Treatment of Chronic Fatigue Syndrome

Abstract & Commentary

By Joseph E. Safdieh, MD, Assistant Professor of Neurology, Weill Medical College, Cornell University. Dr. Safdieh reports no financial relationships relevant to this field of study.This article originally appeared in the June issue of Neurology Alert. At that time it was peer reviewed by M. Flint Beal, MD, Anne Parrish Titzel Professor, Department of Neurology and Neuroscience, Weill Cornell Medical Center, New York, NY. Dr. Beal reports no financial relationship to this field of study.

Synopsis: Chronic fatigue syndrome, as defined by clinical symptoms, may improve with a combination of behavior therapy and graded exercise.

Source: White PD, et al. Comparison of adaptive pacing therapy, cognitive behavior therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): A randomized trial. Lancet 2011;377: 823-836.

Chronic fatigue syndrome (CFS) is a syndrome defined by the presence of disabling fatigue in the absence of an alternative diagnosis. The prevalence of CFS is between 0.2% and 2.6% worldwide and the prognosis is poor if left untreated. Because CFS is a disorder with no scientifically established etiology, treatment often is attempted by treating the fatigue and providing supportive, symptomatic care. Prior small studies have demonstrated that cognitive behavioral therapy (CBT) and graded exercise therapy (GET) may be effective for treating CFS. However, no large trials were performed and CFS advocacy groups have reported that CBT and GET may be harmful. These groups have recommended adaptive pacing therapy (APT). The authors performed a randomized trial to compare the effectiveness of CBT, GET, and APT added to specialist medical care (SMC), and SMC alone.

SMC was provided by physicians with expertise in CFS. Subjects all received standard advice, such as instructions on avoiding extremes of activity and getting adequate rest. SMC physicians also were allowed to use pharmacotherapy to treat individual symptoms. CBT was done on the basis of the fear avoidance theory of CFS, which regards CFS as being reversible and associated with abnormal cognitive and behavioral responses. GET was performed based on the deconditioning and exercise intolerance theories of CFS and was accomplished by gradually escalating mild aerobic activity. APT was based on the theory that CFS is organic and irreversible and for whatever reason, results in a finite amount of available energy. APT focused on achieving optimum adaption to CFS, teaching subjects to maintain activity diaries and to avoid "overdoing it" by not undertaking activities that demand more than 70% of subjects' perceived energy limit.

Of the 3158 patients screened for eligibility, only 641 were able to be randomly allotted to treatment groups. One hundred sixty patients received APT+SMC, 161 received CBT+SMC, 160 received GET+SMC, and 160 received SMC alone. Due to the nature of the study design, subjects were not blinded to treatment type received. Baseline characteristics of the groups were generally similar, with overall mean age of 38, duration of illness of 32 months, 77% female and 92% white.

Compared with SMC alone, mean fatigue scores at 52 weeks were lower in the CBT and GET groups, but not in the APT group. Compared with SMC alone, mean physical function scores were higher in the CBT and GET groups, but not in the APT group. Serious adverse events were very rare (< 2%) in all groups. The authors concluded that CBT and GET can be safely added to SMC to moderately improve outcomes in CFS, but APT is not an effective addition.


CFS is a diagnosis that is defined purely on clinical symptoms. Many neurologists are quite dubious of whether CFS is a "real disease" or a manifestation of depression or another psychiatric or psychological process. Of course, fatigue can be caused by many symptoms, and before labeling a patient with CFS, primary medical and neurological causes should be excluded with appropriate testing. Whatever the cause of CSF is eventually determined to be, there are many patients who clearly experience disabling chronic fatigue and often end up in the care of a neurologist. Once alternative diagnoses, including sleep disorders, are excluded, my approach is not to focus on the "why" but on the "what to do." Pharmacotherapy is certainly an option. Stimulants, antidepressants, and amantadine all play a role. In this paper, we learn that recommending a submaximal escalating exercise program and CBT are useful additions to standard therapy. These therapies are safe and moderately effective. Patients with CFS should be encouraged to participate in basic aerobic exercise regimens and to consider CBT. Research into the etiology of this disorder is ongoing, but there are effective strategies that can be recommended even without understanding the underlying cause.