Chronic Fatigue Syndrome and Fibromyalgia:

Clinical Assessment and Treatment

 

 

Fred Friedberg

Department of Psychiatry and Behavioral Science, State University of New York at Stony Brook

 

 

Leonard A. Jason

Department of Psychology, DePaul University

 

                       

                        JOURNAL OF CUNICAL PSYCHOLOGY, Vol. 57(4), 433-455 (2001)

 

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are closely related illnesses of uncertain etiology. This article reviews the research literature on these biobehavioral conditions, with an emphasis on explanatory mod­els, clinical evaluation of comorbid psychiatric disorders, assessment of stress factors, pharmacologic and alternative therapies, and cognitive-behavioral treatment studies. Furthermore, clinical protocols suitable for professional practice are presented based on an integration of the authors’ clinical observations with published data. The article concludes with the recognition that mental health professionals can offer substantial help to these patients. © 2001 John Wiley & Sons, Inc. J Clin Psychol 67: 433— 455. 2001

 

Keywords: chronic fatigue syndrome; fibromyalgia; clinical assessment

 

 

 

 

 

 

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are enigmatic illness conditions that manifest an array of medical and psychological symptoms. These disabling syn­dromes arc grouped together because they share a number of clinically important char­acteristics, including similar symptomatology and demographics, a wide range of symptom fluctuations and disability, apparently high levels of psychiatric morbidity. poorly under­stood etiologies, an absence of curative interventions, and a low likelihood of recovery. Overlapping symptoms in these conditions may include persistent abnormal fatigue, chronic

 

 

Correspondence concerning this article should be addressed to: Fred Friedberg, P.O. Box 456. Kent, CT 06757 e-mail: ffriedbe@ct1.nai.net

 

 

 

 

 

pain, and neurocognitive difficulties, although fatigue symptoms are more prominent in CFS and pain symptoms are more commàn in FM (Taylor, Jason, & Schoeny, 2000). Both disorders exhibit a broad spectrum of debilitation, from bed-bound confinement and general disability to more circumscribed impairments such as exercise intolerance and cognitive difficulties.

 

Many but not all psychodiagnostic investigations of these illnesses have reported higher-than-expected rates of psychiatric disorder, although the diagnostic methodology used in these studies may have resulted in misleading overestimations of psychiatric cornorbidity (Taylor & Jason, 1998). Whether psychiatric disturbance, if present, is an antecedent or a consequence of these illnesses is part of an ongoing debate about the nature of CFS and FM. It appears safe to say that the relationship between psychiatric illness and these two puzzling somatic conditions is complex and interactive, and is unlikely to be reduced to a single either/or relationship in most cases (Demitrack, 1998). It is also important to note that a significant number of these patients do not have comor­bid psychiatric disorders (Friedberg, 1996).

 

Neither CFS nor FM have clearly defined causes. Without specific diagnostic tests or biological markers, diagnoses are primarily based on patient-reported symptoms. Given the absence of a recognized biomedical etiology and the perception of high levels of psychiatric disorder, these conditions are often viewed by physicians as somatoform dis­orders or simply nonilinesses masquerading as medical diseases (e.g., Shorter, 1995). Medical rejection of the legitimacy of CFS has led to public confusion and skepticism about the nature of the illness, while FM, given its much longer history in medical research and clinical practice, may have achieved a somewhat greater level of credibility.

 

No curative medical treatments are available for these illnesses, although pharmaco­logical and cognitive behavioral approaches may produce significant improvements in coping abilities, symptoms, and functional impairments for some individuals or subsets of patients. Naturalistic outcome studies in CFS (Joyce, Hotopf, & Wessely, 1997) and FM (e.g., Wolfe et aL, 1997) reveal some level of improvement in many patients, but less than 10% report substantial recovery or long-range remission. Finally, epidemiological studies indicate that CFS and FM are common illness conditions in the U.S. population that primarily afflict women. (No American incidence data are available for either ill­ness.) Despite the above described commonalities, it appears that these disorders can be distinguished through factor analysis of symptoms (Robbins et al., 1997; Taylor et al., 2000) and their somewhat different response to treatment interventions.

 

Psychologists can play an important role in the assessment and treatment of CFS and FM, given that (1) cognitive behavioral interventions and other nonpharmacological treat­ments, although not curative, can offer substantial benefits to these individuals, and (2) many physicians have abdicated their role in helping these patients because of the diffi­culties involved in diagnosis, treatment, and ongoing care.

 

 

Case Definition of CFS

 

CFS is defined (Fukuda, Straus, Hickie, Sharpe, Dobbins, & Komaroff, 1994) by at least six months of persistent debilitating fatigue not attributable to any identifiable medical condition. In addition, four secondary symptoms must be present such as postexertional malaise, neurocognitive difficulties, sleep disturbance, multijoint pains, and flu-like symp­toms (Table I ). A large majority of CFS patients report a sudden onset of the illness, often within a few days. Individuals acknowledging substance abuse within two years before onset of CFS and those with diagnosable psychosis or melancholic depression are excluded from the diagnosis of CFS, because it is thought that these psychiatric conditions may be


 

 

Table I

Current U.S. Case Definition of Chronic Fatigue S,yndrorne (Fukuda et a!., 1994,)

 

I.  Medically unexplained chronic fatigue, experience for at least six months, which is of new or definite onset, that is not substantially alleviated by rest, that is not the result of ongoing exertion, and that results in substantial reduction in occupational, educational, social, and personal activities. Anxiety disorders. sornatoform disorders. and nonpsychotic or nonmelancholic depression are not exclusionary.

The following conditions, if present, exclude a diagnosis of CFS: past or current major depression with melancholic or psychotic features, delusional disorders, bipolar disorders. schizophrenia. anorexia nervosa, bulimia, or alcohol or substance abuse within 2 years before the onset of CFS or anytime afterward.

 

2.  Concurrent occurrence of four or more of the following symptoms, which must be persistent or recurrent during six or more months of the illness and do not predate the fatigue:

a.  Self-reported persistent or recurrent impairment in short-term memory or concentration severe enough to cause substantial reductions in previous levels of occupational, educational, social, or personal activities.

b.  Sore throat.

c.  Tender cervical or axillary lymph nodes.

d.  Muscle pain.

e.  Multiple joint pain without joint swelling or redness.

f.  Headaches of a new type, pattern, or severity.

g.  Unrefreshing sleep.

h.  Postexertional malaise lasting more than 24 hours.

 

 

 

 

responsible for the fatigue symptomatology. On the other hand, the presence of nonmel­ancholic depression and anxiety disorders do not exclude a diagnosis of CFS. Because this case definition is based on a panel consensus of CFS researchers and clinicians, rather than empirical data, it is uncertain how accurately the case definition delineates the entity of CFS and distinguishes it from primary psychiatric disorder or psychosocial stress (Jason, Richman, Friedberg, Wagner, Taylor, & Jordan, 1997).

 

According to a recent epidemiologic study (Jason et at., 1999c), approximately 800,000 people in the United States have CFS and 70% of these individuals are women. This total prevalence figure is considerably higher than the original estimate of less than 20,000 reported by the Centers for Disease Control (Reyes et a!., 1997). The higher figure is consistent with subsequent epidemiologic studies in CFS that have used more inclusive and representative surveillance methodologies (Johnson, DeLuca, & Natelson, 1999b). CFS in women is roughly 15 times more common than lung cancer or breast cancer, and is over 40 times more common than AIDS (Jason et al., 1999c). In contrast to the stereo­type of CFS as an illness of white professional women (i.e., Yuppie Flu), African Amer­icans show a roughly equal prevalence with Whites, while Latinos demonstrate about two times greater prevalence than Whites (Jason et al., 1 999c).

 

Case Definition of FM

FM is a chronic musculoskeletal pain disorder characterized by widespread pain of at least three months duration and pain upon palpation at multiple sites called tender points (Wolfe et a!., 1990). A majority of FM patients also complain of CFS-like symptoms including fatigue and nonrestorative sleep, and a sizable minority also report dysmenor­rhea, irritable bowel syndrome, tension, migraine headache, and Raynaud’s phenomenon (Wolfe et al., 1990). People with FM awaken unrefreshed from sleep with intensified muscle stiffness and aching, and prominent fatigue. A large subgroup of FM patients experience depression and anxiety, which may exacerbate symptoms, although it is not clear if such affective states contribute to the development or persistence of the illness.


 

About 55% report abrupt onset of the illness (Demitrack, 1998). According to the most recent prevalence study (Wolfe, Ross, Anderson, Russell, & Hebert, 1995), roughly three to six million people in the U.S. population have FM, and about 90% are women.

 

 

Explanatory Models of CFS and FM

 

A number of hypotheses have been generated to explain these complex biobehavioral conditions. Etiologic models range from purely biological conceptualizations to socio­cultural hypotheses. These models wax and wane in popularity in the scientific commu­nity, depending on the weight of the current evidence for any particular model and the cogency of specific theoretical formulations. We will briefly review several of these models.

 

 

Immune Defect Model

 

Both CFS and FM have been viewed as disorders of the immune system. Given the presence of flu-like symptoms in these illnesses, an underlying viral or bacterial illness has been suspected. Yet no specific pathogen has been consistently and uniquely associ­ated with either illness, including Epstein-Barr virus, cytomegalovirus, and human her­pes virus 6 (Ang & Wilke, 1999; Glaser & Kiecolt-Glaser, 1998). In the absence of an identified pathogenic invader, an immune defect has been hypothesized for CFS in which disease fighting entities remain in an abnormally activated state and produce flu-like symptoms (Straus, Dale, Wright, & Metca!fe, 1988). A number of studies have found low levels of natural killer cells in CFS cases relative to healthy controls; however, no con­vincing evidence has linked natural killer cell activity to disease severity or outcome in CFS (Whiteside & Friberg, 1998). In FM, as well, no consistent evidence has been found for specific immune defects, although subsets have been characterized by defects in T cell activation (Hernanz et a!., 1994), elevated antinuclear antibodies (Smart, Waylonis, & Hackshaw, 1997), and elevated serotonin antibodies (Klein & Berg, 1995).

