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GULF WAR and HEALTH
Treatment for
Chronic Multisymptom Illness
Committee on Gulf War and Health:
Treatment for Chronic Multisymptom Illness
Board on the Health of Select Populations
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THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
NOTICE: The project that is the subject of this report was approved by the
Governing Board of the National Research Council, whose members are drawn
from the councils of the National Academy of Sciences, the National Academy of
Engineering, and the Institute of Medicine. The members of the committee respon-
sible for the report were chosen for their special competences and with regard for
appropriate balance.
This study was supported by Contract VA241-P-2024 between the National Acad-
emy of Sciences and the Department of Veterans Affairs. Any opinions, findings,
conclusions, or recommendations expressed in this publication are those of the
authors and do not necessarily reflect the views of the organizations or agencies
that provided support for the project.
International Standard Book Number-13: 978-0-309-27802-7
International Standard Book Number-10: 0-309-27802-3
Additional copies of this report are available for sale from the National Academies
Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or
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at: www.iom.edu.
Copyright 2013 by the National Academy of Sciences. All rights reserved.
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adopted as a logotype by the Institute of Medicine is a relief carving from ancient
Greece, now held by the Staatliche Museen in Berlin.
Suggested citation: IOM (Institute of Medicine). 2013. Gulf War and Health:
reatment for Chronic Multisymptom Illness. Washington, DC: The National
T
Academies Press.
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“Knowing is not enough; we must apply.
Willing is not enough; we must do.”
—Goethe
Advising the Nation. Improving Health.
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The National Academy of Sciences is a private, nonprofit, self-perpetuating society
of distinguished scholars engaged in scientific and engineering research, dedicated to
the furtherance of science and technology and to their use for the general welfare.
Upon the authority of the charter granted to it by the Congress in 1863, the Acad-
emy has a mandate that requires it to advise the federal government on scientific
and technical matters. Dr. Ralph J. Cicerone is president of the National Academy
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of the National Academy of Sciences, as a parallel organization of outstanding
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sharing with the National Academy of Sciences the responsibility for advising the
federal government. The National Academy of Engineering also sponsors engineer-
ing programs aimed at meeting national needs, encourages education and research,
and recognizes the superior achievements of engineers. Dr. Charles M. Vest is presi-
dent of the National Academy of Engineering.
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Sciences to secure the services of eminent members of appropriate professions in
the examination of policy matters pertaining to the health of the public. The Insti-
tute acts under the responsibility given to the National Academy of Sciences by its
congressional charter to be an adviser to the federal government and, upon its own
initiative, to identify issues of medical care, research, and education. Dr. Harvey V.
Fineberg is president of the Institute of Medicine.
The National Research Council was organized by the National Academy of Sci-
ences in 1916 to associate the broad community of science and technology with the
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ouncil is administered jointly by both Academies and the Institute of Medicine.
Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively,
of the National Research Council.
www.national-academies.org
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COMMITTEE ON GULF WAR AND HEALTH:
TREATMENT FOR CHRONIC MULTISYMPTOM ILLNESS
BERNARD M. ROSOF (Chair), Chairman, Board of Directors,
Huntington Hospital, Huntington, NY
DIANA D. CARDENAS, Professor and Chair, Department of
Rehabilitation Medicine, University of Miami Leonard M. Miller
School of Medicine, Miami, FL
FRANK V. deGRUY, Woodward-Chrisholm Professor and Chair,
Department of Family Medicine, University of Colorado School of
Medicine, Aurora, CO
DOUGLAS A. DROSSMAN, Adjunct Professor of Medicine and
Psychiatry, Center for Functional Gastrointestinal and Motility
Disorders, University of North Carolina School of Medicine, and
Drossman Center for the Education and Practice of Biopsychosocial
Care, Chapel Hill, NC
FRANCESCA C. DWAMENA, Professor and Acting Chair, Department
of Medicine, Michigan State University, East Lansing, MI
JAVIER I. ESCOBAR, Associate Dean for Global Health, University of
Medicine & Dentistry of New Jersey, New Brunswick, NJ
WAYNE A. GORDON, Jack Nash Professor and Vice Chair, Department
of Rehabilitation Medicine, Mount Sinai School of Medicine,
