Cognitive behavior therapy for chronic fatigue syndrome: efficacy and implications

Cognitive Behavior Therapy for Chronic FatigueSyndrome: Efficacy and Implications

Michael Sharpe, MA, MB, MRCP, MRCPsych, Edinburgh, United Kingdom

Cognitive behavior therapy (CBT) is a form of non-pharmacologic treatment. It is based on a model ofchronic fatigue syndrome (CFS) that hypothesizesthat certain cognitions and behavior may perpetuatesymptoms and disability–that is, act as obstacles torecovery. Treatment emphasizes self-help and aimsto help the patient to recover by changing theseunhelpful cognitions and behavior. There is nowgood evidence from 2 independent randomized clin-ical trials to support the efficacy of CBT in patientswith CFS. The treatment effect is substantial, al-though few patients are cured. The urgent clinicalneed is to make this form of treatment available topatients with CFS. One approach is to incorporatethe principles of CBT into routine clinical practice.The preliminary evaluation of these simpler forms ofCBT are promising, although the results of controlledtrials are awaited. At present, intensive individualCBT administered by a skilled therapist remains thetreatment of choice for patients with CFS. Am JMed. 1998;105(3A):104S–109S. © 1998 by ExcerptaMedica, Inc.

Cognitive behavior therapy (CBT) is a form of non-pharmacologic treatment. It is based on a detailedanalysis of the patient’s thinking and beliefs about

their illness (cognitions) and the way they cope with it(behavior). The principal aim of this analysis is to identifywhich cognitions and behavior may be perpetuating thepatient’s symptoms and disability—that is, acting as ob-stacles to recovery. Treatment emphasizes self-help andaims to help the patient to recover by changing unhelpfulcognitions and behavior.1

Although CBT focuses on cognitions and behavior itseffects are not confined to the psychological and behav-ioral realm. Secondary changes in biologic variables mayalso occur, for example, a sustained increase in activitywill improve physical fitness2 and may also have effectson central nervous system (CNS) function.3

Formal CBT is a complex set of techniques, the appli-cation of which requires specialist training.4 Courses of

treatment usually consist of 10 –20 1-hour sessions, inaddition to which patients carry out homework assign-ments. The main ingredients of treatment are listed inTable 1.

Treatment is usually given on an individual basis butmay also be delivered in a group setting. Both the courseof therapy and individual sessions are structured and anoutline of each is listed in Table 2.

Simpler nonpharmacologic interventions, such as in-formation-giving and behavioral programs, may alsohelp patients to recover by changing illness-perpetuatingcognitions and behavior. In this sense, these interven-tions may be regarded as simple forms of CBT.

ESTABLISHED APPLICATIONS FOR CBTThe early applications of CBT focused on the treatmentof patients attending psychological and psychiatric out-patient services. CBT is now a well-established treatmentfor depression, anxiety, phobias, panic disorder, obses-sive– compulsive neurosis, and eating disorders.5

More recently, the range of application has widened toalso include patients attending general medical services.5

Specific applications in this setting include the treatmentof emotional disorders in patients with medical condi-tions such as cancer,6 and the treatment of poorly under-stood medical conditions such as chronic pain, fibromy-algia, or irritable bowel syndrome.7

A COGNITIVE BEHAVIORAL APPROACHTO CHRONIC FATIGUE SYNDROMEChronic fatigue syndrome (CFS) is defined in terms ofsymptoms. Studies have, however, identified other char-acteristics of patients who present with CFS.

Beliefs and CognitionsPatients with CFS commonly regard their fatigue ascaused by a physical disease and may be reluctant to con-sider a role for psychological factors.8 A strong belief in asimple physical etiology for the illness is disadvantageousas it is associated with greater disability9 and a worse out-come.10 A commonly associated belief is that exercise-induced exacerbations of symptoms are evidence of fur-ther depletion of a limited energy supply or even of harm.Such beliefs are associated with thoughts such as: “If Icarry on being active, I will be in bed for weeks.”11 Suchcognitions also appear to be disadvantageous, as patientswho interpret symptoms in this “catastrophic” way aremore disabled than those who do not.12

From the University of Edinburgh Department of Psychiatry, RoyalEdinburgh Hospital, Edinburgh.

