16.04.2014 Views

Intermittent Explosive Disorder - Turner White

Intermittent Explosive Disorder - Turner White

Intermittent Explosive Disorder - Turner White

SHOW MORE
SHOW LESS

You also want an ePaper? Increase the reach of your titles

YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.

®<br />

Psychiatry Board Review Manual<br />

Statement of<br />

Editorial Purpose<br />

The Hospital Physician Psychiatry Board Review<br />

Manual is a study guide for residents and practicing<br />

physicians preparing for board examinations<br />

in psychiatry. Each manual reviews<br />

a topic essential to the current practice of<br />

psychiatry.<br />

PUBLISHING STAFF<br />

PRESIDENT, Group PUBLISHER<br />

Bruce M. <strong>White</strong><br />

editorial director<br />

Debra Dreger<br />

SENIOR EDITOR<br />

Bobbie Lewis<br />

EDITOR<br />

Tricia Faggioli<br />

assistant EDITOR<br />

Farrawh Charles<br />

executive vice president<br />

Barbara T. <strong>White</strong><br />

executive director<br />

of operations<br />

Jean M. Gaul<br />

PRODUCTION Director<br />

Suzanne S. Banish<br />

PRODUCTION assistant<br />

Nadja V. Frist<br />

ADVERTISING/PROJECT Director<br />

Patricia Payne Castle<br />

sales & marketing manager<br />

Deborah D. Chavis<br />

NOTE FROM THE PUBLISHER:<br />

This publication has been developed without<br />

involvement of or review by the American<br />

Board of Psychiatry and Neurology.<br />

<strong>Intermittent</strong> <strong>Explosive</strong><br />

<strong>Disorder</strong><br />

Editor:<br />

Jerald Kay, MD<br />

Professor and Chair, Department of Psychiatry, Wright State University<br />

School of Medicine, Dayton, OH<br />

Contributor:<br />

Kelly Blankenship, DO<br />

Psychiatry Resident, Department of Psychiatry, Wright State University<br />

School of Medicine, Dayton, OH<br />

Table of Contents<br />

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2<br />

Diagnostic and Associated Features . . . . . . . . . . .2<br />

Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . .3<br />

Etiology and Pathophysiology . . . . . . . . . . . . . . . .3<br />

Differential Diagnosis . . . . . . . . . . . . . . . . . . . . . .4<br />

Comorbidity . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5<br />

Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6<br />

Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7<br />

Summary Points . . . . . . . . . . . . . . . . . . . . . . . . . .8<br />

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9<br />

Cover Illustration by Kathryn K. Johnson<br />

Copyright 2008, <strong>Turner</strong> <strong>White</strong> Communications, Inc., Strafford Avenue, Suite 220, Wayne, PA 19087-3391, www.turner-white.com. All rights reserved. No part of<br />

this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, electronic, photocopying, recording, or<br />

otherwise, without the prior written permission of <strong>Turner</strong> <strong>White</strong> Communications. The preparation and distribution of this publication are supported by sponsorship<br />

subject to written agreements that stipulate and ensure the editorial independence of <strong>Turner</strong> <strong>White</strong> Communications. <strong>Turner</strong> <strong>White</strong> Communications retains full<br />

control over the design and production of all published materials, including selection of topics and preparation of editorial content. The authors are solely responsible<br />

for substantive content. Statements expressed reflect the views of the authors and not necessarily the opinions or policies of <strong>Turner</strong> <strong>White</strong> Communications.<br />

<strong>Turner</strong> <strong>White</strong> Communications accepts no responsibility for statements made by authors and will not be liable for any errors of omission or inaccuracies. Information<br />

contained within this publication should not be used as a substitute for clinical judgment.<br />

www.turner-white.com<br />

Psychiatry Volume 11, Part 5


Psychiatry Board Review Manual<br />

<strong>Intermittent</strong> <strong>Explosive</strong> <strong>Disorder</strong><br />