New York, NY
ISABEL V. HOVERMAN, Physician, Austin Internal Medicine
Associates, LLP, Austin, TX
WAYNE JONAS, President and CEO, Samueli Institute, Alexandria, VA
JOANNA G. KATZMAN, Associate Professor, Department of
Neurosurgery, University of New Mexico School of Medicine,
Albuquerque, NM
ELAINE L. LARSON, Associate Dean for Research, Columbia University
School of Nursing, New York, NY
STEPHEN RAY MITCHELL, Dean of Medical Education, Georgetown
University School of Medicine, Washington, DC
KAREN A. ROBINSON, Assistant Professor, Departments of Medicine,
Epidemiology, and Health Policy and Management, Johns Hopkins
University, Baltimore, MD
KASISOMAYAJULA VISWANATH, Associate Professor, Department of
Society, Human Development, and Health, Harvard School of Public
Health, Boston, MA
LORI ZOELLNER, Associate Professor, Department of Psychology,
University of Washington, Seattle, WA
v
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Staff
ABIGAIL MITCHELL, Study Director
CARY HAVER, Associate Program Officer
JONATHAN SCHMELZER, Senior Program Assistant
NORMAN GROSSBLATT, Senior Editor
GARY WALKER, Financial Officer
JIM BANIHASHEMI, Financial Officer
FREDERICK ERDTMANN, Director, Board on the Health of Select
Populations
vi
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Reviewers
This report has been reviewed in draft form by persons chosen for their
diverse perspectives and technical expertise in accordance with procedures
approved by the National Research Council’s Report Review Committee. The
purpose of this independent review is to provide candid and critical comments
that will assist the institution in making its published report as sound as pos-
sible and to ensure that the report meets institutional standards of objectivity,
evidence, and responsiveness to the study charge. The review comments and
draft manuscript remain confidential to protect the integrity of the delibera-
tive process. We thank the following for their review of the report:
Niloofar Afari, University of California, San Diego
Melvin S. Blanchard, Washington University School of Medicine
Paul W. Brandt-Rauf, University of Illinois at Chicago School of
Public Health
Sandro Galea, Columbia University Mailman School of Public Health
Naomi L. Gerber, George Mason University
Thomas V. Holohan, Clinical Evaluation, LLC; formerly Veterans
Health Administration
David R. Nerenz, Henry Ford Health System
Eliseo J. Perez-Stable, University of California, San Francisco
Karen S. Quigley, Northeastern University and Edith Nourse Rogers
Memorial VA Medical Center
Sandra J. W. Smeeding, Veterans Affairs Salt Lake City Health Care
System
Nancy Fugate Woods, University of Washington School of Nursing
vii
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viii REVIEWERS
Although the reviewers listed above have provided many constructive
comments and suggestions, they were not asked to endorse the conclusions
or recommendations, nor did they see the final draft of the report before its
release. The review of the report was overseen by Lynn R. Goldman, Dean,
the George Washington University School of Public Health and Health
Services, and Enriqueta C. Bond, President Emeritus, Burroughs Wellcome
Fund. Appointed by the National Research Council and the Institute of
Medicine, respectively, they were responsible for making certain that an
independent examination of the report was carried out in accordance with
institutional procedures and that all review comments were carefully con-
sidered. Responsibility for the final content of the report rests entirely with
the authoring committee and the institution.
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Preface
The committee was convened to review, evaluate, and summarize the
available scientific and medical literature regarding the best treatments for
chronic multisymptom illness (CMI) in Gulf War veterans. We accepted
that responsibility in recognition of the personal and family sacrifices
that all soldiers—both deployed and nondeployed—undertake in times of
conflict. About 700,000 military personnel served in the 1991 Gulf War,
and as of September 2011, about 2.6 million military personnel had been
deployed to the Iraq and Afghanistan wars. There is no script for the
stresses that are endured; they are personal and many. The committee was
most appreciative of the willingness of many veterans to share their experi-
ences and thoughts with us so that we would be better prepared to move
forward with our task. We undertook a thorough review of the studies1
already completed by the Institute of Medicine (IOM) on this general topic
and then expanded the evidence base by conducting a systematic search of
the available scientific and medical literature regarding the best treatments
for CMI. The committee evaluated the evidence by using the scientifically
rigorous process detailed in this report. As we approached the task at
hand, we stood firm on the concerns for patient-centered care and our
abilities to communicate our thoughts, conclusions, and recommendations
to all interested audiences.
1
IOM (Institute of Medicine). 2001. Gulf War Veterans: Treating Symptoms and Syndromes.