Requests for reprints should be addressed to Michael Sharpe, MA,MB, MRCP, MRCPsych, University of Edinburgh Department of Psy-chiatry, Royal Edinburgh Hospital, Edinburgh EH10 5HF, UnitedKingdom.

104S © 1998 by Excerpta Medica, Inc. 0002-9343/98/$19.00All rights reserved. PII S0002-9343(98)00170-3

BehaviorAlthough many patients can function normally for briefperiods, they typically find themselves unable to sustainactivity. This is because activity leads to an exacerbationof fatigue and other symptoms. If they interpret thesesymptoms in a catastrophic way, as described above, theirunderstandable response is to avoid further activity.9,13

Although avoidance is an effective way of coping insofaras it decreases symptoms in the short term, it has theimportant disadvantage of leading to increased disabilityin the long term.

MoodMood disturbances are common in patients with CFS.Along with frustration, patients often report periods oflow and anxious mood.11 Depressive and anxiety syn-dromes can be diagnosed in more than half of most hos-pital-referred samples.14 In such cases, mood disturbanceundoubtedly contributes to the patient’s symptoms anddisability.

PhysiologyThe precise physiologic mechanisms that underlie thesymptom of fatigue is unknown, although many contrib-utory processes have been identified.15 Candidate mech-anisms include (1) changes in autonomic nervous systemfunction (which may be at least partly due to anxiety anddepression)16; (2) fragmented sleep17; and (3) prolongedinactivity.18 Abnormalities have also been found in brainserotonergic systems19 and in the control of the hypo-thalamic–pituitary–adrenal (HPA) axis.20 The importantfactor about all these processes is that they are potentiallyreversible. Furthermore, they may be modified bychanges in the patient’s cognitions and behavior.

Interpersonal and Social FactorsBoth social and occupational stressors and the beliefs andbehaviors of others may perpetuate illness. Patients oftengive a history of chronic occupational stress before theonset of the illness. If ongoing, such difficulties may alsobe an obstacle to returning to work.11 The beliefs of oth-ers may also be problematic. Both the invalidation of theillness experience on the one hand and reinforcement ofunhelpful beliefs on the other may inhibit the patient’srehabilitation.

A COGNITIVE BEHAVIORALCONCEPTUALIZATION OF CFS

The cognitive behavioral approach takes a comprehen-sive view of the patient. It assumes that all the above fac-tors may be relevant to the perpetuation of CFS, althoughtheir relative importance will vary from person to person.It also assumes that these factors do not simply act inde-pendently but may interact in ways that are mutually re-inforcing. For example, a belief that activity-inducedsymptoms indicate harm may lead to anxiety and to

avoidance of further activity. Inactivity and anxiety leadsto physiologic changes that increase activity-associatedfatigue. When further activity is attempted, the increasein symptoms is even greater than before— confirming thepatient’s original belief. A vicious circle is completed.

These interactions are depicted in the simple cognitivebehavioral model illustrated in Figure 1. Other moreelaborate models have also been proposed.11

A RATIONALE FOR THE APPLICATIONOF CBT TO CFS

The rationale for the application of CBT to CFS is basedon the above observations and associated model. It is hy-pothesized that (1) certain types of illness-related cogni-tions and coping behavior increase disability and lead tochronicity; and (2) they do this by interacting with mooddisturbance, abnormal physiology, and negative factorsin the social environment. It is therefore proposed that ifCBT can help patients to modify their thinking abouttheir illness and associated coping behavior, changes in

Table 1. The Elements of Cognitive Behavior Therapy

● A positive collaborative relationship between therapist andpatient

● A systematic assessment of current cognitions and behavior● An individual cognitive behavioral formulation of the

illness● Cognitive change; e.g., considering less catastrophic

interpretations of symptoms● Behavioral change; e.g., stabilizing activity and overcoming

avoidance● Active solving of personal, occupational, and social

problems

Table 2. Typical Course and Single Session Outlines of Cog-nitive Behavior Therapy (CBT)

