National Academies Press: OpenBook

Gulf War and Health: Treatment for Chronic Multisymptom Illness (2013)

Chapter:5 Review of Treatments for Comorbid and Related Conditions

« Previous: 4 Treatment for Chronic Multisymptom Illness
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

5

Review of Treatments for
Comorbid and Related Conditions

Chronic multisymptom illness (CMI) is a serious condition that imposes an enormous burden of suffering on our nation’s veterans. It can affect every facet of a veteran’s health: physical, psychologic, social, economic, and spiritual; it can impair a person’s capacities whether the person is a soldier, worker, or family member. Despite its impact, CMI remains poorly understood and in need of additional study. The medical community does not yet know exactly which signs and symptoms should be part of the diagnostic criteria, and, as science and discovery change, the definition and diagnostic criteria of CMI may also change.

It is known, however, that a number of events or preconditions are frequently seen in association with CMI. In some cases, a common exposure can lead to more than one condition; for example, an explosion can cause a concussion, deafness, body injury, and pain. Different but similar conditions share symptoms; for example, cognitive impairment can be a feature of CMI and traumatic brain injury (TBI). Some medical conditions can lead to other clinical problems; for example, chronic pain can lead to depression, and chronic lung disease can lead to anxiety. And some common conditions may cluster without obvious explanation. CMI may include symptoms that are not severe enough for diagnosis as a clinically recognized syndrome or that are associated with defined disorders. It is clear that the possibilities are many and that not all are fully defined.

The purpose of this report is to describe the current optimal approach to care for patients who have CMI. In the quest to help patients, the entire spectrum of their complaints must be considered and addressed. A comprehensive, individualized, patient-centered plan of care must acknowledge and

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

address all conditions and comorbidities that are present and their possible interrelationships. This chapter briefly describes 12 common conditions that are comorbid with or related to CMI and presents treatments that are known to be effective. The committee believes that symptoms shared between CMI and those treatments may respond to similar approaches in symptom management. Treatments that are recommended in evidence-based clinical practice guidelines or that have been found effective in systematic reviews are highlighted. The chapter concludes with a general therapeutic approach to patients who have the most common diagnostic clusters.

FIBROMYALGIA

Primary fibromyalgia is a relatively common chronic condition that is thought to be caused by abnormal processing of pain by the central nervous system (Abeles et al., 2007). Using US population estimates from 2005, the estimated prevalence of fibromyalgia in the United States was about 5 million people (Lawrence et al., 2008). It is characterized by chronic widespread pain, fatigue, cognitive symptoms, and sleep disturbance. Anxiety and depression can accompany the syndrome (Wolfe et al., 1990). The diagnostic criteria of the American College of Rheumatology are as follows (Wolfe et al., 2010):

1. Pain over the preceding week identified from a list of 19 areas of the body.

2. Fatigue, waking unrefreshed, and cognitive symptoms (memory disturbance).

3. Symptoms lasting longer than 3 months.

4. Symptoms not explained by any other medical condition.

Other conditions may resemble fibromyalgia closely, including hypothyroidism, polymyalgia rheumatica, rheumatoid arthritis, and systemic lupus erythematosus.

Fibromyalgia and Chronic Multisymptom Illness

Fibromyalgia and CMI share symptoms. The hallmark of fibromyalgia is chronic widespread pain. In CMI, muscle pain and tenderness are very common but are not required for the diagnosis.

Treatments for Fibromyalgia

Many pharmacologic and nonpharmacologic treatments have been demonstrated to be effective for fibromyalgia. Many categories of pharmacologic

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

medications are somewhat to very effective in treatment for this syndrome. Systematic reviews identified several pharmacologic treatments for fibromyalgia. Amitryptyline, a tricyclic medication, was found to have a short-term benefit—6–8 weeks—when given at 25 mg/day (Nishishinya et al., 2008). The serotonin–norepinephrine reuptake inhibitors duloxetine and milnacipran also demonstrated beneficial effects on pain reduction, fatigue, sleep, depression, and quality of life in systematic reviews (Sultan et al., 2008; Uceyler et al., 2008). The neuropathic agent pregabalin has proved to be effective (Choy et al., 2011; Nuesch et al., 2012; Siler et al., 2011; Tzellos et al., 2010). Gabapentin, another neuropathic medication, has also been shown to have modest benefits in patients who have fibromyalgia (Moore et al., 2011). Duloxetine, milnacipran, and pregabalin are approved by the US Food and Drug Administration (FDA) for the management of fibromyalgia. Other medications have shown less consistent beneficial study results, including cyclobenzaprine and the atypical analgesic tramadol (Hauser et al., 2011; Russell et al., 2000).

Nonpharmacologic interventions that have proved beneficial for patients who have fibromyalgia include cognitive behavioral therapy (CBT) (Bernardy et al., 2010) and aerobic exercise (Maquet et al., 2007). Many studies of fibromyalgia have shown benefits of multimodal therapies: a combination of treatments that include exercise, CBT, education, and self-help tools (Hauser et al., 2009). It is well established that most patients benefit from an interdisciplinary and integrative approach to the long-term management of fibromyalgia and that medications alone are rarely beneficial for maintaining effective reduction in chronic pain.

CHRONIC PAIN

Chronic pain is defined as pain that is associated with a chronic medical condition or that persists beyond the expected time for tissue healing and adversely affects the function or well-being of the person (American Society of Anesthesiologists Task Force on Chronic Pain Management and American Society of Regional Anesthesia and Pain Medicine, 2010). Chronic pain affects about 100 million adults in the United States (IOM, 2011b).

Chronic Pain and Chronic Multisymptom Illness

Chronic pain is one of the symptoms that might be associated with CMI. Veterans of the 1991 Gulf War who have CMI may not have had a specific injury but can have common and persistent diffuse chronic pain (for example, joint pain).

Pain is the most frequent presenting complaint of troops returning from the Iraq and Afghanistan wars who are treated at a VA polytrauma clinic

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

(Lew et al., 2009). Many Iraq and Afghanistan war veterans have chronic pain due to specific injuries. As discussed in Chapter 2, the most common health outcome reported in that population is the triad of posttraumatic stress disorder (PTSD), mild TBI, and pain (Walker et al., 2010). The prevalence of CMI in veterans of the Iraq and Afghanistan wars has not been well studied, so it is not known whether the pain reported by these veterans is associated with CMI.

Treatments for Chronic Pain

Treatment for chronic pain requires a long-term approach, coordinated care, and periodic reevaluation. The scientific literature and clinical experience support a multidisciplinary approach to treatment for chronic pain as recommended by guidelines of the American Society of Anesthesiologists Task Force on Chronic Pain Management and American Society of Regional Anesthesia and Pain Medicine (2010).

Pharmacologic management of chronic pain includes nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants, anticonvulsants, opioid therapy, and other agents. Evidence supporting pharmacologic management of chronic pain of varied etiology is strong. Tricyclic medications and serotonin–norepinephrine reuptake inhibitors (SNRIs) are recommended for chronic pain in conjunction with other therapies; there have been multiple randomized controlled trials (RCTs), and the aggregated findings are supported by meta-analyses (American Society of Anesthesiologists Task Force on Chronic Pain Management and American Society of Regional Anesthesia and Pain Medicine, 2010). Pregabalin has been shown to be effective for central neuropathic pain (Moore et al., 2009). The use of NSAIDs or tramadol for chronic back pain is supported by the results of multiple RCTs (American Society of Anesthesiologists Task Force on Chronic Pain Management and American Society of Regional Anesthesia and Pain Medicine, 2010). Although there are data that show that opioids provide effective relief of low back pain and some forms of neuropathic pain for periods ranging from 1 to 9 weeks, the data are limited with respect to the safety and efficacy of long-term opioid therapy for chronic pain. In addition, the risks and potential harm associated with opioid therapy are serious, and guidelines should be followed (VA and DOD, 2010b).

The use of radiofrequency ablation of branch nerves to facet joints for low back pain is supported by results of multiple RCTs and meta-analyses (American Society of Anesthesiologists Task Force on Chronic Pain Management and American Society of Regional Anesthesia and Pain Medicine, 2010). Ablative techniques also are recommended for neck pain, but the evidence comes from a single RCT. The use of transcutaneous electric nerve stimulation for chronic back pain and other types of pain as part of

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

a multimodal treatment is supported by results of multiple RCTs, and the aggregated findings are supported by meta-analyses. There is no strong evidence supporting epidural injections for back pain, but there has been a single RCT on relief of leg pain. Neither is there strong evidence to support intrathecal drug therapies for neuropathic pain or minimally invasive spinal procedures for vertebral compression fractures (American Society of Anesthesiologists Task Force on Chronic Pain Management and American Society of Regional Anesthesia and Pain Medicine, 2010).

A growing body of evidence demonstrates that acupuncture can be useful for chronic pain (Lee et al., 2012; Manheimer et al., 2005; Vickers, 2012). The strongest evidence supports its use in treatment for headache, but it may be effective for other forms of chronic pain, such as low back pain and osteoarthritis. Therefore, acupuncture should be considered for use in customizing pain treatment of patients who have CMI.

CHRONIC FATIGUE SYNDROME

Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis, affects an estimated 4 million people in the United States, according to the Centers for Disease Control and Prevention (CDC), with prevalence estimates ranging from 0.2% to 2.54% (Maquet et al., 2006; Reeves et al., 2007). CFS is more common and more severe in women and people who have Latino and African-American backgrounds, and its prognosis worsens with age (Jason et al., 2011). People who have CFS often have other comorbid conditions, such as obesity and metabolic disorders, depression, irritable bowel syndrome (IBS), fibromyalgia, and multiple chemical sensitivity. Multiple symptoms of each of those conditions can overlap substantially with CMI, including fatigue, nonrestorative sleep, tenderness on palpation, and some mild cognitive dysfunction (CDC, 1994). Definitions of CFS vary, but the diagnosis is the result of careful review of patient history, physical health and mental health examinations, clinical laboratory testing, and indicated imaging studies to rule out other medical and psychologic diagnoses that may explain the symptoms of CFS. Definitions of CFS used by CDC and UK National Health Service are included in Box 5-1.

Chronic Fatigue Syndrome and Chronic Multisymptom Illness

Much research on CFS has targeted infectious triggers associated with low-grade fever, adenopathy, and influenza symptoms. Regardless, no consistent viral agents (such as human herpesvirus 6 and Epstein-Barr virus) have been definitively identified (Glaser and Kiecolt-Glaser, 1998). Fever, adenopathy, and infection-like symptoms tend to decrease over time, and fatigue and other somatic symptoms common in CMI become more prominent

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

BOX 5-1
Definitions of Chronic Fatigue Syndrome

  International CFS Case Definition, 1994a NICE Guidelines for CFS, 2007b
Duration Duration 6 months or longer 4 months or longer in adults
Fatigue Severe chronic fatigue not explained by any medical or psychiatric diagnosis Fatigue with

•   New or specific date of onset, persistent recurrent, unexplained other conditions

•   Substantially activity level

•   Postexertional malaise or fatigue

Symptoms At least four of the following: At least one of the following:

•   Postexertion malaise lasting more than 24 hours

•   Difficulty in sleeping or insomnia

•   Unrefreshing or nonrestorative sleep

•   Muscle or joint pain without inflammation (swelling) manifested as tenderness on palpation in characteristic soft-tissue areas

•   Substantial impairment of short-term memory or concentration

•   Muscle pain

•   Headaches

•   Pain in joints without swelling or redness

•   Painful lymph nodes that are not enlarged

•   Headaches of a new type, pattern, or severity

•   Sore throat

•   Tender lymph nodes in the neck or armpit

•   Poor mental function, such as difficulty in thinking

•   Sore throat that is frequent or recurring

•   Worsening of symptoms after physical or mental exertion

•   Feeling of being unwell or having influenza-like symptoms

•   Dizziness or nausea

•   Heart palpitations without heart disease

And All other medical conditions have been ruled out.

NOTE: CFS = chronic fatigue syndrome; NICE = National Institute for Health and Clinical Excellence.

aCDC, 1994.

bNHS, 2007.

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

(Krilov et al., 1998). Many of the symptoms of CFS and CFS-like illness (meeting some but not all of the criteria for CFS) are similar to those experienced by people who have CMI. Both CMI and CFS include a variety of symptoms—fatigue, cognitive symptoms, and pain.

Treatments for Chronic Fatigue Syndrome

Both US and UK treatment guidelines emphasize the lack of a particular medication or therapy to cure CFS. However, an individualized treatment program and a patient-centered care model to tailor symptom management to a patient’s needs are recommended. Symptoms of CFS may be managed in primary care (CDC, undated; Mayo Clinic staff, 2011; National Collaborating Centre for Primary Care, 2007).