 

Perhaps a more promising potential immune marker in CFS is the upregulated Rnase L enzyme. (Rnase L is the key enzyme that comprises an antiviral defense pathway of the immune system. It is designed to degrade viral RNA.) Upregulated Rnase L has been consistently found in CFS patients in a single group study (Suhadolnik et al., 1994a), and in studies that compared CFS patients to healthy controls (Suhadolnik et al., l994b; DeMeirleir et a!., 2000), and to depression or fibromya!gia patients (DeMeirleir et a!., 2000). In addition, increased activity of the Rnase L pathway has been correlated with a lower state of general health in CFS patients (Suhadolnik et al., 1999), whereas clinical improvements have been associated with Rnase L activity returning to normal (Suhadol­nik et a!., l994a).

 

 

Sleep Disturbance Model

 

Patient reports of significant sleep disturbance are common in these illnesses. In fact, a high frequency of sleep disorders in CFS and FM has been documented in polysomno­graphic studies (Harding, 1998; Krupp, Mendelson, & Friedman, 1991). According to some theorists (Hickie & Davenport, 1999; Moldofsky, 1993), CFS and FM are best viewed as chronic disorders of the sleep—wake cycle characterized by reduction of deep sleep (stage three and stage four slow wave). The loss of normal sleep architecture trig­gers a disturbance of circadian rhythm and associated neurohormones, such as cortisol


 

 

and melatonin, which normally help regulate the sleep—wake cycle. As a result, patients during their waking hours are in a zombie-like state, and during sleep hours are partially awake and restless. The evidence for this theory is stronger for FM patients who consis­tently show a disturbance of stage four slow-wave sleep (e.g., Leventhal, Freundlich, Lewis, Gilier, Henry, & Dinges, 1995). In a related fmding, healthy individuals who are deprived of stage four sleep develop a FM-like syndrome (Moldofsky, Scarisbrick, England, & Smythe, 1975). It has been suggested that abnormal serotonin metabolism, which is important to deep sleep and pain, may be the basis of sleep disturbances in CFS and FM. Restoration of norma! sleep patterns via behavioral methods or medication has been suggested, but firm evidence for the efficacy of these interventions is lacking.

 

 

Neuroendocrine Abnormalities

 

It has been proposed that impaired activation of the hypothalamic-pituitary axis (HPA) in both CFS and FM may be an essential neuroendocrine feature of these conditions (Derni­track, 1998). Both illnesses show HPA dysregulation as manifested by low levels of the stress-related neurohormone, cortisol (Demitrack & Crofford, 1998). Given that behav­ioral hyperreactivity to external stressors has been found in both CFS and FM (e.g., Wood, Bentall, Gopfert, Dewey, & Edwards, 1994), the reported abnormalities of the HPA axis appear to support a possible hormonal correlate of this hyperreactivity. Yet clinical trials of cortisol replacement drugs in CFS have yielded only modest symptom­atic improvements (McKenzie et al., 1998). Thus, the precise role of neuroendocrine disturbance in these illnesses is not clear.

 

 

“Predisposing Personality” Models

 

Compulsive overwork and associated psychopathologies have been proposed as impor­tant precipitants of both CFS and FM. According to the conversion model (Abbey & Garfinkel, 1991), people with CFS, especially women, feel compelled to achieve in all major life domains, including vocational, family, exercise, volunteer, and social activi­ties. Presumably this “do everything” work ethic arises from the new lifestyle options generated by the women’s movement; however, these options become subverted into obligations to perform well in every respect. Such impossibly high standards of accom­plishment propel women into a disabling conversion-like illness that unconsciously allows them to escape from overwhelming responsibilities and consequently receive the family and social support that they had been lacking (Abbey & Garfinkel, 1991). Thus, a cul­turally induced psychological disorder with identifiable primary and secondary gains is hypothesized to explain the CFS symptom complex. Although some evidence for an overachiever lifestyle, premorbid stress, and low social support has been reported, this data could just as plausibly suggest a more complex biopsychosocial model involving an interaction between psychological stress and stress-related neurohormones (Friedberg & Jason, 1998). Furthermore, the absence of control groups in many of these supporting studies leaves open the possibility that compulsive overachievers are not overrepresented in the CFS population, compared to overachievers, who are either healthy or who have other chronic conditions.

In a similar conceptualization that may be applied to FM, the “pain-prone personal­ity” hypothesis (Blumer & Heilbronn, 1981; Engel, 1959) views people with poorly defined chronic pain syndromes as having compulsive tendencies to overachieve in combination with other characteristics, including a lack of assertiveness, difficulty identify-


 

 

ing negative emotions (alexithymia), especially anger, and altruism at the expense of the person’s own well-being. The core element of tl~ese personality traits, according to the model, is an unstable self-esteem that depends excessively on the acceptance and recog~ nition by others through high achievement. This excessive striving for achievement cou­pled with assertiveness deficits may be responsible, according to the model, for persistently elevated levels of stress that eventuate in chronic pain conditions, such as FM, in suscep­tible individuals. Adverse childhood experiences like poverty, lack of affection, repeti­tive trauma, or physical and sexual abuse may also increase illness susceptibility. Although the concept of pain-prone personality was originally conceived as a comprehensive psy­chodynamic theory of many chronic pain conditions, it is more likely to be relevant to FM as one possible factor that contributes to the development and persistence of illness.

Despite the popularity of the pain-prone model in previous decades, its psychologi­cal premises have received limited research attention in chronic pain groups, including FM. Regarding behavioral tendencies to overwork, we found only one related study (Van Houdenhove, Stans, & Verstraeten, 1987) in chronic pain patients, which suggested that these patients were more “action prone” than a healthy control group. Empirical studies have found relationships between unexpressed anger and pain intensity in chronic pain patients (Kerns, Rosenberg, & Jacob, 1994), lower awareness of anger in chronic pain patients compared to other medical patients (Braha & Catchlove, 1986), and greater anger suppression in chronic pain patients as compared to healthy controls (Hatch et al.. 1991). In one comparative study (Dailey, Bishop, Russell, & Fletcher, 1990), 57% of FM patients reported “inability to express yourself” as a problem. This was significantly higher than the proportions of rheumatoid arthritis and healthy controls endorsing this item. In a recent two-year prospective investigation (Greenberg et al., 1999), baseline alexithymia predicted higher pain and greater disability at follow-up, after controlling for baseline pain and disability. It has been suggested that suppressed negative emotions, especially anger, may act to increase pain sensitivity by lowering endogenous opioid levels (Beutler, Engle, Oro’-Beutler, Daldrup, & Meredith, 1986) or increase pain inten­sity via elevated muscle tension at the pain site (Kerns et al., 1994). Finally, a recent literature review of the relationship of trauma to FM found some evidence supporting an association between physical trauma immediately preceding illness onset (White, Carette, Harth, & Teasell, 2000). Furthermore, a prior clinical study (Walker, Keegan, Gardner, Sullivan, Bernstein, & Katon, 1997) that compared patients with fibromyalgia and rheu­matoid arthritis found significantly higher lifetime prevalence rates of all forms of vic­timization in the FM group, both adult and childhood, as well as combinations of adult and childhood trauma. Yet, the scant number of studies of trauma in FM have not found consistent associations between the two variables (Walker et al., 1997).

We conclude that the relationships between pain prone characteristics and FM symp­toms may be a fruitful area of research in elaborating the associations between emotional distress, symptom severity, and functional status; however, the evidence to date must be considered preliminary.

 

 

Symptom Avoidance Model

 

The symptom avoidance model (Surawy, Hackmann, Hawton, & Sharpe, 1995), which is currently applied to CFS, and is based on a chronic pain model that may be relevant to FM (Robbins, Kirmayer, & Kapusta, 1991), postulates that an acute infectious illness in combination with severe psychosocial stressors initiates the persistent fatiguing condi­tion of CFS. As the acute infectious illness subsides, the individual continues to fear


 

 

increasing activity, believing it will increase symptoms. Thus, patients develop a phobic-like avoidance of preillness activities. Ove~ time, patients become more sensitive to ever-lower-intensity symptom flareups, and thus scale back their activities further, creating a cycle of avoidance behavior. According to the symptom avoidance model, these phobic-like tendencies can be counteracted with an increasing schedule of individualized stepwise activities. Two randomized clinical trials, conducted in England, of graded activity-oriented cognitive-behavior therapy in CFS patients (Deale, Chalder, Marks, & Wessely, 1997; Sharpe et al., 1996) have reported substantial improvements in functioning and reductions of symptomatology in 13 to 16 sessions. Although these clinical outcomes are impressive, it is not clear whether the participants in these studies are representative of CFS patients generally (see section on treatment for further discussion).

 

 

Differential Diagnosis

 

Both CFS and FM exhibit some symptoms that overlap with psychiatric disorder. Thus, it is important in the clinical interview to distinguish psychiatric symptoms that may be secondary to these conditions from symptomatology inherent to CFS and FM. Psychiatric symptomatology may be more amenable to behavioral (and pharmacologic) intervention. For purposes of comparison with psychiatric disorder, we will group CFS and FM together in this section.

