MANAGEMENT OF FATIGUE
It is important to manage fatigue in the context of each patient suffering with it. Treatment of CFS, with its various major clinical and functional impacts, should be associated with a "biopsychosocial model" of management. Educating patients about their diagnoses is crucial. Physicians should emphasize distinction among factors that may have predisposed patients to develop, trigger, or perpetuate the illness.65 Progressive muscular rehabilitation, combined with behavioral and cognitive treatment, and appropriate choice of medications are essential parts of therapy.8
We will review the major concepts of CFS management and the evidence behind them.
Supportive and Symptomatic Treatment
Educating patients about CFS and validating their illness experience in addition to establishing a working alliance are the initial steps in the treatment.1,65 Direct the treatment toward the most problematic symptoms, as prioritized by the patient,1 and other illness-perpetuating factors.65 Encourage a well-balanced diet, and discuss with patients their nutritional habits. Advice about preventing over- and under-activity is essential. "Start low and go slow" is the correct advice for activities and exercise, the same as for using medications. Gear activities toward improving function in areas that are of greatest importance in achieving activities of daily living and remain open-minded about alternative therapies (electroacupuncture was helpful in one study95) and discuss them with your patients when appropriate.1 Consider referring or asking for consults and discuss that with patients early in the treatment.
Cognitive Behavioral Therapy
The short-term studies of cognitive behavioral therapy (CBT) in CFS have shown improvement in function and symptom management, especially in conjunction with other treatment modalities and in comparison to relaxation controls.96-99 Reports about good outcome following CBT ranged from 70%99 to none or even worsening of the symptoms.100 CBT was effective in treating symptoms of fatigue, mood, and physical fitness, but no improvement in cognitive function or quality of life was noticed in one study.101 Other studies showed limited effect on pain and fatigue.1 When treating CFS patients, the CBT therapist needs to be familiar with CFS, to be aware of the evidence for CFS as a biologically based disorder, and to validate the patient's experience of living with a misunderstood illness.
Exercise
CFS patients are very sensitive, and any treatment modality including exercise should start low and advance slowly. All exercises need to be followed by a rest period at a 1:3 ratio (i.e., 10 minutes of exercise: 30 minutes of rest). Review of the studies showed that exercise decreased the psychological stress102 and improved fatigue, functional capacity, and fitness significantly better than flexibility treatment,103 especially when associated with mood-enhancing, stress-reducing activities.104,105
Pharmacologic Treatment
Multiple studies have evaluated different treatment interventions, including recombinant erythropoietin, psychostimulants, corticosteroids, anti-inflammatory drugs, L-carnitine, and others.10,106 Antidepressants are the most common medications used in this regard; selegiline had a small but significant therapeutic effect independent of its antidepressant effect.107 Fluoxetine has been shown to improve overall symptoms and measures of immune function in one study,108 but failed in randomized, double-blind studies against placebo109 and graded exercise.110 Bupropion was effective for treatment of the fatigue and depressive symptoms associated with CFS in 9 fluoxetine-resistant patients111 and was also helpful in augmenting paroxetine in one case report.112 Venlafaxine was effective in 2 case reports.113 Moclobemide up to 600 mg a day for 6 weeks showed significant but small reductions in fatigue, depression, anxiety, and somatic amplification, as well as a modest overall improvement.114 Duloxetine may have a theoretical therapeutic benefit because of its characteristic of targeting pain. We could not find any study evaluating it in CFS patients. It is essential to mention that evidence to date does not support superiority of one medication over the others.
Other medications have been studied also. Clonidine enhanced both growth hormone (p=.028) and cortisol release (p=.021) and increased speed in the initial stage of a planning task (p=.023) only without affecting hormonal, physiologic, symptomatic, or neuropsychological measures.115 Low-dose hydrocortisone therapy caused increases in plasma leptin levels, with this biological response being more marked in those CFS subjects who showed a positive therapeutic response to hydrocortisone therapy.116 Essential fatty acid supplement rich in eicosapentaenoic acid was beneficial in a case report.117 Carnitine supplementation has been shown to reduce chronic inflammation and oxidative stress in hemodialysis patients and, in cancer patients, reduce fatigue and improve outcome.118 Treatment with modafinil was not beneficial in patients with CFS in one study.119
No therapeutic effects were found for natural killer cell stimulant,120 low-dose combination therapy of hydrocortisone and fludrocortisone,121 immunologic and antiviral substances, melatonin, or bright-light phototherapy.122
CONCLUSION
Evaluating and managing chronic fatigue is a challenging situation for physicians as it is a challenging and difficult condition for patients. A biopsychosocial approach in the evaluation and management is recommended. More studies about CFS manifestations, evaluation, and management are needed.
Drug names: bupropion (Wellbutrin and others), duloxetine (Cymbalta), clonidine (Catapres, Duraclon, and others), fluoxetine (Prozac and others), hydrocortisone (Cortef, Texacort, and others), modafinil (Provigil), paroxetine (Paxil, Pexeva, and others), selegiline (Eldepryl, Emsam, and others), venlafaxine (Effexor).
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