Two specific therapies are recommended for people who have CFS: CBT and graded exercise therapy (GET) (CDC, 1994; Mayo Clinic staff, 2011; National Collaborating Centre for Primary Care, 2007). CBT provides a framework for patients to change how they think and feel about their illness and teaches behaviors that provide patients with a greater sense of control over symptoms (CDC, undated; National Collaborating Centre for Primary Care, 2007). Exercise has been associated with the body’s natural release of endorphins, natural pain relievers. Both exercise and endorphins have been shown to improve a number of the symptoms of CFS and related syndromes (Cleare, 2003; Harber and Sutton, 1984).

Additional CFS management strategies can be recommended to improve quality of life. Pacing to balance activities and rest throughout the day may be helpful to avoid “crashing” after too much activity; however, evidence is insufficient to determine efficacy (CDC, 1994; National Collaborating Centre for Primary Care, 2007). Disturbance of restorative or deep sleep may play a role in triggering symptoms of CFS (Moldofsky, 1993). Sleep patterns should be changed gradually to introduce a regular sleeping schedule, bedtime routine, noise and light control, and avoidance of caffeine, alcohol, and tobacco (CDC, 1994; National Collaborating Centre for Primary Care, 2007). Clinicians should also encourage patients to learn coping skills through counseling and support groups and to maintain their independence as much as possible (CDC, 1994; Mayo Clinic staff, 2011).

Management may focus on treating specific symptoms. Drug therapy is recommended to manage some symptoms, but clinicians are encouraged to use as few drugs as possible and to use minimal doses because people who have CFS are often more sensitive to medications. Pain may be managed with acetaminophen, aspirin, or NSAIDs, but narcotics are not recommended. Sleep medications or treatments, such as melatonin and continuous positive airway pressure, may be useful if indicated by the patient’s history and improvements are not seen with good sleep hygiene

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

(CDC, 1994; Mayo Clinic staff, 2011; National Collaborating Centre for Primary Care, 2007). It is clear that CFS is not depression, but it may be associated with depression.

Multivitamins can be useful for patients who do not have a balanced diet. Clinicians may offer recommendations to reduce stress and improve sleep, such as relaxation techniques and limitation of caffeine intake. Such relaxation techniques as visualization can be used to manage pain, sleep problems, and comorbid anxiety. Alternative therapies (for example, yoga, Tai Chi, acupuncture, and massage) may help to lessen pain and increase energy (CDC, 1994; Mayo Clinic staff, 2011; National Collaborating Centre for Primary Care, 2007).

SOMATIC SYMPTOM DISORDERS

There appears to be a tendency to experience and communicate psychologic distress in the form of physical symptoms and to seek medical attention for these symptoms (Katon and Walker, 1998; Shorter, 1993). Often, the physical symptoms remain medically unexplained and are associated with increased medical visits and unnecessary medical tests, which may result in iatrogenic complications. Among the many terms used in the literature to label these somatic presentations, somatization symptoms was the most common for decades. That designation has been gradually replaced with more descriptive terms, such as medically unexplained symptoms, unexplained symptoms, and functional somatic symptoms.

In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the new criteria being developed by the American Psychiatric Association, those syndromes are classified under the heading “Somatic Symptom Disorders” (SSDs). Their key characteristic is the presence of or preoccupation with physical symptoms that suggest a medical condition but cannot be satisfactorily explained with traditional physical and laboratory assessments (APA, 2012). DSM-5’s SSDs include illness anxiety disorder, functional neurologic disorder (conversion disorder), psychologic problems that affect a medical condition, and disorders not elsewhere classified. A distinctive characteristic of patients who have SSDs is not a somatic symptom itself but how a patient experiences it, interprets it, and presents it to a clinician. Despite the relevance of these somatic presentations in medicine, their definition and classification remain difficult and controversial, and this has led to frequent revisions of nomenclatures that move the target used to designate “cases” and complicate the clinical recognition and management of the syndromes.

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

Somatic Symptom Disorders and Chronic Multisymptom Illness

Because SSDs typically present with multiple physical symptoms of unclear etiology that tend to persist, the syndromes often overlap with CMI, and differential diagnosis is difficult.

Treatments for Somatic Symptom Disorders

Effective treatments for SSDs include nonpharmacologic approaches, such as CBT and communication with the primary care physician by the psychiatrist or psychologist via consultation letters (Escobar, 2009). Other forms of psychotherapy and biofeedback are also effective (Katsamanis et al., 2011). In some instances, particularly when SSD symptoms are accompanied by anxiety and depression symptoms (a common co-occurrence, particularly in primary care settings), such antidepressants as venlafaxine may be helpful (Kroenke et al., 2006). However, treatments have to be adapted to give proper attention to the somatic component because traditional treatments alone (for example, antidepressants) may not be sufficient.

SLEEP DISORDERS

Sleep disorders are a group of about 70 syndromes characterized by persistent disturbance in sleep that interferes with activities of daily living. The most common syndromes are chronic insomnia, nightmare disorder, rapid eye movement (REM) sleep behavior disorder, circadian-rhythm sleep disorders, and obstructive sleep apnea. Like CMI, sleep disorders are associated with fatigue, mood disturbances, cognitive difficulties, and other somatic symptoms; comorbidity with depression, anxiety, and substance abuse is common.

Sleep Disorders and Chronic Multisymptom Illness

Several types of sleep disorders are among the common symptoms associated with CMI. Nightmare disorders, subjective perceptions of difficulty with sleep initiation or duration, and early awakening (insomnia) have been described in persons who have PTSD, chronic pain disorders, and other comorbid conditions, including general medical and neurologic disorders (Chokroverty, 2000). Other types of sleep disorders are less common in people who have CMI. REM sleep behavior disorder may be idiopathic or secondary to neurologic disorders, such as Parkinson’s disease, stroke, multiple sclerosis, and spinocerebellar ataxia. Obstructive sleep apnea is most common among those who are obese or have congestive heart failure, stroke, or pulmonary hypertension. Circadian-rhythm sleep disorders

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

TABLE 5-1 Best-Practice Guidelines and Recommendations for Treatment for Nightmare Disorders and Chronic Insomnia

Type of Intervention Nightmare Disordera Chronic Insomniab
Pharmacologic Prazosin (for PTSD-associated nightmares) Pharmaceutical agent selected on basis of symptom pattern, treatment goals, past treatment response, patient preference, cost, availability of other treatments, comorbid conditions, concurrent medication interactions, and side effects
Nonpharmacologic CBT, including image rehearsal therapy At least one behavioral intervention of these: stimulus-control therapy, relaxation therapy, or combination CBT

aAmerican Academy of Sleep Medicine (Aurora et al., 2010).

bAmerican Academy of Sleep Medicine (Schutte-Rodin et al., 2008).

NOTE: CBT = cognitive behavioral therapy; PTSD = posttraumatic stress disorder.

may be exogenous (for example, jet lag or difficulties in shift work) or endogenous (for example, advanced sleep-phase disorder or irregular sleep–wake rhythm). Nightmare disorders and insomnia are the two sleep disorders more commonly associated with CMI.

Treatments for Sleep Disorders

Because of the large number of sleep disorders and evidence that effective treatment varies among them, it is vital to evaluate the patient adequately and accurately to characterize the specific symptoms, identify potential comorbid conditions or risk factors, and diagnose the specific type of disorder. Table 5-1 summarizes best-practice guidelines and recommendations for treatment for nightmare disorder and chronic insomnia.

The clinician should consider a number of other approaches that may be useful when individualizing the treatment and management of CMI, such as good sleep hygiene, exercise, acupuncture, and mind–body approaches. Some of those approaches, such as acupuncture, have been documented with systematic reviews (Lee et al., 2012), but they have not yet risen to the level of guidelines.

FUNCTIONAL GASTROINTESTINAL DISORDERS: IRRITABLE
BOWEL SYNDROME AND FUNCTIONAL DYSPEPSIA

The functional gastrointestinal disorders (FGIDs) are best understood as disorders that affect gastrointestinal functioning; the ones most recognized

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

and most relevant to this discussion are IBS and functional dyspepsia (FD) (Drossman, 2006). IBS and FD present as recurrent or prolonged clusters of gastrointestinal symptoms that remain consistent in their features over time and among populations. IBS and FD are common in young adults and are associated with wartime deployment of Gulf War veterans (IOM, 2010).

The diagnosis of an FGID is made by fulfilling standardized symptom-based criteria (“Rome criteria”) for a minimal period, usually 6 months. The criteria for IBS and FD are shown in Boxes 5-2 and 5-3.

Functional Gastrointestinal Disorders and Chronic Multisymptom Illness

The most common symptoms of IBS are abdominal pain or discomfort, diarrhea, constipation, and abdominal bloating, and common symptoms of FD are early satiety with upper abdominal fullness, burning, or pain—all in the absence of other structural abnormalities that explain the symptoms. The symptoms are common in veterans deployed to the 1991 Gulf War (IOM, 2010). There is overlap between symptoms associated with IBS and FD and the gastrointestinal symptoms associated with CMI. A veteran may fulfill criteria for IBS and also have other extraintestinal symptoms and receive a diagnosis of IBS, at another time have gastrointestinal symptoms that are not sufficient for a diagnosis of IBS, and, by virtue of having several other unexplained symptoms, be classified as having CMI. Therefore, from a therapeutic standpoint, these conditions that share symptoms are likely

BOX 5-2
Rome III Diagnostic Criteria
afor Irritable Bowel Syndrome

Recurrent abdominal pain or discomfort at least 3 days per month in last 3 months associated with two or more of

1. Improvement with defecation.

2. Onset associated with a change in frequency of stool.

3. Onset associated with a change in form (appearance) of stool.

_____________

aCriteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis.

SOURCE: Reprinted from Gastroenterology 130(5), Longstreth et al., Functional bowel disorders, pages 1480–1491, Copyright 2006, with permission from Elsevier.

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

BOX 5-3
Rome III Diagnostic Criteria
afor Functional Dyspepsia

Must include

1. One or more of

a. Bothersome postprandial fullness.

b. Early satiation.

c. Epigastric pain.

d. Epigastric burning.

2. No evidence of structural disease (including findings of upper endoscopy) that is likely to explain the symptoms.

_____________

aCriteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis.

SOURCE: Reprinted from Gastroenterology 130(5), Tack et al., Functional gastroduodenal disorders, pages 1466–1479, Copyright 2006, with permission from Elsevier.

to respond to centrally targeted treatments that reduce symptom frequency and intensity and reduce such associated psychologic comorbidities as anxiety and depression.

Treatments for Functional Gastrointestinal Disorders

The general approach to treating IBS and FD is to look at the predominant symptom that requires treatment (for example, diarrhea, nausea, or pain) and then at the severity and intensity of the symptoms, which, when severe, are usually associated with physical and psychologic comorbidities (Drossman et al., 2002; Thiwan and Drossman, 2006).

The symptoms of IBS and FD can vary in severity. They may exist as occasional and mild gastrointestinal symptoms—which are usually treated with diet, lifestyle adjustments, or medications targeted at the bowel—or as more persistent and severe disabling symptoms that occur with other medical conditions (such as fibromyalgia, chest pain, and fatigue) and mental health conditions (such as anxiety, depression, somatization, and PTSD) that require medication targeted toward treating brain–gut dysregulation (Drossman, 2006; Drossman et al., 2002). Appendix B contains information about how brain–gut dysregulation may lead to the types of symptoms associated with IBS, FD, and CMI. The present section focuses

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

on centrally targeted treatments because they are more applicable to treating for CMI.

Pharmacologic Treatments

The rationale for using antidepressants for IBS and FD is related to their central effects—altering pain perception; improving mood, including depression, hypervigilance, and symptom-related anxiety and increased stress reactivity; reducing associated sleep disturbances; and peripheral effects on motility and afferent signaling (Grover and Drossman, 2009). Several systematic reviews and meta-analyses have shown that antidepressants achieve both pain reduction and global symptom improvement (Chang and Drossman, 2004; Ford et al., 2009; Jackson et al., 2000; Lesbros-Pantofickova et al., 2004). The analgesic effect appears to be independent of the actions of antidepressants on mood disturbance, and a clinical response occurs before improvement in psychologic symptoms.

The authors of a systematic review concluded that tricyclic medications and the selective seratonin reuptake inhibitors (SSRIs) reduced global symptoms of IBS and abdominal pain (Ford and Vandvik, 2012). After evaluation of that and other systematic reviews and studies, tricyclic medications and SSRIs have been endorsed by the Rome Foundation (Levy et al., 2006), the American College of Gastroenterology (Brandt et al., 2009), the American Gastroenterology Association (Drossman et al., 2002), and the World Gastroenterology Organization (WGO, 2009) for treatment for IBS. More recently, some clinicians have been using SNRIs to increase adherence because they have fewer side effects than tricyclic medications.

