Current Status and Future Directions
Because there is no known cure, CFS treatment evolves around supportive management. Few therapies thought to be helpful for CFS have been tested for efficacy in double-blind, placebo-controlled trials. A meta-analysis of 59 randomized controlled trials and 11 non-randomized controlled trials of interventions for CFS found that graded exercise therapy and cognitive behavioral therapy have the clearest evidence of benefit. The four randomized controlled trials that assessed the effectiveness of pharmacologic treatment had inconclusive results. Furthermore, there are no drugs approved by the FDA for the treatment of CFS; therefore, most drugs used to treat CFS are done so "off-label." Although there are no evidence-based standards established in the pharmacologic treatment of CFS, the CDC includes pharmacologic therapy as an important option in providing the "aggressive" symptom management many persons with CFS need to increase functional ability and quality of life. Therefore, expert opinion is included in the following summaries as the currently best-available guide for pharmacologic and other treatments for CFS.
Until the causes of CFS are better defined, Lucinda Bateman, MD, one of the few clinicians in the United States who specializes in the treatment of CFS and fibromyalgia, recommends following these general principles of supportive management: diagnose and treat comorbid conditions; prioritize and treat the major disabling symptoms, but revisit diagnosis and economize medications; and encourage patients to "pace" activity to prevent deconditioning without precipitating relapse. Furthermore, Dr. Bateman considers pacing as the most effective way to reduce global CFS symptoms and minimize "flares" or relapse. A randomized controlled trial to evaluate the effectiveness of adaptive pacing therapy as treatment for CFS is currently underway in the United Kingdom.
Treatment will eventually be directed more at the cause of illness as subsets of persons with CFS from specific etiologies are identified. For example, a randomized, double-blind, placebo-controlled clinical trial is currently underway at Stanford University to further investigate the effectiveness of the antiviral drug valganciclovir (Valcyte; Roche Pharmaceuticals, Nutley, NJ), in the treatment of CFS. In a previous open-label study, 9 out of 12 (75%) persons with chronic debilitating fatigue with central nervous system dysfunction and high IgG antibody titers against EBV and human herpesvirus-6 (HHV-6) experienced near total resolution in symptoms with a significant decrease in EBV viral capsid antigen IgG titer and a decrease, although not statistically significant, in HHV-6 IgG titers after a 6-month treatment with valganciclovir.
Dr. Bateman tailors treatment to focus on the most bothersome symptoms in her patients, which can include fatigue, sleep disturbance, pain, orthostatic intolerance, and/or mood. The presence of a symptom does not necessitate treatment if the symptom is not significantly bothersome. Dr. Bateman and other CFS experts recommend economizing the use of medications by using one drug to target several symptoms. For example, anticonvulsant drugs like gabapentin (Neurontin; Pfizer, Inc., New York, NY) can be used effectively to treat sleep, mood, and pain in some CFS patients. Selective serotonin reuptake inhibitors (e.g., sertraline HCL and fluoxetine HCL) and serotonin and norepinephrine reuptake inhibitors (e.g., venlafaxine and duloxetine) can be used to improve cognition as well as to treat mood, pain, and sleep.[31,34]
Fatigue is best managed by reduction in activity and lifestyle adaptations, but medications such as modafanil (Provigil; Cephalon, Inc., Frazer, PA), adderall (Dexedrine; GlaxoSmithKline, Philadelphia, PA), and methylphenidate HCL (Ritalin; Novartis Pharmaceuticals, New York, NY) may also be considered.[31,34] Buproprion XL (Wellbutrin XL; GlaxoSmithKline, Philadelphia, PA) may be helpful with concentration and attention difficulties related to mental fatigue.[31,34]
Sleep disturbance can be minimized with simple sleep hygiene measures ( Table 3 ). However, these measures may be inadequate, and medication to initiate or sustain sleep may become necessary. Sleep "initiators" used for CFS include zolpidem (Ambien; Sanofi-Aventis, Bridgewater, NJ), eszopiclone (Lunesta; Sepracor Inc., Marlborough, MA), and ramelteon (Rozerem; Takeda Pharmaceuticals, Deerfield, IL). Sleep "sustainers" include trazodone (Desyrel; Bristol-Myers Squibb, Princeton, NJ), tricyclic antidepressants, benzodiazepines, and muscle relaxants.[31,34]
Medications for Orthostatic Intolerance
Pharmacologic options to minimize orthostatic intolerance include the drugs midodrine (ProAmatine; Shire Pharmaceuticals, Wayne, PA), fludrocortisone (Florinef; Bristol-Myers Squibb, Princeton, NJ), and propranolol XL (Inderal; Wyeth Pharmaceuticals, Madison, NJ),[31,34] although a randomized drug trial indicated fludrocortisone as monotherapy for orthostatic intolerance can be ineffective. Additional treatment options may also be considered. Administration of an intravenous (IV) infusion of 1 L of normal saline for several consecutive days to weeks to improve orthostatic intolerance and fatigue with CFS has been used successfully by Dr. David Bell, an internationally recognized expert on adult and pediatric CFS, as well as by other CFS clinicians. The mechanism by which this intervention is effective is unknown and warrants scientific inquiry. There is some evidence in cardiology literature that increasing intravascular volume with intravenous normal saline can alter the autonomic response that triggers neurally mediated syncope, a potential endpoint of neurally mediated hypotension with CFS.[29,38] A case report in the literature cites improved performance during graded exercise testing in a woman with CFS after daily treatment with 1 L of 0.9% saline via a central venous line over a period of 417 days. Improvement in a variety of cardiopulmonary measures as well as subjective report by the study participant of improved activity tolerance, reduced muscle fatigue and pain, and improved orthostatic tolerance were cited. Although double-blind studies for efficacy are lacking, the use of intravascular volume expansion for relief of fatigue in CFS patients with orthostatic intolerance is regarded as a "reasonable option" in the scientific literature.