Kelly Blankenship, DO<br />

INTRODUCTION<br />

<strong>Intermittent</strong> explosive disorder (IED) was once considered<br />

a rare disorder; however, recent studies have<br />

indicated that IED is much more prevalent than previously<br />

thought. 1 IED is associated with a high degree<br />

of social impairment. In a study of 253 individuals in<br />

a community sample diagnosed with IED, 81.3% reported<br />

psychosocial difficulties, 50% admitted to difficulties<br />

within their life due to their behavior, and 62.5%<br />

noted significant difficulties with relationships. 2 IED<br />

may lessen in intensity as individuals become older. 3<br />

Diagnosis is difficult, in part due to the vagueness of the<br />

DSM diagnostic criteria. 4 Further, the paucity of IED<br />

studies makes identifying and treating IED a challenge.<br />

Despite these limitations, physicians must assess these<br />

impulsive and aggressive patients and be aware of available<br />

treatment options for these individuals. 5<br />

DIAGNOSTIC AND ASSOCIATED FEATURES<br />

IED is characterized by short-lived episodes of impulsive<br />

aggression that are substantially out of proportion to<br />

the inciting stressor, resulting in destruction of property<br />

or serious assaultive acts. 6 IED is currently listed in the<br />

DSM-IV under impulse-control disorders not elsewhere<br />

classified. 6 Diagnostic criteria and the name of the disorder<br />

have changed over time. In DSM-I, IED was referred<br />

to as passive-aggressive personality, aggressive type, and<br />

in DSM-II, IED was termed explosive personality disorder.<br />

It was not until DSM-III that the term IED was used;<br />

however, the DSM-III criteria excluded patients with<br />

antisocial personality disorder 7 and generalized aggression<br />

or impulsivity, 1 and in the DSM-III-R, patients with<br />

borderline personality disorder were excluded. The<br />

DSM-IV criteria for diagnosing IED no longer excludes<br />

patients with impulsivity or generalized aggression 7 but<br />

includes the criterion that another mental disorder,<br />

substance abuse, or general medical condition must not<br />

better account for the aggressive acts (Table 1). 6 Impulsive<br />

aggression is not unique to IED and can be seen in<br />

multiple psychiatric and medical conditions. Thus, IED<br />

Hospital Physician Board Review Manual<br />

is a diagnosis of exclusion. 3 Of note, some studies use<br />

terms such as “episodic dyscontrol” or “rage attacks” to<br />

describe aggression, making it difficult to pinpoint how<br />

many patients meet the criteria for IED. 4 In addition,<br />

some doubt that IED is an actual diagnosis and believe<br />

that impulsive aggression is a symptom that can be experienced<br />

in multiple diseases. 8<br />

The aggressive episodes are often described by patients<br />

as “spells” or “attacks,” and the symptoms often<br />

appear and resolve in minutes to hours. Symptoms<br />

have been described as an “adrenaline rush” or “seeing<br />

red.” 1 As with other impulse-control disorders, there is<br />

often a feeling of release of tension after the episode.<br />

Aggression related to IED is often ego-dystonic and<br />

patients feel a sense of remorse and regret after the<br />

aggressive act. 3 In a study of 27 patients who met current<br />

or past DSM-IV criteria for IED, 33% complained<br />

of physical autonomic symptoms such as palpitations,<br />

tingling, and tremor prior to the episode, and 52%<br />

complained of a change in their level of awareness. 8<br />

In a study of 443 violent men, those who met<br />

DSM-III criteria for IED (n = 15) felt that an intimate<br />

partner would most likely provoke them. Their attacks<br />

usually occurred without warning, and all of the men<br />

denied wanting the outburst to occur prior to the episode.<br />

Men often attempted to console their victim after<br />

their rageful outburst. 9<br />

Impulsive aggression often has different motivations.<br />

If motivation includes monetary gain, vengeance, selfdefense,<br />

social dominance, expressing a political statement,<br />

or when it occurs as a part of gang behavior, IED<br />

should not be the diagnosis. 3 The impulsive aggression<br />

seen in IED is not the same as the willingly performed<br />

and thought out aggression often seen in criminal behavior.<br />

Thus, when behavior is premeditated, individuals<br />

should not be diagnosed with IED. 4<br />

Because DSM-IV exclusion criteria created difficulties<br />

in diagnosing IED, integrated research criteria<br />

(IED-IR) have been formed. A study that examined<br />

the convergent and discriminate validity of the IED-IR<br />

criteria found that IED-IR individuals who met DSM-IV<br />

diagnostic criteria for IED were no more aggressive or<br />

impaired than IED-IR individuals who did not meet<br />

these criteria. 4 In another attempt to clarify diagnostic<br />

www.turner-white.com


I n t e r m i t t e n t E x p l o s i v e D i s o r d e r<br />

criteria for IED, an interview module for IED (IED-M)<br />

was studied. The IED-M required a minimum number<br />

of aggressive acts (2 times/wk for 1 mo) and the events<br />

must be spontaneous, excessive, and have associated<br />

anguish. 5 A pilot study was performed to evaluate the<br />

validity of the IED-M in detecting IED in children. 10<br />

Olvera et al 10 provided preliminary data that the IED-M<br />

is useful for detecting IED in teenagers.<br />

EPIDEMIOLOGY<br />

As formulated in the DSM-IV-TR, IED is probably a<br />

rare disorder 3 ; however, recent data have indicated that<br />

this may not be true. In a chart review of 830 patients<br />

in 1983, only 1.1% were found to meet DSM-III criteria<br />

for IED. 11 In a second report of 433 aggressive participants,<br />

1.8% qualified for a diagnosis of IED by DSM-III<br />

standards. 7 A 2005 study of 1300 patients seeking mental<br />

health care found that 6.3% met DSM-IV criteria for<br />

lifetime IED and 3.1% met criteria for a current diagnosis<br />

of IED. 7 A face-to-face household survey of 9282<br />

individuals found a lifetime and 12-month incidence of<br />