The benefit of antidepressants for patients who have FD is less conclusive, in part because of the lack of studies of this condition, possible publication bias, and variable results primarily of small studies (Jackson et al., 2000; Mertz et al., 1998; Van Kerkhoven et al., 2008). Nevertheless, the studies are generally positive and, because of the presumed global effects of antidepressants on symptoms, these agents are commonly used in treatment for severe FD.

Nonpharmacologic Treatments

Nonpharmacologic treatments have been used commonly for many decades in treating patients who have IBS and FD because of their effects on reducing psychologic distress and their value in reducing maladaptive coping and health-related anxieties and more recently because of evidence from brain-imaging studies that they help to ameliorate symptoms (Creed et al., 2006; Rainville et al., 1999). They have synergistic effects with medical treatments, offer the advantage of few, if any, side effects, have benefits that

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

continue after treatment, and have demonstrated a favorable cost–benefit relationship over time (Creed et al., 2006). Many treatment protocols involve a combination of relaxation and stress management with primary therapies, such as CBT or interpersonal psychotherapy. The best-designed studies have focused on CBT (Blanchard et al., 2006; Boyce et al., 2003; Drossman et al., 2003; Lackner et al., 2008) and hypnotherapy (Lindfors et al., 2012; Palsson and Whitehead, 2002; Whitehead, 2006; Whorwell et al., 1987; Wilson et al., 2006), and an abundance of robust studies have shown the benefit of both. However, whereas CBT has been very protocol-driven and can be administered by well-trained therapists in private clinical settings, hypnosis has been administered primarily in major referral centers and its efficacy in more private clinical settings is not known. A recent meta-analysis of treatments for IBS found evidence of effectiveness of CBT and hypnosis (Ford and Vandvik, 2012).

DEPRESSION

Depression is a common and disabling mood disorder. Major depressive disorder affects about 6.7% of the US population (NIH, 2012b). It is more common in women, often becomes chronic, and causes considerable impairment over the entire lifespan. Major depression is as disabling as many other chronic medical diseases, such as hypertension, congestive heart failure, and diabetes, and it adds substantial burden and disability when it appears with those disorders (Hays et al., 1995; WFMH, 2010).

The criteria for a diagnosis of major depression include the presence of mood disturbance (sadness or dysphoria) with disturbances of sleep, appetite, energy, and concentration lasting for at least 2 weeks (APA, 2000). Major depression may lead to severe complications, such as suicide. Diagnosis in primary care can be difficult because patients often present with somatic complaints and anxiety symptoms, so the diagnosis can be missed (Dowrick et al., 2005).

Depression and Chronic Multisymptom Illness

Major reasons for considering depression in veterans who have CMI are that symptoms and disabilities common in CMI (such as insomnia, fatigue, and pain in various parts of the body) are also common in severe depression and that depression is one of the clinical conditions most closely related to suicide, an outcome often reported in veterans returning from the Iraq and Afghanistan wars. Major depression often includes somatic disturbances (such as difficulty in sleeping, changes in appetite, changes in

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

libido, and multiple aches and pains), many of which are similar to those in veterans who have CMI, so the differential diagnosis is difficult. The two syndromes can also appear together, so interventions should address both. Symptoms of major depression that are similar to those of CMI include sleep disturbance, fatigue, and pains in different parts of the body (such as headache, facial pain, and musculoskeletal pain). Like patients who have SSD, patients who have CMI often reject diagnostic assessment by mental health specialists, possibly because they perceive referral to a psychiatrist as evidence that their symptoms are not taken seriously by the treating physicians or as evidence that they are mentally ill. Proper management of CMI and depression requires a coordinated, well-integrated approach that should include medical and mental health specialists working together, ideally in a primary care setting.

Treatments for Depression

A number of treatment guidelines outline effective interventions for depression (APA, 2010; Gill et al., 2010; National Collaborating Centre for Mental Health, 2009a,b; Nieuwsma et al., 2012; Rimer et al., 2012; VA and DOD, 2009b). The most recommended treatments are nonpharmacologic approaches (such as CBT, interpersonal therapy, exercise, and acupuncture) and antidepressant medications. People who have mild to moderate depression can be treated effectively at the primary care site, often conservatively with psychotherapy and other nonpharmacologic approaches and frequent clinical monitoring and with new antidepressants (such as SSRIs) that have a good safety profile. More severe depression responds better to antidepressant medications, and at times other interventions may be needed, such as electroconvulsive therapy, particularly in severe cases that present with suicidal ideation and psychotic symptoms. Interpersonal psychotherapy alone or in combination with pharmacotherapy is effective for acute treatment for depression; interpersonal psychotherapy combined with pharmacotherapy has better response rates than pharmacotherapy alone. Several randomized clinical trials in the United States and Europe have documented the efficacy of CBT both acutely and over the long term in leading to a reduction in recurrence. CBT can be effectively implemented in nontraditional ways, such as via telephone or the Internet, to fit the needs of primary care patients.

Lithium carbonate continues to be used as an augmentation strategy, and second-generation antipsychotics—such as aripiprazole, quetiapine, and olanzapine—are used for refractory cases.

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

ANXIETY

Anxiety is a common symptom in patients who are seeking medical treatment. The lifetime prevalence of generalized anxiety disorder in the United States is 5.7% (NIH, 2012a). Anxiety is often a reaction to stress and is frequently associated with several chronic medical conditions, including CMI. Although anxiety may have adaptive qualities (for example, the fight-or-flight response, behavioral activation, and increased awareness), clinical or “pathologic” anxiety becomes chronic and disabling.

Pathologic anxiety is the key feature of the anxiety-disorders category, which includes many subtypes, such as panic disorder, generalized anxiety disorder, social anxiety disorder, phobic disorder, and obsessive–compulsive disorders (APA, 2000).

Diagnostic criteria for anxiety disorder include specific symptom clusters, time frames, and life courses that distinguish the various syndromes, in addition to severity, functional impairment, and symptom persistence and recurrence (APA, 2000).

Anxiety and Chronic Multisymptom Illness

Anxiety disorders are frequent in primary care, often appearing with depression and unexplained physical symptoms. They are also frequently seen in veterans (IOM, 2010) who have CMI and can be effectively recognized and treated in primary care. Generalized anxiety may be the most frequent disorder in primary care. This type of anxiety appears to be closely related to major depression, and nosologic revisions are considering combining the two diagnoses (Watson, 2005).

Treatments for Anxiety

Several guidelines and consensus documents related to treatment for anxiety disorders have been prepared by groups of experts commissioned by several professional organizations—the American Psychiatric Association (APA, 2000), the National Collaborating Centre for Primary Care (McWhinney et al., 2001), the National Institute for Health and Clinical Excellence (National Collaborating Centre for Mental Health and National Collaborating Centre for Primary Care, 2011a), and others (Sheldon et al., 2008). Briefly, the guidelines state that treatment for anxiety disorders includes a number of potential interventions, such as nonpharmacologic approaches (for example, reassurance, psychotherapy, biofeedback, relaxation, and CBT) and pharmacologic treatments (for example, antianxiety and antidepressant [SNRI] medications).

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

POSTTRAUMATIC STRESS DISORDER

PTSD, according to DSM-IV-TR (Text Revision) (APA, 2000), requires the presence of a potentially traumatic event. The person must have

•  Experienced, witnessed, or been confronted by an event or events that involve actual or threatened death or serious injury or a threat to the physical integrity of oneself or others (Criterion A1), and the response must have involved intense fear, helplessness, or horror (Criterion A2).

•  One or more re-experiencing symptoms (Criterion B), such as recurrent thoughts, nightmares, and flashbacks.

•  Three or more avoidance or numbing symptoms (Criterion C), such as efforts to avoid thoughts, feelings, or conversations associated with the trauma; a feeling of detachment or estrangement from others; and restricted range of affect (such as being unable to have loving feelings).

•  Two or more hypervigilance symptoms (Criterion D), such as difficulty in concentrating, exaggerated startle response, and irritability or outbursts of anger.

Those conditions must persist for at least 1 month (Criterion E) and cause clinically significant distress or functional impairment (Criterion F).

There are a variety of screening tools for initially assessing PTSD, including the commonly used Primary Care PTSD Screen (IOM, 2012; Prins et al., 2003). There is no evidence that one screening tool is superior to another (VA and DOD, 2010a). The Institute of Medicine (IOM, 2012) recommends that PTSD screening be conducted at least once per year when primary care clinicians see service members in Department of Defense (DOD) military treatment or at any TRICARE location, as is the case when veterans are seen in Department of Veterans Affairs (VA) facilities. If people screen positive for PTSD, the use of a structured interview, such as the Clinician-Administered PTSD Scale (Blake et al., 1995) or other structured interviews (see IOM, 2012, Table 6-3), may improve the validity and reliability of the diagnosis (IOM, 2012; VA and DOD, 2010a). Evaluation should also address comorbidities, including TBI, depression, other anxiety disorders, alcohol or substance abuse, and the presence of suicidality and risky behaviors (IOM, 2012). In summary, the diagnosis of PTSD rests on careful and comprehensive evaluation performed by a qualified professional (a psychologist, a social worker, a psychiatrist, or a psychiatric nurse-practitioner) under conditions of confidentiality (IOM, 2006).

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

The American Psychiatric Association is expected to release an update of DSM, DSM-5, in 2013. Proposed DSM-5 changes include changes in Criterion A1 to add learning about an event that happened to a relative or close friend, including first responders or others who are continuously exposed to or experience details of traumatic events, and elimination of Criterion A2 because some people, such as trained military professionals, might have an emotional response during a traumatic event (Friedman et al., 2011). All 17 PTSD symptoms are proposed for retention, some with revision or regrouping. Three additional symptoms are proposed: erroneous persistent and exaggerated negative beliefs or expectations about oneself, others, or the world; persistent, distorted blame of self or others about the cause or consequences of a traumatic event; and reckless or self-destructive behavior (Friedman et al., 2011). Finally, removal of the distinction between acute and chronic is proposed. Those changes will make it necessary to update screening, self-reporting, and structured clinical instruments and to establish the reliability and validity of the altered measures.

Posttraumatic Stress Disorder and Chronic Multisymptom Illness

A number of PTSD symptoms are shared with CMI, including difficulty in falling or staying asleep, difficulty in concentrating, irritability or outbursts of anger, marked diminution of interest or participation in important activities, feeling of detachment or estrangement from others, restricted range of affect, and hypervigilance. PTSD is associated with such outcomes as lower quality of life, work-related impairment, and adverse physical health; the last is thought to be at least partially related to poor health behaviors, such as smoking, alcohol use, and physical inactivity (IOM, 2012). Somatic symptoms are commonly seen at higher rates in people who have PTSD than in trauma-exposed people who do not have PTSD and include back and neck pain, headaches, arthritis and rheumatism, chronic pain, gastrointestinal problems, and chronic fatigue (Sledjeski et al., 2008). In some cultures, PTSD often has a somatic focus including bodily heat, bodily pain, gastrointestinal distress, neck soreness, tinnitus, and orthostatic dizziness and shortness of breath (Hinton and Lewis-Fernandez, 2011).

The prevalence of PTSD was low in the 1991 Gulf War; however, veterans who had a PTSD diagnosis reported more symptoms than those who did not (Engel et al., 2000; Ford et al., 2001). Several investigations have suggested that posttraumatic stress symptoms correlate with 1991 Gulf War veterans’ medically unexplained symptoms (Engel et al., 2000; Ford et al., 2001; Storzbach et al., 2000) independently of the effects of somatic or psychiatric distress, health impairment, and stress (Ford et al., 2001).

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

Treatments for Posttraumatic Stress Disorder

A variety of national and international PTSD treatment guidelines are based on reviews of the literature, including the VA–DOD Clinical Practice Guidelines for the Management of PTSD (VA and DOD, 2010a), the American Psychiatric Association Guideline (APA, 2004), the UK National Institute of Health and Clinical Excellence Guideline (National Collaborating Centre for Mental Health, 2005), the Australian National Health and Medical Research Council Guideline (Australian Centre for Posttraumatic Mental Health, 2007), and the International Society for Traumatic Stress Studies Guidelines (Foa et al., 2009). All the guidelines strongly support the use of trauma-focused psychologic treatment for PTSD with an emphasis on short-term trauma-focused CBT (8–12 weekly individual sessions), such as prolonged exposure or cognitive therapy (IOM, 2012). That approach is consistent with an earlier IOM (2007) conclusion that the evidence was sufficient to support the efficacy of exposure therapies in treatment for PTSD. Group-based CBT may be effective, but its outcome may not be as good as that of individual CBT (IOM, 2012).

