Nancy Klimas, MD, is Professor of Medicine at the University of Miami VA Medical Center, where she conducts research on immunologic abnormalities in chronic fatigue syndrome (CFS).

Marsha Wallace, MD, a board-certified internist, is Assistant Professor of Medicine and Healthcare Sciences at George Washington University Hospital in Washington, D.C.


(Excerpted with permission from an article published in the June 2000 issue of The Journal of Women's Health & Gender-Based Medicine.  For information on obtaining reprints of the full article, call the publisher at 914/834-3100.)

How can the primary care physician properly diagnose CFS?

Dr. Klimas:   One sign of the illness is orthostatic intolerance (OI), which causes autonomic dysfunction. This may happen early, or it may be a result of deconditioning. An estimated 60% of women with CFS will have OI.

A typical example is the woman who goes shopping and must stop 15 minutes into the activity because she feels a sudden need to
sit down. This is not a fainting spell, dizziness or fatigue. Rather, the patient is experiencing a bradycardic hypotensive moment, and she sits or lies down to prevent symptoms from worsening.

Patients describe this as the “cognitive cloud of fatigue” because they are going along fine when an abrupt wave of symptoms, such as total body pain or aches, forces them to stop.

Hand in hand with the drop in blood pressure comes a host of nonautonomic symptoms, such as swollen lymph nodes, sore throat, total body pain, myalgia and arthralgia. The presence of OI can and should be tested by a tilt-table test. I caution primary care physicians to have a tilt-table test performed by a cardiologist who has experience with CFS because these patients are at high risk for cardiac complications.

That said, there is a very straightforward workup to exclude other common illnesses that occur with fatigue. Most important is a symptom-driven physical examination with a complete blood count (CBC), Chem23, sedimentation rate, ANA, and TSH,
T3 and T4 levels.

Dr. Wallace:   A classic case will be very obvious. There is little else that can cause such an abrupt change in function and the accepted complex of symptoms. As with migraines, a good medical history is key, as there are no definitive tests available to confirm the condition.

The physician needs to rule out other plausible causes of the symptoms such as sleep disorders, chronic infection, depression, malignancy, systemic illnesses and adrenal insufficiency, based on a thorough history and physical exam.

The process of diagnosis can take months, and as new symptoms or a change in symptoms arises, the diagnosis should be reviewed. As time goes on, I look for more esoteric causes, such as porphyria or
lead poisoning.

What is the recommended approach to treatment?

Dr. Wallace:   It is important to approach management of CFS with the understanding that these patients do not metabolize drugs normally, typically demonstrating a low tolerance for any kind of medication. It is essential to use very small doses and begin one or two drugs at a time to monitor the effect and, after four to six weeks, to introduce additional medication if necessary.

I focus my treatment in five major areas:

Orthostatic Intolerance.  Patients are treated as if they have a diminished blood volume and are dehydrated. The theory is that too much blood pools in their lower extremities. To counteract this, patients are instructed to increase their fluids to two to three quarts a day and to increase salt through intake in food, salt tablets and occasionally intravenous saline. If this is not sufficient, I may  prescribe fludrocortisone to increase blood volume.

Another approach is the use of vasoconstrictors. For this, I prescribe the newly approved drug Midodrine. Although these measures are not always effective, it is all some patients need to regain substantial functioning. Beta-blockers and clonidine are also useful adjuncts that blunt inappropriate tachycardia.

Sleep.  A drug that seems most effective is Ambien, which works well for a specific sleep disorder often seen in CFS and fibromyalgia patients—alpha intrusion into delta sleep. Although it has some potential for addiction, Klonopin is a very good sleep drug because it also helps with pain. I use the smallest dose possible. Another effective sleep drug is Neurontin, which also helps reduce pain.

Tricyclic antidepressants (TCAs) can aid sleep, but if I use them, I use tiny doses (5 to 10 mg). The caution with TCAs is that they can cause low blood pressure and tachycardia.

Pain.  Although controversial, I believe that long-acting narcotics are needed to relieve pain among these patients. Because there is no inflammation causing the pain, NSAIDs are not likely to be effective. Anticonvulsant drugs, such as Neurontin, can be useful.

General Support.  To help with cognitive problems, I rely on stimulating drugs, such as Ritalin, Welbutrin and a new drug, Provigil, which tend to wake up the brain.

For energy levels, there are several complementary preparations I use as adjuncts. I often begin with vitamin B12 injections (up to 5,000 mg three times/week). Other preparations I recommend include NADH, evening primrose oil (up to 5,000 mg/day) and glutathione by injection.

Coping skills.  It is essential to work with patients to accept their limitations. I encourage my CFS patients to do some muscle toning and some light physical activity [as they are able].

Relaxation techniques, such as yoga or meditation, can be useful, but women should be cautious about yoga, which can reduce blood pressure, a preexisting problem for some patients.

Certainly, if concomitant depression is present, it should be treated, in which case the patient’s mood is likely to improve but the chronic fatigue syndrome will not.

Dr. Klimas:  I begin with sleep, borrowing from the research on sleep dysfunction in fibromyalgia. The most effective drugs are TCAs in low doses, preferably Sinequan elixir, which gives patients eight hours of sleep and simultaneously reduces pain.  I begin with 5 mg and work up to 20 to 25 mg.

Next I deal with pain. More often than not, patients arrive with a great deal of pain medication, most of which are short-acting, as-
needed medications.

If the patient is having withdrawal symptoms as the pain medication is wearing off, I wean the person from their current regimen and then look for nonpharmacological alternatives, such as massage, stretching and physical therapy (whirlpool, hot tubs).

These ancillary options, along with NSAIDS, seem to work for all but 4% to 5% of patients. For the few who require pain medication, I choose the long-acting, 24-hour opiates at a low dose.

When autonomic dysfunction is present, the goal is to increase plasma volume. Generally, if the patient has a positive
tilt-table test and increasing salt and water makes her feel better for a few weeks, the kidneys become efficient at getting rid of the extra sodium, at which time the patient should be prescribed fludrocortisone (Florinef).

Another route is to prescribe alpha1-agonists, such as pseudoephedrine. The most selective alpha1-agonist is Midodrine.

The third option, often used in combination with one of the other drugs, is to use a beta-blocker to reduce the pulse, allowing for a longer fill time and slowing of the impulses to the stretch receptors.

The hypothalamic-pituitary-adrenal axis (HPA) interventions have not been well studied. Only cortisol has been looked at on a limited basis, and the results were inconsistent. The danger is that cortisol may have to be given lifelong. Thus, it is premature to recommend this drug until we have a better understanding of its efficacy.

With regard to the immune system, we have a system that is hyperactive but not working properly. There is some controversy about using SSRIs as immunomod-ulators. Anecdotally, I recommend limiting their use to nondepressed CFS patients and giving a four to five month trial to assess improvement.

Are there any alternative treatments contraindicated for CFS?

Dr. Wallace:   I try to discourage my patients from trying expensive, unproven treatments, such as chelation therapy and mercury detoxification (dental fillings removed).