CHRONIC FATIGUE SYNDROME:
A Primer For Physicians and Allied Health Professional
© 1992 Massachusetts CFIDS Association
USE OF MEDICATIONS FOR SYMPTOMATIC RELIEF
There is currently no drug therapy known to cure CFIDS. Common medications can provide symptomatic relief. These drugs are generally administered following normal practice, but this should be modified through experience with individual patients. Since the pathophysiological mechanisms underlying CFIDS symptoms are probably not the same as those for which these drugs were developed, many patients will not respond to conventional drug dosages. Much of the information given here must be regarded as anecdotal, since at this writing, results of controlled studies on the effectiveness of the medications discussed here specifically in CFIDS populations are not available. In many instances, placebo effects have not been ruled out. Several experimental drugs are also under investigation to determine if they can provide relief by affecting one or more basic pathophysiologic mechanisms.
It is important to note that patients with CFIDS frequently experience side effects and may tolerate only small doses of any medication.
Sleep Disorders
As a first step, it is most important to treat any sleep disorders which are associated with CFIDS and/or fibromyalgia[59]. A return to restorative sleep can help reduce the impact of other symptoms such as arthralgias and myalgias. Sleep hygiene techniques, ie: maintaining fixed times for retiring and arising, avoidance of caffeine, etc., may help, but often patients do need medication to restore restful sleep. The possibility of sleep apnea or nocturnal myoclonus should not be overlooked. Patients may be referred to a sleep lab if a poor response to initial therapy is seen.
The medications most often reported to be beneficial include the tricyclics; doxepin (Sinequan, 10-25 mg - available in an elixir form for smaller doses), nortriptyline (Pamelor, 10-50 mg) and amitriptyline (Elavil, 10-50 mg.), as well as the serotonin uptake inhibitor trazodone (Desyrel, 25-100 mg); and, in certain cases the benzodiazepine clonazepam (Klonopin 0.5-1.0 mg). Klonopin, like other benzodiazepines, may be habituating, but it can be used in combination with one of the low dose antidepressants mentioned previously for a possible synergistic effect.
Prescribing physicians should watch for possible morning grogginess and/or cognitive dysfunction secondary to hypnotics or to other sedating medications such as antihistamines. In addition, short acting sedative and antianxiety medications, including alprazolam (Xanax), triazolam (Halcion), and lorazepam (Ativan) may produce a "rebound" or anxiety-like withdrawal effect which can exacerbate CFIDS. Keeping these precautions in mind, the treatment of the sleep disturbance in CFIDS along with lifestyle changes are the most effective interventions presently available.
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HeadacheNon-steroidal anti-inflammatory agents may help with muscle tension forms of headache. It has been reported that Calan SR and other calcium channel blockers are effective for migraines, but headaches may be so severe and disabling that narcotics may be necessary. If a neuritic component is present, carbamazepine (Tegretol) may be of use. Chromolyn sodium (Nasalcrom) has been used successfully for sinus pressure headaches without the possible drowsiness of antihistamine-decongestant alternatives. Diamox, in low doses of the long acting form, is said to be useful for pressure headaches.
Arthralgias and Myalgias
Improved sleep and diet changes help some patients. Flexeril is said to be useful for muscle spasms and fibromyalgia. Clonazepan (Klonopin) and alprazolam (Xanax) and non-steroidal, anti-inflammatory drugs may also be effective. A moderate exercise program, as described previously, should be considered in conjunction with drug therapy.
Gastrointestinal symptoms
H-2 blockers such as Zantac (rantidine, in usual ulcer treatment dosage) have been found useful in about 20% of patients[54]. There may be effects going beyond relief of dyspepsia possibly by means of an impact on immune system functioning.
Hypothyroidism
In those patients with concurrent hypothyroidism, Synthroid or Cytomel should be considered.
Candida Infections
Ketoconazole (Nizoral) and fluconazole (Diflucan) have been recommended in preference over nystatin for systemic Candida infections. Liver function testing is required for long-term therapy. These medications are only effective for proven systemic yeast infections. A mixture of nystatin powder, water and hydrogen peroxide has also been used successfully to treat thrush and tongue coating.
Fatigue
Medications which are being used to treat the symptom of fatigue include buproprion (Wellbutrin) 75 mg. q.d. - 150 mg. t.i.d., amantidine (Symmetryl, 100 mg. q.d. or b.i.d.), fluoxetine (Prozac, 5-20mg) every other day or q.d. (particularly when there is concomitant depression), and vitamin B-6 (not to exceed 150 mg. q.d.). Although controlled studies have not been done, there are anecdotal reports of success using intramuscular vitamin B-12 injections and intramuscular gamma globulin.
Depression
A subset of CFIDS patients do require pharmacologic treatment for associated major depression. Antidepressant medications may need to be prescribed at their usual therapeutic dose by a clinician familiar with their use. Note, however, that some patients can only tolerate lower doses or may need to be shifted to a different class of anti-depressants. Fluoxetine, (Prozac), a powerful serotonin uptake inhibitor seems also to improve energy levels in ways that is beyond its antidepressant effect. (However, it may need to be supplemented by one of the sleep assisting agents mentioned above.) Its availability in elixir form, makes low dose adjustments possible.
EXPERIMENTAL MEDICATIONS IMPACTING PRIMARY PATHOPHYSIOLOGY
Recently, treatment strategies for CFIDS have focused on immunomodulatory agents and antiviral agents. In the former category, some limited success and much controversy have been reported in experiments with gamma globulin, and with Kutapressin[54] (a porcine liver extract probably useful as an immune system modulator and/or antiviral agent). Alpha and gamma interferon have been used, but subcutaneous use at high doses may cause some patients to flare with severe lymphokine-like effects. Immunosuppressive agents such as corticosteroids, cyclosporin and methotrexate have not been helpful and indeed may worsen symptoms.
Naltrexone, an opiate antagonist with possible effects on T and B cells and natural killer cells, has been reported as helpful with cognitive dysfunctions[30]. An FDA-approved multicenter, double blind, trial of Ampligen has recently been completed. Ampligen, a form of mismatched, doublestranded RNA (poly I/poly C), appears to have anti-retroviral activity and is also being investigated for the treatment of AIDS and cancer. The drug seems to have a modulating effect on certain immune system functions. Preliminary reports have indicated significant positive responses in the severely ill CFIDS patients tested, but concern about side effects in some patients warrants continued research of this agent[60]. As with any drug in the investigation process, one must review the most current literature available from the FDA.
The current state of CFIDS diagnosis and management was summarized in a recent pamphlet for physicians published by the NIH[48]:
In brief, no strict recipe for treating CFS (CFIDS) exists, and sometimes several different treatment approaches may have to be tried before the patient reports benefit. Both the physician and the patient need to be open to reasonable treatment alternatives and appreciate the difficulty in assessing their benefit in (CFIDS)
A great deal of controversy and speculation surrounds (CFIDS): is it a single disorder or a heterogeneous mix of problems? What is its relationship to infections, the immune system, and mood disturbances? How can it best be treated? These and many more issues fuel the continuing broad debate, often leaving patients and their physicians frustrated. For now, physicians don't have all the answers. But in treating people with (CFIDS), they can draw on practices that have always made medicine a valued art: exclude alternative problems, ameliorate symptoms, and offer guidance and compassion.