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