IED of 7.3% and 3.9%, respectively. 1<br />

Most studies indicate onset of IED in adolescence.<br />

McElroy et al 8 found an average age of onset of 14 years,<br />

with the disease lasting an average of 20 years. Seventyfour<br />

percent of the participants were male. Kessler et al 1<br />

also found the average disease onset of age 14 years as<br />

well as an average of 43 attacks over an individual’s life<br />

with an average cost of $1359 for damaged objects per<br />

lifetime. In the study, injuries related to the disorder<br />

occurred 180 times for every 100 lifetime cases. Risk<br />

factors included male sex, young age, lower level of<br />

education, being married, employment, and having<br />

decreased revenue within the home. 1 Another study<br />

found that IED showed a linear pattern of occurrence<br />

from young to old and lower to higher education. 7<br />

Individuals who completed a college degree or beyond<br />

were 2 times less likely to meet criteria for IED than<br />

those who had a high school diploma and/or some<br />

college. Further, high school graduates were 2 times<br />

less likely to meet criteria for IED as those who did not<br />

graduate high school. IED was less common in whites<br />

as compared with nonwhites. 7<br />

ETIOLOGY AND PATHOPHYSIOLOGY<br />

www.turner-white.com<br />

Table 1. DSM-IV-TR Diagnostic Criteria for <strong>Intermittent</strong><br />

<strong>Explosive</strong> <strong>Disorder</strong><br />

A. Several discrete episodes of failure to resist aggressive impulses<br />

that result in serious assaultive acts or destruction of property<br />

B. The degree of aggressiveness expressed during the episodes<br />

is grossly out of proportion to any precipitating psychosocial<br />

stressors<br />

C. The aggressive episodes are not better accounted for by another<br />

mental disorder (eg, antisocial personality disorder, borderline<br />

personality disorder, psychotic disorder, manic episode, conduct<br />

disorder, attention-deficit/hyperactivity disorder) and are not<br />

due to the direct physiologic effects of a substance (eg, a drug<br />

of abuse, a medication) or a general medical condition (eg, head<br />

trauma, Alzheimer’s disease)<br />

Adapted with permission from American Psychiatric Association. Diagnostic<br />

and statistical manual of mental disorders. 4th ed., text revision.<br />

Washington (DC): The Association; 2000:667. Copyright 2000, American<br />

Psychiatric Association.<br />

At one time, theories regarding impulsive aggression<br />

included possession by spirits, humeral imbalances, and<br />

moral weakness. As psychiatry advanced, so did its theories<br />

on impulsive aggression. In the latter part of the<br />

19th century, 2 main theories evolved: (1) impulsive aggression<br />

was, at least in part, due to events experienced<br />

in youth and (2) impulsive aggression was the result of<br />

differences in brain chemistry and makeup. 3<br />

In studies involving rhesus monkeys, researchers<br />

found that disrupting early attachment to parental<br />

figures was a risk factor for becoming aggressive at<br />

improper times. 12 In a human study that measured<br />

gender differences in proactive and reactive aggression,<br />

proactive aggression was associated with poor<br />

parenting in both sexes, and reactive aggression was<br />

associated with traumatic experiences at a young age in<br />

females. 13 In monkey studies, female monkeys isolated<br />

from their mother immediately and other monkeys<br />

for the initial 18 months of their life showed deficits in<br />

childrearing, being more indifferent and angry toward<br />

their offspring. 12 From a social learning perspective,<br />

there is an expectation that children learn to parent<br />

from interactions with their own parents. In a study<br />

designed to examine the continuities in aggressive<br />

parenting and behavior in their offspring, persons exposed<br />

to aggressive parenting as children were likely<br />

to parent aggressively as adults. It was also found that<br />

childrearing also had a direct impact on behavior and<br />

relationships experienced as young adults and teenagers.<br />

14 Evidence has suggested that IED is familial and<br />

individuals with a family history of IED have an elevated<br />

risk for the disorder. 15<br />

Decreased levels of serotonin activity, as measured<br />

by cerebrospinal fluid (CSF) concentrations of<br />

5-hydroxyindoleacetic acid (5-HIAA), have been observed<br />

in studies of both humans and monkeys with<br />

Psychiatry Volume 11, Part 5


I n t e r m i t t e n t E x p l o s i v e D i s o r d e r<br />

Table 2. Psychiatric <strong>Disorder</strong>s That Present with Impulsive Aggression<br />

Mental <strong>Disorder</strong><br />

Features<br />

Antisocial personality disorder<br />

Borderline personality disorder<br />

Conduct disorder<br />

Dementia with behavioral disturbance<br />

Personality change caused by a general<br />

medical condition, aggressive type 6<br />

Pervasive pattern of disregard for and violation of the rights of others; symptoms may include irritability<br />

and aggressiveness (eg, repeated physical fights and assaults) 6<br />

Pervasive pattern of instability of relationships, self-image, and affects, and marked impulsivity; symptoms<br />

may include inappropriate, intense anger or difficulty controlling anger (eg, frequent displays of temper,<br />

constant anger, recurrent physical fights) 6<br />

Repetitive and persistent pattern of behavior in which basic rights of others or societal norms and rules<br />

are violated; symptoms may include aggression towards people and animals (eg, bullies/threatens others,<br />

initiates physical fights) or destruction of property 6<br />

Aggression is a common behavioral symptom of dementia. Patients with dementia can become<br />

combative with staff or loved ones who attempt to help them with their personal care 19<br />

Aggression can be caused by multiple neurologic conditions<br />

Posttraumatic stress disorder (PTSD) Although aggression is not included in the diagnostic criteria for PTSD, it is a recognized characteristic 20<br />