Washington, DC: National Academy Press; IOM. 2010. Gulf War and Health, Volume 8:
Update of Health Effects of Serving in the Gulf War. Washington, DC: The National Acad-
emies Press.
ix
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x PREFACE
To focus our efforts, we defined CMI as the presence of a spectrum of
chronic symptoms experienced for 6 months or longer in at least two of
six categories—fatigue, mood and cognition, musculoskeletal, gastrointes-
tinal, respiratory, and neurologic—that may overlap with but are not fully
captured by known syndromes (such as irritable bowel syndrome, chronic
fatigue syndrome, and fibromyalgia) or other diagnoses.
Our review of the literature revealed that specific etiologic agents or
histopathologic findings often are not associated with such symptoms, and
the causes of many of the symptoms ascribed to CMI remain unknown.
However, the lack of diagnostic and etiologic clarity does not undermine
the legitimacy of the reports of the symptoms. The multiple manifestations
of the symptoms make directed treatment more challenging, and clinicians
are often frustrated by the difficulties in managing care for people who have
CMI. However, for veterans whose function and life satisfaction are limited
by their symptoms, it remains no less important.
We hope that our recommendations will make a difference in the
lives of people who have CMI. It is clear that this condition has adversely
affected the health and well-being of a substantial number of our veterans
and their families. Anecdotal reports appear regularly in the mass media.2
We encourage the Department of Veterans Affairs (VA) to apply the prin-
ciples set forth in this report, including at a minimum adequate resources
to ensure early entry into the VA health care system and adherence to the
principles of patient-centered and compassionate care, shared decision
m
aking, and regular clinical follow-up as necessary. Our veterans deserve
the very best health care.
The committee thanks everyone who presented and participated in
discussions during the public meetings, which informed our work and
helped us to develop our approach to and thought process regarding the
statement of task. The wide variety of viewpoints were expressed during
those information sessions provided valuable insight into the complexity
of medical treatment for CMI in Gulf War veterans. The time and effort to
travel to the public meetings and prepare written materials and statements
are greatly appreciated.
The committee is particularly appreciative of the many Gulf War vet-
erans who spoke and submitted written accounts of their experiences in
the gulf and on their return to the United States. They provided valuable
understanding of the symptoms and medical conditions of CMI and of
medical treatment for it as experienced by the many men and women who
served in the Gulf War.
The committee also owes a debt of gratitude to the following persons
who traveled to and presented valuable information at our public meetings:
2
For example, Kristof, N. D. 2012. War wounds. New York Times, August 10, SR1.
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PREFACE xi
Caroline Blaum, University of Michigan Health System; Daniel Clauw,
University of Michigan Health System; Jeffery Dusek, Abbott Northwestern
Hospital; Charles Engel, Deployment Health Clinical Center; Beatrice
Golomb, University of California, San Diego, School of Medicine and San
Diego VA Medical Center; Stephen Hunt, VA Puget Sound Health Care Sys-
tem; Kenneth Kendler, Virginia Commonwealth University; Kurt Kroenke,
Regenstrief Institute; Ronald Poropatich, US Army Medical Research and
Materiel Command; and Matt Reinhard, War-Related Illness and Injury
Study Center, Washington, DC.
The committee thanks Patrick Furey of Consumersphere, a consultant
who provided an analysis of the social media discussion surrounding CMI
in veterans of the Gulf War. We also thank Michael Peterson and Terry
W
alters, of the VA Office of Public Health, for providing helpful back-
ground information.
I would like to thank the committee members for their time commit-
ment to this important project, their diligence in reviewing every detail of
complex issues, and their sensitivity to the concerns of our veterans. Finally,
I thank the IOM staff for their thoroughness, knowledge, research exper-
tise, and guidance throughout this journey to try to make a contribution to
the understanding of a complex subject.