The above guidelines are not as consistent in recommendations with regard to pharmacotherapy for PTSD, although SSRIs are generally thought to be effective (IOM, 2012). There is a lack of evidence to support complementary and alternative medicine approaches to treatment for PTSD, but a number of them are under active investigation (IOM, 2012). Accordingly, the IOM (2012) committee stated that “it is prudent to offer treatment supported by robust evidence before offering treatments that are not so supported” (p. 232). Not everyone who has PTSD responds satisfactorily to initial evidence-based treatment, although definitions of treatment response vary. The presence of psychiatric comorbidity has not been associated with worse treatment outcome and has actually been associated with better PTSD treatment outcome (Olatunji et al., 2010). For those who do not respond to first-line treatment, support for second-line and third-line interventions falls substantially and relies largely on expert clinician opinions (IOM, 2012).

TRAUMATIC BRAIN INJURY

The DOD (Helmick, 2010) defines TBI as

a traumatically induced structural injury and/or physiological disruption of brain function as a result of an external force that is indicated by new onset or worsening of a least one of the following clinical signs immediately following the event:

•  Any period of loss of or decreased level of consciousness

•  Any loss of memory for events immediately before or after the injury

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

•  Any alteration in mental state at the time of injury (for example, confusion, disorientation, and slowed thinking)

•  Neurological deficits (for example, weakness, loss of balance, change in vision, praxis, paresis/plegia, sensory loss, and aphasia) that may or not be transient

•  Intracranial lesion. (VA and DOD, 2009a)

Severity of TBI is stratified as shown in Table 5-2.

In 2010, the Demographics and Clinical Assessment Working Group of the International and Interagency Initiative toward Common Data Elements for Research on Traumatic Brain Injury and Psychological Health simplified the definition of TBI as follows: TBI is defined as an alteration in brain function or other evidence of brain pathology caused by an external force (Menon et al., 2010). The adverse effects of concussive injury in military and civilian life have been observed increasingly, and there is increasing recognition of the importance of the proper management of this spectrum of disorders. In one sample of Army reservists returning from Iraq and Afghanistan, almost 22% screened positive for TBI (Quigley et al., 2012). The extent of exposure of deployed troops to TBI may still be underestimated.

Traumatic Brain Injury and Chronic Multisymptom Illness

People who have TBI report a large variety of physical symptoms (such as loss of balance, pain, and fatigue), cognitive symptoms (memory loss, word-finding difficulties, and reduced processing speed), and behavioral symptoms (depression, anxiety, and anger) (Gordon et al., 2000). Many of the symptoms are shared with those of CMI.

TABLE 5-2 Stratification of Severity of Traumatic Brain Injury

Mild Moderate Severe
Normal structural imaging Normal or abnormal structural imaging Normal or abnormal structural imaging
LOC for up to 30 minutes LOC for 30 minutes to 24 hours LOC for over 24 hours
AOC for up to 24 hours AOC for 24 hours; severity based on other criteria AOC for over 24 hours; severity based on other criteria
PTA for up to 1 day PTA for 1–7 days PTA for over 7 days

NOTES: AOC = alteration of consciousness or mental state; LOC = loss of consciousness;

PTA = posttraumatic amnesia.

SOURCE: VA and DOD, 2009a.

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

Treatments for Traumatic Brain Injury

It is well accepted that TBI results in increased levels of depression and anxiety and in cognitive changes (Ashman et al., 2004; Hibbard et al., 1998). A systematic review completed by Fann and colleagues (2009) reported results of treatments for post-TBI depression. The largest Class I pharmacologic study found that medication did not result in a significant improvement in mood (Ashman et al., 2009). Preliminary research suggests that CBT results in an improvement in both depression and anxiety in people who have TBI (Cantor, 2011; Soo et al., 2011). There are no current guidelines for treatment for the cognitive and mood disorders experienced by people who have TBI. Cognitive rehabilitation therapy (CRT) includes a variety of treatments that have been developed to improve the cognitive function of people who have TBI. Treatments in various domains—including attention, memory, processing speed, and executive function—have been developed. They can be delivered individually or in a group format. Cicerone and colleagues in their three systematic reviews examined more than 370 studies and concluded that “there is substantial evidence to support interventions for attention, memory, social communication skills, executive function, and for comprehensive-holistic neuropsychological rehabilitation after TBI” (Cicerone et al., 2000, 2005, 2011). In contrast, an IOM committee evaluated 60 studies of the efficacy of CRT for TBI and found that although there was some benefit, the evidence was variable and insufficient overall because of many research limitations (IOM, 2011a). The committee emphasized that the lack of evidence did not mean that CRT lacks benefit, and it encouraged additional focused research. The effects of CRT on TBI depended on several factors, including the severity and the recovery phase of the injury, treatment focus and the approach used, and the outcomes measured. There was little evidence that warrants concern for potential harm or adverse events associated with CRT (IOM, 2011a).

The IOM committee concluded that CRT may help people who have cognitive deficits to compensate and improve functioning (IOM, 2011a). CRT is a flexible treatment strategy that can be administered in a variety of settings by many types of medical professionals. It may be tailored to patients’ impairments, such as attention or memory problems, and approaches may be combined into a comprehensive program for patients who have multiple cognitive deficits.

SUBSTANCE-USE AND ADDICTIVE DISORDERS

DSM-IV-TR (APA, 2000) separates the constructs of substance abuse and substance dependence. The former is considered a maladaptive pattern of substance use manifested by recurrent and substantial adverse consequences

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

related to the repeated use of the substance. The latter is considered as a cluster of cognitive, behavioral, and physiologic symptoms that indicates that a person continues to use the substance despite serious consequences, including self-administration that can result in tolerance (for example, the need for increased amounts of the substance to achieve intoxication or the desired effect or the marked diminution of the effect with continued use of the same amount of the substance), withdrawal (for example, the development of a substance-specific syndrome due to the cessation of or reduction of a substance), or compulsive drug-taking behavior. However, a large body of literature on the abuse and dependence criteria in clinical and general population samples suggests that the DSM-IV criteria can be considered as a unidimensional structure, with the criteria interspersed throughout the severity spectrum.

In the proposed revisions in DSM-5, the substance-use and addictive disorders have been reorganized according to substance; they were previously organized according to the diagnosis (that is, use, intoxication, and withdrawal) (APA, 2012). The shift will create new drug-specific categories for disorders of use of alcohol, amphetamines, cannabis, cocaine, hallucinogens, inhalants, opioids, phencyclidine, sedatives and hypnotics, stimulants and polysubstance use, and tobacco. In the reorganization, substance abuse and dependence are combined into a single disorder of graded clinical severity, for which two criteria are required for a diagnosis.

Substance-Use Disorders and Chronic Multisymptom Illness

The co-occurrence of chronic medically unexplained symptoms and substance-use disorders—including disorders of use of alcohol, opiates, and nicotine—is common (Hasin and Katz, 2007). The co-occurrence may be a relationship in itself or be due to a shared association with anxiety and depression (Regier et al., 1990). Regardless, the presence of three or more current general physical symptoms, whether medically unexplained or not, is positively associated with the likelihood of a substance-use disorder (Escobar et al., 2010). Furthermore, if chronic pain is present, there is a high likelihood of alcohol-use or nicotine-use disorder (Ekholm et al., 2009; Park et al., 2012). The medical management of chronic pain may result in the prescription of opioids because the presence of medically unexplained symptoms can interfere with the proper evaluation and management of pain. The combination of CMI and chronic pain may lead to a decision by a clinician to begin or continue opioid therapy, and use of opioids can lead to comorbidities and substance abuse or dependence, particularly in a patient who has a history of substance-use disorder. The risk of developing opioid dependence is low in patients who do not have a history of substance abuse (Friedman et al., 2003).

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

Treatments for Substance-Use Disorders

Pharmacotherapy

Evidence-based pharmacologic treatments are available for management of disorders of alcohol, tobacco, and opioid use. The National Institute on Drug Abuse has published Principles of Drug Addiction Treatment: A Research-Based Guide (NIDA, 2009), and VA and DOD have published a comprehensive clinical practice guideline that includes recommendations for evaluation of and treatment for behaviors or misuse of opiates that suggest addiction (VA and DOD, 2010b). In the case of alcohol disorders, drugs used for treatment include naltrexone (to decrease craving), acamprosate (to help in withdrawal), disulfiram (as a “negative reinforcer”), and possibly topiramate. Management options include nicotine-replacement therapy, bupropion, and varenicline for tobacco addiction and methadone, buprenorphine, and naltrexone for opioid addiction.

Psychotherapy

Evidence-based psychotherapy interventions are available for disorders of alcohol, nicotine, and opioid use. For alcohol-use disorders, behavioral couples therapy (BCT) has the strongest evidence base (Fals-Stewart et al., 2005). It is a manual-based structured therapy that combines CBT strategies with methods that address relationship issues arising from alcohol misuse and more general relationship problems with the aim of reducing distress (National Collaborating Centre for Mental Health, 2011). BCT is recommended for those who have moderate to severe alcohol dependence and should be considered for use in combination with a pharmacologic intervention.

Three other general forms of psychosocial interventions also have a strong evidence base: CBT (for example, relapse prevention, coping, and skills training), social-network and environment-based therapies (for example, cognitive behavioral strategies to build social networks that support change), and behavioral therapies (for example, cue exposure, behavioral self-control training, aversion therapy, and contingency management) (National Collaborating Centre for Mental Health, 2011). As in the case of BCT for moderate to severe dependence, combination with pharmacologic intervention should be considered. Another guideline recommends that appropriate elements of 12-step facilitation and motivational interventions should be provided as a component of assessment and intervention because the evidence is not strong enough to support their use by themselves (National Collaborating Centre for Mental Health, 2011). For nicotine addiction, both individual and group behavioral interventions focused

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

specifically on smoking cessation, usually in combination with pharmacotherapy, have shown evidence of being more useful than self-help strategies (Lancaster and Stead, 2008; Stead and Lancaster, 2008). For opioid users, referral to a mental health specialist is recommended by the VA–DOD guidelines if changes in mood or emotional stability are associated with nonadherent behaviors (VA and DOD, 2010b).

Other Therapies

In people with nonadherent behaviors, tapering of opioid use is safest when handled by clinicians who have expertise in pain or by a center that specializes in withdrawal treatment. It is important to include alternative strategies, such as an exercise program and psychologic support. The exercise program should be structured and include short-term goals to increase motivation to continue exercising. Family support is another key component of successful tapering off of opioid use. Educating the patient and the family about the risks associated with chronic opioid therapy, before the use of opioids, is vital.

SELF-HARM

Suicidal thoughts and ideation are typically defined as having thoughts of wanting to end one’s life (AHRQ, 2004). In its diagnosis, severity of suicide risk is viewed along a continuum ranging from fleeting thoughts, such as that life is not worth living (relatively less severe), to suicidal ideation with intent and a plan (highest severity); the latter is an important risk factor in suicide attempts (AHRQ, 2004). Direct and specific questions about suicide are essential in assessment of the likelihood of suicide.

A variety of suicidality screening measures exist, including suggested questions from VA and DOD (2009c) (see Box 5-4). The ability of the screening measures to predict suicide attempts, particularly brief ones, has not been well studied (Haney et al., 2012; National Collaborating Centre for Mental Health, 2004). Patient Health Questionnaire-9 (PHQ-9) is a well-validated screening tool for assessing depression in primary care and includes one item on suicidality (Kroenke et al., 2001). In assessment, the provider should ask about suicidal thoughts, plans, and behaviors. Specific practice guidelines for assessment of risk have been developed by the American Psychiatric Association (APA, 2003), and VA has conducted a systematic review of suicide risk factors (Haney et al., 2012). Notably, primary care screening for suicide ideation among people who have signs of depression does not increase suicidal thoughts or suicide attempts (Crawford et al., 2011). A negative response to an initial question about suicidal ideation may not be enough to determine suicide risk (Jacobs and Brewer, 2006). A

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

BOX 5-4
Assessing for Suicidal Ideation

1. Are you discouraged about your medical condition (or social situation, etc.)?

2. Are there times when you think about your situation and feel like crying?

3. During those times, what sorts of thoughts go through your head?

4. Have you ever felt that it would not be worth living if the situation did not change (that is, have you thought about ending your life)? If so, how often do you have such thoughts?

5. Have you devised a specific plan to end your life? If so, what is your plan? If the answer is yes, do you have the necessary items to complete that plan readily available?

6. Have you ever acted on any plans to end your life in the past (that is, have you ever attempted suicide)? If the answer is yes, when did this occur? How many times has it occurred in the past? By what means? What was the outcome?

SOURCE: VA and DOD, 2009c.

more detailed, structured, and psychometrically validated measure to assess suicidal ideation is the Columbia-Suicide Severity Rating Scale (FDA, 2012; Posner et al., 2011), which includes items on nonsuicidal self-harm and homicidality. The objective of suicide risk assessment is to clarify the presence or absence of relevant risk and protective factors and then estimate a person’s individual risk for suicide (Jacobs and Brewer, 2006).