impulsive aggression. It has been suggested that decreased<br />

serotonin in CSF concentrations can lead to the<br />

inability to constrain the impulse that causes “offensive<br />

aggression.” This is supported by studies in which monkeys<br />

with decreased CSF serotonin exhibit “risky” behavior.<br />

12 Adolescent male rhesus macaques with low CSF<br />

concentrations showed high levels of aggression and<br />

were at greater risk of death at a young age due to aggression.<br />

16 In rodent studies, there was a noted increase<br />

in aggression with decreased brain serotonin as well as<br />

increased killing among the rodents with low serotonin.<br />

The more aggressive impulses were also seen when serotonergic<br />

neurons were depleted. However, when serotonin<br />

in the brain was replaced, aggression remitted. In<br />

a study comparing murderers with suicide attempters,<br />

suicide attempters had decreased levels of CSF 5-HIAA,<br />

whereas the murderers did not. 16 However, murderers<br />

who killed their sexual partners had extreme low levels<br />

of CSF 5-HIAA. The authors assumed the murders were<br />

performed during times of high affective response and<br />

concluded that serotonin abnormalities are seen in<br />

violence “in states of emotional turmoil.” 16 Aggression<br />

in adults and adolescents after puberty has been seen in<br />

individuals with increased testosterone levels. 5<br />

Specific areas of the brain, including the prefrontal<br />

cortex and the amygdala, have been suspected to be associated<br />

with impulsive aggression. 5 Increased aggressive<br />

behavior has been seen in individuals with lesions in the<br />

frontal or temporal lobes. 17 Impulsivity can be seen in<br />

damage to the frontal lobe. In a study using functional<br />

magnetic resonance imaging to examine response inhibition,<br />

more impulsive individuals activated paralimbic<br />

areas, particularly the right inferior frontal gyrus<br />

extending to the posterior lateral orbitofrontal cortex<br />

and anterior insula, whereas less impulsive individuals<br />

activated higher order association areas when inhibiting<br />

a prepotent response. 18 Other studies have shown that<br />

areas of the prefrontal cortex can be involved in impulsive<br />

aggression, and brain positron emission tomography<br />

has demonstrated a decreased glucose metabolism in<br />

prefrontal and frontal cortex in these patients. 3<br />

DIFFERENTIAL DIAGNOSIS<br />

A medical work-up should be performed before a<br />

diagnosis of IED is given. If the patient has a history<br />

of memory loss, head trauma, or seizures, a neurology<br />

consult may be considered. Imaging studies and<br />

electroencephalography (EEG) may also be helpful. 5<br />

There are many neurologic disorders that can cause aggressiveness,<br />

including brain abscesses, dementia, partial<br />

complex seizures, encephalitis, frontal focal lesions,<br />

and cerebrovascular accident. In these neurologic conditions,<br />

personality change due to a general medical<br />

condition, aggressive type is the correct diagnosis. 3<br />

In patients with IED, physical examination may reveal<br />

nonspecific soft neurologic signs, such as minor<br />

difficulties in hand-eye coordination or small reflex<br />

asymmetries. 3 There may also be hypersensitivity to sensory<br />

stimuli or abnormalities on EEG. 11 In individuals<br />

with anger that occurs suddenly, slowing may be seen<br />

throughout the EEG. 3<br />

IED is a diagnosis of exclusion, and, as such, other<br />

psychiatric diagnoses must first be ruled out (Table 2). Because<br />

many psychiatric disorders can present with a history<br />

of impulsive aggression, distinguishing IED from other<br />

psychiatric disorders can be difficult. Antisocial personality<br />

disorder, borderline personality disorder, conduct disorder,<br />

dementia with behavioral disturbance, oppositional<br />

Hospital Physician Board Review Manual<br />

www.turner-white.com


I n t e r m i t t e n t E x p l o s i v e D i s o r d e r<br />

Table 3. Lifetime <strong>Intermittent</strong> <strong>Explosive</strong> <strong>Disorder</strong> (IED) Diagnosis and Other Comorbid Axis I Diagnoses<br />

