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1
Introduction
The purpose of this report is to evaluate and recommend treatments
for the array of medically unexplained symptoms—termed chronic multi
symptom illness (CMI)—experienced by veterans of the Gulf War. CMI
is sometimes referred to as Gulf War syndrome or Gulf War illness. The
definition of CMI used in this report is included in Chapter 2.
Throughout modern history, many soldiers returning from combat
have experienced postcombat illnesses (Hyams et al., 1996; Jones, 2006;
Jones and Wessely, 2005). Efforts to define the illnesses have resulted in
descriptive names, such as irritable heart, Da Costa’s syndrome, shell shock,
combat fatigue, and posttraumatic stress disorder (PTSD). Many soldiers
who have postcombat illnesses have long-term unexplained symptoms that
cannot now be attributed to any diagnosable pathophysiologic etiology or
disease; such symptoms are referred to as medically unexplained. CMI dif-
fers from such postcombat illnesses as PTSD that have a defined complex of
symptoms (Jones, 2006; Mahoney, 2001; Zavestoski et al., 2004). Soldiers
who have CMI often have nonspecific physical symptoms (such as fatigue,
joint and muscle pain, and gastrointestinal symptoms) and cognitive symp-
toms (such as reduced processing speed and memory difficulties) in addition
to symptoms that are commonly associated with depression and anxiety.
PRIOR EFFORTS TO ADDRESS CHRONIC
MULTISYMPTOM ILLNESS IN GULF WAR VETERANS
In efforts to understand CMI and how to treat for it, substantial
resources have been devoted to determining its underlying cause. Govern-
11
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12 GULF WAR AND HEALTH
ment agencies in the United States and elsewhere have pursued or funded
ambitious research programs to study CMI (Mahoney, 2001; Zavestoski et
al., 2004). Most research on the cause of CMI has focused on environmen-
tal toxicants to which military personnel may have been exposed. Those
toxicants include a long list of chemical, biologic, and physical agents
(Persian Gulf War Veterans Act of 1998, Public Law 277, 105th Cong.,
October 8, 1998; Veterans Programs Enhancement Act of 1998, Public
Law 368, 105th Cong., October 21, 1998). The focus on toxicants may be
attributed, at least in part, to “a general fear of toxins spread as a result
of modern industrial life” (Jones and Wessely, 2005). Many agents used
in combat operation may be harmful to humans, depending on exposure
routes and quantities. Concern about health effects of exposure to toxicants
during war became ingrained in our culture with the Vietnam War, when
a herbicide, Agent Orange, was implicated as a source of serious health
problems in veterans and others who were exposed.
The present committee is not the first Institute of Medicine (IOM) com-
mittee to evaluate treatments for CMI in Gulf War veterans. In 2001, IOM
released a report, Gulf War Veterans: Treating Symptoms and Syndromes,
which examined how to manage medically unexplained physical symptoms
(MUPS; termed CMI in this report) (IOM, 2001). The committee that
wrote that report found sparse evidence on treatments for MUPS and so
was unable to recommend specific treatments. It did, however, recommend
a general approach for the management of patients who had MUPS. That
approach included
• Using diagnostic testing and medication only as medically necessary.
• Using appropriate reassurance strategies to comfort patients.
• Setting realistic goals in collaboration with patients.
• Encouraging patients to exercise regularly to improve functioning.
• Encouraging patients to involve their families and friends, if appro-
priate, in their care.
• Coordinating care among clinicians so that patients do not bounce
from specialist to specialist, receive many unnecessary diagnostic
procedures, and end up on multiple unnecessary medications.
• Introducing specialty mental health consultation, if needed. (“Most
patients with MUPS do not require psychiatric treatment or psy-
chological testing.”) (IOM, 2001).
In 2006 and again in 2010, IOM committees reviewed and evaluated
the scientific literature on the health status of 1991 Gulf War veterans.
Both committees found that veterans of the 1991 Gulf War who had been
deployed reported more symptoms than their nondeployed counterparts
(IOM, 2006b, 2010a). The later report concluded that there is “suffi-
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INTRODUCTION 13
cient evidence of association between deployment to the Gulf War and
chronic multisymptom illness” (p. 210), that “the excess of unexplained
medical symptoms reported by deployed Gulf War veterans cannot be reli-
ably ascribed to any known psychiatric disorder” (p. 109), and that the
u
nexplained symptoms might “result from interplay between . . . biological
and psychological factors” (p. 260).