Self-Harm and Chronic Multisymptom Illness

The presence of physical symptoms is consistently associated with suicide attempts and suicide completion. Somatization disorder is significantly associated with suicide attempts even when the effects of both a comorbid major depressive disorder and a comorbid personality disorder are controlled for; this indicates that the potential for suicide in patients who have somatization disorder should not be overlooked when a diagnosable depressive disorder or personality disorder is not present (Chioqueta and Stiles, 2004). People who completed suicide complained frequently of such somatic symptoms as gastrointestinal discomfort, headache and dizziness, and back problems during their contacts with nonpsychiatric physicians

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

within a month before their death (Pan et al., 2009). The presence of other factors and diagnoses that often co-occur with CMI—specifically, chronic pain, activity limitations, PTSD, depression, and alcohol-use and drug-use disorders—is commonly associated with suicidality (Haney et al., 2012; Ilgen et al., 2010; US Army, 2010). Suicidality does not occur exclusively in the presence of depression (Haney et al., 2012; US Army, 2010).

Like civilian suicides, military suicides often involve problems in relationships with intimate partners, parents, or fellow unit members and tend to occur in men, who are more impulsive and use more violent means than women do (CDC, 2009; IOM, 2012). The presence of multiple stressors—including relationship, job, and physical problems—is associated with completed military suicides (Black, 2011). Three-fourths of suicide completers had contact with primary care clinicians within a year of suicide, in contrast with only one-third who had contact with mental health services. Almost half of people who committed suicide visited their physicians within a month of their death (Luoma et al., 2002). That finding is consistent with the statistic that people in military-like careers (including police and firefighting) are more prone to seek medical care because of physical than because of behavioral-health symptoms (US Army, 2010). Despite the high rate of medical contacts, most suicide completers are not identified as being at risk beforehand. Accordingly, given the association of physical symptoms with psychiatric disorders and the role of physical symptoms themselves, enhanced awareness of their link to suicide risk in nonpsychiatric settings may help to reduce suicide rates (Pan et al., 2009).

Treatments for Self-Harm

The American Psychiatric Association practice guidelines (2003) state that the documented efficacy of antidepressants in treating acute depressive episodes and their long-term benefit in patients who have recurrent forms of severe anxiety or depressive disorders support their use as part of a comprehensive care plan in people who are experiencing suicidal thoughts or behaviors. They recommend selection of an antidepressant that has a low risk of acute-overdose lethality, such as an SSRI or other newer antidepressant, and prescribing of conservative quantities, especially for patients who are not well known. Because antidepressant effects may not be observed for days or weeks after treatment starts, patients should be monitored closely early in treatment and educated about the probable delay in symptom relief (APA, 2003). There is a potential for increased risk of suicidal thoughts or behavior in children and adolescents (up to the age of 25 years) who are treated with SSRIs, although their benefit may outweigh the risk associated with them in children and adolescents who have major depression and anxiety disorders (Bridge et al., 2007). The British National

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

Institute of Health and Clinical Excellence clinical guidelines (National Collaborating Centre for Mental Health and National Collaborating Centre for Primary Care, 2011b) note that drug treatment should not be offered as a specific intervention to reduce self-harm and recommend considering offering 3 to 12 sessions of a psychologic intervention that is structured specifically for people who harm themselves.

Clinical consensus suggests that psychosocial interventions and specific psychotherapeutic approaches are of benefit (APA, 2003). Psychotherapies, such as interpersonal psychotherapy and CBT, that directly target self-harm (Joiner and Van Orden, 2008) may be appropriate for suicidal behavior, particularly when it occurs in the context of depression. CBT may be used to decrease two important risk factors for suicide: hopelessness and suicide attempts in depressed outpatients (APA, 2003). For patients who harm themselves repeatedly, dialectic behavior therapy, a form of CBT that teaches emotion-regulation skills, may be appropriate treatment because it is associated with decreased self-injurious behaviors, including suicide attempts (APA, 2003; National Collaborating Centre for Mental Health and National Collaborating Centre for Primary Care, 2011b).

For suicide attempters who refuse postdischarge treatment, caring letters reduce the risk of suicide (Fleischmann et al., 2008; Motto and Bostrom, 2001). Such letters are typically sent at regular intervals over at least 2 years after discharge and include a brief nondemanding statement of care, such as, “Dear ____: It has been some time since you were here at the hospital, and we hope things are going well for you. If you wish to drop us a note, we would be glad to hear from you.”

GENERAL THERAPEUTIC APPROACH

In this chapter, the committee has reviewed treatments considered effective for conditions related to or comorbid with CMI. As in the case of CMI, there is ambiguity in the definitions or diagnoses of several of these conditions. However, there are shared symptoms and resulting disabilities among these conditions, as well as with CMI, and many of the treatments found to be effective for one of these conditions may be beneficial for others, including CMI. Table 5-3 shows that several treatments are considered effective in managing more than one of the related and comorbid conditions. There is substantial evidence in guidelines and from systematic reviews that tricyclic medications, SSRIs, and SNRIs may be used effectively in the management of patients who have conditions related to CMI. For example, SSRIs or SNRIs are recommended as therapy for seven of the conditions: fibromyalgia, somatic-symptom disorders, IBS, anxiety, depression (including depression resulting from chronic pain or CFS), PTSD, and self-harm.

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

TABLE 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

Condition Pharmacologic Nonpharmacologic
Fibromyalgia

•  SNRIs (duloxetine and milnacipram)

•  CBT

 

•  Tricyclic medication (amitriptyline)

•  Aerobic exercise

 

•  Pregabalin

•  Combination of exercise, CBT, education, and self-help books

 

•  Gabapentin

Chronic pain

•  Tricyclic medications

•  Radiofrequency ablation of medial branch nerves to facet joints for low back pain

 

•  SNRIs and SSRIs

•  Acupuncture for headaches and low back pain

 

•  NSAIDs

•  Transcutaneous electric nerve stimulation for temporary relief of low back pain

 

•  Anticonvulsants

•  Epidural steroids for leg pain

 

•  Opioids

•  Physical or restorative therapy

   

•  Psychologic treatment (for example, CBT, biofeedback, relaxation training)

   

•  Botulinum-toxin injections for chronic migraines

Chronic fatigue syndrome

•  NSAIDs for pain symptoms

•  CBT

 

•  Melatonin for problems in sleeping

•  Graded exercise therapy

 

•  Antidepressants for depression and to improve sleep quality

•  Lifestyle changes (for example, regular sleeping schedule; avoidance of caffeine, alcohol, and tobacco; and dietary changes)

   

•  Alternative therapies (for example, yoga, Tai Chi, acupuncture, and massage)

   

•  CPAP for problems in sleeping

Somatic-symptom disorders

•  SNRI (venlafaxine) if anxiety and depression symptoms are present

•  CBT and other forms of psychotherapy

   

•  Biofeedback

   

•  Consultation letters to primary-care physicians

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Condition Pharmacologic Nonpharmacologic
Sleep disorders

•  For nightmare disorder, prazosin

•  For nightmare disorder, CBT, including image rehearsal therapy

 

•  For chronic insomnia, select pharmaceutical agent on basis of symptom pattern, treatment goals, past treatment response, patient preference, cost, vailability of other treatments, comorbid conditions, concurrent medication interactions, and side effects

•  For chronic insomnia, stimulus-control therapy or relaxation therapy, or combination CBT

Irritable bowel syndrome

•  Tricyclic medications

•  CBT

 

•  SSRIs and SNRIs

•  Hypnosis

     
Functional dyspepsia No treatments identified  
Depression

•  Tricyclic medications

•  CBT

 

•  SSRIs

•  Interpersonal therapy

   

•  Exercise

   

•  Acupuncture

   

•  Electroconvulsive therapy (for severe depression only)

Anxiety

•  Antianxiety medications

•  CBT

 

•  SSRIs

•  Reassurance

   

•  Psychotherapy

   

•  Relaxation

Posttraumatic stress disorder

•  SSRIs

•  CBT

Traumatic brain injury No treatments identified

•  CBT

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Condition Pharmacologic Nonpharmacologic
Substance-use and addictive disorders For alcohol-use disorders: For alcohol-use disorders:
 

•  Naltrexone

•  Behavioral couples therapy

 

•  Acamprosate

•  CBT

 

•  Disulfiram

•  Social network and environment-based therapies

 

•  Topiramate (possibly)

•  Other behavioral therapies (for example, cue exposure, behavioral self-control training, aversion therapy, and contingency management)

  For tobacco-use disorders:  
 

•  Nicotine-replacement therapy

 
 

•  Bupropion

 
 

•  Varenicline

 
  For opioid-use disorders: For tobacco-use disorders:
 

•  Methadone

•  Individual and group interventions focused on smoking cessation

 

•  Buprenorphine

 
 

•  Naltrexone

 
    For opioid-use disorders:
   

•  Referral to a pain specialist or center that specializes in withdrawal treatment

Self-harm

•  SSRIs

•  CBT, including dialectic behavior therapy Interpersonal therapy

NOTES: CBT = cognitive behavioral therapy; CPAP = continuous positive airway pressure;

NSAIDs = nonsteroidal anti-inflammatory drugs; SNRIs = serotonin–norepinephrine reuptake inhibitors; SSRIs = selective serotonin reuptake inhibitors.

There also is substantial evidence in guidelines and from systematic reviews that CBT is effective in managing more than one of the related conditions. CBT has been shown to be effective in nearly all the conditions examined in this chapter. It is important to note that there are multiple types of CBT and that the choice of the appropriate type to use for a particular patient will depend on the person’s symptoms.

As summarized in this chapter, many other treatments, both pharmacologic and nonpharmacologic, have been shown to be effective in managing conditions related to and comorbid with CMI. Because symptoms of CMI have a pattern of presentation similar to those of the other conditions, treatments found to be effective for the conditions should be considered as parts of an integrated and multimodal treatment plan for patients who have CMI.

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

REFERENCES

Abeles, A. M., M. H. Pillinger, B. M. Solitar, and M. Abeles. 2007. Narrative review: The pathophysiology of fibromyalgia. Annals of Internal Medicine 146(10):726-734.

AHRQ (Agency for Healthcare Research and Quality). 2004. Screening for Suicide Risk: A Systematic Evidence Review for the U.S. Preventive Task Force. Rockville, MD. http://www.ahrq.gov/downloads/pub/prevent/pdfser/suicidser.pdf (accessed November 13, 2012).

American Society of Anesthesiologists Task Force on Chronic Pain Management and American Society of Regional Anesthesia and Pain Medicine. 2010. Practice guidelines for chronic pain management. Anesthesiology 112(4):810-833.

APA (American Psychiatric Association). 2000. Diagnostic and Statistical Manual of Mental Disorders, IV. Washington, DC: APA.

APA. 2003. Practice Guidelines for the Assessment and Treatment of Patients with Suicidal Behaviors. http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1673332 (accessed November 13, 2012).

APA. 2004. Practice Guidelines for Treatment of PTSD and Acute Stress Disorder. http://psychiatryonline.org/content.aspx?bookid=&sectionid=1670530 (accessed November 13, 2012).

APA. 2010. Practice Guidelines for the Treatment of Patients with Major Depressive Disorder. http://psychiatryonline.org/data/Books/prac/PG_Depression3rdEd.pdf (accessed November 13, 2012).

APA. 2012. DSM-5 Development. http://www.dsm5.org/Pages/Default.aspx (accessed November 13, 2012).

Ashman, T. A., L. A. Spielman, M. R. Hibbard, J. M. Silver, T. Chandna, and W. A. Gordon. 2004. Psychiatric challenges in the first 6 years after traumatic brain injury: Cross-sequential analyses of Axis I disorders. Archives of Physical Medicine and Rehabilitation 85(4):S36-S42.

Ashman, T. A., J. B. Cantor, W. A. Gordon, S. Flanagan, A. Ginsberg, C. Engmann, L. A. Spielman, M. Egan, A. F. Ambrose, and B. Greenwald. 2009. A randomized controlled trial of setraline for the treatment of depression in individuals with traumatic brain injury. Archives of Physical Medicine & Rehabilitation 90:733-740.

Aurora, R. N., R. S. Zak, S. H. Auerbach, K. R. Casey, S. Chowdhuri, A. Karippot, R. K. Maganti, K. Ramar, D. A. Kristo, S. R. Bista, C. I. Lamm, and T. I. Morgenthaler. 2010. Best practice guide for the treatment of nightmare disorder in adults. Journal of Clinical Sleep Medicine 6(4):389-401.

Australian Centre for Posttraumatic Mental Health. 2007. Australian Guidelines for the Treatment of Adults with Acute Stress Disorder and Posttraumatic Stress Disorder. Melbourne, Australia: National Health and Medical Research Council. http://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/mh13.pdf (accessed November 13, 2012).