Study<br />

Patients with IED<br />

and Other Impulse-<br />

Control <strong>Disorder</strong>s, %<br />

Patients with IED<br />

and ≥ 1 DSM-IV<br />

Axis I Diagnosis, %<br />

Patients with<br />

IED and Anxiety<br />

<strong>Disorder</strong>, %<br />

Patients with<br />

IED and Mood<br />

<strong>Disorder</strong>, %<br />

Patients with IED<br />

and Substance Use<br />

<strong>Disorder</strong>, %<br />

Kessler et al 1 * 44.9 81.8 58.1 37.4 35.1<br />

Coccaro et al 7 7.3 — 78 75.6 59.8<br />

McElroy et al 8 44 96 48 93 48<br />

*Statistics used were for broadly defined lifetime IED.<br />

defiant disorder, personality change caused by a general<br />

medical condition, aggressive type, and posttraumatic<br />

stress disorder (PTSD) all involve aggression. 5 A diagnosis<br />

of IED should be considered only after other diagnoses<br />

for impulsive aggression have been invalidated. 3<br />

When distinguishing IED from personality disorders,<br />

it is often helpful to consider baseline behavior. Aggressive<br />

behavior demonstrated on a normal daily basis is<br />

in stark contrast to the discrete episodes of impulsive<br />

aggressiveness seen in IED. 3 In children, symptoms of<br />

bipolar disorder and IED can be similar. 21<br />

The inappropriate expression of anger is a key feature<br />

in borderline personality disorder. 22 Patients with<br />

borderline personality disorder or antisocial personality<br />

disorder often describe a history of lifetime of continuance<br />

impulsive aggression instead of discrete episodes<br />

of aggression. 3 Aggression (physical, verbal, or sexual)<br />

is commonly seen in older individuals with dementia.<br />

The physical aggression seen in this disease process<br />

is often the prompt that leads to nursing home placement.<br />

19 Aggression may also be seen if individuals are<br />

under the influence or withdrawing from a substance.<br />

IED would not be diagnosed in either circumstance. 23<br />

A study addressing anger and aggression in outpatient<br />

psychiatric patients found that generalized anxiety<br />

disorder and drug abuse/dependence were linked to<br />

higher rates of aggression. IED, bipolar I disorder, and<br />

PTSD were most likely to be linked with current aggressive<br />

behavior. 24 Although aggression is not officially<br />

recognized as a characteristic of PTSD, new evidence<br />

is emerging to support that aggression does occur in<br />

PTSD. Fifty couples in which the male was a Vietnam<br />

veteran were questioned. All of the men exhibited<br />

PTSD symptoms. The survey found that 100% of these<br />

men participated in psychological aggression against<br />

their mate, 92% engaged in verbal aggression, and 34%<br />

had 1 or more episodes of physical aggression. 20<br />

Another type of aggression, anger attacks, may be<br />

seen in depressed patients and usually occur when a<br />

person feels emotionally trapped and experiences outbursts<br />

of anger. These attacks may include irritability,<br />

www.turner-white.com<br />

autonomic symptoms, and exaggerated reaction to a<br />

small irritant with rage. Three studies indicated that in<br />

patients with major depression, anger attacks were seen<br />

between 38% and 44% of the time. Studies indicate<br />

that 30% to 40% of patients with any type of depression<br />

have anger attacks. 25<br />

COMORBIDITY<br />

Studies have indicated that most individuals with<br />

IED have a least 1 other lifetime DSM-IV diagnosis<br />

(Table 3). 1,7,8 In a report of 27 cases of IED, 26 (96%)<br />

met requirements for at least 1 other DSM-IV Axis I diagnosis,<br />

and 19 (70%) patients met criteria for 3 or more<br />

diagnoses. 8 Of the 27 patients, 25 (93%) met criteria for<br />

a mood disorder during their lifetime, and 14 (52%)<br />

met lifetime criteria for bipolar disorder. Thirteen patients<br />

were diagnosed with a type of anxiety disorder,<br />

13 were diagnosed with a substance abuse/dependence<br />

disorder, 6 were diagnosed with eating disorders, and<br />

12 had other impulse-control disorders. 8 Five patients<br />

reported a diagnosis of attention-deficit/hyperactivity<br />

disorder as a child. Some participants with mood and<br />

substance use disorders reported changes in their IED<br />

symptoms with changes in mood or substance use. Six<br />

participants noted worsening IED symptoms during<br />

depression, while 5 noted a worsening of IED during<br />

mania. Of the 7 women included in the study, 5 noted<br />

that IED worsened during their premenstrual period.<br />

All individuals with substance use disorders reported<br />

differences in IED symptomatology with substance use;<br />

7 patients noted an increase in IED symptoms with alcohol<br />

use whereas 2 noted a decrease, and 5 individuals<br />

stated that marijuana decreased their IED symptoms.<br />

Incidence of headache in the sample was high, with 12<br />

of the participants reporting migraines. 8<br />

Coccaro et al 7 studied 1300 patients requesting outpatient<br />

treatment and found that in addition to meeting<br />

criteria for IED, 75.6 % also met criteria for a lifetime<br />

mood disorder, 32.7% met criteria for personality<br />

Psychiatry Volume 11, Part 5


I n t e r m i t t e n t E x p l o s i v e D i s o r d e r<br />

disorders, 59.8% met criteria for a substance use disorder,<br />

and 78% met criteria for anxiety disorders. The<br />

National Comorbidity Survey Replication found that<br />

81.8% of individuals with lifetime broad IED also had<br />

at least 1 or more other lifetime DSM-IV diagnosis. 1 In<br />

this study, the odds ratios of IED with impulse-control<br />

and substance use disorders were not higher than those<br />

with mood and anxiety disorders. Based on these data,<br />

the author proposed that IED may be as much related<br />

to affective instability and dysregulation as to problems<br />

with impulse control. This study also found that IED<br />

had an earlier age of onset than most comorbidities,<br />

suggesting that IED could be a “risk factor” for diseases<br />