An outline of a typical course of CBTSessions 1–3 Assessment and formulation of problemSessions 4–14 Identification of illness perpetuating

cognitions and coping behaviorsGeneration of more adaptive cognitions and

coping behaviorsPatient tests novel approach and adopts if

found to be helpfulSessions 15–16 Consolidation and planning of further self-

helpAn outline of a single session of CBTReview of previous session and homework tasksSetting of agenda for the sessionDiscussion focusing on target problemExploration of alternative understanding of problemPlan homework to test alternative understanding by changing

behavior

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other aspects of the illness will occur and a degree of re-covery will follow. In this way, patients learn how to im-prove their health by their own efforts.

EVIDENCE FOR THE EFFICACY OF CBTFOR PATIENTS WITH CFS

The Queen Square StudyThe first attempt to apply CBT to patients suffering fromCFS was an uncontrolled study of a simple form of CBTin which severely ill patients were encouraged to gradu-ally increase their activity. Many patients refused to takepart, but a substantial proportion of those who did exhib-ited large and sustained improvements in their function-ing.21

The Sydney TrialThe first randomized trial of CBT for patients with CFSwas published in 1993.22 In this Australian study, a rela-tively brief form of CBT was compared with standardmedical care. The investigators found no difference be-tween these treatments in their ability to decrease func-tional impairment at the final 3-month follow-up evalu-ation.

The Oxford TrialThe second randomized trial of CBT compared a moreintensive form of CBT with standard medical care andwas carried out by my own group at Oxford University.23

In this trial, subjects were randomly allocated to receiveeither standard medical care alone or medical care andCBT. The patients were consecutive referrals from pri-mary care to a specialist in an infectious disease clinic. Allpatients invited to participate in the trial met the 1994Centers for Disease Control and Prevention (CDC) casedefinition for CFS24 and were required to have a signifi-cant level of disability (none were able to maintain theiroccupation). Of those eligible for inclusion, only 2 pa-

tients refused to participate. A total of 60 patients wererecruited into the study. Their mean age was 36 years, andtwo thirds were women. The mean duration of illness wasapproximately 2.5 years, and the mean Karnofsky scalescore25 was approximately 70.

Standard medical care consisted of assessment, makinga diagnosis of CFS, giving encouragement and advice,and providing follow-up in primary care. The patientswho were allocated to receive CBT attended the hospitalfor weekly sessions of CBT for 16 weeks over a 4-monthperiod of time. The CBT focused on regaining activities,and “homework” was assigned between treatment ses-sions where patients were encouraged to try out new waysof coping. Outcome evaluations were performed at theend of this period and after a further 8 months.

A good outcome was defined as the attainment of anormal level of daily functioning, indicated by a Karnof-sky score $80. Ratings were rated blind to the patients’treatment condition. Other outcome measures includedself-rated disability, days in bed, fatigue, anxiety and de-pression, and a timed walking test. No patients droppedout of treatment and all were accounted for at follow-up.

Approximately three quarters of the patients who re-ceived CBT had a good outcome at 12 months, comparedwith only one quarter who had received medical carealone. Fatigue, self-rated disability, depression, and thedistance walked on the timed walking test also improvedmore with CBT. Interestingly, most of the improvementoccurred during the 8 months after the course of CBT hadbeen completed.

The King’s College TrialThe third randomized trial of CBT for CFS was con-ducted by Deale and colleagues26 from King’s College,London. In this trial, a form of CBT similar to that used inthe Oxford study was compared with relaxation therapy.Both these therapies involved a similar amount of thera-pist–patient contact, thereby controlling for any nonspe-cific therapeutic effect of time with a therapist. The resultsobtained were very similar to those of the Oxford trial.This replication by an independent research group servedboth to replicate the finding of the Oxford trial and todemonstrate that the action of CBT is not due merely totime with a therapist.