 

 

Depression

 

CFS/FM and depression may share symptoms of persistent fatigue, pain, sleep distur­bance, poor concentration, psychomotor retardation, and loss of sexual desire (Jason, Richman, Friedberg, Wagner, Taylor, & Jordan, 1997). Yet the fatigue and pain symptoms in CFS/FM tend to be more debilitating in comparison to depression. For instance, depressed clients do not suddenly become disabled by fatigue or pain as patients with CFS/FM often report. Although pain symptoms, such as headache and back pain are not uncommon in primary depression (Simon, Von Korif, Piccinelli, Fullerton, & Ormel, 1999), the pain in FM tends to be intense, debilitating, and widespread, rather than local­ized. In addition, neurocognitive symptoms in CFS and FM appear to be more severe. For example, memory and concentration difficulties as well as mental confusion in CFS/FM are sometimes so profound that they may disable an individual from working. Although sleep disturbance, psychomotor retardation, and loss of sexual desire are common to both CFS/FM and depression, no established clinical strategy is available to specifically asso­ciate these symptoms with each illness. The important point is that these symptoms are not necessarily depression related. Therefore, standard CBT techniques to counteract depression symptoms may not ameliorate these symptoms if they are, in part, manifes­tations of CFS/FM.

For the purposes of differential diagnosis, several symptoms that distinguish CFS/FM and depression can be identified in the clinical setting. CFS/FM patients often complain of postexertional malaise and prolonged fatigue after excrcise—symptoms that are quite atypical in primary depression. In fact, primary depression patients often respond to activity and exercise regimes with substantial mood elevation, rather than symptom flare­ups (e.g., Moore &. Blumenthal, 1998). This is a key distinction between CFS/FM and depression. In addition, painful lymph nodes, flu-like symptoms, pressure-like headaches (CFS), migraine headaches (FM), and alcohol intolerance (CFS) all tend to be much more common in the CFS/FM constellation of symptoms, and are much less likely to be reported in primary depression (Komaroff et al., 1996).


 

 

Another important difference between CFS/FM and depression is the prominent loss of interest commonly found in primary depression that contrasts with strong feelings of motivation in CFS/FM patients. Rather than experiencing a loss of interest, CFS/FM patients report a loss of ability to pursue desired activities. For example, if the primary depression patient is asked to list five things he or she would want to do, the answer might be “nothing.” On the other hand, the CFS/FM patient would quickly list a number of things that he or she would like to do if not impaired by illness. Even when depression co-occurs with CFS/FM, depressed mood tends to be the most prominent feature of the depressive syndrome, rather than loss of interest (Johnson, DeLuca, & Natelson, I 996c).

Finally, cognitive differences between CFS and depression patients have been iden­tified using the Fatigue-Related Cognition Scale (Friedberg & Krupp, 1994; Friedberg & Jason, 1998). CFS patients were significantly more likely to endorse tendencies to dwell on fatigue, to have no control over fatigue, and to think they were dying due to their fatigue. By contrast, the familiar cognitive symptoms of depression, such as thoughts of worthlessness, self-criticism, and suicidal or death ideation, were much more common in primary depression patients.

 

 

Somatization Disorder

 

Although CFS/FM and somatization disorder share many characteristics, including pain, gastrointestinal, pseudoneurologic, and sexual symptoms, there are important differ­ences. CFS is characterized by sudden onset, usually in the late 20s to early 30s, while the initial symptoms of somatization disorder begin in adolescence and progress gradually to full-blown somatization by age 25 (American Psychiatric Association, 1994). With regard to FM, the requirement of 11 out of 18 (painful) tender points for the diagnosis of FM may help to distinguish it from somatization disorder because the pain symptoms in somatization disorder do not reach the level of severity required for multiple highly sensitive tender points. Given that both CFS/FM and somatization are medically unexplained, it may not be possible to clearly delineate all of the symptoms of these disorders (Johnson et al., 1996a).

 

 

Anxiety

 

CFS/FM is often accompanied by persistent anxiety (e.g., Fischler, Cluydts, Dc Gucht, Kaufman, & De Meirleir, 1997) that may or may not fulfill criteria for generalized anx­iety disorder. CFS/FM may be distinguished from generalized anxiety disorder by focus­ing on the most prominent feature in each disorder. For CFS, severe fatigue, for FM, widespread pain, and for generalized anxiety disorder, excessive persistent anxiety that is not necessarily accompanied by severe pain or profound fatigue. Yet persistent clinically significant anxiety in CFS/FM may be an inherent feature of these illnesses or a second­ary reaction to symptoms and impairments. It may not be possible to identify the precise relationship of anxiety symptoms to CFS/FM. Regardless of origin, identified anxiety can be effectively treated with standard cognitive-behavioral interventions.

 

 

Activity-Induced Chronic Fatigue

 

Finally, CFS (and FM in patients who also have the symptom of postexertional malaise) may be distinguished from activity-induced chronic fatigue in healthy people. In CFS, two types of patients have been identified by cluster analysis (Jason & Taylor, 2000): one



 

 

type is distinguished by severe postexertional fatigue and fatigue that is somewhat alle­viated by rest, while the second type is characterized by severe overall symptomatology, severe postexertional fatigue, and fatigue that is not alleviated by rest. Although rest is apparently more beneficial to the first type of patient, rest alone (or in combination with other lifestyle adjustments) is unlikely to restore healthy energy levels. By comparison, healthy people who are persistently fatigued by active schedules, high levels of stress, and lack of sleep will show remission from these symptoms when sleep is adequate and rest and leisure time are incorporated into their lifestyle.

 

 

Treatment

 

No pharmacological or alternative treatment has been developed specifically for CFS or FM. Pharmacologic interventions alone may benefit less than 50% of FM patients (Leventhal, 1999). In addition, drug hypersensitivity and adverse reactions to medica­tions are not uncommon in these patients. Cognitive-behavioral treatments also appear to benefit only certain subsets of these patients. Yet for those individuals who report symp­tomatic improvements, complete symptom remission is rare. Despite these sobering obser­vations, a quantitative review of FM treatment studies (Rossy et al., 1999) suggests that pharmacological and nonpharmacological treatments are generally efficacious in practi­cal as well as statistical terms and comparable to effects sizes found in treatment studies of arthritis and migraine headache. In contrast, the low number of CFS treatment studies shows a far less consistent picture (Johnson et al., l999b). Clinical outcomes in cognitive-behavioral intervention studies, for example, range from a return to normal functioning in the majority of patients (Sharpe et al., 1996) to no statistically significant change (Lloyd Ct al., 1993). It is important to remember that the mental health professional, unlike the experimenter administrating a standardized clinical protocol, can offer highly individu­alized treatment for these patients. Such tailored interventions can result in substantial improvements in coping abilities, affective distress, symptom status, and, for some indi­viduals, physical and social functioning as well.

 

 

Pharmacologic and Alternative Interventions in CFS

 

In the absence of curative medical interventions for CFS, symptomatic treatment has received attention in a small number of studies. Although a viral illness or an immune defect has been suspected as a causal factor in CFS, few controlled studies of antiviral and immunomodulatory medications have been conducted in CFS. One immunomodula­tory drug, mismatched, double stranded RNA (Ampligen), has shown promise in an ini­tial randomized clinical trial (Strayer et al., 1994) and in ongoing open trials conducted by a number of physicians throughout the country. On the other hand, reports of poor outcomes and adverse reactions in a recent patient newsletter (Kansky & Tai, 1999) suggest that Ampligen studies require rigorous replication and long-term follow-up assessments.

Given the linkage between fatigue and depression, initial antidepressant treatment studies of CFS have been undertaken. Yet two controHed studies of fluoxetine (Prozac) in CFS patients have reported either no effect on CFS or depression symptoms (Vercoulen, Swanink, Zitman, Vreden, & Hoofs, 1996) or a temporary effect on depression symptoms only (Wearden et al., 1998). Previously established associations between fatigue and low blood pressure have provided the rationale for a different approach to treatment of CFS. The pharmacological treatment of neurally mediated hypotension, a type of abnormally


 

 

low blood pressure found in some CFS patients, has shown encouraging outcomes in open trials (e.g., Bou-Holaigah, Rowe, Kaii, & Calkins, 1995), although controlled clin­ical studies and long-term follow-up assessments are needed to establish the efficacy of this intervention.

Promising new alternative therapies for CFS include: (a) massage, which has pro­duced significant reductions in the somatic symptoms and emotional stress of the illness in a randomized clinical trial (Field et al., 1997); (b) oral supplementation with essential fatty acids, which has been associated with significant symptomatic improvements in two controlled studies (Behan, Behan, & Horrobin, 1990; Plioplys & Plioplys, 1997), although a recent randomized clinical trial (Warren. McKendrick, & Peet. 1999) failed to replicate these earlier findings; and (c) NADH (nicotinamide adenine dinucleotide), a respiratory enzyme that triggers energy production in the body, which has been tested in a random­ized, double blind placebo-controlled crossover study (Forsyth, Preuss, MacDowell, Chiazze, Birkmayer, & Bellanti, 1999). About one-third of patients responded favorably to NADH reporting at least 10% improvement in symptom scores.

Other alternative treatments that have been offered for CFS include homeopathy, shark cartilage, blue-green algae, vitamin/mineral/amino acid supplementation, mag­nets, and clinical ecology. Unfortunately, none of these treatments or approaches have been empirically evaluated in published studies. CFS patient ratings of helpful treatments (Friedberg, 1995) have ranked antiallergy and antiyeast diets as well as biofeedback and stress management as among the most helpful treatment (24—30% favorable to highly favorable ratings).