A number of IOM reports have examined associations between health
outcomes and exposures that military personnel may have been subject to
during their service in the 1991 Gulf War—chemical exposures (for exam-
ple, to combustion products, pesticides, pyridostigmine bromide, sarin,
and solvents), biologic exposures (for example, to infectious agents and
vaccines), and physical exposures (for example, to depleted uranium) (IOM,
2000, 2003, 2004, 2005, 2006a,b, 2007, 2008, 2010a). In sum, those
reports did not find evidence that would support a confident attribution of
the array of unexplained symptoms reported by veterans of the 1991 Gulf
War to any specific chemical, biologic, or physical exposure.
There is a lack of consensus among expert groups regarding the cause
of CMI in 1991 Gulf War veterans. Most experts who have studied the
issue have not identified what they consider to be a likely cause of CMI.
However, the Department of Veterans Affairs (VA) Research Advisory
Committee on Gulf War Veterans’ Illness (RAC) conducted a review of the
evidence and concluded that Gulf War illness was causally associated with
use of pyridostigmine bromide pills and exposure to pesticides used during
deployment (RAC, 2008). IOM reviewed the epidemiologic and experi
mental studies cited in the RAC report and concluded that the evidence was
not robust enough to establish a causal relationship between pyridostigmine
bromide or pesticides and CMI (IOM, 2010a).
Despite many years of research, there is no consensus among physi-
cians, researchers, and others as to the cause of CMI in 1991 Gulf War
veterans, and there is a growing belief that a causal factor or agent may
not be identified (IOM, 2010a; Mahoney, 2001). It is also possible that an
underlying physiologic abnormality may not be identified. The 2010 IOM
committee recommended “a renewed research effort with substantial com-
mitment to well-organized efforts to better identify and treat multisymptom
illness in Gulf War veterans” (IOM, 2010a).
THE CHARGE TO THE COMMITTEE
The present study was mandated by Congress in the Veterans Benefits
Act of 2010 (Public Law 111-275, October 13, 2010). The law directs the
secretary of veterans affairs “to enter into an agreement with the Institute of
Medicine of the National Academies to carry out a comprehensive review of
the best treatments for CMI in Persian Gulf War veterans and an evaluation
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14 GULF WAR AND HEALTH
of how such treatment approaches could best be disseminated throughout
the Department of Veterans Affairs to improve the care and benefits pro-
vided to veterans.” In August 2011, VA asked that IOM conduct a study
to address that charge, and IOM appointed the Committee on Gulf War
and Health: Treatment for Chronic Multisymptom Illness. The complete
charge to the committee is in Box 1-1. A description of how the committee
approached its charge can be found in Chapter 3 and its evaluation of the
evidence, conclusions, and recommendations are presented in Chapters 4–8.
BOX 1-1
The Committee’s Charge
The Institute of Medicine (IOM) will convene a committee to compre-
hensively review, evaluate, and summarize the available scientific and
medical literature regarding the best treatments for chronic multisymptom
illness among Gulf War veterans.
In its evaluation, the committee will look broadly for relevant informa-
tion. Information sources to pursue could include, but are not limited to
• Published peer-reviewed literature concerning the treatment of
multisymptom illness among the 1991 Gulf War veteran population;
• Published peer-reviewed literature concerning treatment of mul-
tisymptom illness among Operation Enduring Freedom, Opera-
tion Iraqi Freedom, and Operation New Dawn active-duty service
members and veterans;
• Published peer-reviewed literature concerning treatment of multi-
symptom illness among similar populations such as allied military
personnel; and
• Published peer-reviewed literature concerning treatment of popula-
tions with a similar constellation of symptoms.
In addition to summarizing the available scientific and medical lit-
erature regarding the best treatments for chronic multisymptom illness
among Gulf War veterans, the IOM will
• Recommend how best to disseminate this information throughout
the Department of Veterans Affairs to improve the care and ben-
efits provided to veterans.
• Recommend additional scientific studies and research initiatives to
resolve areas of continuing scientific uncertainty.
• Recommend such legislative or administrative action as the IOM
deems appropriate in light of the results of its review.