such as major depression, generalized anxiety disorder,<br />

panic disorder, and substance abuse disorders. However,<br />

there are no published data to confirm this suspicion.<br />

1 There is also some speculation that IED is also<br />

associated with bipolar disorder, as many individuals<br />

who meet criteria for IED also have a lifetime diagnosis<br />

of bipolar disorder. 4<br />

TREATMENT<br />

There are few studies evaluating treatment for IED. 5<br />

Further, the U.S. Food and Drug Administration has<br />

not approved any medications for the treatment of aggression.<br />

24 The National Comorbidity Survey Replication<br />

indicated that individuals who sought treatment<br />

for IED often waited until well after their first episode,<br />

and when they did seek treatment, it was commonly for<br />

another comorbid condition. 1 Many people with IED<br />

will eventually seek mental health treatment but not<br />

for their anger episodes. It could be that many patients<br />

may not feel that anger is a reason to seek psychiatric<br />

treatment. 1 One study found that only 20% of individuals<br />

with IED who sought treatment described IED as the<br />

reason for mental health treatment. 7<br />

PHARMACOLOGIC THERAPY<br />

Although there is a paucity of studies defining<br />

treatment for IED, McElroy 26 published an algorithm<br />

for treating angry or combative individuals (Figure).<br />

According to this algorithm, patients with unipolar depression<br />

should be started on a serotonin reuptake inhibitor,<br />

other antidepressants, or lamotrigine, whereas<br />

those with bipolar depression with a history of mania<br />

or mixed episodes should be treated with a mood<br />

stabilizer, antipsychotics, other antiepileptics, or antiandrogens.<br />

If there is no affective component, it should<br />

be determined whether the individual presented with<br />

compulsive or impulsive primary symptomatology. If<br />

the patient complains of compulsivity, selective serotonin<br />

reuptake inhibitors (SSRIs) or other serotonin<br />

agents are used. If the patient complains of impulsivity,<br />

SSRIs, other antidepressants, mood stabilizers, antiepileptics,<br />

β blockers, stimulants, or antiandrogens should<br />

be prescribed. 26 In a study of 27 patients with IED, 20<br />

received treatment with either a mood stabilizer or<br />

SSRI. At least a moderate response to medication was<br />

described by 60% of the individuals. 8<br />

Lithium has been found to be effective in decreasing<br />

aggression in several studies in differing patient populations.<br />

In a study involving 66 young nonpsychotic adult<br />

and adolescent prisoners (age range, 16–24 yr), lithium<br />

was superior to placebo in demonstrating reduced aggressive<br />

episodes. 27 In a 6-week, double-blind, placebocontrolled<br />

study of adolescents with conduct disorder,<br />

patients taking lithium demonstrated reduced aggression<br />

compared with those taking placebo. 28<br />

Improvements in aggression have been seen in<br />

adolescent males with the addition of valproic acid. In<br />

a placebo-crossover, double-blind, parallel-group study<br />

of 20 teens diagnosed with oppositional defiant disorder<br />

or conduct disorder and problematic temper and<br />

mood liability, valproic acid was superior to placebo in<br />

demonstrating reduced aggression. 29<br />

Several studies have shown that carbamazepine lessens<br />

aggression in multiple psychiatric disorders. Two open<br />

studies performed by Mattes 30 and Mattes et al 31 found<br />

that carbamazepine lessened aggression in rageful patients.<br />

Both studies included patients with multiple diagnoses;<br />

12 of 28 and 19 of 34 patients, respectively, had<br />

been diagnosed with IED. In a randomized, double-blind<br />

study by Neppe, 32 aggression was 1.5 times less common<br />

when treated with carbamazepine compared with placebo.<br />

These individuals were chronic psychiatric hospitalized<br />

inpatients who did not have epilepsy but had abnormal<br />

temporal lobe findings on EEG. 32 Phenytoin has<br />

also been shown to decrease impulsive aggression. In a<br />

double-blind, placebo-controlled, crossover study performed<br />

on 60 inmates, the inmates with impulsive aggression<br />

had reductions in aggressive behavior. 33<br />

In a study of impulsive aggression in 40 patients with<br />

a personality disorder, patients treated with fluoxetine<br />

showed a significant reduction in aggressive symptoms<br />

compared with the placebo group, as measured by the<br />

Overt Aggression Scale Modified for Outpatients. 34 All<br />

40 participants in this study were found to fulfill IED research<br />

criteria. 15 SSRIs may take approximately 3 months<br />

to reach full benefit in patients with IED; thus, a sufficient<br />

trial of an SSRI should include at least 3 months.<br />

Symptoms also tend to reappear shortly after the medication<br />

is discontinued. 15<br />

Hospital Physician Board Review Manual<br />

www.turner-white.com


I n t e r m i t t e n t E x p l o s i v e D i s o r d e r<br />

Depressive/unipolar<br />

SRIs<br />

Other antidepressants<br />

Lamotrigine<br />

Is there an affective<br />

component?<br />

Affective symptoms/<br />

syndrome<br />

Manic or mixed/bipolar<br />

Mood stabilizers (eg, divalproex,<br />

lithium, carbamazepine)<br />

Antipsychotics (typical and atypical)<br />

Other antiepileptics (eg, gabapentin,<br />

phenytoin)<br />

Antiandrogens<br />

Combinations<br />

Compulsive<br />

SRIs<br />

5-HT agents<br />

Combinations<br />

No affective symptoms/<br />

syndrome<br />

Impulsive<br />

SRIs<br />

Other antidepressants<br />

Mood stabilizers<br />

Antiepileptics<br />

b Blockers<br />

Stimulants<br />

Antiandrogens<br />

Combinations<br />

Figure. Algorithm for treating agitation and violence. SRI = serotonin reuptake inhibitor. (Reprinted with permission from McElroy SL.<br />

Recognition and treatment of DSM-IV intermittent explosive disorder. J Clin Psychiatry 1999;60 Suppl 15:12–6. Copyright © 1999, Physicians<br />