Bernardy, K., N. Fuber, V. Kollner, and W. Hauser. 2010. Efficacy of cognitive-behavioral therapies in fibromyalgia syndrome: A systematic review and metaanalysis of randomized controlled trials. Journal of Rheumatology 37(10):1991-2005.

Black, S. A. 2011. Prevalence and risk factors associated with suicides in Army soldiers. Military Psychology 23:433-451.

Blake, D. D., F. W. Weathers, L. M. Nagy, D. G. Kaloupek, F. D. Gusman, D. S. Charney, and T. M. Keane. 1995. The development of a clinician-administered PTSD scale. Journal of Traumatic Stress 8(1):75-90.

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

Blanchard, E. B., J. M. Lackner, R. Gusmano, G. D. Gudleski, K. Sanders, L. Keefer, and S. Krasner. 2006. Prediction of treatment outcome among patients with irritable bowel syndrome treated with group cognitive therapy. Behaviour Research and Therapy 44(3):317-337.

Boyce, P. M., N. J. Talley, B. Balaam, N. A. Koloski, and G. Truman. 2003. A randomized controlled trial of cognitive behavior therapy, relaxation training, and routine clinical care for the irritable bowel syndrome. American Journal of Gastroenterology 98(10):2209-2218.

Brandt, L. J., W. D. Chey, A. E. Foxx-Orenstein, E. M. M. Quigley, L. R. Schiller, P. S. Schoenfeld, B. M. Spiegel, N. J. Talley, and P. Moayyedi. 2009. An evidence-based position statement on the management of irritable bowel syndrome. American Journal of Gastroenterology 104:S1-S36.

Bridge, J. A., S. Iyengar, C. B. Salary, R. P. Barbe, B. Birmaher, H. A. Pincus, L. Ren, and D. A. Brent. 2007. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: A meta-analysis of randomized controlled trials. Journal of the American Medical Association 297(15):1683-1696.

Cantor, J. B. 2011. A Randomized Controlled Trial of Psychotherapies for Post-TBI Depression: Initial Findings, A Presentation. Paper presented at American Congress of Rehabilitation Medicine.

CDC (Centers for Disease Control and Prevention). 1994. Chronic Fatigue Syndrome: The 1994 Case Definition. http://www.cdc.gov/cfs/case-definition/1994.html (accessed November 13, 2012).

CDC. 2009. Suicide: Facts at a Glance. http://www.cdc.gov/ViolencePrevention/pdf/Suicide-DataSheet-a.pdf (accessed Septmeber 27, 2012).

CDC. Undated. Chronic Fatigue Syndrome: A Tool Kit for Providers. http://www.cdc.gov/cfs/pdf/cfs-toolkit.pdf (accessed November 13, 2012).

Chang, L., and D. A. Drossman. 2004. Psychotropic drugs and management of patients with functional gastrointestinal disorders. Advanced Therapy in Gastroenterology and Liver Disease. Hamilton, Ontario: BC Decker.

Chioqueta, A. P., and T. C. Stiles. 2004. Suicide risk in patients with somatization disorder. The Journal of Crisis Intervention and Suicide Prevention 25:3-7.

Chokroverty, S. 2000. Diagnosis and treatment of sleep disorders caused by co-morbid disease. Neurology 54(5 Suppl 1):S8-S15.

Choy, E., D. Marshall, Z. L. Gabriel, S. A. Mitchell, E. Gylee, and H. A. Dakin. 2011. A systematic review and mixed treatment comparison of the efficacy of pharmacological treatments for fibromyalgia. Seminars in Arthritis and Rheumatism 41(3):335-345.

Cicerone, K. D., C. Dahlberg, K. Kalmar, D. M. Langenbahn, J. F. Malec, T. F. Bergquist, T. Felicetti, J. T. Giacino, J. P. Harley, D. E. Harrington, J. Herzog, S. Kneipp, L. Laatsch, and P. A. Morse. 2000. Evidence-based cognitive rehabilitation: Recommendations for clinical practice. Archives of Physical Medicine and Rehabilitation 81(12):1596-1615.

Cicerone, K. D., C. Dahlberg, J. F. Malec, D. M. Langenbahn, T. Felicetti, S. Kneipp, W. Ellmo, K. Kalmar, J. T. Giacino, J. P. Harley, L. Laatsch, P. A. Morse, and J. Catanese. 2005. Evidence-based cognitive rehabilitation: Updated review of the literature from 1998 through 2002. Archives of Physical Medicine and Rehabilitation 86(8):1681-1692.

Cicerone, K. D., D. M. Langenbahn, C. Braden, J. F. Malec, K. Kalmar, M. Fraas, T. Felicetti, L. Laatsch, J. P. Harley, T. Bergquist, J. Azulay, J. Cantor, and T. Ashman. 2011. Evidence-based cognitive rehabilitation: Updated review of the literature from 2003 through 2008. Archives of Physical Medicine and Rehabilitation 92(4):519-530.

Cleare, A. J. 2003. The neuroendocrinology of chronic fatigue syndrome. Endocrine Reviews 24(2):236-252.

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

Crawford, M. J., L. Thana, C. Methuen, P. Ghosh, S. V. Stanley, J. Ross, F. Gordon, G. Blair, and P. Bajaj. 2011. Impact of screening for risk of suicide: Randomised controlled trial. British Journal of Psychiatry 198(5):379-384.

Creed, F., R. L. Levy, L. A. Bradley, C. Fransisconi, D. A. Drossman, and B. D. Naliboff. 2006. Psychosocial aspects of functional gastrointestinal disorders. In Rome III: The Functional Gastrointestinal Disorders. 3rd ed, edited by D. A. Drossman, E. Corazziari, M. Delvaux, R. C. Spiller, N. J. Talley and W. G. Thompson. McLean, VA: Degnon Associates, Inc. Pp. 295-368.

Dowrick, C., C. Katona, R. Peveler, and H. Lloyd. 2005. Somatic symptoms and depression: Diagnostic confusion and clinical neglect. British Journal of General Practice 55(520):829-830.

Drossman, D. A. 2006. The functional gastrointestinal disorders and the Rome III process. In Rome III: The Functional Gastrointestinal Disorders. 3rd ed, edited by D. A. Drossman, E. Corazziari, M. Delvaux, R. Spiller, N. J. Talley and W. G. Thompson. McLean, VA: Degnon Associates, Inc. Pp. 1-29.

Drossman, D. A., M. Camilleri, E. A. Mayer, and W. E. Whitehead. 2002. AGA technical review on irritable bowel syndrome. Gastroenterology 123(6):2108-2131.

Drossman, D. A., B. B. Toner, W. E. Whitehead, N. E. Diamant, C. B. Dalton, S. Duncan, S. Emmott, V. Proffitt, D. Akman, K. Frusciante, T. Le, K. Meyer, B. Bradshaw, K. Mikula, C. B. Morris, C. J. Blackman, Y. M. Hu, H. G. Jia, J. Z. Li, G. G. Koch, and S. I. Bangdiwala. 2003. Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders. Gastroenterology 125(1):19-31.

Ekholm, O., M. Gronbaek, V. Peuckmann, and P. Sjogren. 2009. Alcohol and smoking behavior in chronic pain patients: The role of opioids. European Journal of Pain 13(6):606-612.

Engel, C. C., Jr., X. Liu, B. D. McCarthy, R. F. Miller, and R. Ursano. 2000. Relationship of physical symptoms to posttraumatic stress disorder among veterans seeking care for Gulf War-related health concerns. Psychosomatic Medicine 62(6):739-745.

Escobar, J. 2009. Somatoform disorders. In Kaplan and Sadock’s Comprehensive Textbook of Psychiatry. 9th ed, edited by B. J. Sadock, V. A. Sadock and P. Ruiz. Philadelphia: Lippincott Williams & Wilkins.

Escobar, J. I., B. Cooke, C. N. Chen, M. A. Gara, M. Alegria, A. Interian, and E. Diaz. 2010. Whether medically unexplained or not, three or more concurrent somatic symptoms predict psychopathology and service use in community populations. Journal of Psychosomatic Research 69(1):1-8.

Fals-Stewart, W., T. J. O’Farrell, G. R. Birchler, J. Cordova, and M. L. Kelley. 2005. Behavioral couples therapy for alcoholism and drug abuse: Where we’ve been, where we are, and where we’re going. Journal of Cognitive Psychotherapy 19(3):229-246.

Fann, J. R., T. Hart, and K. G. Schomer. 2009. Treatment for depression after traumatic brain injury: A systematic review. Journal of Neurotrauma 26(12):2383-2402.

FDA (Food and Drug Administration). 2012. Guidance for Industry: Suicidal Ideation and Behavior: Prospective Assessment of Occurrence in Clinical Trials. http://www.fda.gov/downloads/Drugs/.../Guidances/UCM225130.pdf (accessed November 11, 2012).

Fleischmann, A., J. M. Bertolote, D. Wasserman, D. De Leo, J. Bolhari, N. J. Botega, D. De Silva, M. Phillips, L. Vijayakumar, A. Varnik, L. Schlebusch, and H. T. T. Thanh. 2008. Effectiveness of brief intervention and contact for suicide attempters: A randomized controlled trial in five countries. Bulletin of the World Health Organization 86(9):703-709.

Foa, E. B., T. M. Keane, J. Friedman, and J. A. Cohen. 2009. Effective Treatments for PTSD: Practice Guidelines from the International Society for Traumatic Stress Studies. 2nd ed. New York: Guilford Publications.

Ford, A. C., and P. O. Vandvik. 2012. Irritable bowel syndrome. Clinical Evidence. 01:410.

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

Ford, A. C., N. J. Talley, P. S. Schoenfeld, E. M. Quigley, and P. Moayyedi. 2009. Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: Systematic review and meta-analysis. Gut 58(3):367-378.

Ford, J. D., K. A. Campbell, D. Storzbach, L. M. Binder, W. K. Anger, and D. S. Rohlman. 2001. Posttraumatic stress symptomatology is associated with unexplained illness attributed to Persian Gulf War military service. Psychosomatic Medicine 63(5):842-849.

Friedman, M. J., P. A. Resick, R. A. Bryant, and C. R. Brewin. 2011. Considering PTSD for DSM-5. Depression and Anxiety 28(9):750-769.

Friedman, R., V. Li, and D. Mehrotra. 2003. Treating pain patients at risk: Evaluation of a screening tool in opioid-treated pain patients with and without addiction. Pain Medicine 4(2):182-185.

Gill, A., R. Womack, and S. Safranek. 2010. Does exercise alleviate symptoms of depression? Journal of Family Practice 59(9):530-531.

Glaser, R., and J. K. Kiecolt-Glaser. 1998. Stress-associated immune modulation: Relevance to viral infections and chronic fatigue syndrome. American Journal of Medicine 105(3A):35S-42S.

Gordon, W. A., L. Haddad, M. Brown, M. R. Hibbard, and M. Sliwinski. 2000. The sensitivity and specificity and self-reported symptoms in people with traumatic brain injury. Brain Injury 14(1):21-33.

Grover, M., and D. A. Drossman. 2009. Psychopharmacologic and behavioral treatments for functional gastrointestinal disorders. Gastroenterology Endoscopy Clinics of North America 19(1):151-170.

Haney, E. M., M. E. O’Neil, S. Carson, A. Low, K. Peterson, L. M. Denneson, C. Oleksiewicz, and D. Kansagara. 2012. Suicide Risk Factors and Risk Assessment Tools: A Systematic Review. Department of Veterans Affairs—Evidence-Based Synthesis Program. http://www.hsrd.research.va.gov/publications/esp/suicide-risk.pdf (accessed November 11, 2012).

Harber, V. J., and J. R. Sutton. 1984. Endorphins and exercise. Sports Medicine 1(2):154-171. http://www.ncbi.nlm.nih.gov/pubmed/6091217 (accessed November 11, 2012).

Hasin, D., and H. Katz. 2007. Somatoform and substance use disorders. Psychosomatic Medicine 69(9):870-875.

Hauser, W., K. Bernardy, B. Arnold, M. Offenbacher, and M. Schiltenwolf. 2009. Efficacy of multicomponent treatment in fibromyalgia syndrome: A meta-analysis of randomized controlled clinical trials. Arthritis & Rheumatism-Arthritis Care & Research 61(2):216-224.

Hauser, W., F. Petzke, N. Uceyler, and C. Sommer. 2011. Comparative efficacy and acceptability of amitriptyline, duloxetine and milnacipran in fibromyalgia syndrome: A systematic review with meta-analysis. Rheumatology 50(3):532-543.

Hays, R. D., K. B. Wells, C. D. Sherbourne, W. Rogers, and K. Spritzer. 1995. Functioning and well-being outcomes of patients with depression compared with chronic general medical illnesses. Archives of General Psychiatry 52(1):11-19.

Helmick, K. 2010. Cognitive rehabilitation for military personnel with mild traumatic brain injury and chronic post-concussional disorder: Results of April 2009 Consensus Conference. Neurorehabilitation 26(3):239-255.