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INTRODUCTION 15
THE GULF WAR VETERAN POPULATION
Veterans are considered to have served in the Gulf War if they were
on active military duty in the Southwest Asia theater of military opera-
tions during the period from the 1991 Gulf War (Operation Desert Storm)
through the Iraq War (Operation Iraqi Freedom and Operation New Dawn)
(VA, 2012b). The Gulf War officially began on August 2, 1990, when Iraqi
troops invaded Kuwait. US and coalition troops arrived in the theater in
January 1991, and combat was over on February 28, 1991. A cease-fire
with Iraq was signed in April 1991, and the last US troops participating in
the ground war arrived back in the United States in June of that year. Dur-
ing the 1990s, US troops participated in a variety of military activities in
the Southwest Asia theater of operation. The United States has not formally
declared an end to the Gulf War, and the Iraq War is considered part of the
same military mission (VA, 2011). For the purpose of this report, although
Afghanistan is not in the Southwest Asia theater of operation, veterans of
the Afghanistan War (Operation Enduring Freedom) are included in the
Gulf War veteran population. A substantial number of soldiers have served
in both the Iraq and Afghanistan theaters of operation. Three populations
of Gulf War veterans are referred to in this report: 1991 Gulf War veterans,
Iraq War veterans, and Afghanistan War veterans.
About 700,000 military personnel participated in the 1991 Gulf War
(VA, 2012a). Estimates of the numbers of 1991 Gulf War veterans who
have CMI range from 175,000 to 250,000 (about 25–35% of the 1991
Gulf War veteran population) (IOM, 2010a; RAC, 2008). As noted above
and discussed in more detail in later chapters, 1991 Gulf War veterans
who have CMI experience a large constellation of symptoms. A number of
research studies have been conducted to determine whether those symptoms
can be grouped into symptom clusters (see the 2010 IOM report for a sum-
mary of the studies), but the research has identified no symptom clusters,
or syndromes.
There is evidence that CMI in 1991 Gulf War veterans may not resolve
over time. Many of the symptoms reported by veterans of that war are
chronic. Ill veterans in general (not only those who have CMI) who were
deployed to the gulf in 1991 are more likely than nondeployed veterans
who served during the same era to report persistent health problems and
to develop new ones (Li et al., 2011). Health outcomes assessed by Li et
al. (2011) include chronic fatigue syndrome–like illness, functional impair-
ment, limitation of activities, clinic visits and hospitalizations, and self-
perception of health.
As discussed above, Gulf War veterans include military personnel who
served in the Iraq war and, for the purpose of this report, the Afghanistan
war, in addition to those who served in the 1991 war. As of September
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16 GULF WAR AND HEALTH
2011, 2.6 million military personnel have been deployed to Iraq or Afghani-
stan (GAO, 2011).
Deployments to the Iraq and Afghanistan war theaters differ somewhat
from deployments to the 1991 Gulf War. Women make up about 11% of
US military personnel who have served in Iraq and Afghanistan compared
with about 7% in the 1991 Gulf War (IOM, 2010a,b). Nearly one-fourth
of military personnel who have served in Iraq and Afghanistan have been
from the National Guard and reserves compared with about 17% in the
1991 Gulf War (IOM, 2010a,b). National Guard and reserve personnel
are substantially older than active-duty personnel; for example, 73.6% of
reserve officers are over 35 years old compared with 44.2% of active-duty
officers (IOM, 2010b). Military personnel in the Iraq and Afghanistan wars
have been exposed to more hostile fire, including blasts from improvised
explosive devices. Their deployments are longer than those in the 1991
Gulf War, and repeated deployments are common. Personnel who have at
least one prior deployment are more likely to screen positive for PTSD and
major depression and to report chronic pain than those who have no prior
deployments (Kline et al., 2010).
Three health conditions often are associated with service in the Iraq and
Afghanistan wars: PTSD, traumatic brain injury (TBI), and chronic pain.
Lew et al. (2009) reviewed medical records of 340 Iraq and Afghanistan war
veterans at a VA polytrauma center and found that the prevalence of PTSD
was 68.2%, of persistent postconcussive symptoms from TBI 66.8%, and
of chronic pain 81.5%. A substantial number of those veterans—42.1%—
had all three conditions. Other studies have also reported high rates of that
triad of conditions (Reisinger et al., 2012; Walker et al., 2010). Symptoms
reported by Iraq and Afghanistan war veterans include headaches, chronic
pain (particularly lower back and joint pain), sleep disturbances, fatigue,
irritability, and concentration, attention, and memory problems (Walker et
al., 2010). Many symptoms experienced by Iraq and Afghanistan war vet-
erans overlap with those experienced by 1991 Gulf War veterans.