Postgraduate Press.)<br />

β Blockers may also be used to treat aggression in<br />

some patients, but they have worrisome side effects,<br />

such as bradycardia, dizziness, and hypotension, and the<br />

appropriate dose is difficult to determine. 15,35 Studies<br />

evaluating pindolol in brain damaged patients showed a<br />

lessening of aggression in these patients. 5 Another study<br />

demonstrated a lessening of aggression in adolescents<br />

who were given α 2<br />

agonists. 36 However, their use in this<br />

setting has been questioned due to reports of sudden<br />

death in young patients taking α 2<br />

agonists with other<br />

drugs. The side effects include worsening depression,<br />

sedation, and decreased blood pressure. 5<br />

Recent studies have shown atypical antipsychotics to<br />

be effective in treating aggression. 37,38 Atypical antipsychotics<br />

have a preferred side effect profile compared<br />

with typical antipsychotics. 5<br />

NONPHARMACOLOGIC THERAPY<br />

Cognitive behavioral therapy has been shown to decrease<br />

anger and aggression in individuals with anger<br />

problems. These trials were not specific to IED patients;<br />

thus, more studies are needed to confirm the effectiveness<br />

of cognitive behavioral therapy in patients with<br />

IED. 15 In a small sample (n = 4) of patients who received<br />

insight-oriented or supportive psychotherapy when exhibiting<br />

IED signs, 3 of 4 found that it was useful for<br />

constraining their impulsive aggression. All 4 patients<br />

receiving family, couples, or group therapy reported no<br />

reduction in aggressive behavior with therapy. 8<br />

CONCLUSION<br />

IED is characterized by impulsive aggression occurring<br />

in discrete episodes. Impulsive aggression is seen<br />

in multiple conditions; thus, IED is a diagnosis of exclusion,<br />

and other conditions in which aggression is seen<br />

should first be ruled out before IED is diagnosed. IED<br />

also occurs in association with other psychiatric disorders,<br />

adding to the difficulty in making an appropriate<br />

diagnosis. Although the etiology is uncertain, IED has<br />

been hypothesized to originate as a result of either<br />

childhood events or alterations in brain chemistry,<br />

particularly alterations in serotonin. 3 Age of onset is<br />

www.turner-white.com<br />

Psychiatry Volume 11, Part 5


I n t e r m i t t e n t E x p l o s i v e D i s o r d e r<br />

adolescence, and risk factors include male sex, young<br />

age, being married, a decreased household income,<br />

and a high degree of social impairment. Studies evaluating<br />

IED are sparse, and studies evaluating treatments<br />

for IED are even more so. Currently, there are no drugs<br />

approved for the treatment of aggression; however, studies<br />

have demonstrated decreased aggression in certain<br />

populations with the use of pharmacologic agents, such<br />

as lithium, atypical antipsychotics, valproic acid, phenytoin,<br />

SSRIs, and β blockers, and psychotherapy.<br />

SUMMARY POINTS<br />

• Recent studies have indicated that IED is much more<br />

prevalent than previously thought; a recent study of<br />

9282 individuals found an incidence of 7.3% for lifetime<br />

diagnosis of IED and 3.9% 12-month incidence<br />

rate.<br />

• Diagnosis of IED can be difficult due to vagueness of<br />

the diagnostic criteria and the frequency of impulsive<br />

aggression seen in other illnesses.<br />

• When diagnosing IED, it is important to remember<br />

that the episodes of rage are short and substantially<br />

out of proportion to the stressor causing the event,<br />

and the episodes result in property damage or assault<br />

of individuals.<br />

• IED is a diagnosis of exclusion; thus, all other causes<br />

of rage and outbursts must be excluded before giving<br />

this diagnosis. Other diagnoses that can mimic<br />

IED include neurologic disorders, antisocial personality<br />

disorder, borderline personality disorder,<br />

conduct disorder, dementia with behavioral disturbance,<br />

oppositional defiant disorder, and PTSD.<br />

• Aggression of different forms is very common when<br />

patients are withdrawing or under the influence of<br />

different substances. These individuals should not<br />

be diagnosed with IED.<br />

• Patients with IED are at risk for high impairment in<br />

multiple aspects of their life. Many report difficulties<br />

psychosocially, and individuals with IED often have<br />

difficulties with significant relationships throughout<br />

their life.<br />

• The intensity of IED tends to lessen as the patient<br />

becomes older.<br />

• IED-related behavior is not the same as well-planned<br />

criminal behavior. If the behavior is premeditated,<br />

individuals should not be given a diagnosis of IED.<br />

• Although the average age of onset of IED appears<br />

to be in adolescence, most patients do not seek<br />

treatment until they are much older. The reason for<br />

seeking treatment is most often another psychiatric<br />

condition they have comorbidly.<br />

• Most patients with IED have at least 1 other lifetime<br />

DSM-IV diagnosis. It is common for individuals with<br />

this disorder to met criteria for 3 or more diagnoses.<br />

Mood and anxiety disorders are often seen comorbidly<br />

in patients with IED.<br />

• Risk factors for IED include male sex, young age,<br />

low level of education, marriage, employment, and<br />

having decreased revenue in the home.<br />

• IED is thought to arise as a result of experiences<br />

from youth and differences in brain chemistry. Early<br />

disruption of attachment to a primary caregiver or<br />

aggressive parenting has been shown to be risk factors<br />

for aggressive behaviors as adults. A decreased<br />

level of serotonin activity in the CSF has been seen<br />

in aggressive individuals.<br />

• Studies have indicated that certain areas of the<br />

brain, including the prefrontal cortex and amygdala,<br />

are involved in aggression. Individuals with<br />

lesions in the frontal or temporal lobe have been<br />

shown to have increased aggression.<br />

• According to McElroy, violent individuals with unipolar<br />

depression should be started on a serotonin reuptake<br />

inhibitor, another antidepressant, or lamotrigine.<br />

Individuals with bipolar depression and a history of<br />

mania should be treated with a mood stabilizer, antipsychotics,<br />

other antiepileptics, or antiandrogens.<br />

• If no affective component is present, patients should<br />

be evaluated for compulsive verses impulsive primary<br />

symptomatology. If the patient has compulsive<br />

symptoms, SSRIs or other sertonin agents are<br />

indicated. If the patient has impulsivity symptoms,<br />

SSRIs, other antidepressants, mood stabilizers, antiepileptics,<br />

β blockers, stimulants, or antiandrogens<br />

are indicated.<br />

• In certain populations, studies have indicated that<br />

pharmacologic treatments, such as lithium, valproic<br />

acid, carbamazepine, phenytoin, fluoxetine, or atypical<br />

antipsychotics, are more effective than placebo<br />

in treating aggression.<br />

• Nonpharmacologic therapy, such as cognitive behavioral<br />

therapy, can help decrease anger episodes<br />

in patients with anger problems. A small study<br />

indicated that insight-oriented and supportive psychotherapy<br />

was helpful in controlling aggression in<br />

some patients when exhibiting signs of IED.<br />

Hospital Physician Board Review Manual<br />

www.turner-white.com


I n t e r m i t t e n t E x p l o s i v e D i s o r d e r<br />

REFERENCES<br />

1. Kessler RC, Coccaro EF, Fava M, et al. The prevalence<br />

and correlates of DSM-IV intermittent explosive disorder<br />

in the National Comorbidity Survey Replication. Arch<br />

Gen Psychiatry 2006;63:669–78.<br />

2. Coccaro EF, Schmidt CA, Samuels JF, Nestadt G. Lifetime<br />

and 1-month prevalence rates of intermittent explosive<br />

disorder in a community sample. J Clin Psychiatry 2004;<br />

65:820–4.<br />

3. Tasman A, Kay J, Lieberman JA. Psychiatry. 2nd ed.<br />

Hoboken (NJ): Wiley; 2003.<br />

4. McCloskey MS, Berman ME, Noblett KL, Coccaro EF.<br />

<strong>Intermittent</strong> explosive disorder-integrated research diagnostic<br />

criteria: convergent and discriminant validity.<br />

J Psychiatr Res 2006;40:231–42.<br />

5. Olvera RL. <strong>Intermittent</strong> explosive disorder: epidemiology,<br />

diagnosis and management. CNS Drugs 2002;16:<br />

517–26.<br />

6. American Psychiatric Association. Diagnostic and statistical<br />

manual of mental disorders: DSM-IV-TR. 4th ed.,<br />

text revision. Washington (DC): American Psychiatric<br />

Association; 2000.<br />

7. Coccaro EF, Posternak MA, Zimmerman M. Prevalence<br />

and features of intermittent explosive disorder in a clinical<br />

setting. J Clin Psychiatry 2005;66:1221–7.<br />

8. McElroy SL, Soutullo CA, Beckman DA, et al. DSM-IV intermittent<br />

explosive disorder: a report of 27 cases. J Clin<br />

Psychiatry 1998;59:203–11.<br />

9. Felthous AR, Bryant SG, Wingerter CB, Barratt E. The<br />

diagnosis of intermittent explosive disorder in violent<br />

men. Bull Am Acad Psychiatry Law 1991;19:71–9.<br />

10. Olvera RL, Pliszka SR, Konyecsni WM, et al. Validation<br />

of the Interview Module for <strong>Intermittent</strong> <strong>Explosive</strong> <strong>Disorder</strong><br />