Nonpharmacologic interventions for orthostatic intolerance include increasing oral fluids; increasing dietary salt or salt tablet supplementation up to 2000 mg/day as tolerated; avoiding overheating and prolonged standing; wearing support hose; and, if able to tolerate exercise, performing physical activity in a supine or seated position, or in water.[31,41]
Graded activity and exercise are advisable to avoid deconditioning without causing relapse. With graded exercise, an individual is instructed to start any activity slowly and to gradually increase the level and duration of the activity. Persons with CFS should be taught that all exercise must be followed with rest in a ratio of 1:3 (1 minute of exercise followed by 3 minutes of rest). Some individuals cannot tolerate longer than 2 to 5 minutes of exercise without risking a relapse. A systematic Cochrane review of five randomized controlled trials investigating the effect of exercise on CFS found that exercise therapy can lessen fatigue and improve physical functioning, but persons with CFS had a higher dropout rate than controls. The authors conclude that exercise therapy may benefit some persons with CFS, that rest and pacing may be more acceptable than exercise therapy to individuals with the disorder, and that additional randomized studies are needed to measure outcomes such as adverse effects and quality of life over time. Caution in prescribing exercise therapy to persons with CFS is supported by research findings that indicate the functional capacity of individuals with CFS, as measured by cardiopulmonary exercise testing, can range from no impairment to severe impairment, and that relapse in physical symptoms of CFS may be delayed by as much as 5 days after exercise.
Alternative therapies, such as acupuncture, meditation, and biofeedback, have been helpful to some persons with CFS, although scientific evidence to support these treatments is lacking. Yoga and tai chi may be effective for individuals with CFS who can tolerate more activity. Few clinical trials address the efficacy of nutritional and herbal supplements in the treatments of CFS. The meta-analysis of interventions for CFS previously cited in this paper indicated that one or two trials showed that essential fatty acid and magnesium supplementation had beneficial effects in the reduction of symptoms.
Persons with CFS and their families face numerous challenges. Variable and unpredictable symptoms cause difficulty in day-to-day planning; limited stamina interferes with activities of daily living; memory and concentration problems seriously impact work or school performance; and uncertain prognosis, loss of independence, loss of economic security, and alterations in relationships with family and friends oftentimes complicate the illness experience. Validation of the illness experience and support for how disabling symptoms can be paramount in establishing a therapeutic relationship between the health care provider and individuals with CFS. A therapist can be helpful for persons with CFS struggling with the grief, anger, guilt, depression and anxiety that commonly accompany any chronic illness. The use of cognitive behavioral therapy has been helpful for some with CFS, but evidence indicates results are inconsistent.
Because employment and schooling may be profoundly affected for persons with CFS, it is important to realize that the disorder is a disabling condition for which affected individuals may be protected under the Americans with Disabilities Act. Primary health care providers are usually needed to participate in the disability application process for people with CFS and careful documentation of clinical care is paramount to facilitate the benefit process.
J Midwifery Womens Health. 2008;53(4):289-301. © 2008 Elsevier Science, Inc.
Cite this: Chronic Fatigue Syndrome: Implications for Women and Their Health Care Providers During the Childbearing Years - Medscape - Jul 01, 2008.