Hibbard, M. R., S. Uysal, K. Kepler, J. Bogdany, and J. Silver. 1998. Axis I psychopathology in individuals with traumatic brain injury. Journal of Head Trauma Rehabilitation 13(4):24-39.

Hinton, D. E., and R. Lewis-Fernandez. 2011. The cross-cultural validity of posttraumatic stress disorder: Implications for DSM-5. Depression and Anxiety 28(9):783-801.

Ilgen, M. A., A. S. B. Bohnert, R. V. Ignacio, J. F. McCarthy, M. M. Valenstein, H. M. Kim, and F. C. Blow. 2010. Psychiatric diagnoses and risk of suicide in veterans. Archives of General Psychiatry 67(11):1152-1158.

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

IOM (Institute of Medicine). 2006. Gulf War and Health, Volume 4: Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press.

IOM. 2007. Treatment of PTSD: An Assessment of the Evidence. Washington, DC: The National Academies Press.

IOM. 2010. Gulf War and Health, Volume 8: Update of Health Effects of Serving in the Gulf War. Washington, DC: The National Academies Press.

IOM. 2011a. Cognitive Rehabilitation Therapy for Traumatic Brain Injury: Evaluating the Evidence. Washington, DC: The National Academies Press.

IOM. 2011b. Relieving Pain in America: A Blue Print for Transforming Prevention, Care, Education, and Research. Washington, DC: The National Academies Press.

IOM. 2012. Treatment for Posttraumatic Stress Disorder in Military and Veteran Populations: Initial Assessment. Washington, DC: The National Academies Press.

Jackson, J. L., P. G. O’Malley, G. Tomkins, E. Balden, J. Santoro, and K. Kroenke. 2000. Treatment of functional gastrointestinal disorders with antidepressant medications: A meta-analysis. American Journal of Medicine 108(1):65-72.

Jacobs, D. G., and M. L. Brewer. 2006. Application of the APA Practice Guidelines on suicide to clinical practice. CNS Spectrums 11(6):447-454.

Jason, L. A., N. Porter, J. Hunnell, A. Brown, A. Rademaker, and J. A. Richman. 2011. A natural history study of chronic fatigue syndrome. Rehabilitation Psychology 56(1):32-42.

Joiner, T. E., and K. A. Van Orden. 2008. The interpersonal-psychological theory of suicidal behavior indicates specific and crucial psychotherapeutic targets. International Journal of Cognitive Therapy 1(1):80-89.

Katon, W. J., and E. A. Walker. 1998. Medically unexplained symptoms in primary care. Journal of Clinical Psychiatry 59(Suppl 20):15-21.

Katsamanis, M., P. M. Lehrer, J. I. Escobar, M. A. Gara, A. Kotay, and R. Liu. 2011. Psychophysiologic treatment for patients with medically unexplained symptoms: A randomized controlled trial. Psychosomatics 52(3):218-229.

Krilov, L. R., M. Fisher, S. B. Friedman, D. Reitman, and F. S. Mandel. 1998. Course and outcome of chronic fatigue in children and adolescents. Pediatrics 102(2):360-366.

Kroenke, K., R. L. Spitzer, and J. B. W. Williams. 2001. The PHQ-9: Validity of a brief depression severity measure. Journal of General Internal Medicine 16(9):606-613.

Kroenke, K., N. Messina, I. Benattia, J. Graepel, and J. Musgnung. 2006. Venlafaxine extended release in the short-term treatment of depressed and anxious primary care patients with multisomatoform disorder. Journal of Clinical Psychiatry 67(1):72-80.

Lackner, J. M., J. Jaccard, S. S. Krasner, L. A. Katz, G. D. Gudleski, and K. Holroyd. 2008. Self-administered cognitive behavior therapy for moderate to severe irritable bowel syndrome: Clinical efficacy, tolerability, feasibility. Clinical Gastroenterology and ;Hepatology 6(8):899-906.

Lancaster, T., and L. F. Stead. 2005. Individual behavioural counselling for smoking cessation. Cochrane Database of Systematic Reviews Issue 2. Art. No.: CD001292.

Lawrence, R. C., D. T. Felson, C. G. Helmick, L. M. Arnold, H. Choi, R. A. Deyo, S. Gabriel, R. Hirsch, M. C. Hochberg, G. G. Hunder, J. M. Jordan, J. N. Katz, H. M. Kremers, and F. Wolfe. 2008. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Arthritis and Rheumatism 58(1):26-35.

Lee, C., J. Smith, M. Sprengel, C. Crawford, D. Wallerstedt, R. Welton, A. York, A. Duncan, and W. B. Jonas. 2012. An assessment of the effectiveness of acupuncture for the trauma spectrum response: Results of a rapid evidence assessment of the literature (REAL). BMC Complementary and Alternative Medicine 12(Suppl 1).

Lesbros-Pantoflickova, D., P. Michetti, M. Fried, C. Beglinger, and A. L. Blum. 2004. Meta-analysis: The treatment of irritable bowel syndrome. Alimentary Pharmacology & Therapeutics 20(11-12):1253-1269.

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

Levy, R. L., K. W. Olden, B. D. Naliboff, L. A. Bradley, C. Francisconi, D. A. Drossman, and F. Creed. 2006. Psychosocial aspects of the functional gastrointestinal disorders. Gastroenterology 130(5):1447-1458.

Lew, H. L., J. D. Otis, C. Tun, R. D. Kerns, M. E. Clark, and D. X. Cifu. 2009. Prevalence of chronic pain, posttraumatic stress disorder, and persistent postconcussive symptoms in OIF/OEF veterans: Polytrauma clinical triad. Journal of Rehabilitation Research and Development 46(6):697-702.

Lindfors, P., P. Unge, P. Arvidsson, H. Nyhlin, E. Bjornsson, H. Abrahamsson, and M. Simren. 2012. Effects of gut-directed hypnotherapy on IBS in different clinical settings: Results from two randomized, controlled trials. American Journal of Gastroenterology 107(2):276-285.

Longstreth, G. F., W. G. Thompson, W. D. Chey, L. A. Houghton, F. Mearin, and R. C. Spiller. 2006. Functional bowel disorders. Gastroenterology 130(5):1480-1491.

Luoma, J. B., C. E. Martin, and J. L. Pearson. 2002. Contact with mental health and primary care providers before suicide: A review of the evidence. American Journal of Psychiatry 159(6):909-916.

Manheimer, E., A. White, B. Berman, K. Forys, and E. Ernst. 2005. Acupuncture for low back pain. Annals of Internal Medicine 143(9):695-695.

Maquet, D., C. Demoulin, and J. M. Crielaard. 2006. Chronic fatigue syndrome: A systematic review. Annales de Readaptation et de Médecine Physique 49(6):337-347, 418-327.

Maquet, D., C. Demoulin, J. L. Croisier, and J. M. Crielaard. 2007. Benefits of physical training in fibromyalgia and related syndromes. Annales de Readaptation et de Médecine Physique 50(6):356-362, 363-368.

Mayo Clinic Staff. 2011. Chronic Fatigue Syndrome: Treatments and Drugs. http://www.mayoclinic.com/health/chronic-fatigue-syndrome/ds00395/dsection=treatments-and-drugs (accessed November 11, 2012).

McWhinney, I. R., R. M. Epstein, and T. R. Freeman. 2001. Rethinking somatization. Advances in Mind Body Medicine 17(4):235-239.

Menon, D. K., K. Schwab, D. W. Wright, and A. I. Maas. 2010. Position statement: Definition of traumatic brain injury. Archives of Physical Medicine and Rehabilitation 91(11):1637-1640.

Mertz, H., R. Fass, A. Kodner, F. Yan-Go, S. Fullerton, and E. A. Mayer. 1998. Effect of amitryptiline on symptoms, sleep, and visceral perception in patients with functional dyspepsia. American Journal of Gastroenterology 93(2):160-165.

Moldofsky, H. 1993. Fibromyalgia, sleep disorder and chronic fatigue syndrome. Ciba Foundation Symposia 173:262-279.

Moore, R. A., S. Straube, P. J. Wiffen, S. Derry, and H. J. McQuay. 2009. Pregabalin for acute and chronic pain in adults. Cochrane Database of Systematic Reviews Issue 3. Art. No.: CD007076.

Moore, R. A., P. J. Wiffen, S. Derry, and H. J. McQuay. 2011. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews Issue 3. Art. No.: CD007938.

Motto, J. A., and A. G. Bostrom. 2001. A randomized controlled trial of postcrisis suicide prevention. Psychiatric Services 52(6):828-833.

National Collaborating Centre for Mental Health. 2004. Self Harm: The Short-Term Physical and Psychological Management and Secondary Prevention of Self-Harm in Primary and Secondary Care. London: National Institute for Health and Clinical Excellence.

http://www.nice.org.uk/nicemedia/pdf/CG016NICEguideline.pdf (accessed November 11, 2012).

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

National Collaborating Centre for Mental Health. 2005. Post-Traumatic Stress Disorder (PTSD): The Management of PTSD In Adults and Children in Primary and Secondary Care. London: National Institute of Health and Clinical Excellence. http://www.nice.org.uk/nicemedia/live/10966/29769/29769.pdf (accessed November 11, 2012).

National Collaborating Centre for Mental Health. 2009a. Depression in Adults with a Chronic Physical Health Problem. London: National Institute of Health and Clinical Excellence. http://www.nice.org.uk/CG91 (accessed November 11, 2012).

National Collaborating Centre for Mental Health. 2009b. Depression: The Treatment and Management of Depression in Adults. London: National Institute of Health and Clinical Excellence. http://www.nice.org.uk/nicemedia/pdf/Depression_Update_FULL_GUIDELINE.pdf (accessed November 11, 2012).

National Collaborating Centre for Mental Health. 2011. Alcohol Dependence and Harmful Alcohol Use. London: National Institute for Health and Clinical Excellence. http://guidance.nice.org.uk/CG115 (accessed November 11, 2012).

National Collaborating Centre for Mental Health and National Collaborating Centre for Primary Care. 2011a. Generalized Anxiety Disorder and Panic Disorder (With Or Without Agoraphobia) in Adults: Management in Primary, Secondary and Community Care. London: National Institute for Health and Clinical Excellence. http://www.nice.org.uk/nicemedia/live/13314/52599/52599.pdf (accessed November 11, 2012).

National Collaborating Centre for Mental Health and National Collaborating Centre for Primary Care. 2011b. Longer-term Care and Treatment of Self-harm. London: National Institute for Health and Clinical Excellence. http://www.nice.org.uk/nicemedia/live/13619/57175/57175.pdf (accessed November 11, 2012).

National Collaborating Centre for Primary Care. 2007. Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (or Encephalopathy): Diagnosis and Management of CFS/ME in Adults and Children. London: National Institute for Health and Clinical Excellence. http://www.nice.org.uk/nicemedia/live/11824/36193/36193.pdf (accessed November 11, 2012).

NIDA (National Institute on Drug Abuse). 2009. Principles of Drug Addiction Treatment: A Research-based Guide. Bethesda, MD: National Institutes of Health. http://www.drugabuse.gov/sites/default/files/podat_0.pdf (accessed November 11, 2012).

Nieuwsma, J. A., R. B. Trivedi, J. McDuffie, I. Kronish, D. Benjamin, and J. W. Williams. 2012. Brief psychotherapy for depression: A systematic review and meta-analysis. International Journal of Psychiatry in Medicine 43(2):129-151.

NIH (National Institutes of Health). 2012a. Generalized Anxiety Disorders Among Adults. http://www.nimh.nih.gov/statistics/1GAD_ADULT.shtml (accessed September 27, 2012).

NIH. 2012b. The Numbers Count: Mental Disorders in America. http://www.nimh.nih.gov/health/publications/the-numbers-count-mental-disorders-in-america/index.shtml (accessed September 27, 2012).

Nishishinya, B., G. Urrutia, B. Walitt, A. Rodriguez, X. Bonfill, C. Alegre, and G. Darko. 2008. Amitriptyline in the treatment of fibromyalgia: A systematic review of its efficacy. Rheumatology 47(12):1741-1746.

Nuesch, E., W. Hauser, K. Bernardy, J. Barth, and P. Juni. 2012. Comparative efficacy of pharmacological and non-pharmacological interventions in fibromyalgia syndrome: Network meta-analysis. Annals of the Rheumatic Diseases Epub.

Olatunji, B. O., J. M. Cisler, and D. F. Tolin. 2010. A meta-analysis of the influence of comorbidity on treatment outcome in the anxiety disorders. Clinical Psychology Review 30(6):642-654.

Palsson, O. S., and W. E. Whitehead. 2002. The growing case for hypnosis as adjunctive therapy for functional gastrointestinal disorders. Gastroenterology 123(6):2132-2135.