Bernard M. Rosof, Chair
Committee on Gulf War and Health:
Treatment for Chronic Multisymptom Illness
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Contents
ABBREVIATIONS AND ACRONYMS xix
SUMMARY 1
1 INTRODUCTION 11
Prior Efforts to Address Chronic Multisymptom Illness in
Gulf War Veterans, 11
The Charge to the Committee, 13
The Gulf War Veteran Population, 15
Gulf War Veterans’ Experiences with Diagnosis of and
Treatment for Chronic Multisymptom Illness, 16
Organization of This Report, 17
References, 18
2 CHARACTERIZING CHRONIC MULTISYMPTOM ILLNESS 21
Terminology, 21
The Committee’s Working Definition of Chronic
Multisymptom Illness, 23
Chronic Multisymptom Illness in Civilian and Veteran
Populations, 24
Veteran vs Civilian Populations, 26
Managing vs Curing Chronic Multisymptom Illness, 26
References, 27
xiii
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xiv CONTENTS
3 METHODS 29
Systematic Review of Treatments for Chronic Multisymptom
Illness, 30
Treatments for Comorbid Conditions with Shared Symptoms, 32
Additional Sources of Information, 34
Current Research on Chronic Multisymptom Illness, 35
References, 35
4 TREATMENT FOR CHRONIC MULTISYMPTOM ILLNESS 37
Pharmacologic Interventions, 38
Other Biologic Interventions, 40
Psychotherapies, 41
Mind–Body Approaches, 56
Exercise, 79
Discussion, 79
References, 87
5 REVIEW OF TREATMENTS FOR COMORBID AND
RELATED CONDITIONS 93
Fibromyalgia, 94
Chronic Pain, 95
Chronic Fatigue Syndrome, 97
Somatic Symptom Disorders, 100
Sleep Disorders, 101
Functional Gastrointestinal Disorders: Irritable Bowel Syndrome
and Functional Dyspepsia, 102
Depression, 106
Anxiety, 108
Posttraumatic Stress Disorder, 109
Traumatic Brain Injury, 111
Substance-Use and Addictive Disorders, 113
Self-Harm, 116
General Therapeutic Approach, 119
References, 123
6 PATIENT-CENTERED CARE OF VETERANS WHO HAVE
CHRONIC MULTISYMPTOM ILLNESS 133
Clinician Training, Practice Behaviors, and Chronic
Multisymptom Illness, 133
Improving Communication Skills and the Patient–Clinician
Relationship, 136
Information and Communication Technologies, Communication
Inequalities, and Chronic Multisymptom Illness, 146
References, 149
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CONTENTS xv
7 IMPLEMENTATION AND MODELS OF CARE FOR
VETERANS WHO HAVE CHRONIC MULTISYMPTOM
ILLNESS 155
Models of Care for Chronic Multisymptom Illness in the
Department of Veterans Affairs Health Care System, 156
Gulf War Veterans’ Experience of Care, 161
An Approach to Organizing Services for Care of Veterans
Who Have Chronic Multisymptom Illness, 167
Select Models of Care Used by Other Organizations, 173
Disseminating Evidence-Based Guidelines Through the
Department of Veterans Affairs System, 173
Clinicians’ Behavior Change: System and Interpersonal
Determinants, 175
Summary, 176
References, 177
8 RECOMMENDATIONS 183
Treatments for Chronic Multisymptom Illness, 183
Improving Care of Veterans Who Have Chronic Multisymptom
Illness, 186
Dissemination of Information, 188
Improving Data Collection and Quality, 190
Research Recommendations, 190
References, 192
APPENDIXES
A Committee Biographic Sketches 195
B Possible Factors Underlying Chronic Multisymptom Illness 203
C Examples of Effective and Ineffective Patient–Clinician
Discussions 207
INDEX 211
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Boxes, Figures, and Tables
BOXES
1-1 The Committee’s Charge, 14
2-1 Symptoms and Related Functional Impairment Reported by
Veterans of Operation Iraqi Freedom, Operation Enduring
Freedom, and Operation New Dawn, 25
5-1 Definitions of Chronic Fatigue Syndrome, 98
5-2 Rome III Diagnostic Criteria for Irritable Bowel Syndrome, 103
5-3 Rome III Diagnostic Criteria for Functional Dyspepsia, 104
5-4 Assessing for Suicidal Ideation, 117
6-1 Additional Resources for Clinicians, 145
7-1 Department of Veterans Affairs (VA) Health Care Enrollment
Priority Groups, 164
C-1 Example of an Ineffective Patient–Clinician Discussion, 208
C-2 Example of an Effective Patient–Clinician Discussion, 209
xvii
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xviii BOXES, FIGURES, AND TABLES
FIGURES
3-1 Summary of search and review process, 33
7-1 Institute for Healthcare Improvement Plan Do Study Act model, 171
B-1 Putative mechanism by which the body perceives symptoms, 204
TABLES
3-1 AHRQ’s Strength-of-Evidence Grades and Definition, 34
4-1 Strength of Evidence on Pharmacologic Interventions, 41
4-2 Pharmacologic Interventions, 42
4-3 Strength of Evidence on Other Biologic Interventions, 48
