A variety of therapeutic approaches have been described as benefiting patients with chronic fatigue syndrome (CFS). Since no cause for CFS has been identified and the pathophysiology remains unknown, treatment programs are directed at relief of symptoms, with the goal of the patient regaining some level of pre-existing function and well-being. Although desirable, a rapid return to pre-illness health may not be realistic, and patients who expect this prompt recovery and do not experience it may exacerbate their symptoms because of overexertion, become frustrated, and may become more refractory to rehabilitation.

Pharmacologic Therapy

Pharmacologic therapy is directed toward the relief of specific symptoms experienced by the individual patient. Patients with CFS appear particularly sensitive to many medications, especially those that affect the central nervous system. Thus, the usual treatment strategy is to begin with very low doses and to gradually increase dosage as necessary and as tolerated. It is important to remember that use of any drug for symptom relief should be attempted only if an underlying cause for the symptom in question has not been found. The best example is use of a sleep-enhancing medication for non-restorative sleep. Although the patient may state that they sleep better, the sleep disorder remains obscured and thus treatment of the sleep disorder not given. It is also important to remember that all medications can cause untoward side effects, which may lead to new symptoms.

Prescription Medications

Nonsteroidal antiinflammatory drugs: These drugs can be used to relieve pain in CFS patients. Some are available as over-the-counter medications. Examples include naproxen (Aleve, Anaprox, Naprosen), ibuprofen (Advil, Bayer Select, Motrin, Nuprin), and piroxicam (Feldene). Prescription drugs include tramadol hydrochloride (Ultram), celecoxib (Celebrex), and refecoxib (Vioxx). These medications are generally safe when used as directed, but can cause a variety of adverse effects, including kidney damage, gastrointestinal bleeding, abdominal pain, nausea, and vomiting. Some patients may become dependent on certain of these agents.

Low-dose tricyclic antidepressants: Tricyclic agents may be prescribed for CFS patients to improve sleep and to relieve mild, generalized pain. Examples include doxepin (Adapin, Sinequan), amitriptyline (Elavil, Etrafon, Limbitrol, Triavil), desipramine (Norpramin), and nortriptyline (Pamelor). Effective dosages are often much lower than those used to treat depression. Some adverse reactions include dry mouth, drowsiness, weight gain, and elevated heart rate.

Other antidepressants: Newer antidepressants have been used to treat depression in CFS patients, although non-depressed CFS patients receiving treatment with serotonin reuptake inhibitors have been found by some health care providers to benefit from this treatment as well or better than depressed patients. Examples of antidepressants used to treat patients with CFS include serotonin reuptake inhibitors, such as fluoxetine (Prozac), restrain (Zoloft), and paroxetine (Paxil); venlafaxine (Effexor); trazodone (Desyrel); and bupropion (Wellbutrin). A number of adverse reactions, varying with the specific drug, may be experienced, but include agitation, sleep disturbances, and increased fatigue.

Anxiolytic agents: Anxiolytic agents may be used to treat symptoms of anxiety in CFS patients. Examples include alprazolam (Xanax) and lorazepam (Ativan). Clonazepam (Klonopin) is another member of this family of drugs that is used to control exaggerated nervous systems problems such as vertigo, burning or exaggerated tenderness in the skin, and "nervous" limb movements, may also be useful. However, they should not be used in the general treatment of CFS. Common adverse reactions include sedation, amnesia, and symptoms accompanying acute withdrawal (insomnia, abdominal and muscle cramps, vomiting, sweating, tremors, and convulsions).

Stimulants: Fatigue by itself is not a good indication for symptomatic therapy. However, if the fatigue represents lethargy or daytime sleepiness, treatment may be indicated. Trials of a wakefulness agent, modofanil (Provigil), have been completed, but the results have not yet been published. In a small group of patients with excessive sleepiness, the drug decreased symptoms compared with placebo. This drug is currently indicated only with the diagnoses of narcolepsy and excess daytime sleepiness when identified by the proper sleep studies.