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

Pan, Y. J., M. B. Lee, H. C. Chiang, and S. C. Liao. 2009. The recognition of diagnosable psychiatric disorders in suicide cases’ last medical contacts. General Hospital Psychiatry 31(2):181-184.

Park, S., M. J. Cho, S. Seong, S. Y. Shin, J. Sohn, B. J. Hahm, and J. P. Hong. 2012. Psychiatric morbidities, sleep disturbances, suicidality, and quality-of-life in a community population with medically unexplained pain in Korea. Psychiatric Research 198(3):509-515.

Posner, K., G. K. Brown, B. Stanley, D. A. Brent, K. V. Yershova, M. A. Oquendo, G. W. Currier, G. A. Melvin, L. Greenhill, S. Shen, and J. J. Mann. 2011. The Columbia-Suicide Severity Rating Scale: Initial validity and internal consistency findings from three multisite studies with adolescents and adults. American Journal of Psychiatry 168(12):1266-1277.

Prins, A., P. Ouimette, R. Kimerling, R. P. Cameron, D. S. Hugelshofer, J. Shaw-Hegwer, A. Thrailkill, F. D. Gusman, and J. I. Sheikh. 2003. The primary care PTSD screen (PC-PTSD): Development and operating characteristics. Primary Care Psychiatry 9(1):9-14.

Quigley, K. S., L. M. McAndrew, L. Almeida, E. A. D’Andrea, C. C. Engel, H. Hamtil, and A. J. Ackerman. 2012. Prevalence of environmental and other military exposure concerns in Operation Enduring Freedom and Operation Iraqi Freedom veterans. Journal of Occupational & Environmental Medicine 54(6):659-664.

Rainville, P., R. K. Hofbauer, T. Paus, G. H. Duncan, M. C. Bushnell, and D. D. Price. 1999. Cerebral mechanisms of hypnotic induction and suggestion. Journal of Cognitive Neuroscience 11(1):110-125.

Reeves, W. C., J. F. Jones, E. Maloney, C. Heim, D. C. Hoaglin, R. S. Boneva, M. Morrissey, and R. Devlin. 2007. Prevalence of chronic fatigue syndrome in metropolitan, urban and rural Georgia. Population Health Metrics 5(5).

Regier, D. A., M. E. Farmer, D. S. Rae, B. Z. Locke, S. J. Keith, L. L. Judd, and F. K. Goodwin. 1990. Comorbidity of mental-disorders with alcohol and other drug-abuse: Results from the Epidemiologic Catchment-Area (ECA) Study. Journal of the American Medical Association 264(19):2511-2518.

Rimer, J., K. Dwan, D. A. Lawlor, C. A. Greig, M. McMurdo, W. Morley, and G. E. Mead. 2012. Exercise for depression. Cochrane Database of Systematic Reviews Issue 7. Art. No.: CD004366.

Russell, I. J., M. Kamin, R. M. Bennett, T. J. Schnitzer, J. A. Green, and W. A. Katz. 2000. Efficacy of tramadol in treatment of pain in fibromyalgia. Journal of Clinical Rheumatology 6(5):250-257.

Schutte-Rodin, S., L. Broch, D. Buysse, C. Dorsey, and M. Satei. 2008. Clinical guideline for the evaluation and management of chronic insomnia in adults. Journal of Clinical Sleep Medicine 4(5):487-504.

Sheldon, L. K., S. Swanson, A. Dolce, K. Marsh, and J. Summers. 2008. Putting evidence into practice: Evidence-based interventions for anxiety. Clinical Journal of Oncology Nursing 12(5):789-797.

Shorter, E. 1993. Paralysis to Fatigue: A History of Psychosomatic Illness in the Modern Era. New York, NY: The Free Press.

Siler, A. C., H. Gardner, K. Yanit, T. Cushman, and M. McDonagh. 2011. Systematic review of the comparative effectiveness of antiepileptic drugs for fibromyalgia. Journal of Pain 12(4):407-415.

Sledjeski, E. M., B. Speisman, and L. C. Dierker. 2008. Does number of lifetime traumas explain the relationship between PTSD and chronic medical conditions? Answers from The National Comorbidity Survey Replication (NCS-R). Journal of Behavioral Medicine 31(4):341-349.

Soo, C., R. L. Tate, and A. Lane-Brown. 2011. A systematic review of Acceptance and Commitment Therapy (ACT) for managing anxiety: Applicability for people with acquired brain injury? Brain Impairment 12(1):54-70.

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

Stead, L. F., and T. Lancaster. 2008. Intervention review: Group behaviour therapy programmes for smoking cessation. The Cochrane Library Issue 2. Art. No.: CD001007.

Storzbach, D., K. A. Campbell, L. M. Binder, L. McCauley, W. K. Anger, D. S. Rohlman, C. A. Kovera, and C. Portland Env Hazards Res. 2000. Psychological differences between veterans with and without Gulf War unexplained symptoms. Psychosomatic Medicine 62(5):726-735.

Sultan, A., H. Gaskell, S. Derry, and R. A. Moore. 2008. Duloxetine for painful diabetic neuropathy and fibromyalgia pain: Systematic review of randomised trials. BMC Neurology 8:29.

Tack, J., N. J. Talley, M. Camilleri, G. Holtmann, P. Hu, J. R. Malagelada, and V. Stanghellini. 2006. Functional gastroduodenal disorders. Gastroenterology 130(5):1466-1479.

Thiwan, S. M., and D. A. Drossman. 2006. Treatment of functional GI disorders with psychotropic medicines: A review of evidence with a practical approach. Gastroenterology and Hepatology 2(9):678-688.

Tzellos, T. G., K. A. Toulis, D. G. Goulis, G. Papazisis, V. A. Zampeli, A. Vakfari, and D. Kouvelas. 2010. Gabapentin and pregabalin in the treatment of fibromyalgia: A Systematic review and a meta-analysis. Journal of Clinical Pharmacy and Therapeutics 35(6):639-656.

Uceyler, N., W. Hauser, and C. Sommer. 2008. A systematic review on the effectiveness of treatment with antidepressants in fibromyalgia syndrome. Arthritis & Rheumatism 59(9):1279-1298.

US Army. 2010. Army Health Promotion/Risk Reduction/Suicide Prevention Report 2010. Washington, DC. http://www.apd.army.mil/pdffiles/p600_24.pdf (accessed November 11, 2012).

VA (Department of Veterans Affairs) and DOD (Department of Defense). 2009a. Clinical Practice Guideline: Management of Concussion/Mild Traumatic Brain Injury. http://www.healthquality.va.gov/mtbi/concussion_mtbi_full_1_0.pdf (accessed November 11, 2012).

VA and DOD. 2009b. Clinical Practice Guideline: Management of Major Depressive Disorder (MDD). http://www.healthquality.va.gov/MDD_FULL_3c.pdf (accessed November 11, 2012).

VA and DOD. 2009c. VA/DOD Essentials for Depression Screening and Assessment in Primary Care. http://www.healthquality.va.gov/mdd/MDDTool1VADoDEssentialsQuadFoldFinalHiRes.pdf (accessed November 11, 2012).

VA and DOD. 2010a. Clinical Practice Guideline for Management of Post-Traumatic Stress. http://www.healthquality.va.gov/ptsd/PTSD-FULL-2010a.pdf (accessed November 11, 2012).

VA and DOD. 2010b. Clinical Practice Guideline: Management of Opioid Therapy for Chronic Pain. http://www.healthquality.va.gov/COT_312_Full-er.pdf (accessed November 11, 2012).

Van Kerkhoven, L. A. S., R. J. F. Laheij, N. Aparicio, W. A. De Boer, S. Van Den Hazel, A. Tan, B. J. M. Witteman, and J. Jansen. 2008. Effect of the antidepressant venlafaxine in functional dyspepsia: A randomized, double-blind, placebo-controlled trial. Clinical Gastroenterology and Hepatology 6(7):746-752.

Vickers, A. J. 2012. Acupuncture for chronic pain: Individual patient data meta-analysis. Archives of Internal Medicine.

Walker, R. L., M. E. Clark, and S. H. Sanders. 2010. The “postdeployment multi-symptom disorder”: An emerging syndrome in need of a new treatment paradigm. Psychological Services 7(3):136-147.

Watson, D. 2005. Rethinking the mood and anxiety disorders: A quantitative hierarchical model for DSM-V. Journal of Abnormal Psychology 114 (4):522-536.

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×

WFMH (World Federation for Mental Health). 2010. Mental Health and Chronic Physical Illnesses: The Need for Continued and Integrated Care. http://www.wfmh.org/2010DOCS/WMHDAY2010.pdf (accessed November 11, 2012)

WGO (World Gastroenterology Organisation). 2009. Irritable Bowel Syndrome: A Global Perspective. Munich.

Whitehead, W. E. 2006. Hypnosis for irritable bowel syndrome: The empirical evidence of therapeutic effects. International Journal of Clinical and Experimental Hypnosis 54(1):7-20.

Whorwell, P. J., A. Prior, and S. M. Colgan. 1987. Hypnotherapy in severe irritable bowel syndrome: Further experience. Gut 28(4):423-425.

Wilson, S., T. Maddison, L. Roberts, S. Greenfield, S. Singh, and I. B. S. R. G. Birmingham. 2006. Systematic review: The effectiveness of hypnotherapy in the management of irritable bowel syndrome. Alimentary Pharmacology & Therapeutics 24(5):769-780.

Wolfe, F., H. A. Smythe, M. B. Yunus, R. M. Bennett, C. Bombardier, D. L. Goldenberg, P. Tugwell, S. M. Campbell, M. Abeles, P. Clark, A. G. Fam, S. J. Farber, J. J. Fiechtner, C. M. Franklin, R. A. Gatter, D. Hamaty, J. Lessard, A. S. Lichtbroun, A. T. Masi, G. A. McCain, W. J. Reynolds, T. J. Romano, I. J. Russell, and R. P. Sheon. 1990. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: Report of the Multicenter Criteria Committee. Arthritis and Rheumatism 33(2):160-172.

Wolfe, F., D. J. Clauw, M. A. Fitzcharles, D. L. Goldenberg, R. S. Katz, P. Mease, A. S. Russell, I. J. Russell, J. B. Winfield, and M. B. Yunus. 2010. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care and Research 62(5):600-610.

Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page93
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page94
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page95
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page96
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page97
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page98
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page99
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page100
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page101
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page102
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page103
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page104
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page105
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page106
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page107
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page108
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page109
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page110
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page111
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page112
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page113
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page114
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page115
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page116
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page117
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page118
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page119
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page120
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page121
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page122
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page123
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page124
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page125
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page126
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page127
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page128
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page129
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page130
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page131
Suggested Citation:"5 Review of Treatments for Comorbid and Related Conditions." Institute of Medicine. 2013. Gulf War and Health: Treatment for Chronic Multisymptom Illness. Washington, DC: The National Academies Press. doi: 10.17226/13539.
×
Page132
Next: 6 Patient-Centered Care of Veterans Who Have Chronic Multisymptom Illness »
Gulf War and Health: Treatment for Chronic Multisymptom Illness Get This Book
×
Buy Paperback | $49.00 Buy Ebook | $39.99
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

Chronic multisymptom illness (CMI) is a serious condition that imposes an enormous burden of suffering on our nation's veterans. Veterans who have CMI often have physical symptoms (such as fatigue, joint and muscle pain, and gastrointestinal symptoms) and cognitive symptoms (such as memory difficulties). For the purposes of this report, the committee 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, gastrointestinal, respiratory, and neurologic—that may overlap with but are not fully captured by known syndromes (such as CFS, fibromyalgia, and IBS) or other diagnoses. Despite considerable efforts by researchers in the United States and elsewhere, there is no consensus among physicians, researchers, and others as to the cause of CMI. There is a growing belief that no specific causal factor or agent will be identified. Many thousands of Gulf War veterans1 who have CMI live with sometimes debilitating symptoms and seek an effective way to manage their symptoms. 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), and there is evidence that CMI in 1991 Gulf War veterans may not resolve over time. Preliminary data suggest that CMI is occurring in veterans of the Iraq and Afghanistan wars as well.

In addition to summarizing the available scientific and medical literature regarding the best treatments for chronic multisymptom illness among Gulf War veterans, Gulf War and Health: Volume 9: Treatment for Chronic Multisymptom Illness recommends how best to disseminate this information throughout the VA to improve the care and benefits provided to veterans, recommends additional scientific studies and research initiatives to resolve areas of continuing scientific uncertainty and recommends such legislative or administrative action as the IOM deems appropriate in light of the results of its review.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    Switch between the Original Pages, where you can read the report as it appeared in print, and Text Pages for the web version, where you can highlight and search the text.

    « Back Next »
  6. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  7. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  8. ×

    View our suggested citation for this chapter.

    « Back Next »
  9. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!