 

 

Pharmacologic and Alternative Treatments in FM

 

In a meta-analysis of 49 FM treatment studies (Rossy et al., 1999), treatment with anti-depressants and muscle relaxants was significantly associated with improved outcomes, which included self-report of FM symptoms and affective distress. On the other hand, treatment with nonsteroidal anti-inflammatory drugs (e.g., ibuprofen) was not signifi­cantly associated with improved outcomes on any measure. With respect to antidepres­sants, tricyclics may diminish the sleep disturbance and pain associated with FM, whereas selective serotonin reuptake inhibitors (SSRI) may be more useful for coexistent depres­sion (Leventhal, 1999). Tricyclic antidepressants for FM, often prescribed in doses too small to have an antidepressant effect, may increase non-REM stage four sleep by increas­ing serotonin levels (Maurizo & Rogers, 1997). In a combination therapy trial of tricyclic and SSRI drugs (Goldenberg, Mayskiy, Mossey, Ruthazer, & Schmidt, 1996), amitryp­taline and fluoxetine significantly reduced pain, improved sleep, and increased patient function and well-being in a randomized double-blind crossover study. The therapeutic effects of amitryptaline or fluoxetine alone were significant, but not as good as the com­bination. Despite these encouraging clinical outcomes, no pharmacologic treatment in FM has been associated with significantly improved daily functioning, e.g., self-report of daily activities (Rossy et al., 1999). Treating physicians must be willing to adj List dosages and try different medications in different combinations to identify the most effective regime for each patient (Maurizo & Rogers, 1997).

Many patients are interested in the usefulness of nonprescription or alternative ther­apies because traditional therapies provide inadequate control of fibromyalgia symptoms. Several studies, including two controlled trials of S-adensyl-L-methionine (SAMe), an anti-inflammatory drug with analgesic and antidepressant effects, generally revealed sig­nificant improvements in self-report of depression, pain, and number of tender points in FM (Rossy et al., 1999). Although SAMe can be purchased over the counter, the bio­


 

 

availability for oral usage is very low (Stramentinoli, Gualano, & Galli-Kienle, 1979); thus, it is not clear what dosage would be effective. Another purportedly therapeutic supplement, Super Malic, a combination of malic acid and magnesium, produced improve­ments in FM symptoms in an open trial, but failed to show significant improvement in a blinded controlled trial (Rossy et al., 1999). Finally, acupuncture, based on limited data in FM, may be useful as a pain reduction treatment (Berman, Ezzo, Hadhazy, & Swyers, 1999). For a significant minority of FM patients, effective medications will most likely reduce (but not eliminate) pain, improve sleep, and lessen anxiety and depression.

 

 

Cognitive Behavioral Treatment Studies in CFS

 

Cognitive behavioral intervention in CFS has generated controversy among patients, phy­sicians, and researchers about the appropriateness and efficacy of such treatments. England-based randomized clinical trials of graded activity-oriented cognitive-behavior therapy (GA/CBT; Deale et al., 1997; Sharpe et al., 1996) and graded exercise (Fulcher & White, 1997) in CFS patients have reported substantial improvements in functioning and reduc­tions in symptomatology at treatment termination with greater improvements reported at follow-up assessments. Patient organizations, while acknowledging a role for CBT as a coping treatment, have protested that CBT alone will not reverse these illness conditions for all or even most patients. In addition, illness advocates fear that the apparent suc­cesses of GA/CBT may be used as confirmatory evidence that these illnesses are indeed uncomplicated psychiatric disorders, and thus discourage biological research on causal factors and medical treatment.

On the other hand, health professionals who are familiar with GA/CBT outcomes are more likely to believe that this type of intervention is helpful to patients. We are inclined to be cautious about recommending GA/CBT as well as graded exercise until a U.S.-based clinical trial is done. It appears that this form of CBT targets fear-based avoidance behavior, and thus will be most effective for clients with this mechanism of avoidance. On the other hand, our clinical experience suggests that GA/CBT for clients who do not exhibit fear-based avoidance may be counterproductive and trigger symptom flareups.

A recent theoretical paper (Friedberg, 1999) argued for the existence of two quali­tatively distinct subgroups in CFS, a high function/low symptomatology subgroup and a low function/high symptomatology subgroup. The low functioning group is more likely to show phobic-like avoidance of activity that can be successfully treated with graduated behavioral schedules. The high functioning group, which tends to maintain vocational, family and other responsibilities, is less likely to be impaired by a fear-based avoidance. Subsequent empirical study of the high/low functioning hypothesis (Friedberg, 200lb) has verified the existence of high and low function CFS subjects based on three weeks of activity records using an electronic step counter. The low function group exhibited sig­nificantly higher scores on the Beck Anxiety Inventory but not on the Beck Depression Inventory, suggesting the possibility of anxiety-based avoidance in these individuals.

The approach that we recommend for most clients with CFS is a form of CBT based on coping skills therapy and envelope theory (see discussion below). This combined approach seeks to enhance physical function and quality of life by monitoring energy, fatigue, and activity levels and then making adjustments in daily activity that minimize fatigue and improve perceived energy. In contrast, graded activity approaches, in our view, are less individualized to the patient’s symptom parameters and activity levels, and thus will be less effective as a generic prescription for patients with CFS.



 

 

Cognitive-Behavioral Treatment Studies in FM

 

In the previously cited meta-analysis of FM treatments (Rossy et al., 1999), all nonphar­macological treatments, including physical exercise (aerobics and stretching), cognitive-behavioral treatments, or a combination of these two produced significant improvements in physical status (e.g., number of tender points), self-report of FM symptoms, and psy­chological distress, while only CBT interventions yielded significant improvements in daily functioning as well. Interestingly, CBT treatments were significantly more effica­cious in improving self-report of FM symptoms and functioning in comparison to phar­macological treatments alone. In addition, more recent behavioral treatment studies in FM have generally shown significant levels of improvements in pain symptoms (e.g., Keel, Bodoky, Gerhard, & Muller, 1998) and psychological variables such as depression (Nicassio et al., 1997) and self-efficacy (Gowans, DeHueck, Voss, & Richardson, 1999). Successful CBT studies in FM patients have shown maintenance of treatment gains in the active intervention conditions at follow-up assessments (e.g., Bennett et al., 1996; Wigers, Styles, & Vogel, 1996).

Interdisciplinary approaches to FM also show favorable outcomes. For example, an interdisciplinary treatment protocol for FM, that included education, support groups, stress reduction and cognitive therapy, antidepressants, trigger point injections, and aer­obic conditioning reported significant improvements in functional impairment, quality of life, pain analog scores, number of tender points, total myalgic score, attitude index and behavior, and depression and anxiety scores (Maurizo & Rogers, 1997). As in CF-S, a case has been made for individualizing treatment in FM in accordance with (functional and psychosocial) subgroup membership (Turk, Okifuji, Sinclair, & Starz, 1998). Illness self-management is also recommended for patients with FM and should ideally include some combination of stretching exercises, massage, relaxation techniques, and walking exercise.

 

 

Cognitive-Behavioral Treatment in the Clinical Setting

 

To complement the above data-based literature review, this section focuses on the authors’ clinically based strategies for helping these patients. While some of these strategies have preliminary research support, others are as yet untested.

Although CFS and FM may often be persistent and intractable conditions, the styles of thinking, quality of mood, and level of distress experienced by these patients will determine their quality of life as much or more than the more salient dimensions of physical functioning and illness severity. Perhaps this is the challenge for the practi­tioner: to convince the client that, in the absence of substantial remission or recovery, quality of life can be significantly improved and maintained. This section provides a straightforward model of stress creation in these illnesses and summarizes the techniques of CBT that we have found to be most helpful for these patients.

 

The Interactive Stress-Symptom Model. The symptoms and limitations engendered by the onset of CFS and FM initially produces a dramatic reduction in positively reinforc­ing events for the patient. This behavioral process triggers understandably negative thoughts and maladaptive coping strategies that lead to dysfunctional emotions such as anxiety, depression, and anger in vulnerable individuals. These emotions, in the aggregate, pro­duce more fatigue and pain, and will meld imperceptibly into the patient’s experience of the illness. Although patients often recognize the impact of major stressful events on their symptoms, they are much less likely to recognize the damaging effect of low level stress-



 

 

ors. In fact, routine daily hassles are more strongly related to FM symptoms than major life events (Dailey et al., 1990). For this re~son, we recommend that patients keep a stress and activity record (see Figure 1; Jason, Tryon, Taylor, King, Frankenberry, & Jordan, 1 999d) for one to two weeks during the initial stages of treatment. This record helps them to become aware of the negative interactions between stress, symptoms, and activity levels and will provide targets for clinical intervention. Once stress—symptom patterns have been identified, then the cognitive-behavioral techniques described below can help to reduce pain and fatigue, alleviate affective distress, improve well-being, uplift mood, and perhaps improve physical and social functioning.

 

 

Relaxation Training. Because many of these patients enter therapy with overwhelm­ing feelings of stress and discouragement about their illnesses, an initial relaxation pro­cedure may be the most efficient way to interrupt and reduce high levels of negative affect. Relaxation will alleviate emotional stress, release muscular tension and ease associated pain, improve sleep, and restore some sense of well-being (Friedberg & Krupp, 1994). These patients may sometimes report an increase in fatigue or pain after the initial relaxation procedure. This may be an indication of their level of sleep depri­vation, suggesting the use of relaxation to improve sleep, or it may be a temporary reac­tion to the rapid alleviation of tension and stress. Specific relaxation strategies for CFS and FM have been elaborated elsewhere (Friedberg & Jason, 1998). Calming techniques should be practiced both with and without a relaxation tape, so that the skill may be generalized and used whenever stress or CFS/FM symptoms begin to increase or become overwhelming.

