biobehav Rev 2006;30:292–303.
18. Horn NR, Dolan M, Elliott R, et al. Response inhibition and impulsivity: an fMRI study. Neuropsychologia
2003;41:1959–66.
19. Raskind MA. Evaluation and management of aggressive
behavior in the elderly demented patient. J Clin Psychiatry 1999;60:Suppl 15:45–9.
20. Yehuda R. Managing anger and aggression in patients
with posttraumatic stress disorder. J Clin Psychiatry 1999;
60 Suppl 15:33–7.
21. Davanzo P, Yue K, Thomas MA, et al. Proton magnetic
resonance spectroscopy of bipolar disorder versus intermittent explosive disorder in children and adolescents.
Am J Psychiatry 2003;160:1442–52.
22. Hollander E. Managing aggressive behavior in patients
with obsessive-compulsive disorder and borderline personality disorder. J Clin Psychiatry 1999;60 Suppl 15:
38–44.
23. Stern TA, Herman JB, editors. Psychiatry update and
board preparation. New York: McGraw-Hill; 2000.
7. Coccaro EF, Posternak MA, Zimmerman M. Prevalence
and features of intermittent explosive disorder in a clinical setting. J Clin Psychiatry 2005;66:1221–7.
24. Posternak MA, Zimmerman M. Anger and aggression
in psychiatric outpatients. J Clin Psychiatry 2002;63:
665–72.
8. McElroy SL, Soutullo CA, Beckman DA, et al. DSM-IV intermittent explosive disorder: a report of 27 cases. J Clin
Psychiatry 1998;59:203–11.
25. Fava M, Rosenbaum JF. Anger attacks in patients with
depression. J Clin Psychiatry 1999;60 Suppl 15:21–4.
9. Felthous AR, Bryant SG, Wingerter CB, Barratt E. The
diagnosis of intermittent explosive disorder in violent
men. Bull Am Acad Psychiatry Law 1991;19:71–9.
10. Olvera RL, Pliszka SR, Konyecsni WM, et al. Validation
of the Interview Module for Intermittent Explosive Disorder (M-IED) in children and adolescents: a pilot study.
Psychiatry Res 2001;101:259–67.
11. Monopolis S, Lion JR. Problems in the diagnosis of intermittent explosive disorder. Am J Pyschiatry 1983;140:
1200–2.
12. Kalin NH. Primate models to understand human aggression. J Clin Psychiatry 1999;60 Suppl 15:29–32.
13. Connor DF, Steingard RJ, Anderson JJ, Melloni RH Jr.
Gender differences in reactive and proactive aggression.
Child Psychiatry Hum Dev 2003;33:279–94.
14. Conger RD, Neppl T, Kim KJ, Scaramella L. Angry and
aggressive behavior across three generations: a prospective, longitudinal study of parents and children. J Abnorm Child Psychol 2003;31:143–60.
15. Coccaro EF. Intermittent explosive disorder: taming temper tantrums in the volatile, impulsive adult. Curr Psychiatry Online 2003;2:1–10.
16. Krakowski M. Violence and serotonin: influence of im-
www.turner-white.com
26. McElroy SL. Recognition and treatment of DSM-IV intermittent explosive disorder. J Clin Psychiatry 1999;60
Suppl 15:12–6.
27. Sheard MH, Marini JL, Bridges CI, Wagner E. The effect
of lithium on impulsive aggressive behavior in men. Am
J Psychiatry 1976;133:1409–13.
28. Malone RP, Delaney MA, Luebbert JF, et al. A doubleblind placebo-controlled study of lithium in hospitalized
aggressive children and adolescents with conduct disorder. Arch Gen Psychiatry 2000;57:649–54.
29. Donovan SJ, Stewart JW, Nunes EV, et al. Divalproex
treatment for youth with explosive temper and mood
lability: a double-blind, placebo-controlled crossover design [published erratum appears in Am J Psychiatry 2000;
157:1038]. Am J Psychiatry 2000;157:818–20.
30. Mattes JA. Carbamezapine for uncontrolled rage outbursts. Lancet 1984;2:1164–5.
31. Mattes JA, Rosenberg J, Mays D. Carbamazepine versus
propranolol in patients with uncontrolled rage outbursts: a random assignment study. Psychopharmacol
Bull 1984;20:98–100.
32. Neppe VM. Carbamazepine as adjunctive treatment in
non-epileptic chronic inpatients with EEG temporal
lobe abnormalities. J Clin Psychiatry 1983;44:326–31.
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33. Barratt ES, Stanford MS, Felthous A, Kent TA. The effects
of phenytoin on impulsive and premeditated aggression: a controlled study. J Clin Psychopharmacol 1997;
17:341–9.
34. Coccaro EF, Kavoussi RJ. Fluoxetine and impulsive aggressive behavior in personality disordered subjects. Arch
Gen Psychiatry 1997;54:1081–8.
35. Sadock BJ, Sadock VA. Kaplan & Sadock’s synopsis of
psychiatry: behavioral sciences/clinical psychiatry. 9th ed.
Philadelphia: Lippincott Williams & Wilkins; 2003.
36. Kemph JP, DeVane CL, Levin GM, et al. Treatment of aggressive children with clonidine: results of an open pilot
study. J Am Acad Child Adoles Psychiatry 1993;32:577–81.
37. Buitelaar JK, van der Gaag RJ, Cohen-Ketternis P, Melman
CT. A randomized controlled trial of risperidone in the
treatment of aggression in hospitalized adolescents with
subaverage cognitive abilities. J Clin Psychiatry 2001;62:
239–48.
38. Jibson MD, Tandon R. New atypical antipsychotic medications. J Psychiatr Res 1998;32:215–28.
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