4-4 Other Biologic Interventions, 48
4-5 Strength of Evidence on Psychotherapies, 55
4-6 Psychotherapies, 56
4-7 Strength of Evidence on Biofeedback Interventions, 73
4-8 Biofeedback Interventions, 74
4-9 Strength of Evidence on Cognitive Rehabilitation Therapies, 76
4-10 Cognitive Rehabilitation Therapy, 76
4-11 Strength of Evidence on Complementary and Alternative
Therapies, 78
4-12 Complementary and Alternative Therapies, 80
4-13 Strength of Evidence on Exercise Interventions, 84
4-14 Exercise Interventions, 84
5-1 Best-Practice Guidelines and Recommendations for Treatment for
Nightmare Disorders and Chronic Insomnia, 102
5-2 Stratification of Severity of Traumatic Brain Injury, 112
5-3 Summary of Treatments Recommended in Guidelines or Found to
Be Effective in Systematic Reviews for Conditions Comorbid with
and Related to Chronic Multisymptom Illness, 120
6-1 Behaviors That Influence Accurate Data Collection, 142
6-2 Characteristics of Users of Social Media, 148
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Abbreviations and Acronyms
AACH American Academy on Communication in Healthcare
ACP American College of Physicians
AHRQ Agency for Healthcare Research and Quality
ALS amyotrophic lateral sclerosis
AMSTAR Assessment of Multiple Systematic Reviews
AOC alteration of consciousness
APA American Psychiatric Association
BMI body mass index
CACTUS Classical Acupuncture Treatment for People with
Unexplained Symptoms
CAM complementary and alternative medicine
CBOC community-based outpatient clinic
CBT cognitive behavioral therapy
CDC Centers for Disease Control and Prevention
CFS chronic fatigue syndrome
CI confidence interval
CINAHL Cumulative Index to Nursing and Allied Health Literature
CMI chronic multisymptom illness
CPAP continuous positive airway pressure
CPG clinical practice guideline
CQI continuous quality improvement
CRT cognitive rehabilitation therapy
xix
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xx ABBREVIATIONS AND ACRONYMS
DARE Database of Abstracts of Reviews of Effects
DNA deoxyribonucleic acid
DOD Department of Defense
DSM Diagnostic and Statistical Manual of Mental Disorders
DU depleted uranium
EBI evidence-based information
ECHO Extension for Community Healthcare Outcomes
ECT electroconvulsive therapy
EMC enhanced medical care
EMDR eye-movement desensitization and reprocessing
FD functional dyspepsia
FDA Food and Drug Administration
FGID functional gastrointestinal disorder
FPOW former prisoner of war
FSS functional somatic syndrome
FY fiscal year
GET graded exercise therapy
GI gastrointestinal
GMT geographically adjusted income threshold
GWI Gulf War illness
GWV Gulf War–deployed veterans
GWVI Gulf War veterans illness
IBS irritable bowel syndrome
ICT information and communication technology
IHI Institute for Health Improvement
IOM Institute of Medicine
LOC loss of consciousness
ME myalgic encephalomyelitis
MI motivational interviewing
mTBI mild traumatic brain injury
MUPS medically unexplained physical symptoms
MUS medically unexplained symptoms
NHS National Health Service (UK)
NICE National Institute for Health and Clinical Excellence (UK)
NSAID nonsteroidal anti-inflammatory drug
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ABBREVIATIONS AND ACRONYMS xxi
OEF Operation Enduring Freedom
OIF Operation Iraqi Freedom
OND Operation New Dawn
OR odds ratio
PC primary care
PCMH patient-centered medical home
PCS postconcussive symptom
PD-PACT postdeployment patient-aligned care team
PIT psychodynamic interpersonal therapy
PTA posttraumatic amnesia
PTSD posttraumatic stress disorder
RAC VA Research Advisory Committee on Gulf War Veterans’
Illnesses
RCT randomized controlled trial
REAC-BS radioelectric asymmetric brain stimulation
REM rapid eye movement
RoB risk of bias
SCAN Specialty Care Access Network
SHAD Shipboard Hazard and Defense
SIGLE System for Information on Grey Literature in Europe
SNRI serotonin norepinephrine reuptake inhibitor
SSD somatic symptom disorder
SSRI selective serotonin reuptake inhibitor
TBI traumatic brain injury
TENS transcutaneous electric nerve stimulation
UK United Kingdom
VA Department of Veterans Affairs
VAMC VA medical center
VA-OIG VA Office of the Inspector General
VBA Veterans Benefits Administration
VHA Veterans Health Administration
VISN Veterans Integrated Service Network
WGO World Gastroenterology Organisation
WRIISC War-Related Illness and Injury Study Center
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