 

Pleasant Mood Induction. Because people with CFS and FM spend much of their time struggling with their symptoms in an attempt to be as functional as possible, they

 

 

Daily Energy and Fatigue

                                Record

                                Oleast                                100~most

 

 

 

Date/Day______________________

                               Steps                                               Perceived                                               Expanded                                               Fatigue                                               Positive                                               Negative Daily

                                                                                              Energy                                               Energy

(energy you have)

(energy used up)

Feeings

Feelings

~ctivities

 

,—____________


 

 

often neglect opportunities to engage in pleasant experiences. Pleasant mood induction is a technique that involves listing a number of enjoyable, low-effort activities that the client could experience in session via imagery or in the real worid by convenience scheduling. Empirical evidence from a one year prospective study of CFS patients (Ray, Jefferies, & Weir, 1995) suggests that pleasant experiences may lead to substan­tial improvements in symptoms, functioning, and emotional well-being. Similarly, in FM patients, pain has been found to be inversely related to daily mood uplifts (Dailey et a!., 1990). The incorporation of pleasant experiences can help the patient to realign life priorities such that work, family responsibility, and leisure time are in a healthier balance.

 

Activity Pacing and Envelope Theory. Activity pacing involves moderating the overwork—collapse pattern often reported by these patients prior to becoming ill and subsequently maintained at a lower level during their illnesses (Friedberg & Jason, 1998). The overwork—collapse pattern is characterized by overscheduling of activity when symp­toms recede followed by symptom exacerbations and behavioral collapse when energy levels decline. Activity records (Figure 1) can help the clinician identify these up-and-down behavioral patterns and subsequently design constructive modifications in collab­oration with the patient. These modifications may include suggestions to (a) schedule rest and relaxation intervals, even when feeling less symptomatic, (b) complete work in an incremental, stepwise pattern, rather than in a single massive effort, and (c) focus on the progress achieved in reaching short-term goals, rather than viewing less accessible long-term goals as the only acceptable level of accomplishment. An inexpensive step counter can be used to document physical activity levels, the presence of an overwork—~ollapse pattern, and the effectiveness of activity pacing in reducing symptom—exacerbating behaviors.

Envelope theory (Jason et al., l999b; Pesek, Jason, & Taylor, 2000) posits that fatigue symptoms are exacerbated when levels of expended energy (energy used up) exceed perceived energy (energy that one has at any particular moment). On the other hand, when perceived energy and expended energy are roughly matched, fatigue symptoms will lessen and perceived energy will increase over time. Activity pacing, in part, in­volves moderating up-and-down activity patterns such that expended energy does not exceed perceived energy. Thus, patients can learn activity pacing and envelope theory techniques by monitoring their daily levels of energy and activity (Figure 1) and then making up or down adjustments such that fatigue symptoms decrease and perceived energy improves.

 

 

Graded Activity and Exercise

 

A subset of patients with CFS and FM may benefit from graded activity, which involves progressive scheduling of activities starting with low effort physical and social tasks and increasing to more demanding endeavors as tolerance of exertion improves. For instance, a low functioning individual with CFS might begin with greater interactions with his or her family by joining them for meals and then progress to light housework and eventual short walks outdoors. It is difficult to determine beforehand which clients may benefit from such an approach. If the client acknowledges some level apprehension about increas­ing exertion, this may indicate the utility of a brief trial of graded activity. If prescribed activity scheduling triggers prolonged symptom flareups, then the activities should be reduced or discontinued. On the other hand, if symptoms do not intensify with mild increases in exertion, then progressive scheduling should be continued. Although it is



 

 

more likely that selected low functioning individuals will benefit from graded activity, some high functioning patients who hold full-time jobs, but still express some trepidation about increasing activity may also improve their physical capacities (Friedberg, 2001a).

In FM, a number of studies have demonstrated the benefits of aerobic exercise, usually walking. This more consistent evidence for FM patients may be due to the lower frequency of the symptoms of postexertional malaise and prolonged fatigue after exer­cise in comparison to CFS. Thus, a graduated walking program can be formulated as part of the overall CBT intervention. However, if even low-level exercise (e.g., 5—10 minutes walking every other day) results in worsening symptoms, it should be discontinued.

 

 

Cognitive Coping Skills

 

Coping skills involves teaching the client how to use constructive thoughts to adapt to illness-related affective distress. An important target for coping involves the anger and frustration of patients who unsuccessfully attempt to overcome illness limitations. Spe­cifically, the patient may endorse anger-inducing self-demands such as, “I should be able to control this illness!” or “I can’t stand being limited this way!” These beliefs can be disputed (Ellis, 1997: Gandy, 1999) with questions such as “Why should you be able to control this illness, where is the evidence?” Once these beliefs are effectively challenged, they can be replaced with coping statements that encourage tolerance of illness-related limitations.

Discouragement is another pervasive emotion in CFS and FM. This emotion is sec­ondary to the symptom limitations and disturbed relationships that result from these illnesses. Although discouragement is an understandable reaction, it can become destruc­tive when patients dwell on illness thoughts such as “I’m so sick!; I’m so sick!” Cogni­tive distraction techniques are useful here, such as generating pleasant imagery, reading an absorbing short story, and so forth. Finally, a profound sense of guilt is a common reaction to the patient’s inability to help others as they had prior to becoming ill. Learning to avoid self-condemnation (Ellis, 1997) and positively focusing on what useful things can be done for others will help to reduce the intensity of the guilt.

It should also be noted that unexpressed anger, which has been reported in chronic pain patients (Bráha & Catchlove, 1986; Kerns et al., 1994; Hatch, Schoenfeld, Boutros, Seleshi. Moore, & Cyr-Provost, 1991) may also characterize a large subset of FM patients. (It is not known if unexpressed anger is specifically associated with FM or if it simply reflects deficits in the adjustment/coping process that may pertain to a variety of illness groups.) This hidden anger is often fueled by unmet expectations of support and encour­agement from others. Yet this subgroup of patients, who often fear conflict and disap­proval, may view anger expression as unacceptable and perhaps unjustified. The stress generated by the emotion of anger may lead to increased somatic anxiety symptoms or increased pain (Greenberg et a!., 1999). The therapist’s task is to help the patient identify the latent anger and the failed expectations that sustain it. Then, the individual’s right to express anger in an appropriate way to significant others can be encouraged. As more realistic expectations are constructed for the self and others, anger will diminish, and FM symptoms may become less intrusive.

Clinicians may increase their understanding of the patient’s illness experience and coping abilities by using the four phase model of chronic illness (Fennell, 1995; Jason, Fennell, Klein, Fricano, Halpert, & Taylor, 1999a). This model traces the path of adjust­ment of the patient from the initial trauma of onset to eventual resolution of illness conflicts. Identifying the client’s phase of adjustment may allow for better targeted interventions.


 

 

Coping with Disbelief

 

Coping with disbelief is another potentially stress-reducing goal for many individuals with CFS and FM (Friedberg & Jason, 1998). Disbelief among physicians initially arises when medical tests and evaluations prove negative. Patient are often told that there is nothing wrong with them or that they are “OK.” Such illness skepticism is often shared by family and friends, who are deceived by the healthy appearance of the patient and baffled by the wide fluctuations in symptom severity that allow a patient to be quite functional one day only to be in bed the next. To people close to the patient, these dra­matic changes may be viewed as a voluntary choice rather than the result of unpredictable fluctuations of a poorly understood illness. A scale that measures beliefs toward people with CFS has been recently developed (Shlaes, Jason, & Ferrari, 1999).

In session, patients can learn coping ideas to counteract their anger and hurt about disbelief from others (Friedberg, 1996). Statements such as, “I cannot convince anyone I’m ill who does not want to believe it” and “their disbelief does not negate the reality of my illness” should be assigned as homework, and used in the real-life situation when disbelief arises. In addition, appropriate assertive behavior can help clients redirect use­less discussions with skeptical others about the reality of their illness.

 

 

Memory Assistance

 

Memory-assistance techniques may help these patients cope with short-term memory and concentration difficulties (Friedberg & Jason, 1998). The use of memory aids such as calendars and appointment book can be most helpful to organize the patient’s day. In addition, relaxation tapes, by providing a respite from fatiguing mental effort, will reduce confusion, improve attention, and restore some level of mental energy and clarity. To reduce cognitive overload, the following suggestions can be introduced by the treating clinician: (1) Allow extra time to complete activities. (2) Minimize distractions. For exam­ple, the client can be advised not to read with the radio on or attempt to balance a check­book while others are in the room talking. (3) Pattern daily activities into a routine that will minimize the stress on fragile cognitive capacities. (4) Break down all tasks and activities into incremental steps and focus on one step at a time. (5) Watch for signs of increased mental fatigue and take necessary rest breaks.

 

 

Cognitive-Behavior Therapy and Personality Dimensions

 

What is the role of personality disorder in CFS and FM? In our view, specific personality traits (not necessarily disorders) do play a role in the onset and persistence of CFS and FM for a subset of individuals. These traits tend to drive behavior to the extremes of overwork and excessive dependency. We will briefly illustrate each of these stress factors.