Antimicrobials: An infectious cause for CFS has not been identified, and antibiotics, antivirals, and antifungal agents should not be prescribed for treatment of CFS, unless the patient has been diagnosed with a concurrent infection. A controlled trial of the antiviral drug acyclovir found no benefit for the treatment of patients with CFS. Indiscriminate use of antimicrobials can have a myriad of adverse effects, including increasing the risk for resistant organisms.

Anti-allergy therapy: Some CFS patients have histories of allergy, and these symptoms may flare periodically. Non-sedating antihistamines may be helpful for CFS patients with allergies. Examples include desloratadine (Clarinex), fexofenadine (Allegra), and ceterizine (Zyrtec). However, anti-allergy therapy has no efficacy in the treatment of CFS itself. Some of the more common adverse reactions associated with use of these medications include drowsiness, fatigue, and headache. Sedating antihistamines such as Benadryl can also be of benefit to patients at bedtime. The tricyclic antidepressants mentioned above also have potent antihistamine effects.

Antihypotensive and antitachycardia therapy: CFS does not respond to treatment with antihypotensive or antitachycardic drugs and general use of such medications may be harmful. However, such medications may be useful in specific circumstances. For example, fludrocortisone (Florinef) has been prescribed for CFS patients who have had a positive tilt table test. However controlled studies have not found Florinef alone effective in the general treatment of CFS patients. Beta blockers such as atenolol (Tenormin) have also been prescribed for patients with orthostatic hypotension. Midodrine (Proamatine), an agent that directly increases blood pressure, may be useful in selected patients identified by an abnormal tilt test. Increased salt and water intake is also recommended for these patients but should be done only under supervision of a health care provider. Adverse reactions include elevated blood pressure and fluid retention.

Experimental Drugs and Treatments

Ampligen is a synthetic nucleic acid product that was designed to stimulate the production of interferons, a family of immune response modifiers that are also known to have antiviral activity. Although it may not directly induce interferon, reports of double-blinded, placebo-controlled studies of CFS patients documented modest improvements in cognition and performance among Ampligen recipients compared with the placebo group. These preliminary results will need to be confirmed by further study. The Food and Drug Administration (FDA) does not approve Ampligen for widespread use, and the administration of this drug in CFS patients should be considered experimental. Ampligen is not widely available, is costly, and is generally not reimbursable through insurance programs. Finally, although most recipients of Ampligen tolerated the drug well, adverse reactions, such as liver damage, were reported and are still incompletely characterized.

Gamma globulin is pooled human immune globulin and contains antibody molecules directed against a broad range of common infectious agents. Gamma globulin is ordinarily used as a means for passively immunizing persons whose immune system has been compromised, or who have been exposed to an agent that might cause more serious disease in the absence of immune globulin. Gamma globulin is not effective in the treatment of CFS. Serious adverse reactions are uncommon, although in rare instances gamma globulin may initiate anaphylactic shock.

Corticosteroids. Controlled studies of corticosteroids have been conducted because some patients with CFS had a slight decrease in urinary cortisol levels. Some benefits were noted in patients treated with low dose hydrocortisone but the effects disappeared after one month. High dose replacement therapy had some benefit but was complicated by attendant adrenal suppression.

Dehydroepiandrosterone (DHEA) was reported in preliminary studies to improve symptoms in some patients. However, in subsequent studies, this finding has not been confirmed and the use of DHEA in patients should be regarded as experimental. Its use should be limited to patients with documented abnormalities in DHEA levels and function.

High colonic enemas have no demonstrated value in the treatment of CFS. The procedure can promote intestinal disease.

Kutapressin is a crude extract from pig's liver. It is not readily available and there is no scientific evidence that it has any value in the treatment of CFS patients. Kutapressin can elicit allergic reactions.

Neurosurgery. Unpublished reports of malformations at the base of the skull (Chiari malformations) as being causative of CFS have been circulated, and surgical intervention has been suggested in some of those unsubstantiated reports. Surgical intervention is not recommended at this time.