Summary of TrialsIn summary, the 2 trials that evaluated intensive individ-ually administered CBT with a rehabilitative emphasisfound it to be substantially superior to both basic medicalcare and to relaxation therapy. Furthermore, the benefitobtained appeared to persist for at least 8 months after theend of treatment and even to increase with time. Theabove trials of CBT are summarized in Table 3.

When interpreting these findings it is important to beaware that although CBT has been convincingly demon-strated to be effective in decreasing the disability and

Figure 1. An example of a simple cognitive behavioral modelfor chronic fatigue syndrome.


106S September 28, 1998 THE AMERICAN JOURNAL OF MEDICINEt Volume 105 (3A)

symptoms of many persons with CFS, it is not a panacea.Some patients benefit little, and many, if not most, pa-tients continue to complain of excess fatigue. WhetherCBT can be improved to achieve more complete recoveryremains to be seen.

THE PROCESS OF CBT IN PATIENTSWITH CFSHow Does It Work?In both the King’s College and the Oxford trials, im-provement was associated with change in the belief thatphysical activity should be avoided. It may be, therefore,that this belief is crucial in perpetuating disability bymaintaining avoidance behavior. The link between be-havioral change and physiologic change remains hypo-thetical, however. Although increases in activity improvephysical fitness,2 this is not associated with clinical im-provement. When other biologic abnormalities underly-ing fatigue can be reliably identified, it will be importantto determine whether these also change as a result of CBTand whether these changes are associated with symptom-atic improvement.

What Are the Active Ingredients of CBT?CBT is a complex therapy. At present it remains unclearwhether all the components of formal CBT are necessary,or whether a simpler approach based on $1 componentswould be as effective. A recent randomized treatmenttrial evaluated the benefit of simple, graded increases inactivity in selected patients with CFS. The carefullyplanned and supervised increases in activity were accom-panied by only limited explanation and discussion. Theeffect was compared with that of exercises designed toincrease flexibility.2 Graded exercise was found to be sub-stantially more effective in improving patients’ disabilityand symptoms, suggesting that this treatment is effectivein at least some patients. Patients were not harmed ormade worse by this treatment. However, another ran-domized trial that evaluated graded exercise, this time inunselected patients, suffered a high refusal and dropoutrate.27 This finding confirms the view that the cognitivecomponent of CBT is important in enabling patients toattempt and sustain behavioral changes.

Which Patients Respond?Can we predict which patients will respond to CBT? Sub-group analysis of the 2 positive CBT trials23,26 offers someindications. In neither trial did duration of illness or thepresence of comorbid depressive or anxiety diagnosispredict response. Predictors of poor response in theKing’s trial26 were the active pursuit of medical retire-ment and disability claims, and in the Oxford trial, poorsocial and occupational functioning before becoming ill(unpublished data). The observations are tentative, how-ever, and at present CBT is worth trying in all patientswith CFS.T

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THE IMPLICATIONS OF THE EVIDENCEFOR THE EFFECTIVENESS OF CBT

The evidence reviewed above has a number of implica-tions for the clinical management of patients with CFS:These include the following: (1) we now have an evi-dence-based approach to treatment for patients withCFS; (2) patients are very unlikely to be made worse by atreatment that involves increases in activity; and (3) asubstantial part, at least, of patients’ disability is reversiblewith appropriate treatment.

How Does It Affect Our Understanding of CFS?It must be emphasized that these results do not indicatethat CFS is a purely “mental” condition. They do, how-ever, strongly suggest that avoidance of activity and asso-ciated illness beliefs are important illness-perpetuatingfactors and clearly demonstrate that both symptoms anddisability are at least partly reversible. This is importantwhen advising patients and others about the nature oftreatment and the outcome.

What Are the Implications for ClinicalServices?CBT is the only treatment for CFS that has, so far, beenshown to be substantially helpful to patients with CFS ina randomized clinical trial that has been replicated in anindependent center. It could, therefore, be argued that allclinical services that purport to cater to patients with CFSshould offer this form of intensive individual CBT. This isnot currently the case. The obstacles to such a develop-ment are partly attitudinal and partly practical.28 Themain attitudinal block stems from the view that to em-brace this treatment would be to admit that CFS is apurely “mental” condition—a viewpoint that is mis-guided but understandable. The main practical obstacleto such service development is the shortage of appropri-ately skilled therapists. What can be done to improve thesituation?