 

Overwork. Personality data in CFS studies suggest the presence of tendencies to overwork that are manifested by compulsive traits (Pepper, Krupp, Friedberg, Descher, & Coyle, 1993), “action proneness” (Van Houdenhove, Onghena, Neerinckx, & Hellin, 1995), “hard-driving” tendencies (Lewis, Cooper, & Bennett, 1996), and overcommitted lifestyles (Ware, 1993). For a subgroup of individuals with CFS and FM, a high level of preonset achievement motivation gives rise to an exhausting behavioral pattern of com­pelled accomplishment in all major life domains, including employment, childcare, and volunteer activities. One of our patients described the fleeting rewards of such behavior as the “the euphoria of accomplishment.” However, self-esteem is enhanced only tempo-



 

 

rarily as a result of such activities. Rather than affimiing self-worth, the individual believes that he or she is merely acceptable or “OFt” for brief periods when achieving in signifi­cant ways. Some patients may attempt to sustain this overwork pattern after they become ill. An interesting longitudinal study (Nicassio, Schoenfeld-Smith, Rodojevic, & Schu­man, 1995) of pain-coping mechanisms in FM patients pre- and posttreatment confirmed the potential harm of “active” coping, i.e., doing too much, which was associated with increased pain, greater depression, and lower well-being:

 

Because of the high degree of pain in FM, active coping may be maladaptive if such tenden­cies cause patients to ignore appropriate limits to their behavior when their pain is already severe. In this regard, it is possible that active coping may unwittingly exacerbate muscular or other physiological mechanisms that may contribute to FM pain. Alternatively, intense pain may drive patients to cope actively in an effort to control the pain, thus contributing to a vicious cycle of pain and dysfunction. (p. 1557)

 

Behavioral interventions for compulsive overwork that are likely to promote stress relief and symptom reductions involve (a) improving tolerance of the frustrations of not achieving daily goals (Ellis, 1997); (b) uprooting the performance-based self-esteem (Gandy, 1999) that contributes to the unhealthy propensity to overwork; and (c) incorpo­rating low effort leisure activity, self-focused relaxation or meditation, and other rela­tively passive pursuits to refresh and unwind both physically and mentally (Friedberg & Krupp, 1994). A well-balanced lifestyle of work, rest, and leisure is likely to result in a less intrusive, less damaging illness.

It should be noted that overwork may be a much more common phenomenon in today’s work-focused culture. A sociological monograph (Schor, 1991) that tracked work and recreation habits in the United States found that Americans worked more and enjoyed less leisure time in the 1990s compared to the 1970s. The study suggested that general­ized overwork may lead to more stress-related disorders.

 

Unhealthy Dependency Needs. In the clinical experience of the first author, some CFS and FM patients exhibit a behavioral pattern that involves persistent, but unsuccess­ful attempts to obtain love and approval from their dysfunctional source families (or their significant others) who are incapable of providing such supportive feelings and behav­iors. At the same time, these clients have a profound fear of rejection and hurt, yet they avoid relationships with people who might evolve into healthy closeness and intimacy. The patient chooses the “safe” route of seeking acceptance from those who cannot pro­vide it. These life choices will, in their view, protect them from the potential disappoint­ments of close interpersonal relationships.

Cognitive-behavioral intervention initially involves educating this specifi.c type of client to understand and ultimately accept the futility of their efforts to change their family and significant others. Then the individual can begin to recognize that, rather than irrationally seeking salvation and total acceptance, he or she can risk hurt, rejection, and negative judgments in forming potentially healthy relationships. This is a wrenching psychological adjustment that may require many sessions for clients to absorb and inter­nalize. Once relieved of the stress of maintaining unrealistic expectations, CFS/FM symp­toms may lessen—sometimes to a substantial degree.

 

Patient Resistance. It is important to note that initial behavioral interventions designed to moderate patterns of overactivity may be rejected by individuals with CFS and FM because their feelings of self-worth are dependent on maintaining an overextended life­style. This potential resistance may be challenged by helping clients to realize the nega­


 

 

tive consequences of maintaining a work ethic that creates symptoms rather than alleviates them. It can be explained that these illnesses are, in part, the result of an uncompromising lifestyle of continuous activity and obligation that is incompatible with good health and well-being. These illnesses may be a signal of sorts to decelerate activity and over-responsibility. Because achievement is closely linked to self-worth, and approval and recognition from others, the patient can be helped by learning to break this damaging linkage rather than judge him or herself in a negative way (Ellis, 1997).

A proportion of these clients may show considerable improvements when they iden­tify and change illness-exacerbating behavioral patterns that may contribute to the onset and persistence of CFS and FM. We are not suggesting that psychological treatment is a cure for these illnesses, but rather that carefully constructed psychological interventions can help to counteract damaging activity patterns and lead to improvements.

 

 

Conclusion

 

CFS and FM are poorly understood illnesses that share a number of important character­istics. The abundance of theoretical models regarding these illnesses may be contrasted with the dearth of empirical evidence available to support them. For instance, the con­troversy over the efficacy and generality of theory-driven cognitive-behavioral treat­ments for CFS has yet to be resolved. In addition, participants in clinical studies are usually recruited from tertiary care centers. Thus, it is not clear if they are representative generally of people with these illnesses. In the clinical setting, the differential diagnosis of CFS/FM and overlapping psychiatric disorders is an important assessment task that will lead to better targeted interventions. Given the absence of effective medical inter­ventions for these conditions, psychologists can indeed help these patients. Although it is unlikely that psychological intervention will eventuate in recovery or remission, improve­ments in emotional reactivity, symptom severity, and even functional limitations may be achieved. In the initial phases of therapy, an array of helpful cognitive, behavioral, and relaxation techniques can lessen affective distress, reduce muscular tension, and moder­ate destructive patterns of overactivity. Once a strong therapeutic rapport is established, patients’ core philosophical beliefs about work, leisure, and relationships can be fully identified. Then potentially healthy changes in their behavior can be formulated and illness improvements may follow. The research literature on these illnesses has only begun to point the clinician to particular interventions that may be effective for these underserved patients.

 

 

References

 

Abbey. S.E., & Garfinkel, P.E. (1991). Neurasthenia and chronic fatigue syndrome: The role of

culture in the making of a diagnosis. American Journal of Psychiatry. 148, 1638—1 646.

American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC: Author.

 

Ang. D., & Wilkes, W.S. (1999). Diagnosis, etiology, and therapy of fibrornyalgia. Comprehensive

Therapy, 25, 221—227.

Behan, P.O., Behan, W.M.H.. & Horrobin, D. (1990). Effects of high doses of essential fatty acids on the posiviral fatigue syndrome. Acta Neurologica Scandinavia, 82, 209—2 16.

Bennett, R.M., Burckhardt, C.S.. Clark, S.R., O’Reilly, C.A., Wiens, A.N., & Campbell, S.M. (1996). Group treatment of fibromyalgia: A 6 month outpatient program. Journal of Rheuma­tology, 23, 521—528.


 

 

Berman, B.M., Ezzo, J., Hadhazy, V., & Swyers, J. P. (1999). Is acupuncture effective in the treat­ment of fibromyalgia? Journal of Family Practice, 48. 213—2 18.

Beutler. L.E., Engle. D., Oro’-Beutler, E., Daldrup, R., & Meredith, K. (1986). Inability to express intense affect: A common link between depression and pain. Journal of Consulting and Clin­ical Psychology, 54, 752—759.

Blurner. D., & Heilbronn, M. (1981). The pain-prone disorder: A clinical and psychological profile. Psychosomatics, 22, 395—397, 40 1—402.

Bou-Holaigah, 1., Rowe, P.C., Kan, J., & Calkins, H. (1995). The relationship between neurally mediated hypotension and the Chronic Fatigue Syndrome. Journal of the American Medical Association. 274, 961—967.

Braha, R.E., & Catchlove, R.F. (1986). Pain and anger: Inadequate expression in chronic pain patients. Pain Clinics, 1, 125—129.

Dailey, P.A., Bishop, G.D., Russell, 1.J.. & Fletcher, E. (1990). Psychological stress and the fibrositis/ fibromyalgia syndrome. Journal of Rheumatology, 17, 13 80—1385.

Deale A., Chalder, T., Marks, 1., & Wessely, S. (1997). Cognitive behaviour therapy for chronic fatigue syndrome: A randomized controlled trial. American Journal of Psychiatry, 154,408—414.

DeMeirleir, K., Bisbal, C., Campine, I., DeBecker, P., Salehzada, T.. Demetteze. E., & Lebleu, B. (2000). A 37kDa 2—5A binding protein as a potential biomarker for chronic fatigue syndrome. American Journal of Medicine. 108, 99—I 05.

Demitrack, M.A. (1998). Chronic fatigue syndrome and fibromyalgia. Dilemmas in diagnosis and clinical management. Psychiatric Clinics of North America, 21, 67 1—692.

Demitrack, M.A., & Crofford, L.J. (1998). Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue. Annals of the New York Academy of Sciences, 840, 684—697.

 

Ellis, A. (1997). Using rational emotive behavior therapy techniques to cope with disability. Pro­fessional Psychology: Research and Practice, 28, 17—22.

Engel, G.L. (1959). “Psychogenic” pain and the pain-prone patient. American Journal of Medicine, 26, 899—918.

Fennell, P.A. (1995). A four stage progressive model of CFS. Journal of Chronic Fatigue Syn­drome, 1, 69—79.

Field, T.M., Sunshe, W., Hernandez-Reif, M,, Quintino, 0., Schanberg, S., Kuhn, C., & Burman, I. (1997). Massage therapy effects on depression and somatic symptoms in chronic fatigue syn­drome. Journal of Chronic Fatigue Syndrome, 3, 43—52.

Fischler, B., Cluydts, R., De Gucht, Y., Kaufman, L., & De Meirleir K. (1997). Generalized anxiety disorder in chronic fatigue syndrome. Acta Psychiatrica Scandinavica, 95, 405—4 13.

Forsyth, L.M., Preuss, H.G., MacDowel!, A.L., Chiazze, L., Birkmayer, G.D., & Bellanti, J.A. (1999). Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome. Annals of Allergy, Asthma, & Immunology, 82, 185—19!.

Friedberg, F. (1995). Coping with chronic fatigue syndrome. Nine things you can do. Oakland. CA:

New Harbinger.

 

Friedberg, F. (1996). Chronic Fatigue Syndrome: A new clinical application. Professional Psychol­ogy. Research amid Practice, 27, 487—494.

Friedberg, F. (1999). A subgroup analysis of cognitive-behavioral treatment studies. Journal of Chronic Fatigue Syndrome, 5, 149—159.