GULF WAR VETERANS’ EXPERIENCES WITH DIAGNOSIS OF
AND TREATMENT FOR CHRONIC MULTISYMPTOM ILLNESS
During the 1991 Gulf War and on returning to the United States after
deployment, ill veterans have sought help for the diagnosis of and treatment
for their CMI. Many were seen initially by clinicians at VA facilities but
became frustrated because VA clinicians diagnosed psychologic conditions
(for example, depression, anxiety disorders, stress-related complaints, and
somatoform disorders) (Shriver and Waskul, 2006; Swoboda, 2006). Often,
they received no diagnosis at all (Zavestoski et al., 2004) or received many
diagnoses and were confused by what they “officially” had (Furey, 2012).
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INTRODUCTION 17
In some cases, the veterans sought answers to their health problems from
private clinicians, often at great personal financial expense.
Losing trust in medical professionals, veterans have also searched for
information about their symptoms and potential diagnoses and treatments
through the Internet, medical books and articles, newspapers, their peers,
and other sources (Swoboda, 2006). An analysis of veterans’ Internet use
related to CMI suggests that their primary means of Internet communica-
tion is discussion boards, although blogs (including microblogs), Facebook,
and media-sharing are also used (Furey, 2012). Their searches sometimes
have led them to alternative medical treatments, such as unconventional
diets, detoxification, vitamins, physical and manipulative therapies, reli-
gious and metaphysical practices, and “New Age” and self-improvement
philosophies (Furey, 2012; Swoboda, 2006).
Because those who are ill do not have a disease with a distinct etiology,
veterans of the 1991 Gulf War believe that the legitimacy of their illness
is often called into question by clinicians, family members, friends, and
others (Shriver and Waskul, 2006). The stress caused by the necessity to
prove repeatedly that they are ill can add to the veterans’ health problems
by creating anxiety, which in turn may exacerbate the veterans’ symptoms
(Zavestoski et al., 2004).
Some ill 1991 Gulf War veterans, believing that they are being given
wrong diagnoses and are being inadequately treated by clinicians, view
themselves as “victims of an entrenched medical discourse that makes
it difficult for many practitioners to recognize new patterns of illness”
( woboda, 2006, p. 247). They are left feeling distrustful of and betrayed
S
by the health care system (Furey, 2012). Therefore, it is not surprising that
a different approach to managing veterans who have CMI has been pro-
posed (Mahoney, 2001; Zavestoski et al., 2004). Mahoney (2001) stated
that clinicians should approach CMI with “a person-centered rather than a
disease-centered model of care that allows patients more control over their
diagnoses and treatment plans, that helps patients understand that the word
psychosomatic is not pejorative, and that concentrates less on finding the
origin of disease than on treating its symptoms” (p. 581).
ORGANIZATION OF THIS REPORT
The committee’s work is presented in seven additional chapters. Chap-
ter 2 explains the terminology surrounding CMI and how the term is used
by the committee. It also covers what is known about CMI (for example,
the understanding of its course) and why the committee believes that it is
appropriate to evaluate the literature on CMI in populations other than
Gulf War veterans as part of its analysis. Chapter 3 describes how the
committee approached its charge, including its strategy for assessing treat-
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18 GULF WAR AND HEALTH
ments for CMI. Chapter 4 summarizes the evidence on treatments for CMI
and the committee’s evaluation of it. Chapter 5 discusses evidence-based
treatment practices for conditions that either have overlapping symptoms
with CMI or present comorbidly with CMI (for example, chronic fatigue
syndrome, fibromyalgia, irritable bowel syndrome, depression, and anxi-
ety). Chapter 6 describes how the way in which clinicians engage with their
patients can affect the course of CMI. Chapter 7 provides information
on VA’s current model of care for veterans who have CMI and describes
alternative models of care and how they may be implemented by VA health
care system. Finally, Chapter 8 presents the committee’s recommendations.
Brief biographies of the committee members are in Appendix A, a discus-
sion of possible factors underlying the symptoms of CMI in Appendix B,
and examples of ineffective and effective clinician–patient discussions in
Appendix C.
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INTRODUCTION 19
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