Expert Opinion Paper
Medical Advisory Board of the National Multiple Sclerosis Society
Treatment Recommendations for Physicians
Fatigue is the most common MS symptom—experienced by 75 to 95% of people with the disease. Approximately 50 to 60% of people with MS describe fatigue as one of their most troubling symptoms, regardless of their disease course or level of disability. The Social Security Administration recognizes fatigue as a significant cause of unemployment among people with MS.
Fatigue was recently defined by the Fatigue Management Panel of the Multiple Sclerosis Council on Clinical Practice Guidelines as:
A subjective lack of physical and/or mental energy that is perceived by the individual or caregiver to interfere with usual and desired activities.
Based on clinical experience and careful review of the medical literature and research findings pertaining to MS-related fatigue, the Medical Advisory Board of the National MS Society makes the following recommendations:
b. Adjustment of any medications that may be producing excessive fatigue and/or sleepiness. Many common medications, including anticonvulsants, antihistamines, antihypertensives, sedatives, and certain antidepressants, have fatigue and/or sleepiness as a side effect.
c. Management of any conditions or symptoms that interfere with sleep (e.g., sleep apnea, leg spasms, depression, MS symptoms such as bladder dysfunction, spasticity, or pain). Research indicates that 25 to 35% of people with MS experience disturbed sleep, which may contribute significantly to daytime fatigue.
d. Management of any MS symptoms that may be producing additional fatigue. Symptoms such as weakness, spasticity, and ataxia may significantly increase the amount of exertion needed to carry out daily activities.
e. Education about energy effectiveness strategies—defined as “the identification
and development of activity modifications to reduce fatigue through a systematic
analysis of daily work, home, and leisure activities. . . .” These strategies
are frequently taught by a nurse or rehabilitation specialist (e.g., occupational
and/or physical therapist)
ii. Use of assistive devices to conserve energy
iii. Environmental modifications to make activities more energy-efficient
iv. Cooling strategies to avoid the fatigue caused by elevations in core body temperature due to heat, exercise-related exertion, and fever
v. Regular aerobic exercise, geared to the person’s ability, to promote cardiovascular health, strength, improved mood, and reduce fatigue
vi. Stress management techniques
a. Pharmacologic management of chronic fatigue that remains after other factors have been addressed. Although no drugs have been approved by the U.S. Food and Drug Administration specifically for MS, recommended medications include:i. Amantadine (Symmetrel®): An antiviral agent that has been used to treat MSrelated fatigue since the early 1980s. Approximately 20 to 40% of mild to moderately disabled people with MS experience significant reductions in fatigue while using amantadine. Side effects are generally mild. The recommended dose of amantadine is 100 mg morning and early afternoon.b. Maintenance of energy effectiveness strategies as previously described
ii. Modafinil (Provigil®): A wakefulness-promoting agent currently approved by the FDA for the treatment of narcolepsy, which has been shown to reduce selfreported fatigue in people with MS. The recommended dose of modafinil is 200 mg per day.
iii. Pemoline (Cylert®): A central nervous system stimulant that has been used for many years to treat MS-related fatigue. While study results have been contradictory, pemoline may be an effective therapy for people with MS who do not respond to amantadine or modafinil. The usual effective dose is 75–140 mg per day (titrated slowly from a starting dose of 18.75 mg), divided into 2–3 equal doses prior to mid-afternoon. As directed by the Food and Drug Administration, Abbott Laboratories, the manufacturer of Cylert®, has recommended evaluation of liver function prior to starting this medication, followed by bi-weekly liver function evaluations while the drug is being used. [Note: Although hepatotoxicity has been reported primarily in children taking Cylert® for other conditions, no toxicity has been reported in patients with MS. Nevertheless, extra care should be taken when prescribing this medication to any patient who is using Cylert® in combination with other drugs that may be hepatotoxic.]
iv. Methylphenidate (Ritalin®): A central nervous system stimulant that has been used to treat MS-related fatigue. The usual effective dose is 10–20 mg early in the morning and again at noon. Those individuals who experience little or no fatigue in the morning can take a single dose in the early afternoon.
Note: Prokarin, a drug containing histamine, caffeine, and other undisclosed ingredients, has been marketed to pharmacists for compounding (creating a preparation using the ingredients) for individual patients. It was reported in a recent controlled trial to reduce fatigue in a small sample of patients with either relapsing-remitting or progressive MS. It is the opinion of this board that whileProkarin does not appear to be harmful, its level of benefit does not justify itsvery high cost.
Fatigue is a complex, potentially debilitating symptom experienced by
the majority of people with MS. Anyone experiencing ongoing fatigue, or
the sudden onset of severe, disabling fatigue should consult his or her
physician so that the factor(s) contributing to the fatigue can be identified
and effectively managed. Successful treatment of fatigue may require a
variety of interventions, including behavioral adaptations, environmental
modifications, and medication.
Copyright © 2002, National Multiple Sclerosis Society