Friedberg, F. (2001a). Operant behavior therapy in chronic fatigue syndrome. Manuscript submit­ted for publication.

Friedberg, F. (2001b). A subgroup analysis in chronic fatigue syndrome. A time series approach. Manuscript submitted for publication.

Friedberg, F., & Jason, L.A. (1998). Understanding chronic fatigue syndrome: An empirical guide to assessment and treatment. Washington. DC: American Psychological Association.


 

 

Friedberg, F, & Krupp, L.B. (1994). A comparison of cognitive behavioral treatment for chronic fatigue syndrome and primary depression. Clinical Infectious Diseases, 18(Suppl. 1), S105— Silo.

Fukuda, K., Straus, S.E., Hickie, I., Shaipe, M.C., Dobbins, J.G., & Komaroff, A. (1994). The chronic fatigue syndrome: A comprehensive approach to its definition and study. Annals of internal Medicine, 121, 953—959.

Futcher, K.Y., & White, RD. (1997). Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. British Medical Journal, 314, 1647—1652.

Gandy, G.L. (1999). Rational-emotive behavior therapy (REBT): A cognitive-behavioral approach to acceptance and adjustment to disability. In G.L. Gandy, M.E. Davis, Jr. et al. (Eds.), Coun­seling in the rehabilitation process: Community services for mental and physical disabilities (2nd ed., pp. 234—250). Springfield, IL: Charles C. Thomas.

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

Goldenberg, D.L., Mayskiy, M.. Mossey, C., Ruthazer, R.. & Schmid, C. (1996). A randomized, double-blind crossover trial of fluoxetine and amitriptyline in the treatment of ‘fibromyalgia. Arthritis and Rheumatism, 39, 1852—1859.

Gowa.ns, S.E., deHueck, A., Voss, S., & Richardson, M. (1999). A randomized, controlled trial of exercise and education ‘for individuals with fibromyalgia. Arthritis Care & Research, 12,

120—128.

Greenberg, M.A., Dowling, V.L., Hatcher, M.S., Cox, B.J., Marcus, R.E., & Paget, S.A. (1999, March). Emotion-management predicts health outcomes in fibromyalgia. Poster session pre­sented at the annual meeting of the Society of Behavioral Medicine, San Diego, CA.

Harding, S.M. (1998). Sleep in fibromyalgia patients: Subjective and objective findings. American Journal of the Medical Science, 315, 367—376.

 

Hatch, J.P., Schoenfeld, L.S., Boutros, N.N., Seleshi, E., Moore, P.J., & cyr-Provost, M. (1991). Anger and hostility in tension-type headache. Headache, 31, 302—304.

Hemanz, W., Valenzuela, A., Quijada, J., Garcia, A., de Ia Iglesia, J.L., Gutierrez, A., Povedano, J., Moreno, I., & Sanchez, B. (1994). Lymphocyte subpopulations in patients with primary fibro­myalgia. Journal of Rheumatology. 21, 2122—2 124.

Hickie, I., & Davenport, T. (1999). The case of Julio: A behavioral approach based on reconstruct­ing the sleep-wake cycle. Cognitive and Behavioral Practice, 6, 442—450.

Jason, L.A., Fennel!, P.A., Klein, S.. Fricano, G., Halpert, J., & Taylor, R.R. (1999a). An investi­gation of the different phases of the CFS illness. Journal of Chronic Fatigue Syndrome, 5,

35—54.

Jason, L.A., Melrose, H., Lerman, A., Burroughs, V., Lewis, K., King, C.P., & Frankenberry, E.L. (1999b). Managing Chronic Fatigue Syndrome: Overview and case study. AAOHN Journal, 47, 17—21.

Jason, L.A., Richman, J.A., Friedberg, F., Wagner, L., Taylor, R., & Jordan, KM. (1997). Politics, science, and the emergence of a new disease: The case of Chronic Fatigue Syndrome. Amer­ican Psychologist, 52, 973—983.

Jason, L.A., Richrnan, J.A., Rademaker,A.W., Jordan, K.M.. Pliop!ys, A.V., Taylor, R.R., MeCreedy, W.. Huang, C.. & Plioplys, S. (1999c). A community-based study of Chronic Fatigue Syn­drome. Archives of Internal Medicine, 159. 2129—2137.

Jason. L.A., Tryon, W.W., Taylor, R.R., King, C., Frankenberry, E.L., & Jordan, K.M. (l999d). Monitoring and assessing symptoms of Chronic Fatigue Syndrome: Use of time series regres­sion. Psychological Reports, 85, 121—130.

Johnson, S.K,, DeLuca, J., & Natelson, B.H. (1996a). Assessing somatization disorder in the Chronic Fatigue Syndrome. Psychosomatic Medicine, 58, 50—57.

Johnson. S.K., DeLuca, J., & Natelson, B.H. (1999b). Chronic Fatigue Syndrome: Reviewing the research findings. Annals of Behavioral Medicine, 50, 258—271.


 

 

Johnson, S.K., DeLuca, J., & Natelson, B. (l996c). Depression in fatiguing illness: Comparing patients with chronic fatigue syndrome, multiple sclerosis and depression. Journal ofAffective Disorders, 39, 2 1—30.

Joyce, J., Hotopf, M., & Wessely, S. (1997). The prognosis of chronic fatigue and chronic fatigue syndrome: A systematic review. Quarterly Journal of Medicine, 90, 223—233.

Kansky, G., & Tai, C. (1999, FaIl). Ampligen report exposed: patients duped. The National Forum, 3,1, 8—11.

 

Keel, P.1, Bodoky. C., Gerhard. U., & Muller W. (1998). Comparison of integrated group therapy and group relaxation training for fibromyalgia. Clinical Journal of Pain, 14, 232—238.

Ke.rns, R.D., Rosenberg, R., & Jacob, M.C. (1994). Anger expression and chronic pain. Journal of Behavioral Medicine, 17, 57—67.

Klein, R., & Berg, P.A. (1994). A comparative study on antibodies to nucleoli and 5-hydroxy-tryptamine in patients with fibromyalgia syndrome and tryptophan-induced eosinophilia­myalgia syndrome. Clinical Investigator, 72, 541—549.

Komaroff A.L., Fagioli, L.R., Geiger, A.M., Doolittle, T.H., Lee, J., Kornish, R.J., Gleit, M.A., Guerriero, R.T. (1996). An examination of the working case definition of Chronic Fatigue Syndrome. The American Journal of Medicine, 100, 56—64.

Krupp, L.B., Mendelson, W.B., & Friedman R. (1991). An overview of chronic fatigue syndrome. Journal of Clinical Psychiatry, 52, 403—4 10.

Leventhal, L.J. (1999). Management of fibromyalgia. Annals of Internal Medicine, 131, 850—858. Leventhal, L., Freundlich, B., Lewis, J., Gillen, K., Henry, J., & Dinges, D. (1995). Controlled

study of sleep parameters in patients with fibrornyalgia. Journal of Clinical Rheumatology, 1,

110—113.

Lewis, S., Cooper, C.L., & Bennett, D. (1994). Psychosocial factors and chronic fatigue syndrome. Psychological Medicine, 24, 661—671.

Lloyd, A.R.. Hickie, 1,. Brockman, A.. Hickie, C., Wilson, A., Dwyer, J.. & Wakefield, D. (1993). Immunologic and psychologic therapy for patients with Chronic Fatigue Syndrome: A double-blind, placebo-controlled trial. The American Journal of Medicine, 94, 197—203.

Maurizo, S.J., & Rogers, IL. (1997). Recognizing and treating fibromyalgia. The Nurse Practi­tioner, 22, 18—28, 31.

McKenzie, R., O’FaIlon, A., Dale, J., Demitrack, M., Sharma, G., Deloria, M., Garcia-Borreguero, D., Blackwelder, W., & Straus, S.E. (1998). Low-dose hydrocortisone for treatment of chronic fatigue syndrome: A randomized controlled trial. JAMA, 280. 1061—1066.

Moldofsky, H. (1993). Sleep and the chronic fatigue syndrome. In M. Dawson & T. D. Sabin (Eds.), Chronic Fatigue Syndrome (pp. 141—152). Boston: Little, Brown.

Moldofsky, H.. Scarisbrick, P., England, R., & Smythe, H. (1975). Musculoskeletal symptoms and non-REM sleep disturbance in patients with “fibrositis syndrome” and healthy subjects. Psy­chosomatic Medicine, 34, 341.

Moore, K.A., & Blumenthal, J.A. (1998). Exercise training as an alternative treatment for depres­sion among older adults. Alternative Therapies in Health & Medicine, 4, 48—56.

Nicassio, P.M., Radojevic, V., Weisman, M.H., Schuman, C., Kim, J., Schoenfeld-Smith, K., & Krall, T. (1997). A comparison of behavioral and educational interventions ‘for fibromyalgia. Journal of Rheumatology, 24, 2000—2007.

Nicassio, P.M.. Schoenfeld-Smith, K., Radojevic. V., & Schuman, C. (1995). Pain coping mecha­nisms in fibromyalgia: Relationship to pain and functional outcomes Journal of Rheumatol­ogy, 22, 1552—1558.

Pepper, C.M.. Krupp, L.B., Friedberg, F., Doscher, C.. & Coyle, P.K. (1993). A comparison of neuropsychiatric characteristics in chronic fatigue syndrome, multiple sclerosis, and major depression. The Journal of Neuropsychiatry and Clinical Neurosciences, 5, 200—205.

Pesek, J.R., Jason, L.A., & Taylor, R.R. (2000). An empirical investigation of the envelope theory. Journal of Human Behavior in the Social Environment, 3, 59—77.


 

 

Plioplys, A.V., & Plioplys, 5. (1997). Amantadine and L-carnitine treatment of chronic fatigue syndrome. Neuropsychobiology, 35, 16—23.