(M-IED) in children and adolescents: a pilot study.<br />

Psychiatry Res 2001;101:259–67.<br />

11. Monopolis S, Lion JR. Problems in the diagnosis of intermittent<br />

explosive disorder. Am J Pyschiatry 1983;140:<br />

1200–2.<br />

12. Kalin NH. Primate models to understand human aggression.<br />

J Clin Psychiatry 1999;60 Suppl 15:29–32.<br />

13. Connor DF, Steingard RJ, Anderson JJ, Melloni RH Jr.<br />

Gender differences in reactive and proactive aggression.<br />

Child Psychiatry Hum Dev 2003;33:279–94.<br />

14. Conger RD, Neppl T, Kim KJ, Scaramella L. Angry and<br />

aggressive behavior across three generations: a prospective,<br />

longitudinal study of parents and children. J Abnorm<br />

Child Psychol 2003;31:143–60.<br />

15. Coccaro EF. <strong>Intermittent</strong> explosive disorder: taming temper<br />

tantrums in the volatile, impulsive adult. Curr Psychiatry<br />

Online 2003;2:1–10.<br />

www.turner-white.com<br />

16. Krakowski M. Violence and serotonin: influence of impulse<br />

control, affect regulation, and social functioning.<br />

J Neuropsychiatry Clin Neurosci 2003;15:294–305.<br />

17. Haller J, Kruk MR. Normal and abnormal aggression:<br />

human disorders and novel laboratory models. Neurosci<br />

Biobehav Rev 2006;30:292–303.<br />

18. Horn NR, Dolan M, Elliott R, et al. Response inhibition<br />

and impulsivity: an fMRI study. Neuropsychologia<br />

2003;41:1959–66.<br />

19. Raskind MA. Evaluation and management of aggressive<br />

behavior in the elderly demented patient. J Clin Psychiatry<br />

1999;60:Suppl 15:45–9.<br />

20. Yehuda R. Managing anger and aggression in patients<br />

with posttraumatic stress disorder. J Clin Psychiatry 1999;<br />

60 Suppl 15:33–7.<br />

21. Davanzo P, Yue K, Thomas MA, et al. Proton magnetic<br />

resonance spectroscopy of bipolar disorder versus intermittent<br />

explosive disorder in children and adolescents.<br />

Am J Psychiatry 2003;160:1442–52.<br />

22. Hollander E. Managing aggressive behavior in patients<br />

with obsessive-compulsive disorder and borderline personality<br />

disorder. J Clin Psychiatry 1999;60 Suppl 15:<br />

38–44.<br />

23. Stern TA, Herman JB, editors. Psychiatry update and<br />

board preparation. New York: McGraw-Hill; 2000.<br />

24. Posternak MA, Zimmerman M. Anger and aggression<br />

in psychiatric outpatients. J Clin Psychiatry 2002;63:<br />

665–72.<br />

25. Fava M, Rosenbaum JF. Anger attacks in patients with<br />

depression. J Clin Psychiatry 1999;60 Suppl 15:21–4.<br />

26. McElroy SL. Recognition and treatment of DSM-IV intermittent<br />

explosive disorder. J Clin Psychiatry 1999;60<br />

Suppl 15:12–6.<br />

27. Sheard MH, Marini JL, Bridges CI, Wagner E. The effect<br />

of lithium on impulsive aggressive behavior in men. Am<br />

J Psychiatry 1976;133:1409–13.<br />

28. Malone RP, Delaney MA, Luebbert JF, et al. A doubleblind<br />

placebo-controlled study of lithium in hospitalized<br />

aggressive children and adolescents with conduct disorder.<br />

Arch Gen Psychiatry 2000;57:649–54.<br />

29. Donovan SJ, Stewart JW, Nunes EV, et al. Divalproex<br />

treatment for youth with explosive temper and mood<br />

lability: a double-blind, placebo-controlled crossover design<br />

[published erratum appears in Am J Psychiatry 2000;<br />

157:1038]. Am J Psychiatry 2000;157:818–20.<br />

30. Mattes JA. Carbamezapine for uncontrolled rage outbursts.<br />

Lancet 1984;2:1164–5.<br />

31. Mattes JA, Rosenberg J, Mays D. Carbamazepine versus<br />

propranolol in patients with uncontrolled rage outbursts:<br />

a random assignment study. Psychopharmacol<br />

Bull 1984;20:98–100.<br />

32. Neppe VM. Carbamazepine as adjunctive treatment in<br />

non-epileptic chronic inpatients with EEG temporal<br />

lobe abnormalities. J Clin Psychiatry 1983;44:326–31.<br />

Psychiatry Volume 11, Part 5


I n t e r m i t t e n t E x p l o s i v e D i s o r d e r<br />

33. Barratt ES, Stanford MS, Felthous A, Kent TA. The effects<br />

of phenytoin on impulsive and premeditated aggression:<br />

a controlled study. J Clin Psychopharmacol 1997;<br />

17:341–9.<br />

34. Coccaro EF, Kavoussi RJ. Fluoxetine and impulsive aggressive<br />

behavior in personality disordered subjects. Arch<br />

Gen Psychiatry 1997;54:1081–8.<br />

35. Sadock BJ, Sadock VA. Kaplan & Sadock’s synopsis of<br />

psychiatry: behavioral sciences/clinical psychiatry. 9th ed.<br />

Philadelphia: Lippincott Williams & Wilkins; 2003.<br />

36. Kemph JP, DeVane CL, Levin GM, et al. Treatment of aggressive<br />

children with clonidine: results of an open pilot<br />

study. J Am Acad Child Adoles Psychiatry 1993;32:577–81.<br />

37. Buitelaar JK, van der Gaag RJ, Cohen-Ketternis P, Melman<br />

CT. A randomized controlled trial of risperidone in the<br />

treatment of aggression in hospitalized adolescents with<br />

subaverage cognitive abilities. J Clin Psychiatry 2001;62:<br />

239–48.<br />

38. Jibson MD, Tandon R. New atypical antipsychotic medications.<br />

J Psychiatr Res 1998;32:215–28.<br />

test yourself with self-assessment questions<br />

Questions for self-assessment in selected specialties are available on Hospital Physician’s Web site.<br />

Go to www.turner-white.com, click on Hospital Physician, then click on “Self-Assessment Questions.”<br />

Copyright 2008 by <strong>Turner</strong> <strong>White</strong> Communications Inc., Wayne, PA. All rights reserved.<br />

10 Hospital Physician Board Review Manual www.turner-white.com

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!