First, the case should be made for the training of moretherapists so that specialist services can be offered. Sec-ond, a case can be made for the adoption of the principlesof CBT by clinicians (physicians, nurses, or others) withlittle or no training in psychological therapies, as part oftheir routine clinical practice when seeing patients withCFS and similar conditions.

CBT for CFS in Routine Clinical PracticeIn many clinical settings where patients with CFS areseen, CBT is simply not available. In such cases it may bepossible to apply the principles of formal CBT listed inTable 1 and described elsewhere.15,29 This approach maybe regarded as CBT-informed practice.

The starting points for CBT-informed practice are acomprehensive “biopsychosocial” approach to the pa-tient’s problems, an empathic acceptance of the reality oftheir symptoms, and a collaborative relationship. From

this basis, the patient is encouraged toward the view thatalthough their illness has a physical basis, psychologicaland social factors are also likely to be relevant to theirrecovery; they are also informed of the evidence indicat-ing that, in many cases of CFS, the illness is neither per-manent nor untreatable.

An analysis of the potentially important obstacles torecovery in their particular case is then made by a briefindividualized review of their beliefs, behavior, and situ-ation. This may be aided by the use of simple diaries. Thepatient is then encouraged to consider change. For exam-ple, they are then encouraged to question a belief thatthey cannot improve, to normalize and then increasetheir level of activity in a gradual way, and to activelytackle practical problems in relationships and employ-ment.

If the patient is willing to consider change, they arehelped to “try out” this new approach under the ongoingsupervision of the clinician. The emphasis is on self-helpwith support and guidance.

Several investigators are currently evaluating such sim-plified forms of CBT. In these experimental therapies,relatively brief patient contact is supplemented by de-tailed self-help manuals. The initial results of these stud-ies appear to be encouraging, but the results of random-ized trials are required before simple CBT-informedpractice can be accepted as definitely effective. Further-more, whereas such an approach is particularly likely tobe helpful in milder and less chronic cases, referral forspecialist CBT may still be required for established casesof CFS.

FUTURE RESEARCH

There is now an urgent need for the forms of CBT thathave been evaluated in the treatment of CFS to be furtherdeveloped. One need is to develop and evaluate brieferand simpler treatment approaches such as those de-scribed above to allow more patients to benefit from theapproach. The second is to maximize the effectiveness ofthe therapy to determine the greatest possible therapeuticeffect that can be achieved. The third is in the applicationand evaluation of CBT for certain special groups.

ChildrenThe need for effective treatments for children and adoles-cents with CFS is urgent. Although CBT has been re-ported to be helpful,30 no randomized trials have yet beenpublished.

FibromyalgiaCBT may also be useful in the related syndrome of fibro-myalgia. The only randomized trial so far published indi-cated only a modest benefit from CBT. However, the CBTused in this study was given in a group format and wasweakened by poor compliance.31 Evaluations of intensive


108S September 28, 1998 THE AMERICAN JOURNAL OF MEDICINEt Volume 105 (3A)

individual CBT of a type similar to that found to be effec-tive in CFS are therefore required.

CONCLUSIONS

The cognitive behavioral model offers a plausible andconstructive understanding of what may otherwise bethought of as a mysterious illness. It leads to a flexibleindividualized approach to treatment that is well suited toa heterogeneous condition such as CFS. Although the ini-tial evidence for the efficacy of this approach was mixed,the most recent studies demonstrate that it can producenot only better illness adjustment but also a major reduc-tion in disability for the majority of patients. Given thefinancial impact of CFS, this type of treatment is likely tobe cost-effective. The implications for medical servicesand for clinical practice require a major re-evaluation ofhow patients with this chronic disabling condition aremanaged in the future.

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Cognitive behavior therapy for chronic fatigue syndrome: efficacy and implications