Ray, C., Jeff”•eries, S.. & Weir, W.R.C. (1995). Life-events and the course of chronic fatigue syn­drome. British Journal of Medical Psychology, 68, 323—331.

Reyes, M., Gary, H.E., Jr., Dobbins, 1G., Randall, B., Steele, L., Fukuda, K., Holmes, G.P., Con­nell, D.G., Mawle, A.C., Schmid, D.S., Stewart, J. A., Schonberger, L.B., Gunn, W.J., & Reeves, W.C. (1997). Descriptive epidemiology of Chronic Fatigue Syndrome: CDC surveillance in four cities. Morbidity and Mortality Weekly Report Surveillance Summaries, 46( No. SS-2),

1—13.

Robbins, J.M., Kirmayer, L.J., & Hemami, S. (1997). Latent variable models of functional somatic distress. Journal of Nervous & Mental Disease. 185, 606—615.

Robbins, J.M., Kirmayer, L.J.. & Kapusta, M.A. (1990). Illness worry and disability in fibromyalgia syndrome. International Journal of Psychiatry in Medicine, 20, 49—63.

Rossy. L.A., Buckelew. S.P., DolT, N., Hagglund, K.J., Thayer, J.F., McIntosh. M.J., Hewett, J.E., & Johnson, J.C. (1999). A meta-analysis of fibromyalgia treatment interventions. Annals of Be­havioral Medicine, 21, 180—191.

Schor, J. (1991). The overworked American: The unexpected decline of leisure. New York: Basic Books.

Sharpe, M., Hawton, K., Simkin, S., Surawy, C., Hackrnann, A., Klirnes, I., Peto, T., Warrell. D., & Seagroatt, V. (1996). Cognitive behaviour therapy for the chronic fatigue syndrome: A ran­domized controlled trial. British Medical Journal, 312, 22—26.

Shlaes, J.L., Jason, L.A., & Ferrari, J.R. (1999). The development of the Chronic Fatigue Syn­drome Attitudes Test: A psychometric analysis. Evaluation and the Health Professions, 22,

442—465.

Shorter, E. (1995). Sucker-punched again. Physicians meet the disease-of-the-month syndrome . Journal of Psychosomatic Research, 39, 115—118.

Simon, G.E., Von Korif, M., Piccinelli, M., Fullerton, C., & Ormel, J. (1999). An international study of the relation between somatic symptoms and depression. New England Journal of Medicine, 341, 1329—1335.

Smart, P.A., Waylonis, OW., & Hackshaw~ K.V. (1997). Immunologic profile of patients with fibromyalgia. American Journal of Physical Medicine & Rehabilitation, 76, 231—234.

Stramentinoli, 0., & Gualano, M., & Galli-Kienle, M. (1979). Intestinal absorption of S-adenosyl­L-methionine. Journal of Pharmacology & Experimental Therapeutics, 209, 323—326.

Straus, S.E., Dale, J.K., Wright, R., & Metcalfe, D.D. (1988). Allergy and the chronic fatigue syndrome. Journal of Allergy and Clinical Immunology, 81, 791—795.

Strayer, D.R., Carter. W.A., Brodsky, I., Cheney, P., Peterson, D., Salvato, P., Thompson, C., Love­less, M., Shapiro, D.E., Elsasser, W., & Gillespie, D.H. (1994). A controlled clinical trial with a specifically configured RNA drug, poly(l)poly (C12U), in Chronic Fatigue Syndrome. Clin­ical Infectious Diseases, I 8(Suppl 1), S88—S95.

Suhadolnik, Ri., Peterson, D.L., Cheney. P.R., Horvath, S.E., Reichenbach, N.L.. O’Brien, K., Lombardi, V., Welsch, S., Furr. E.G., Charubala. R., & P’fleiderer, W. (1999). Biochemical dysregulation of the 2—5A synthetase/RNase L antiviral defense pathway in chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome, 5, 223—242.

Suhadolnik, R.J., Reichenbach, N.L., Hitzges, P.. Adelson, M.E., Peterson, D.L., Cheney, P., Sal­vato, P., Thompson. C., Loveless. M., Muller, W.E.G., Schroder, H.C., Strayer, D.. & Carter, W. (I 994a). Changes in the 2—5A synthetase/Rnase L antiviral pathway in a controlled clinical trial with Poly(I)-Poly(CI2U) in chronic fatigue syndrome. In Vivo, 8, 599—604.

Suhadolnik, R.J., Reichenbach, N.L., Hitzges, P., Sobol, R.W., Peterson, D.L., Henry, B., Ablashi, D.V., Muller, W.E.G., Schroder, H.C., Carter, W.C.. & Strayer, D.R. (1994b). Upregulation of the 2—5A synthetase/RNase L antiviral pathway associated with chronic fatigue syndrome. Clinical Infectious Diseases, I 8(Suppl 1), S96—I 04.


 

 

 

                                Chronic Fatigue Syndrome and Fibromyalgia                                455

 

 

Surawy, C., Hackmann, A., Hawton, K., & Sharpe, M. (1995). Chronic fatigue syndrome: A cog­nitive approach. Behavior Research and Therapy, 33, 535—544.

Taylor, R.R., & Jason, L.A. (1998). Comparing the DIS with the SCID: Chronic fatigue syndrome and psychiatric comorbidity. Psychology and Health, 13, 1087—1104.

Taylor, R R., Jason, L.A., & Schoeny, M.E. (2000). Evaluating latent variable models of functional somatic distress in a community-based sample. Manuscript submitted ‘for publication.

Turk, D.C., Okifi.iji, A., Sinclair, J.D., & Starz, T.W. (1998). Differential responses by psychosocial subgroups of fibromyalgia syndrome patients to an interdisciplinary treatment. Arthritis Care & Research, ii, 397—404.

Van Houdenhove, B., Onghena, P., Neerinckx, E., & Hellin, J. (1995). Does high “action-proneness” make people more vulnerable to Chronic Fatigue Syndrome? A controlled psycho­metric study. Journal of Psychosomatic Research, 39, 633—640.

Van Houdenhove, B., Stans, L., & Verstraeten, D. (1987). Is there a link between “pain-proneness” and “action-proneness”? Pain, 29, 113—117.

Vercoulen, J.H.M.M., Swanink, C.M.A., Zitman, F.G.. Vreden, G.S., & Hoo’fs, M.P.E. (1996). Ran­domized, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome. The Lancet, 347, 858—862.

Walker, E.A., Keegan, D., Gardner, G., Sullivan. M., Bernstein, D., & Katon, W.J. (1997). Psycho­social ‘factors in ‘fibromyalgia compared with rheumatoid arthritis: II. Sexual, physical, and emotional abuse and neglect. Psychosomatic Medicine, 59, 572—577.

Ware, N.C. (1993). Society, mind and body in chronic ‘fatigue syndrome: An anthropological view. In G.R. Boch & J. Whelan (Eds.), Chronic fatigue syndrome (pp. 62—8 1). New York: Wiley.

Warren, G.. McKendrick, M., & Peel, M. (1999). The role of essential fatty acids in chronic fatigue

syndrome. A case-controlled study of red-cell membrane essential fatty acids (EFA) and a

placebo-controlled treatment study with high dose of. Acta Neurologica Scandinavia, 99,

112—i 16.

Wearden, A.J., Morriss, R.K., Mullis, R., Strickland, P.L., Pearson, D.J., Appleby, L., Campbell, I.T., & Morris, J.A. (1998). Randomised, double-blind, placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome. British Journal of Psychiatry, 172, 485—490.

White, K.P., Carette, S., Harth. M., & Teasell, R.W. (2000). Trauma and fibromyalgia: is there an association and what does it mean? Seminars in Arthritis & Rheumatism, 29, 200—2 16.

Whiteside, T.L., & Friberg, D.L. (1998). Natural killer cells and natural killer cell activity in chronic fatigue syndrome. American Journal of Medicine, 105. 27S—34S.

Wigers, S.H., Stiles, T.C., & Vogel, P.A. (1996). Effects of aerobic exercise versus stress manage­ment treatment in fibromyalgia. A 4.5 year prospective study. Scandinavian Journal of Rheu­matology, 25, 77—86.

Wolfe, F., Anderson, J., Harkness, D., Bennett, R.M., Caro, X.J., Goldenberg, D.L., Russell, I.J., & Yunus, M.B. (1997). Health status and disease severity in fibroniyalgia: Results of a six-center longitudinal study. Arthritis & Rheumatism, 40, 1571—1579.

Wolfe, F., Ross, K., Anderson, I., Russell, l.J., Hebert, L. (1995). The prevalence and characteristics of fibromyalgia in the general population. Arthritis and Rheumatism, 38, 19—28.

Wolfe, F., Smythe, H.A., Ynnus, M.B., Bennett, R.M., Bombardier, C.. Goldenberg, D.L.. Tugwell, P., Campbell, S.M., Abeles. M., Clark, P., Fam, A.G., Farber, S.J., Fiewchtner, 11, Franklin, C.M., Gatter, R.A., Harnaty, D., Lessard, J., Lichtbroun, A.S., Masi, A.T., McCain G.A., Reyn­olds, W.J., Rornano, T.J.. Russell, I.J., & Sheon, R.P. (1990). The American College of Rheu­matology 1990 criteria for the classification of fibrornyalgia. Arthritis and Rheumatology, 33,

160—1 72.

Wood. G.C.. Bentall, R.P., Gopfert, M., Dewey, M.E., & Edwards, R.H.T. (1994). The differential response of chronic fatigue, neurotic and muscular dystrophy patients to experimental psy­chological stress. Psychological Medicine, 24, 357—364.